Materiały źródłowe

• #1 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  Major depressive disorder (MDD) has been ranked as the third cause of the burden of disease worldwide in 2008 by WHO, which has projected that this disease will rank first by 2030. […] The etiology of Major depressive disorder is believed to be multifactorial, including biological, genetic, environmental, and psychosocial factors. MDD was earlier considered to be mainly due to abnormalities in neurotransmitters, especially serotonin, norepinephrine, and dopamine. This has been evidenced by the use of different antidepressants such as selective serotonin receptor inhibitors, serotonin-norepinephrine receptor inhibitors, dopamine-norepinephrine receptor inhibitors in the treatment of depression. […] However, recent theories indicate that it is associated primarily with more complex neuroregulatory systems and neural circuits, causing secondary disturbances of neurotransmitter systems.

• #2

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Due to the clinical and etiological heterogeneity of major depressive disorder, it has been difficult to elucidate its pathophysiology. […] Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality. […] This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. […] Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors. […] The above-mentioned studies consistently show that the influence of genetic factors is around 30-40%. […] In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD.

• #3 Major depressive disorder: hypothesis, mechanism, prevention and treatment | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01738-y

  Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear, and additional diagnostic and therapeutic strategies for MDD still are needed. The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis hypothesis, cytokine hypothesis, neuroplasticity hypothesis and systemic influence hypothesis, but these hypothesis cannot completely explain the pathological mechanism of MDD. […] Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD, thus in recent years, great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies, further revealing the disease features of MDD. Furthermore, some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention, some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms.

• #4

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Due to the clinical and etiological heterogeneity of major depressive disorder, it has been difficult to elucidate its pathophysiology. […] Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality. […] This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. […] Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors. […] The above-mentioned studies consistently show that the influence of genetic factors is around 30-40%. […] In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD.

• #5 Major depressive disorder – Wikipedia

  https://en.wikipedia.org/wiki/Major_depressive_disorder

  Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, with about 40% of the risk being genetic. […] The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA-axis dysfunction, and structural or functional abnormalities of emotional circuits. […] The monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. […] HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. […] Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior, creating a pro-inflammatory profile in MDD. […] The newer field of psychoneuroimmunology suggests that cytokines may impact depression.

• #6 Major Depressive Disorder (MDD) | Takeda U.S. Medical

  https://www.takedamedconnect.com/diseases-and-conditions/neuroscience/major-depressive-disorder

  Major depression is one of the most common mental disorders in the United States, and an estimated 5% of adults suffer from depression globally. […] Major depressive disorder (MDD) is a chronic, heterogeneous disorder that causes changes in an individuals mood, thoughts, and behavior. […] While in recent years considerable advances have been made to understand the genetic risk factors associated with depression, its fundamental etiology remains poorly understood. […] Known risk factors are female sex, childhood history of abuse, family history and recent life stressors; however, we have yet to determine exactly how genetics influence environmental risk factors and vice versa. […] The genetic component to depression is thought to contribute 30-40% of variance, while non-genetic / environmental factors are thought to have an influence of 60-70%.

• #7 Major Depressive Disorder (MDD) | Takeda U.S. Medical

  https://www.takedamedconnect.com/diseases-and-conditions/neuroscience/major-depressive-disorder

  Major depression is one of the most common mental disorders in the United States, and an estimated 5% of adults suffer from depression globally. […] Major depressive disorder (MDD) is a chronic, heterogeneous disorder that causes changes in an individuals mood, thoughts, and behavior. […] While in recent years considerable advances have been made to understand the genetic risk factors associated with depression, its fundamental etiology remains poorly understood. […] Known risk factors are female sex, childhood history of abuse, family history and recent life stressors; however, we have yet to determine exactly how genetics influence environmental risk factors and vice versa. […] The genetic component to depression is thought to contribute 30-40% of variance, while non-genetic / environmental factors are thought to have an influence of 60-70%.

• #8 Major Depressive Disorder (MDD) | Takeda U.S. Medical

  https://www.takedamedconnect.com/diseases-and-conditions/neuroscience/major-depressive-disorder

  Numerous hypotheses have implicated different physiologic systems in depression, based on observed variations in function, including: […] Structural and functional abnormalities in neural circuitry […] Chronic stress and hyperactivity of the hypothalamic-pituitary-adrenal axis […] Biogenic monoamines, such as serotonin […] Inflammation, indicated by pro-inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, IL-1 and tumor necrosis factor alpha (TNF-) […] Neuropeptides such as substance P […] Hormone dysregulation, including thyroid hormones, estrogen dysregulation, and vasopressin. […] Research continues regarding these factors in relation to the pathogenesis of MDD.

• #9 Major depressive disorder: hypothesis, mechanism, prevention and treatment | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01738-y

  Due to the complexity of the pathological mechanism of MDD, accurate diagnostic approaches and pharmacological therapeutic strategies are relatively limited. Several hypothesis were developed to explain MDD pathogenesis pathogenic including (i) the hypothalamic-pituitary-adrenal (HPA) axis dysfunction hypothesis, (ii) the monoamine hypothesis, (iii) the inflammatory hypothesis, (iv) the genetic and epigenetic anomaly hypothesis, (v) the structural and functional brain remodeling hypothesis, and (vi) the social psychological hypothesis. […] However, none of these hypotheses alone can fully explain the pathological basis of MDD, while many mechanisms proposed by these hypotheses interact with each other. In recent years, great progress has been made in identifying novel pharmacological therapies, diagnostic criteria, and nonpharmacological preventive measures for MDD, initiating related clinical trials.

• #10 Major depressive disorder – Wikipedia

  https://en.wikipedia.org/wiki/Major_depressive_disorder

  Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, with about 40% of the risk being genetic. […] The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA-axis dysfunction, and structural or functional abnormalities of emotional circuits. […] The monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. […] HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. […] Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior, creating a pro-inflammatory profile in MDD. […] The newer field of psychoneuroimmunology suggests that cytokines may impact depression.

• #11 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  Major depressive disorder (MDD) has been ranked as the third cause of the burden of disease worldwide in 2008 by WHO, which has projected that this disease will rank first by 2030. […] The etiology of Major depressive disorder is believed to be multifactorial, including biological, genetic, environmental, and psychosocial factors. MDD was earlier considered to be mainly due to abnormalities in neurotransmitters, especially serotonin, norepinephrine, and dopamine. This has been evidenced by the use of different antidepressants such as selective serotonin receptor inhibitors, serotonin-norepinephrine receptor inhibitors, dopamine-norepinephrine receptor inhibitors in the treatment of depression. […] However, recent theories indicate that it is associated primarily with more complex neuroregulatory systems and neural circuits, causing secondary disturbances of neurotransmitter systems.

• #12

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. […] Serotonin is the most extensively studied neurotransmitter in depression. […] Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD. […] While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine. […] Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. […] Risk factors for depressive episodes change during the course of the illness.

• #13 Pathophysiology of depression | PPT

  https://www.slideshare.net/NemkumarJain2/pathophysiology-of-depression-93240319

  Depression is a mood disorder characterized by persistently low mood and loss of interest for at least two weeks. It affects thoughts, behavior, feelings and well-being. […] Major depressive disorder, also known as clinical depression, is characterized by a persistent low mood and loss of interest over at least two weeks. The exact causes are unknown but may involve genetic, biological, environmental, and psychological factors like stress, childhood trauma, and substance abuse. The pathophysiology of depression involves deficiencies in neurotransmitters like serotonin, norepinephrine, and dopamine according to the monoamine hypothesis. […] Pathophysiology 1) Monoamine Hypothesis: depression is related to a deficiency in the amount or function of cortical and limbic serotonin (5- HT), norepinephrine (NE), and dopamine (DA).

• #14 Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant

  https://www.mdpi.com/1420-3049/27/16/5091

  The monoamine hypothesis was formulated in the mid-1960s due to the underactivity of brain monoamines such as serotonin, dopamine, and NA in patients’ brains. […] The mechanisms of action for this hypothesis with antidepressants are: (1) inhibition of the reuptake of 5HT and/or NA; (2) antagonistic presynaptic inhibition of 5HT and/or NA; and (3) inhibition of monoamine oxidase (MAO). […] The inflammation theory has also been linked to depression, which surprises many people. […] Previous studies have shown that depressed people have increased levels of inflammatory mediators, such as C-reactive protein (CRP) and pro-inflammatory cytokines. […] The neurotrophin hypothesis also has a vital role in the pathophysiology of depression. […] BDNF promotes neurogenesis, which is part of neuroplasticity. […] The alteration of BDNF levels is known to be detrimental to neurogenesis in the hippocampus, specifically in the dentate gyrus region. […] The same effect has been observed in long-term depression (LTD).

• #15 Pathophysiology | Major Depression Case Study

  https://u.osu.edu/majordepressioncasestudy2018/pathophysiology/

  Normal physiology of patients mood, perception, emotion and behavior focuses majorly on neurotransmitters in the brain. There is a genetic predisposition in major depression that runs in families. However, due to the large variance in symptoms, developmental and environmental factors also must be evaluated in the contributing factors to major depression. Major depression can be classified as when an emotional state, such as sadness, becomes chronic and uncontrollable. There are antidepressant drugs that can increase neurotransmitters in the body leading to another theory called the monoamine hypothesis of depression. In this hypothesis, there is a deficit in the concentration of the brain norepinephrine, dopamine, and/or serotonin resulting in depression. Chronic activation of the HPA system and chronic glucocorticoid secretion are found in 30-70% of individuals with major depression suggesting the correlation between the dysfunctional system and depression. Depressed individuals post-mortem brains have shown widespread decrease in serotonin 5-HT1a receptor subtype binding in the frontal, temporal, and limbic cortex as well as serotonin transporter binding in the cerebral cortex and hippocampus, reflecting a dysfunction in the raphe-serotonin system.

• #16

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. […] Serotonin is the most extensively studied neurotransmitter in depression. […] Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD. […] While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine. […] Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. […] Risk factors for depressive episodes change during the course of the illness.

• #17 Major depressive disorder pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Major_depressive_disorder_pathophysiology

  The exact pathogenesis of major depressive disorder is not fully understood. However, it is thought that major depressive disorder is the result of decreased levels of serotonin, norepinephrine, and dopamine. […] The exact pathogenesis of major depressive disorder is not completely understood; however, following etiologies have been suggested to play a role in the development of major depressive disorder. […] Serotonin depletion has been most commonly shown to be associated with depression. For this reason, serotonergic agents are first-line treatment of major clinical depression. […] Abnormal norepinephrine metabolites have been shown in blood, urine, and CSF in patients with major depressive disorder. Serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine) increase both serotonin and norepinephrine levels and are used as the first-line treatment of major depressive disorder.

• #18 Major depressive disorder pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Major_depressive_disorder_pathophysiology

  Major depressive disorder may be associated with decreased dopaminergic activity. It has been suggested that patients with major depressive disorder may have dysfunctional masolimbic dopamine pathway and/or hypoactive dopamine D1 receptors. Reduced dopamine concentrations with drugs (e.g. reserpine) or certain pathologic conditions (e.g. Parkinson’s disease) have been linked to symptoms of depression. In addition, drugs increasing dopamine concentrations, such as amphetamine, bupropion, and tyrosine can reduce depressive symptoms. […] Stressful life events may result in permanent neuronal alterations, subsequently predisposing an individual to mood disorders. The most often associated life event linked to the development of depression is losing a parent before age 11.

• #19 Different Mechanisms Between Melancholic and Atypical Depression | IntechOpen

  https://www.intechopen.com/chapters/48427

  The dopamine (DA) system has been reported to be highly associated with the symptomatology of depression, as the proposed pathogenesis of melancholic depression involves decreased DA transmission. […] The neuroplasticity hypothesis proposes that depression results from an inability to make the appropriate neuronal proliferation in response to stress. […] Major depressive disorder is considered to be a clinically heterogeneous disorder and the diagnosis is based on a patients symptoms, not on any laboratory tests. […] Currently, researchers have determined that MDD results from the interaction of multiple genetic factors and various environmental factors, such as childhood adversity and many stressful life events. […] For example, melancholic depression is associated with hyperactivity of the HPA axis while atypical depression is associated with hypoactivity of the HPA axis. […] Researchers have searched for biological mechanisms according to depression subtypes in an effort to understand the pathogenesis of depression subtypes.

• #20 Major depressive disorder pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Major_depressive_disorder_pathophysiology

  Major depressive disorder may be associated with decreased dopaminergic activity. It has been suggested that patients with major depressive disorder may have dysfunctional masolimbic dopamine pathway and/or hypoactive dopamine D1 receptors. Reduced dopamine concentrations with drugs (e.g. reserpine) or certain pathologic conditions (e.g. Parkinson’s disease) have been linked to symptoms of depression. In addition, drugs increasing dopamine concentrations, such as amphetamine, bupropion, and tyrosine can reduce depressive symptoms. […] Stressful life events may result in permanent neuronal alterations, subsequently predisposing an individual to mood disorders. The most often associated life event linked to the development of depression is losing a parent before age 11.

• #21 Major depressive disorder – Wikipedia

  https://en.wikipedia.org/wiki/Major_depressive_disorder

  Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, with about 40% of the risk being genetic. […] The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA-axis dysfunction, and structural or functional abnormalities of emotional circuits. […] The monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. […] HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. […] Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior, creating a pro-inflammatory profile in MDD. […] The newer field of psychoneuroimmunology suggests that cytokines may impact depression.

• #22 Major depressive disorder: hypothesis, mechanism, prevention and treatment | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01738-y

  Due to the complexity of the pathological mechanism of MDD, accurate diagnostic approaches and pharmacological therapeutic strategies are relatively limited. Several hypothesis were developed to explain MDD pathogenesis pathogenic including (i) the hypothalamic-pituitary-adrenal (HPA) axis dysfunction hypothesis, (ii) the monoamine hypothesis, (iii) the inflammatory hypothesis, (iv) the genetic and epigenetic anomaly hypothesis, (v) the structural and functional brain remodeling hypothesis, and (vi) the social psychological hypothesis. […] However, none of these hypotheses alone can fully explain the pathological basis of MDD, while many mechanisms proposed by these hypotheses interact with each other. In recent years, great progress has been made in identifying novel pharmacological therapies, diagnostic criteria, and nonpharmacological preventive measures for MDD, initiating related clinical trials.

• #23

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. […] Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA). […] There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. […] Sickness behavior as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. […] Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain.

• #24 Pathophysiology | Major Depression Case Study

  https://u.osu.edu/majordepressioncasestudy2018/pathophysiology/

  Normal physiology of patients mood, perception, emotion and behavior focuses majorly on neurotransmitters in the brain. There is a genetic predisposition in major depression that runs in families. However, due to the large variance in symptoms, developmental and environmental factors also must be evaluated in the contributing factors to major depression. Major depression can be classified as when an emotional state, such as sadness, becomes chronic and uncontrollable. There are antidepressant drugs that can increase neurotransmitters in the body leading to another theory called the monoamine hypothesis of depression. In this hypothesis, there is a deficit in the concentration of the brain norepinephrine, dopamine, and/or serotonin resulting in depression. Chronic activation of the HPA system and chronic glucocorticoid secretion are found in 30-70% of individuals with major depression suggesting the correlation between the dysfunctional system and depression. Depressed individuals post-mortem brains have shown widespread decrease in serotonin 5-HT1a receptor subtype binding in the frontal, temporal, and limbic cortex as well as serotonin transporter binding in the cerebral cortex and hippocampus, reflecting a dysfunction in the raphe-serotonin system.

• #25 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250507/Ten-year-data-confirm-exercise-is-a-powerful-tool-against-depression.aspx

  Depressive disorders arise due to dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, reduced responsiveness to glucocorticoids, increased secretion of corticotropin-releasing hormone (CRH), and increased pituitary size and activity. […] Even ten years after their original meta-analysis, the specific neurobiological changes involved in the anti-depressive effects of exercise and physical activity remain unclear. […] Researchers have proposed that the effects of exercise and physical activity may be attributed to physiological changes in hypothalamic-pituitary-adrenal (HPA) axis function, monoamine metabolism, neurotrophic factors, and neuroinflammation. […] These hypotheses are supported by many systemic reviews that have similarly reported the impact of physical activity on the serotonergic system and HPA axis.

• #26 Different Mechanisms Between Melancholic and Atypical Depression | IntechOpen

  https://www.intechopen.com/chapters/48427

  A reduced sensitivity to cortisol, leading to an impaired negative feedback mechanism has been attributed to resistant GR function. […] In contrast, the CRH peptide mediates the regulation of the HPA axis as well as autonomic and behavioral responses during stress. […] Most studies in melancholic depression have found that relative HPA axis hyperactivity occurs, compared to non-depressed states, and that this is more likely to occur in more severe forms of depression. […] It has been presented that a relatively hyperactive HPA axis leads to the symptoms of melancholic depression, while a relatively hypoactive stress response leads to the symptoms of atypical depression. […] The serotonin system has been thoroughly investigated in a variety of MDD studies. […] The norepinephrine (NE) system has been studied in depression, particularly the action of NE reuptake inhibitors.

• #27 Pathophysiology of depression | PPT

  https://www.slideshare.net/NemkumarJain2/pathophysiology-of-depression-93240319

  Patho-physiology 2) Neurotrophic hypothesis: Brain Derived growth factor (BNDF) promotes the growth and development of immature neurons including mono-aminergic neurons, enhances the survival and function of adult neurons. Low BNDF level may be responsible for loss of mono-aminergic neurons and loss of function or atrophy of hippocampus and other brain areas. […] Pathophysiology 3) Neuroendocrine hypothesis: Dexamethasone suppression test doesn’t reduce cortisol level in 50% of depression patients; indicates imbalance in stress HPA axis (hypothalamus-pituitary-adrenal gland axis). Dysregulation in HPA axis results in increased corticotropin releasing factor (CRF) from hypothalamus (result of hippocampus atrophy), Enlarged adrenal gland and increased secretion of cortisol (glucocorticoids).

• #28 Major Depressive Disorder: Pathophysiology and Clinical Managemen

  https://www.longdom.org/open-access/major-depressive-disorder-pathophysiology-and-clinical-management-30556.html

  Depression is a chronic mental disorder that causes changes in mood, thoughts, behavior and physical health. […] There are diverse theories on the pathogenesis of depression most based on measurement of indirect markers, post-mortem studies and neuro-imaging techniques. […] Even though there are numerous studies attempting to shed light on the pathophysiology of depression, it still remains elusive. This is in fact the major reason for the slow paced drug development against this disease. […] Various structural and functional studies report abnormalities in the areas of the brain that are responsible for the regulation of mood, reward response and executive functions. […] Chronic stress and hyperactivity of the HPA axis (causing chronic hypercortisolemia) have been hypothesized to play a prominent role in the incidence of depression and even in recurrence after complete remission.

• #29 What causes depression? – Harvard Health

  https://www.health.harvard.edu/mind-and-mood/what-causes-depression

  In fact, animal studies have shown that antidepressants do spur the growth and enhanced branching of nerve cells in the hippocampus. […] If that’s the case, depression medications could be developed that specifically promote neurogenesis, with the hope that patients would see quicker results than with current treatments. […] Activity in the amygdala is higher when a person is sad or clinically depressed, and this continues even after recovery from depression. […] The hippocampus is smaller in some depressed people, and research suggests that ongoing exposure to stress hormones impairs the growth of neurons in this part of the brain.

• #30 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. […] Several lines of evidence have pointed towards a strong relationship between inflammatory processes and the pathophysiology of MDD. […] Indeed, evidence has shown that systemic inflammatory markers, mainly interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) are commonly elevated in MDD-affected individuals as compared to controls, suggesting the presence of chronic low-grade inflammation in MDD. […] Importantly, immune system activation is observed in both clinical studies and in animal models of MDD, since the relationship between the peripheral immune system and neuroimmunological mechanisms is associated with the onset and maintenance of depressive symptoms.

• #31 Biomarkers of Major Depressive Disorder: Knowing is Half the Battle

  https://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2021.19.1.12

  Various literatures also support that endocrine and metabolism changes are associated with MDD. […] Accumulating evidence suggests that at least a portion of MDD patients show characteristics pathological changes regarding different clinical pathological biomarkers. […] The aetiology of depression is, as is the case with any other psychiatric disorders, incredibly complex, involving psycho-social, genetic, epigenetics and neuroendocracy. […] This complexity has direct consequences for our accuracy in the diagnosis and subtypes of depression, for our comprehension of pathophysiology and for our ability to design and choose effective treatment strategies. […] In MDD pathophysiology, inflammation is seen to play a significant role. […] Many factors that considered important for MDDs etiopathogenesis are influenced by inflammatory mediators.

• #32 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. […] Several lines of evidence have pointed towards a strong relationship between inflammatory processes and the pathophysiology of MDD. […] Indeed, evidence has shown that systemic inflammatory markers, mainly interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) are commonly elevated in MDD-affected individuals as compared to controls, suggesting the presence of chronic low-grade inflammation in MDD. […] Importantly, immune system activation is observed in both clinical studies and in animal models of MDD, since the relationship between the peripheral immune system and neuroimmunological mechanisms is associated with the onset and maintenance of depressive symptoms.

• #33 Biomarkers of Major Depressive Disorder: Knowing is Half the Battle

  https://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2021.19.1.12

  This means that inflammatory markers can be used to diagnose and treat depression. […] The regularly and consistently increased in case of depression is IL-6 and C-reactive protein. […] Higher standards just or no gaps in European research. […] Nonetheless, a recent study has suggested unique translation results for IL-1b backed by a highly important trend of elevated IL-1b ribonucleic acid prediction of weak antidepressant reaction. […] The potential will have predictive levels as biomarkers are correlated with the patients likelihood of depression. […] The effective implication of the above methods will contribute to improved modeling of therapeutic resistance. […] The basic biochemical results of all generally administered depressive medications were analyzed in depth, taking into consideration the validity of the therapy findings as well. […] The vast research on depression indicates a large variety of biomarkers that may help patients with depression enhance their diagnosis.

• #34 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. […] Several lines of evidence have pointed towards a strong relationship between inflammatory processes and the pathophysiology of MDD. […] Indeed, evidence has shown that systemic inflammatory markers, mainly interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) are commonly elevated in MDD-affected individuals as compared to controls, suggesting the presence of chronic low-grade inflammation in MDD. […] Importantly, immune system activation is observed in both clinical studies and in animal models of MDD, since the relationship between the peripheral immune system and neuroimmunological mechanisms is associated with the onset and maintenance of depressive symptoms.

• #35 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Peripheral inflammatory pathways can also reach the central nervous system through several mechanisms, including the gut-microbiota-brain axis, which plays an important role in psychiatric disorders, including MDD. […] Tryptophan metabolism and the kynurenine (KYN) pathway (which can be influenced by increases in inflammatory cytokines triggered by changes in gut microbiota and neuroinflammation) are also thought to be involved in the onset of MDD. […] Indeed, an imbalance in the KYNA/QA ratio, with a reduction of KYNA and an excessive production of QA, has been observed in MDD patients. […] Neuroinflammation can be caused by numerous factors including stress, infections, autoimmune diseases, and gut dysbiosis. […] The main events underlying microglial and astrocytic activation during the neuroinflammatory process are shown in Figure 1.

• #36

  https://apcz.umk.pl/JEHS/article/view/42852

  Depressive disorders are a significant problem. They lead to suffering, loss of interest and may contribute to suicide attempts. Despite the large number of available medications, 10-35% of patients fail to achieve remission. Therefore, for these ongoing researches are underway to thoroughly understand the pathophysiology of depression. […] The purpose of the study was to review the latest literature on the kynurenine pathway importance in depression, and to discover its links with theories relating to the pathogenesis of depression. […] Animal studies confirm the importance of the kynurenine pathway in animal models of depression. Peripherally directed inflammatory stimuli in humans lead to peripheral activation of the kynurenine pathway. The regulation of the kynurenine pathway in the brain is specific to a particular region as well as to a given type of depression. […] Understanding changes in kynurenine pathway transmission in a particular type of depression may be helpful in developing new, more effective drugs.

• #37 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Peripheral inflammatory pathways can also reach the central nervous system through several mechanisms, including the gut-microbiota-brain axis, which plays an important role in psychiatric disorders, including MDD. […] Tryptophan metabolism and the kynurenine (KYN) pathway (which can be influenced by increases in inflammatory cytokines triggered by changes in gut microbiota and neuroinflammation) are also thought to be involved in the onset of MDD. […] Indeed, an imbalance in the KYNA/QA ratio, with a reduction of KYNA and an excessive production of QA, has been observed in MDD patients. […] Neuroinflammation can be caused by numerous factors including stress, infections, autoimmune diseases, and gut dysbiosis. […] The main events underlying microglial and astrocytic activation during the neuroinflammatory process are shown in Figure 1.

• #38 The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms | Journal of Neuroinflammation | Full Text

  https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03312-3

  The blood-brain barrier (BBB) is a highly selective, semi-permeable barrier that separates the peripheral circulatory system from the brain and the central nervous system (CNS). It restricts the entry of non-specific immune cells and harmful substances into the brain, protecting the nervous system from external threats. However, when the organism is attacked by inflammation, the permeability and integrity of the BBB is compromised, allowing inflammatory factors to enter, exacerbating the neuroinflammatory response and participating in the onset of various neurological diseases including Alzheimers disease, multiple sclerosis, Parkinsons disease and MDD. […] In patients with MDD, the HPA axis got activated, leading to release of glucocorticoids. Glucocorticoids bind to glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) located in the prefrontal cortex and limbic system, degrading tight junction proteins, enabling the passage of immune cells and inflammation mediators through the BBB, which affect brain function and cause depressive symptoms.

• #39 The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms | Journal of Neuroinflammation | Full Text

  https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03312-3

  In conclusion, the central immune mechanisms in MDD reveal inflammation as a pivotal orchestrator in disease pathophysiology, driving complex interactions between BBB disruption, neuroinflammation, and neuronal dysfunction. BBB compromise allows peripheral inflammatory mediators to enter the brain, activating microglia and disrupting neural homeostasis. The balance of pro- and anti-inflammatory cytokines, along with neurotrophic factors, critically influences neuronal function, synaptic plasticity, and neurogenesis. This inflammatory cascade particularly affects key brain regions including the hippocampus, amygdala, frontal lobe, and striatum, which ultimately leads to the manifestation of characteristic clinical symptoms of MDD.

• #40 Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications | Neuroscience Bulletin

  https://link.springer.com/article/10.1007/s12264-021-00638-3

  The neurotrophic hypothesis of depression postulates that a deficit of neurotrophic support leads to neuronal atrophy, the reduction of neurogenesis, and the destruction of glia support, while antidepressants attenuate or reverse these pathophysiological processes. […] The immune-inflammation hypothesis has attracted much attention, suggesting that the interactions between inflammatory pathways and neural circuits and neurotransmitters are involved in the pathogenesis and pathophysiological processes of depression. […] The pathogenesis of depression is complex and all the hypotheses should be integrated to consider the many interactions between various systems and pathways.

• #41 Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant

  https://www.mdpi.com/1420-3049/27/16/5091

  Depression is a debilitating psychiatric disorder impacting an individual’s quality of life. It is the most prevalent mental illness across all age categories, incurring huge socio-economic impacts. Most depression treatments currently focus on the elevation of neurotransmitters according to the monoamine hypothesis. […] The inflammatory hypothesis proposes that depression is caused by the interaction of inflammatory cytokine with the hypothalamic–pituitary–adrenal (HPA) axis, consequently affecting the synthesis and reuptake of neurotransmitters, which subsequently triggers glucocorticoid resistance, glutamate excitotoxicity, and the reduction of brain-derived neurotrophic factor (BDNF) expression. […] The neurotrophic hypothesis states that neurotrophic factors are essential to the development of neurons by promoting synaptic growth and maintaining neuronal survival.

• #42 Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant

  https://www.mdpi.com/1420-3049/27/16/5091

  Depression is a debilitating psychiatric disorder impacting an individual’s quality of life. It is the most prevalent mental illness across all age categories, incurring huge socio-economic impacts. Most depression treatments currently focus on the elevation of neurotransmitters according to the monoamine hypothesis. […] The inflammatory hypothesis proposes that depression is caused by the interaction of inflammatory cytokine with the hypothalamic–pituitary–adrenal (HPA) axis, consequently affecting the synthesis and reuptake of neurotransmitters, which subsequently triggers glucocorticoid resistance, glutamate excitotoxicity, and the reduction of brain-derived neurotrophic factor (BDNF) expression. […] The neurotrophic hypothesis states that neurotrophic factors are essential to the development of neurons by promoting synaptic growth and maintaining neuronal survival.

• #43 Pathophysiology of depression | PPT

  https://www.slideshare.net/NemkumarJain2/pathophysiology-of-depression-93240319

  Patho-physiology 2) Neurotrophic hypothesis: Brain Derived growth factor (BNDF) promotes the growth and development of immature neurons including mono-aminergic neurons, enhances the survival and function of adult neurons. Low BNDF level may be responsible for loss of mono-aminergic neurons and loss of function or atrophy of hippocampus and other brain areas. […] Pathophysiology 3) Neuroendocrine hypothesis: Dexamethasone suppression test doesn’t reduce cortisol level in 50% of depression patients; indicates imbalance in stress HPA axis (hypothalamus-pituitary-adrenal gland axis). Dysregulation in HPA axis results in increased corticotropin releasing factor (CRF) from hypothalamus (result of hippocampus atrophy), Enlarged adrenal gland and increased secretion of cortisol (glucocorticoids).

• #44 Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant

  https://www.mdpi.com/1420-3049/27/16/5091

  The monoamine hypothesis was formulated in the mid-1960s due to the underactivity of brain monoamines such as serotonin, dopamine, and NA in patients’ brains. […] The mechanisms of action for this hypothesis with antidepressants are: (1) inhibition of the reuptake of 5HT and/or NA; (2) antagonistic presynaptic inhibition of 5HT and/or NA; and (3) inhibition of monoamine oxidase (MAO). […] The inflammation theory has also been linked to depression, which surprises many people. […] Previous studies have shown that depressed people have increased levels of inflammatory mediators, such as C-reactive protein (CRP) and pro-inflammatory cytokines. […] The neurotrophin hypothesis also has a vital role in the pathophysiology of depression. […] BDNF promotes neurogenesis, which is part of neuroplasticity. […] The alteration of BDNF levels is known to be detrimental to neurogenesis in the hippocampus, specifically in the dentate gyrus region. […] The same effect has been observed in long-term depression (LTD).

• #45

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. […] A series of magnetic resonance spectroscopy studies consistently showed reductions in total gamma-aminobutyric acid (GABA) concentrations in the prefrontal and occipital cortex in acute depression. […] Several lines of evidence suggest a dysfunction of the glutamate neurotransmitter system in MDD. […] Sleep disturbances and daytime fatigue are diagnostic criteria for MDD, suggesting impaired sleep-wake regulation in depressed patients. […] Based on these findings, circadian abnormalities have been hypothesized to be etiologically associated with MDD. […] The main strengths and weaknesses of the various neurobiological hypotheses of depression are summarized in Table 1. […] The identification of reliable predictors of therapeutic outcomes will allow for the development of personalized medicine that has the potential to individually tailor interventions and to open up new pathways in the evaluation of novel therapeutic approaches.

• #46 Major Depressive Disorder: Pathophysiology and Clinical Managemen

  https://www.longdom.org/open-access/major-depressive-disorder-pathophysiology-and-clinical-management-30556.html

  There is now a compelling argument that in order for depression to surface there needs to be a complex gene-environmental interaction that alters an individual response to stressful life situations. […] The monoamine hypothesis of depression came into the picture after the serendipitous discovery of the first antidepressant drugs that were otherwise developed for other medical conditions. […] The claim that depression is an inflammatory disorder is gaining popularity nowadays. […] Significant atrophy of certain prefrontal cortex areas and hippocampus observed in depression as well as decreased levels of nerve growth factors (NGF) such as BDNF has led to the neurotrophic hypothesis. […] There is increasing evidence that this neuropeptides are involved in the modulation of stress-related behaviors and mood by acting on neurokinin type-1 receptors (NK-1).

• #47

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. […] A series of magnetic resonance spectroscopy studies consistently showed reductions in total gamma-aminobutyric acid (GABA) concentrations in the prefrontal and occipital cortex in acute depression. […] Several lines of evidence suggest a dysfunction of the glutamate neurotransmitter system in MDD. […] Sleep disturbances and daytime fatigue are diagnostic criteria for MDD, suggesting impaired sleep-wake regulation in depressed patients. […] Based on these findings, circadian abnormalities have been hypothesized to be etiologically associated with MDD. […] The main strengths and weaknesses of the various neurobiological hypotheses of depression are summarized in Table 1. […] The identification of reliable predictors of therapeutic outcomes will allow for the development of personalized medicine that has the potential to individually tailor interventions and to open up new pathways in the evaluation of novel therapeutic approaches.

• #48 Ethiopathogenesis of Depressive Disorders

  https://clinical-practice-and-epidemiology-in-mental-health.com/VOLUME/10/PAGE/166/FULLTEXT/

  In the pathofisiology of MDD is involved the neural systems, the emotion processing, the reward seeking, and the regulate emotion system. […] Over the past two decades, various hypotheses have been debated and three main neurotrasmitters, norephinephrine, dopamine, and serotonin have long been considered in the pathophysiology and treatment of mood disorders, although other neurotransmitter systems may as well be involved in mood disorders. […] The first etiological hypothesis postulated to explain symptoms of depression was the monoamine hypothesis. […] Currently the most popular hypothesis for the etiology of depression seems to involve the monoaminergic receptors and the downstream molecular events that this receptors trigger, including the gene expression. […] In the pathophysiology of depression, an increasing interest has been attributed to the glutamatergic system. […] Antidepressants used in clinical practice modify the glutamate metabolism and some clinical trials shown that antiglutamatergic substances (riluzole) and NMDA-receptor antagonists (ketamine) possessed antidepressant properties.

• #49

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. […] A series of magnetic resonance spectroscopy studies consistently showed reductions in total gamma-aminobutyric acid (GABA) concentrations in the prefrontal and occipital cortex in acute depression. […] Several lines of evidence suggest a dysfunction of the glutamate neurotransmitter system in MDD. […] Sleep disturbances and daytime fatigue are diagnostic criteria for MDD, suggesting impaired sleep-wake regulation in depressed patients. […] Based on these findings, circadian abnormalities have been hypothesized to be etiologically associated with MDD. […] The main strengths and weaknesses of the various neurobiological hypotheses of depression are summarized in Table 1. […] The identification of reliable predictors of therapeutic outcomes will allow for the development of personalized medicine that has the potential to individually tailor interventions and to open up new pathways in the evaluation of novel therapeutic approaches.

• #50 Major depressive disorder pathway | Abcam

  https://www.abcam.com/en-us/technical-resources/pathways/major-depressive-disorder-pathway?srsltid=AfmBOoq-O0AOlGrAelEumdSuY6nHcHqCb5GgF73hS9YPBPQCov5Gv-p7

  Major depressive disorder (MDD) is a leading cause of disability worldwide. […] One of the earliest proposed mechanisms underlying MDD is a deficiency in monoamine levels, including serotonin (5-HT), noradrenaline, and dopamine. […] Nonetheless, MDD is linked with interferences in other neurotransmitters in the brain, as well as cerebrospinal fluid and peripheral tissues. […] Glutamate levels are decreased in specific brain regions of individuals with MDD, which may contribute to a reduced response to emotional stimuli. […] Recent genome-wide association studies have identified several key genes related to MDD. […] Another hypothesis stipulates the disruption of neurotrophic support as the primary mechanism triggering MDD-related synaptic and brain-related alterations. […] In major depressive disorder, activation of these pathways may be imbalanced. […] Understanding the connections between the various molecular pathways involved in MDD may be an unrealistic goal.

• #51 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Several clinical and preclinical studies have investigated how the immune system and inflammatory pathways are involved in the neurobiology of MDD and have suggested that MDD can be viewed as a systemic disorder. […] This review aims to highlight the main inflammatory mechanisms involved in the pathophysiology of MDD, including the roles of glial cells, the peripheral immune system, and gut dysbiosis. […] The involvement of the glutamatergic system in MDD is supported by the rapid antidepressant effect of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist. […] Research has shown that immuno-inflammatory pathways, including neuroinflammation, with microglial activation, astrocyte atrophy, and the release of inflammatory cytokines, are involved in the dysfunction of the glutamatergic system found in MDD.

• #52

  https://www1.racgp.org.au/newsgp/clinical/new-treatment-for-resistant-depression-added-to-pb

  This can result in more severe symptoms including significantly longer depressive episodes, suicidal thoughts and an inability to experience joy. […] Esketamine is effective for some patients with complex presentations but requires close monitoring by skilled clinicians to maintain safety as there are considerable risks along with the potential benefits. […] According to clinical guidelines, esketamine must be used in conjunction with a newly initiated oral antidepressant and administered under clinical supervision via nasal spray. […] A glutamate receptor modulator, esketamine works by increasing glutamate levels a neurotransmitter involved in a persons mood and thought processes to stimulate and restore message transmission within the brain. […] However, research is ongoing, with questions persisting around the treatments impact on suicidality and its long-term effects, with careful monitoring advised for patients with suicidal ideation prior to commencement of treatment. […] There are also contraindications to using esketamine that doctors must be aware of, with the treatment not suitable for patients who would be placed at risk by increases in blood pressure or intracranial pressure, such as those with a history of aneurysm.

• #53 Major Depressive Disorder: Pathophysiology and Clinical Managemen

  https://www.longdom.org/open-access/major-depressive-disorder-pathophysiology-and-clinical-management-30556.html

  Depression is a chronic mental disorder that causes changes in mood, thoughts, behavior and physical health. […] There are diverse theories on the pathogenesis of depression most based on measurement of indirect markers, post-mortem studies and neuro-imaging techniques. […] Even though there are numerous studies attempting to shed light on the pathophysiology of depression, it still remains elusive. This is in fact the major reason for the slow paced drug development against this disease. […] Various structural and functional studies report abnormalities in the areas of the brain that are responsible for the regulation of mood, reward response and executive functions. […] Chronic stress and hyperactivity of the HPA axis (causing chronic hypercortisolemia) have been hypothesized to play a prominent role in the incidence of depression and even in recurrence after complete remission.

• #54 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  GABA, an inhibitory neurotransmitter, and glutamate and glycine, both of which are major excitatory neurotransmitters are found to play a role in the etiology of depression as well. […] Structural and functional brain imaging of depressed individuals has shown increased hyperintensities in the subcortical regions, and reduced anterior brain metabolism on the left side, respectively. […] Family, adoption, and twin studies have indicated the role of genes in the susceptibility of depression. […] The learned helplessness theory has associated the occurrence of depression with the experience of uncontrollable events. […] Major depressive disorder can be managed with various treatment modalities, including pharmacological, psychotherapeutic, interventional, and lifestyle modification. […] Combination treatment, including both medications and psychotherapy, has been found to be more effective than either of these treatments alone.

• #55 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  GABA, an inhibitory neurotransmitter, and glutamate and glycine, both of which are major excitatory neurotransmitters are found to play a role in the etiology of depression as well. […] Structural and functional brain imaging of depressed individuals has shown increased hyperintensities in the subcortical regions, and reduced anterior brain metabolism on the left side, respectively. […] Family, adoption, and twin studies have indicated the role of genes in the susceptibility of depression. […] The learned helplessness theory has associated the occurrence of depression with the experience of uncontrollable events. […] Major depressive disorder can be managed with various treatment modalities, including pharmacological, psychotherapeutic, interventional, and lifestyle modification. […] Combination treatment, including both medications and psychotherapy, has been found to be more effective than either of these treatments alone.

• #56 Major vs. persistent depressive disorder: Understanding dysthymia

  https://www.medicalnewstoday.com/articles/major-depressive-disorder-vs-persistent-depressive-disorder

  MDD also reduces the amount of gray matter in the brain. Gray matter is involved in numerous processes, including speech, decision-making, and self-control. […] Research into the causes of PDD is ongoing, but scientists believe that the disruption of the neurotransmitters serotonin, epinephrine, norepinephrine, and glutamate plays a role. […] Researchers have also found that certain parts of the brain, such as the orbitofrontal cortex and the hippocampus, are smaller in people with PDD than in those without. […] Genetic, social, and physical factors cause PDD and MDD. Various parts of the brain play important roles in the development of these disorders.

• #57 The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms | Journal of Neuroinflammation | Full Text

  https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03312-3

  In conclusion, the central immune mechanisms in MDD reveal inflammation as a pivotal orchestrator in disease pathophysiology, driving complex interactions between BBB disruption, neuroinflammation, and neuronal dysfunction. BBB compromise allows peripheral inflammatory mediators to enter the brain, activating microglia and disrupting neural homeostasis. The balance of pro- and anti-inflammatory cytokines, along with neurotrophic factors, critically influences neuronal function, synaptic plasticity, and neurogenesis. This inflammatory cascade particularly affects key brain regions including the hippocampus, amygdala, frontal lobe, and striatum, which ultimately leads to the manifestation of characteristic clinical symptoms of MDD.

• #58 What causes depression? – Harvard Health

  https://www.health.harvard.edu/mind-and-mood/what-causes-depression

  Researchers believe that more important than levels of specific brain chemicals nerve cell connections, nerve cell growth, and the functioning of nerve circuits have a major impact on depression. […] Areas that play a significant role in depression are the amygdala, the thalamus, and the hippocampus. […] Research shows that the hippocampus is smaller in some depressed people. […] The more bouts of depression a woman had, the smaller the hippocampus. […] Stress, which plays a role in depression, may be a key factor here, since experts believe stress can suppress the production of new neurons (nerve cells) in the hippocampus. […] Researchers are exploring possible links between sluggish production of new neurons in the hippocampus and low moods. […] The answer may be that mood only improves as nerves grow and form new connections, a process that takes weeks.

• #59 What causes depression? – Harvard Health

  https://www.health.harvard.edu/mind-and-mood/what-causes-depression

  In fact, animal studies have shown that antidepressants do spur the growth and enhanced branching of nerve cells in the hippocampus. […] If that’s the case, depression medications could be developed that specifically promote neurogenesis, with the hope that patients would see quicker results than with current treatments. […] Activity in the amygdala is higher when a person is sad or clinically depressed, and this continues even after recovery from depression. […] The hippocampus is smaller in some depressed people, and research suggests that ongoing exposure to stress hormones impairs the growth of neurons in this part of the brain.

• #60 What causes depression? – Harvard Health

  https://www.health.harvard.edu/mind-and-mood/what-causes-depression

  Researchers believe that more important than levels of specific brain chemicals nerve cell connections, nerve cell growth, and the functioning of nerve circuits have a major impact on depression. […] Areas that play a significant role in depression are the amygdala, the thalamus, and the hippocampus. […] Research shows that the hippocampus is smaller in some depressed people. […] The more bouts of depression a woman had, the smaller the hippocampus. […] Stress, which plays a role in depression, may be a key factor here, since experts believe stress can suppress the production of new neurons (nerve cells) in the hippocampus. […] Researchers are exploring possible links between sluggish production of new neurons in the hippocampus and low moods. […] The answer may be that mood only improves as nerves grow and form new connections, a process that takes weeks.

• #61 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Underlying each depressive symptom may in fact be a unique mechanism comprising multiple malfunctioning neural circuits. […] The structure and function of these brain regions are modulated by monoaminergic neurotransmission. […] Disturbances in the functional connectivity in these and related neural networks appear to be integrally involved in the onset and progression of major depression. […] Importantly, these and related biochemical lesions provide a mechanistic rationale for antidepressant therapy. […] Interrelationships between clinical symptoms, affected neural systems, and antidepressant mechanisms of action may help clinicians customize pharmacotherapy to a patients unique clinical profile. […] Mechanism-based pharmacotherapy is the linchpin of personalized treatment, and provides a rational basis on which to make initial therapeutic choices for newly diagnosed patients, and those struggling with unremitting symptoms.

• #62 What causes depression? – Harvard Health

  https://www.health.harvard.edu/mind-and-mood/what-causes-depression

  In fact, animal studies have shown that antidepressants do spur the growth and enhanced branching of nerve cells in the hippocampus. […] If that’s the case, depression medications could be developed that specifically promote neurogenesis, with the hope that patients would see quicker results than with current treatments. […] Activity in the amygdala is higher when a person is sad or clinically depressed, and this continues even after recovery from depression. […] The hippocampus is smaller in some depressed people, and research suggests that ongoing exposure to stress hormones impairs the growth of neurons in this part of the brain.

• #63 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Underlying each depressive symptom may in fact be a unique mechanism comprising multiple malfunctioning neural circuits. […] The structure and function of these brain regions are modulated by monoaminergic neurotransmission. […] Disturbances in the functional connectivity in these and related neural networks appear to be integrally involved in the onset and progression of major depression. […] Importantly, these and related biochemical lesions provide a mechanistic rationale for antidepressant therapy. […] Interrelationships between clinical symptoms, affected neural systems, and antidepressant mechanisms of action may help clinicians customize pharmacotherapy to a patients unique clinical profile. […] Mechanism-based pharmacotherapy is the linchpin of personalized treatment, and provides a rational basis on which to make initial therapeutic choices for newly diagnosed patients, and those struggling with unremitting symptoms.

• #64 Depression: Causes, symptoms, treatment, and more

  https://www.medicalnewstoday.com/articles/8933

  Depression can also occur as a symptom or comorbidity of another mental health condition, such as those below. […] Depression is a common symptom of bipolar disorder. People with bipolar disorder experience periods of depression that may last weeks. […] Depression can lead to changes in levels of neurotransmitters, which are molecules that transmit messages between nerve cells. In the long run, it may also cause physical changes to the brain, including reduced gray matter volume and increased inflammation. […] Depression can affect concentration and decision making. It may also reduce attention span and cause difficulty with information processing and memory.

• #65 Depressive Disorders – Psychiatric Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/psychiatric-disorders/mood-disorders/depressive-disorders

  Neuroendocrine dysregulation may be a factor, with particular emphasis on 3 axes: hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, and hypothalamic-pituitary-growth hormone. […] Major life stresses, especially separations and losses, commonly precede episodes of major depression; however, such events do not usually cause lasting, severe depression except in people predisposed to a mood disorder. […] People who have had an episode of major depression are at higher risk of subsequent episodes. […] The presence of other psychiatric disorders increases risks for major depressive disorder. […] Women are at higher risk, but no theory explains why. […] In peripartum-onset depression, symptoms develop during pregnancy or within 4 weeks after delivery; endocrine changes have been implicated, but the specific cause is unknown.

• #66 Depressive Disorders – Psychiatric Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/psychiatric-disorders/mood-disorders/depressive-disorders

  Neuroendocrine dysregulation may be a factor, with particular emphasis on 3 axes: hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, and hypothalamic-pituitary-growth hormone. […] Major life stresses, especially separations and losses, commonly precede episodes of major depression; however, such events do not usually cause lasting, severe depression except in people predisposed to a mood disorder. […] People who have had an episode of major depression are at higher risk of subsequent episodes. […] The presence of other psychiatric disorders increases risks for major depressive disorder. […] Women are at higher risk, but no theory explains why. […] In peripartum-onset depression, symptoms develop during pregnancy or within 4 weeks after delivery; endocrine changes have been implicated, but the specific cause is unknown.

• #67 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  GABA, an inhibitory neurotransmitter, and glutamate and glycine, both of which are major excitatory neurotransmitters are found to play a role in the etiology of depression as well. […] Structural and functional brain imaging of depressed individuals has shown increased hyperintensities in the subcortical regions, and reduced anterior brain metabolism on the left side, respectively. […] Family, adoption, and twin studies have indicated the role of genes in the susceptibility of depression. […] The learned helplessness theory has associated the occurrence of depression with the experience of uncontrollable events. […] Major depressive disorder can be managed with various treatment modalities, including pharmacological, psychotherapeutic, interventional, and lifestyle modification. […] Combination treatment, including both medications and psychotherapy, has been found to be more effective than either of these treatments alone.

• #68

  https://journals.lww.com/nrronline/fulltext/2018/13070/molecular_mechanism_of_noradrenaline_during_the.6.aspx

  Repeated stress exposure cumulatively increases the risk of developing MDD. […] The higher activity of LC neurons play a major role in stress induced depression and may be very important and critical for understanding the biological basis of stress induced depression and its etiology. […] Chronic stress elicits the activation of the LC noradrenergic neurons, medullary A1 and A2 nuclei in the ventrolateral medulla (VLM) and nucleus tractus solitarius (NTS). […] It has been reported that the hyperactivation of HPA-axis is observed in the patients with MDD. […] The central noradrenergic system is considered to play an important role in emotion and has also been implicated in affective disorders after the sustained central responses to the chronic stress, such as fear and anxiety. […] The mechanisms of action of antidepressant are not very well understood during depressive mood in LC neurons.

• #69 Major depressive disorder pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Major_depressive_disorder_pathophysiology

  Major depressive disorder may be associated with decreased dopaminergic activity. It has been suggested that patients with major depressive disorder may have dysfunctional masolimbic dopamine pathway and/or hypoactive dopamine D1 receptors. Reduced dopamine concentrations with drugs (e.g. reserpine) or certain pathologic conditions (e.g. Parkinson’s disease) have been linked to symptoms of depression. In addition, drugs increasing dopamine concentrations, such as amphetamine, bupropion, and tyrosine can reduce depressive symptoms. […] Stressful life events may result in permanent neuronal alterations, subsequently predisposing an individual to mood disorders. The most often associated life event linked to the development of depression is losing a parent before age 11.

• #70 Major depressive disorder pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Major_depressive_disorder_pathophysiology

  Major depressive disorder may be associated with decreased dopaminergic activity. It has been suggested that patients with major depressive disorder may have dysfunctional masolimbic dopamine pathway and/or hypoactive dopamine D1 receptors. Reduced dopamine concentrations with drugs (e.g. reserpine) or certain pathologic conditions (e.g. Parkinson’s disease) have been linked to symptoms of depression. In addition, drugs increasing dopamine concentrations, such as amphetamine, bupropion, and tyrosine can reduce depressive symptoms. […] Stressful life events may result in permanent neuronal alterations, subsequently predisposing an individual to mood disorders. The most often associated life event linked to the development of depression is losing a parent before age 11.

• #71 Major Depressive Disorder (MDD) | Takeda U.S. Medical

  https://www.takedamedconnect.com/diseases-and-conditions/neuroscience/major-depressive-disorder

  Major depression is one of the most common mental disorders in the United States, and an estimated 5% of adults suffer from depression globally. […] Major depressive disorder (MDD) is a chronic, heterogeneous disorder that causes changes in an individuals mood, thoughts, and behavior. […] While in recent years considerable advances have been made to understand the genetic risk factors associated with depression, its fundamental etiology remains poorly understood. […] Known risk factors are female sex, childhood history of abuse, family history and recent life stressors; however, we have yet to determine exactly how genetics influence environmental risk factors and vice versa. […] The genetic component to depression is thought to contribute 30-40% of variance, while non-genetic / environmental factors are thought to have an influence of 60-70%.

• #72 Depression (major depressive disorder) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/depression/symptoms-causes/syc-20356007

  Depression is a mood disorder that causes feelings of sadness that won’t go away. […] While there’s no single cause of depression, most experts believe there’s a combination of biological, social, and psychological factors that contribute to depression risk. […] Changes in brain chemistry, especially disruptions in neurotransmitters like serotonin, that play an important role in regulating many bodily functions, including mood, sleep, and appetite, are thought to play a particularly important role in depression. […] Neurotransmitters are naturally occurring brain chemicals that likely play a role in depression. Recent research indicates that changes in the function and effect of these neurotransmitters and how they interact with neurocircuits involved in maintaining mood stability may play a significant role in depression and its treatment. […] Changes in the body’s balance of hormones may be involved in causing or triggering depression. […] Depression is more common in people whose blood relatives also have this condition. Researchers are trying to find genes that may be involved in causing depression.

• #73 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Peripheral inflammatory pathways can also reach the central nervous system through several mechanisms, including the gut-microbiota-brain axis, which plays an important role in psychiatric disorders, including MDD. […] Tryptophan metabolism and the kynurenine (KYN) pathway (which can be influenced by increases in inflammatory cytokines triggered by changes in gut microbiota and neuroinflammation) are also thought to be involved in the onset of MDD. […] Indeed, an imbalance in the KYNA/QA ratio, with a reduction of KYNA and an excessive production of QA, has been observed in MDD patients. […] Neuroinflammation can be caused by numerous factors including stress, infections, autoimmune diseases, and gut dysbiosis. […] The main events underlying microglial and astrocytic activation during the neuroinflammatory process are shown in Figure 1.

• #74 The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms | Journal of Neuroinflammation | Full Text

  https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03312-3

  Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to depressive disorders. This review elucidates the complex interplay between peripheral and central immune components underlying depressive disorder pathology. Peripherally, systemic inflammation, gut immune dysregulation, and immune dysfunction in organs including gut, liver, spleen and adipose tissue influence brain function through neural and molecular pathways. […] Within the central nervous system, aberrant microglial and astrocytes activation, cytokine imbalances, and compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, and promoting neuronal injury. The crosstalk between peripheral and central immunity creates a vicious cycle exacerbating depressive neuropathology. Unraveling these multifaceted immune-mediated mechanisms provides insights into major depressive disorders pathogenic basis and potential biomarkers and targets. Modulating both peripheral and central immune responses represent a promising multidimensional therapeutic strategy.

• #75 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Peripheral inflammatory pathways can also reach the central nervous system through several mechanisms, including the gut-microbiota-brain axis, which plays an important role in psychiatric disorders, including MDD. […] Tryptophan metabolism and the kynurenine (KYN) pathway (which can be influenced by increases in inflammatory cytokines triggered by changes in gut microbiota and neuroinflammation) are also thought to be involved in the onset of MDD. […] Indeed, an imbalance in the KYNA/QA ratio, with a reduction of KYNA and an excessive production of QA, has been observed in MDD patients. […] Neuroinflammation can be caused by numerous factors including stress, infections, autoimmune diseases, and gut dysbiosis. […] The main events underlying microglial and astrocytic activation during the neuroinflammatory process are shown in Figure 1.

• #76 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Peripheral inflammatory pathways can also reach the central nervous system through several mechanisms, including the gut-microbiota-brain axis, which plays an important role in psychiatric disorders, including MDD. […] Tryptophan metabolism and the kynurenine (KYN) pathway (which can be influenced by increases in inflammatory cytokines triggered by changes in gut microbiota and neuroinflammation) are also thought to be involved in the onset of MDD. […] Indeed, an imbalance in the KYNA/QA ratio, with a reduction of KYNA and an excessive production of QA, has been observed in MDD patients. […] Neuroinflammation can be caused by numerous factors including stress, infections, autoimmune diseases, and gut dysbiosis. […] The main events underlying microglial and astrocytic activation during the neuroinflammatory process are shown in Figure 1.

• #77

  https://link.springer.com/article/10.1007/s44254-025-00103-8

  The present study aims to evaluate the effects of electroconvulsive therapy (ECT) on depressive behaviors. In addition, we explore mechanisms by which ECT alters the composition and functioning of gut microbiota through the microbiota-gut-brain axis. […] Several studies have demonstrated that the pathophysiological mechanisms underlying depression involve a range of abnormalities in both the central nervous system (CNS) and peripheral nervous systems. […] A significant role of gut microbiota in the onset, progression and treatment of depression, leading to the concept of the microbiota-gut-brain axis (MGBA) has been proposed. […] ECT is thought to enhance neuroplasticity, improve synaptic functioning, regulate neurotransmitter systems and curb neuroinflammation. […] The present study aims to determine whether ECT alleviates depressive symptoms through modulation of the MGBA.

• #78

  https://link.springer.com/article/10.1007/s44254-025-00103-8

  ECT exerts its antidepressant effects by modulating gut microbiota and enhancing the functionality of the gut-brain axis. […] ECT may help restore a healthy balance in the microbiota, thereby enhancing the production of beneficial metabolites such as short-chain fatty acids (SCFAs); these have been shown to exert neuroprotective effects and reduce inflammation in the brain. […] ECT treatment significantly increased the diversity of the gut microbiota, particularly influencing the relative abundance of phyla such as Bacteroidota, Verrucomicrobiota, Bacillota, Actinomycetota and Pseudomonadota. […] The restoration of beneficial bacteria, such as Bacteroidetes and Verrucomicrobia, not only enhanced gut homeostasis but may also influence the synthesis of neurotransmitters (like serotonin and -aminobutyric acid), thereby affecting mood regulation and sleep quality. […] These ECT-driven microbial and metabolic shifts may collectively rebalance host-microbiota crosstalk, offering a pathway for therapeutic efficacy.

• #79

  https://link.springer.com/article/10.1007/s44254-025-00103-8

  ECT exerts its antidepressant effects by modulating gut microbiota and enhancing the functionality of the gut-brain axis. […] ECT may help restore a healthy balance in the microbiota, thereby enhancing the production of beneficial metabolites such as short-chain fatty acids (SCFAs); these have been shown to exert neuroprotective effects and reduce inflammation in the brain. […] ECT treatment significantly increased the diversity of the gut microbiota, particularly influencing the relative abundance of phyla such as Bacteroidota, Verrucomicrobiota, Bacillota, Actinomycetota and Pseudomonadota. […] The restoration of beneficial bacteria, such as Bacteroidetes and Verrucomicrobia, not only enhanced gut homeostasis but may also influence the synthesis of neurotransmitters (like serotonin and -aminobutyric acid), thereby affecting mood regulation and sleep quality. […] These ECT-driven microbial and metabolic shifts may collectively rebalance host-microbiota crosstalk, offering a pathway for therapeutic efficacy.

• #80 Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  https://www.mdpi.com/2073-4409/13/5/423

  Peripheral inflammatory pathways can also reach the central nervous system through several mechanisms, including the gut-microbiota-brain axis, which plays an important role in psychiatric disorders, including MDD. […] Tryptophan metabolism and the kynurenine (KYN) pathway (which can be influenced by increases in inflammatory cytokines triggered by changes in gut microbiota and neuroinflammation) are also thought to be involved in the onset of MDD. […] Indeed, an imbalance in the KYNA/QA ratio, with a reduction of KYNA and an excessive production of QA, has been observed in MDD patients. […] Neuroinflammation can be caused by numerous factors including stress, infections, autoimmune diseases, and gut dysbiosis. […] The main events underlying microglial and astrocytic activation during the neuroinflammatory process are shown in Figure 1.

• #81 Major depressive disorder: hypothesis, mechanism, prevention and treatment | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01738-y

  Due to the complexity of the pathological mechanism of MDD, accurate diagnostic approaches and pharmacological therapeutic strategies are relatively limited. Several hypothesis were developed to explain MDD pathogenesis pathogenic including (i) the hypothalamic-pituitary-adrenal (HPA) axis dysfunction hypothesis, (ii) the monoamine hypothesis, (iii) the inflammatory hypothesis, (iv) the genetic and epigenetic anomaly hypothesis, (v) the structural and functional brain remodeling hypothesis, and (vi) the social psychological hypothesis. […] However, none of these hypotheses alone can fully explain the pathological basis of MDD, while many mechanisms proposed by these hypotheses interact with each other. In recent years, great progress has been made in identifying novel pharmacological therapies, diagnostic criteria, and nonpharmacological preventive measures for MDD, initiating related clinical trials.

• #82 Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications | Neuroscience Bulletin

  https://link.springer.com/article/10.1007/s12264-021-00638-3

  The neurotrophic hypothesis of depression postulates that a deficit of neurotrophic support leads to neuronal atrophy, the reduction of neurogenesis, and the destruction of glia support, while antidepressants attenuate or reverse these pathophysiological processes. […] The immune-inflammation hypothesis has attracted much attention, suggesting that the interactions between inflammatory pathways and neural circuits and neurotransmitters are involved in the pathogenesis and pathophysiological processes of depression. […] The pathogenesis of depression is complex and all the hypotheses should be integrated to consider the many interactions between various systems and pathways.

• #83 Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications | Neuroscience Bulletin

  https://link.springer.com/article/10.1007/s12264-021-00638-3

  The neurotrophic hypothesis of depression postulates that a deficit of neurotrophic support leads to neuronal atrophy, the reduction of neurogenesis, and the destruction of glia support, while antidepressants attenuate or reverse these pathophysiological processes. […] The immune-inflammation hypothesis has attracted much attention, suggesting that the interactions between inflammatory pathways and neural circuits and neurotransmitters are involved in the pathogenesis and pathophysiological processes of depression. […] The pathogenesis of depression is complex and all the hypotheses should be integrated to consider the many interactions between various systems and pathways.

• #84 Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression | Translational Psychiatry

  https://www.nature.com/articles/tp2015137

  Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamicpituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). […] We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. […] Our results support that the examined pathophysiological mechanisms are involved in MDDs etiology. These same mechanisms, however, are less important in clinical progression from first to later MDD episodes and toward chronicity. […] Several biological mechanisms with a possible role in major depressive disorder (MDD)s pathophysiology have been identified, and it has been hypothesized that these mechanisms may have a role both in the etiology and progression of the disorder.

• #85 Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression | Translational Psychiatry

  https://www.nature.com/articles/tp2015137

  We examined whether progression of MDD at a clinical level (that is, that what patient/clinicians experience as more advanced disease stage, which is multiple episodes and/or chronicity) is paralleled by more pronounced dysregulation in pathophysiological mechanisms, as evidence for that is scarce. […] Our finding that the pathophysiological mechanisms are involved in the etiology of depression confirms previous meta-analysis and longitudinal studies. […] We have tested the hypothesis that the examined mechanisms could also be associated with clinical progression of MDD. […] Together these results strongly suggest that the examined mechanisms are not more dysregulated in clinically progressed MDD. […] In conclusion, three candidate pathophysiologic mechanisms (inflammation, HPA-axis and vitamin D) show increased dysregulation across controls and at-risk stages of development of MDD, suggesting involvement in the etiology of MDD. Nevertheless, the same mechanisms did not show more dysregulation in clinical progression of MDD toward multiple episodes and/or chronicity. This suggests that pathophysiological mechanisms for etiology and clinical disease progression are not necessarily overlapping.

• #86 Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression | Translational Psychiatry

  https://www.nature.com/articles/tp2015137

  We examined whether progression of MDD at a clinical level (that is, that what patient/clinicians experience as more advanced disease stage, which is multiple episodes and/or chronicity) is paralleled by more pronounced dysregulation in pathophysiological mechanisms, as evidence for that is scarce. […] Our finding that the pathophysiological mechanisms are involved in the etiology of depression confirms previous meta-analysis and longitudinal studies. […] We have tested the hypothesis that the examined mechanisms could also be associated with clinical progression of MDD. […] Together these results strongly suggest that the examined mechanisms are not more dysregulated in clinically progressed MDD. […] In conclusion, three candidate pathophysiologic mechanisms (inflammation, HPA-axis and vitamin D) show increased dysregulation across controls and at-risk stages of development of MDD, suggesting involvement in the etiology of MDD. Nevertheless, the same mechanisms did not show more dysregulation in clinical progression of MDD toward multiple episodes and/or chronicity. This suggests that pathophysiological mechanisms for etiology and clinical disease progression are not necessarily overlapping.

• #87 Ethiopathogenesis of Depressive Disorders

  https://clinical-practice-and-epidemiology-in-mental-health.com/VOLUME/10/PAGE/166/FULLTEXT/

  The etiopathogenesis of depressive disorders is always complex and multifactorial. […] In conclusion, the currently available data seem to support the hypothesis that some people are biologically predisposed to depression (genetics that affects neurotransmitters, CNS disorders), but on this predisposition are engrafted temperamental, attachment styles and environmental factors.

• #88 Imaging the pathophysiology of major depressive disorder – from localist models to circuit-based analysis | Biology of Mood & Anxiety Disorders | Full Text

  https://biolmoodanxietydisord.biomedcentral.com/articles/10.1186/2045-5380-4-5

  Evidence for alterations of Glu transmission in MDD have long been reported, but findings have been mixed, with increased Glu levels observed in plasma samples and post-mortem tissue as compared to decreased levels found in neuroimaging studies. […] Dysregulation of stress hormones has been widely reported in MDD (albeit with significant variance), and is believed to partially mediate some of the observed structural alterations associated with the disorder, especially within the hippocampus and mPFC. […] By beginning to localize the functional architecture of brain regions that are affected by stress hormones and inflammation and by linking such abnormalities to specific cardinal symptoms of MDD (for example, anhedonia), these studies are playing a critical role in advancing a more precise understanding of depression symptomatology.

• #89 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Underlying each depressive symptom may in fact be a unique mechanism comprising multiple malfunctioning neural circuits. […] The structure and function of these brain regions are modulated by monoaminergic neurotransmission. […] Disturbances in the functional connectivity in these and related neural networks appear to be integrally involved in the onset and progression of major depression. […] Importantly, these and related biochemical lesions provide a mechanistic rationale for antidepressant therapy. […] Interrelationships between clinical symptoms, affected neural systems, and antidepressant mechanisms of action may help clinicians customize pharmacotherapy to a patients unique clinical profile. […] Mechanism-based pharmacotherapy is the linchpin of personalized treatment, and provides a rational basis on which to make initial therapeutic choices for newly diagnosed patients, and those struggling with unremitting symptoms.

• #90 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Individual patients with depression present with unique symptom clusters before, during, and even after treatment. […] The prevalence of persistent, unresolved symptoms and their contribution to patient functioning and disease progression emphasize the importance of finding the right treatment choice at the onset and the utility of switching medications based on suboptimal responses. […] The likelihood of long-term treatment success is improved with early and accurate diagnosis, continual multidimensional assessment, and rational pharmacotherapy tailored to the patients symptomatology, coexisting disorders, and treatment needs. […] There are no validated biological tests that can be used to diagnose depression. […] Understanding the relationship between the symptoms of depression and how they adversely affect patient functioning is essential for optimized clinical decision making.

• #91 Unipolar depression: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/unipolar-depression-pathogenesis

  Unipolar depression is a major public health problem associated with increased functional disability and mortality. The illness likely represents a group of heterogeneous disorders that are phenotypically similar. Efforts to understand the pathogenesis of depression, as well as its neurobiology, are intended to discern these different diseases or subtypes. […] This topic reviews the pathogenesis of unipolar depression.

• #92 Different Mechanisms Between Melancholic and Atypical Depression | IntechOpen

  https://www.intechopen.com/chapters/48427

  The dopamine (DA) system has been reported to be highly associated with the symptomatology of depression, as the proposed pathogenesis of melancholic depression involves decreased DA transmission. […] The neuroplasticity hypothesis proposes that depression results from an inability to make the appropriate neuronal proliferation in response to stress. […] Major depressive disorder is considered to be a clinically heterogeneous disorder and the diagnosis is based on a patients symptoms, not on any laboratory tests. […] Currently, researchers have determined that MDD results from the interaction of multiple genetic factors and various environmental factors, such as childhood adversity and many stressful life events. […] For example, melancholic depression is associated with hyperactivity of the HPA axis while atypical depression is associated with hypoactivity of the HPA axis. […] Researchers have searched for biological mechanisms according to depression subtypes in an effort to understand the pathogenesis of depression subtypes.

• #93 Depression – Neurotorium

  https://neurotorium.org/depression/

  The heterogeneity of major depressive disorder, with specific reference to immunometabolic depression. […] Basic mechanisms of antidepressant action reuptake inhibition and enzyme inhibition. […] This slide deck includes the key components of neurosynaptic transmission, neurotransmitters and hypotheses about the underlying causes of depression.

• #94 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Individual patients with depression present with unique symptom clusters before, during, and even after treatment. […] The prevalence of persistent, unresolved symptoms and their contribution to patient functioning and disease progression emphasize the importance of finding the right treatment choice at the onset and the utility of switching medications based on suboptimal responses. […] The likelihood of long-term treatment success is improved with early and accurate diagnosis, continual multidimensional assessment, and rational pharmacotherapy tailored to the patients symptomatology, coexisting disorders, and treatment needs. […] There are no validated biological tests that can be used to diagnose depression. […] Understanding the relationship between the symptoms of depression and how they adversely affect patient functioning is essential for optimized clinical decision making.

• #95 Depression – Neurotorium

  https://neurotorium.org/depression/

  Depression is a leading cause of disability worldwide and is a major contributor to the overall global burden of disease. A common feature of the disorder is the presence of sad, empty, or irritable mood, accompanied by somatic and cognitive changes that significantly affect the individuals capacity to function. […] Depression is a clinically heterogeneous disorder. […] Major depressive disorder (MDD) is characterized by discrete episodes of at least 2 weeks duration (although most episodes last considerably longer) involving clear-cut changes in affect, cognition, and neurovegetative functions and inter-episode remissions. […] Depression often has a remitting and relapsing course, and symptoms may persist between episodes. Severity of the disorder is determined by both the number and severity of symptoms, as well as the degree of functional impairment.

• #96 Major Depressive Disorder – Cognitive and Neurobiological Mechanisms | IntechOpen

  https://www.intechopen.com/books/4555

  Major depressive disorder (MDD) is a complex and heterogeneous disorder, phenotypically and biologically. MDD may be caused by complex interaction between genes and environment in susceptible individuals. Thus, a combination of certain genetic polymorphism, environmental stress, and personal susceptibility ultimately may induce MDD. […] Gene-environment interactions in the pathophysiology of MDD lead to advancement in personalized medicine by means of genotyping for inter-individual variability in drug action and metabolism. Gene-environment interactions may explain why some subjects become depressed while others remain unaffected. The aim of this book is to describe current knowledge of MDD from the point of view of neurobiology, molecular genetics and cognition. The authors address a deep understanding of cognitive and neurobiological mechanisms involved in MDD.

• #97 Different Mechanisms Between Melancholic and Atypical Depression | IntechOpen

  https://www.intechopen.com/chapters/48427

  The dopamine (DA) system has been reported to be highly associated with the symptomatology of depression, as the proposed pathogenesis of melancholic depression involves decreased DA transmission. […] The neuroplasticity hypothesis proposes that depression results from an inability to make the appropriate neuronal proliferation in response to stress. […] Major depressive disorder is considered to be a clinically heterogeneous disorder and the diagnosis is based on a patients symptoms, not on any laboratory tests. […] Currently, researchers have determined that MDD results from the interaction of multiple genetic factors and various environmental factors, such as childhood adversity and many stressful life events. […] For example, melancholic depression is associated with hyperactivity of the HPA axis while atypical depression is associated with hypoactivity of the HPA axis. […] Researchers have searched for biological mechanisms according to depression subtypes in an effort to understand the pathogenesis of depression subtypes.

• #98 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Underlying each depressive symptom may in fact be a unique mechanism comprising multiple malfunctioning neural circuits. […] The structure and function of these brain regions are modulated by monoaminergic neurotransmission. […] Disturbances in the functional connectivity in these and related neural networks appear to be integrally involved in the onset and progression of major depression. […] Importantly, these and related biochemical lesions provide a mechanistic rationale for antidepressant therapy. […] Interrelationships between clinical symptoms, affected neural systems, and antidepressant mechanisms of action may help clinicians customize pharmacotherapy to a patients unique clinical profile. […] Mechanism-based pharmacotherapy is the linchpin of personalized treatment, and provides a rational basis on which to make initial therapeutic choices for newly diagnosed patients, and those struggling with unremitting symptoms.

• #99 Major depressive disorder: mechanism-based prescribing for personalize | NDT

  https://www.dovepress.com/major-depressive-disorder-mechanism-based-prescribing-for-personalized-peer-reviewed-fulltext-article-NDT

  Underlying each depressive symptom may in fact be a unique mechanism comprising multiple malfunctioning neural circuits. […] The structure and function of these brain regions are modulated by monoaminergic neurotransmission. […] Disturbances in the functional connectivity in these and related neural networks appear to be integrally involved in the onset and progression of major depression. […] Importantly, these and related biochemical lesions provide a mechanistic rationale for antidepressant therapy. […] Interrelationships between clinical symptoms, affected neural systems, and antidepressant mechanisms of action may help clinicians customize pharmacotherapy to a patients unique clinical profile. […] Mechanism-based pharmacotherapy is the linchpin of personalized treatment, and provides a rational basis on which to make initial therapeutic choices for newly diagnosed patients, and those struggling with unremitting symptoms.

• #100 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  GABA, an inhibitory neurotransmitter, and glutamate and glycine, both of which are major excitatory neurotransmitters are found to play a role in the etiology of depression as well. […] Structural and functional brain imaging of depressed individuals has shown increased hyperintensities in the subcortical regions, and reduced anterior brain metabolism on the left side, respectively. […] Family, adoption, and twin studies have indicated the role of genes in the susceptibility of depression. […] The learned helplessness theory has associated the occurrence of depression with the experience of uncontrollable events. […] Major depressive disorder can be managed with various treatment modalities, including pharmacological, psychotherapeutic, interventional, and lifestyle modification. […] Combination treatment, including both medications and psychotherapy, has been found to be more effective than either of these treatments alone.

• #101 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  GABA, an inhibitory neurotransmitter, and glutamate and glycine, both of which are major excitatory neurotransmitters are found to play a role in the etiology of depression as well. […] Structural and functional brain imaging of depressed individuals has shown increased hyperintensities in the subcortical regions, and reduced anterior brain metabolism on the left side, respectively. […] Family, adoption, and twin studies have indicated the role of genes in the susceptibility of depression. […] The learned helplessness theory has associated the occurrence of depression with the experience of uncontrollable events. […] Major depressive disorder can be managed with various treatment modalities, including pharmacological, psychotherapeutic, interventional, and lifestyle modification. […] Combination treatment, including both medications and psychotherapy, has been found to be more effective than either of these treatments alone.

• #102 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  Electroconvulsive therapy is found to be more efficacious than any other form of treatment for severe major depression. […] The prognosis of MDD is good in patients with mild episodes, the absence of psychotic symptoms, better treatment compliance, a strong support system, and good premorbid functioning. […] MDD is one of the leading causes of disability worldwide. It not only causes a severe functional impairment but also adversely affects the interpersonal relationships, thus lowering the quality of life.

• #103 Intranasal Esketamine Linked to Reduction of Depressive Symptoms in Teens

  https://www.psychiatryadvisor.com/news/intranasal-esketamine-linked-to-reduction-of-depressive-symptoms-in-teens/

  In adolescents with major depressive disorder (MDD) at imminent risk for suicide, intranasal esketamine combined with standard-of-care therapy (SOC) produced rapid reductions in depressive symptoms, according to results published in the Journal of the American Academy of Child Adolescent Psychiatry. […] The results support further investigation of esketamine nasal spray for the rapid reduction of depressive symptoms in larger trials of adolescents. […] The results support further investigation of esketamine nasal spray for the rapid reduction of depressive symptoms in larger trials of adolescents, the study authors concluded.

• #104

  https://www1.racgp.org.au/newsgp/clinical/new-treatment-for-resistant-depression-added-to-pb

  Australians with depression who have not responded to traditional medications will soon have access to a new type of treatment under the Pharmaceutical Benefits Scheme (PBS). Esketamine (sold as Spravato) uses a form of ketamine administered via a nasal spray and will be available through the PBS from 1 May for adults with treatment resistant depression. To be eligible, patients must have a major depressive disorder that has not responded adequately to at least two different antidepressants of adequate dose and duration. […] For the first time, we have a Government-funded medicine specifically for people trapped in an acute depressive episode despite treatment with multiple antidepressants, he said. […] People with treatment resistant depression have complex and often urgent mental health care needs.

• #105

  https://www1.racgp.org.au/newsgp/clinical/new-treatment-for-resistant-depression-added-to-pb

  This can result in more severe symptoms including significantly longer depressive episodes, suicidal thoughts and an inability to experience joy. […] Esketamine is effective for some patients with complex presentations but requires close monitoring by skilled clinicians to maintain safety as there are considerable risks along with the potential benefits. […] According to clinical guidelines, esketamine must be used in conjunction with a newly initiated oral antidepressant and administered under clinical supervision via nasal spray. […] A glutamate receptor modulator, esketamine works by increasing glutamate levels a neurotransmitter involved in a persons mood and thought processes to stimulate and restore message transmission within the brain. […] However, research is ongoing, with questions persisting around the treatments impact on suicidality and its long-term effects, with careful monitoring advised for patients with suicidal ideation prior to commencement of treatment. […] There are also contraindications to using esketamine that doctors must be aware of, with the treatment not suitable for patients who would be placed at risk by increases in blood pressure or intracranial pressure, such as those with a history of aneurysm.

• #106 Biomarkers of Major Depressive Disorder: Knowing is Half the Battle

  https://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2021.19.1.12

  Major depressive disorder (MDD) is a heterogeneous disease which is why there are currently no specific methods to accurately test the severity, endophenotype or therapy response. […] The literature accessible indicates that markers involved in inflammatory, neuro-trophic and metabolic processes and components of neurotransmitters and neuroendocrine systems are rather strong indicators to be considered clinically and can be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomics and neuroimaging assessments. […] Several lines of evidence suggest that a portion of MDD is a dopamine agonist-responsive subtype. […] This review analyzes concise reports on the pathophysiological biomarkers of MDD and therapeutic reactions via peripheral developmental factors, inflammative cytokines, endocrine factors and metabolic markers.

• #107 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250507/Ten-year-data-confirm-exercise-is-a-powerful-tool-against-depression.aspx

  To optimize the antidepressant effects of physical activity, biomarkers of depressive disorders must be monitored regularly. The optimal dose-response relationship must also be determined to provide clinicians with clear guidelines for prescribing this strategy for the treatment of depression symptoms.

• #108

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2950973/

  Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. […] A series of magnetic resonance spectroscopy studies consistently showed reductions in total gamma-aminobutyric acid (GABA) concentrations in the prefrontal and occipital cortex in acute depression. […] Several lines of evidence suggest a dysfunction of the glutamate neurotransmitter system in MDD. […] Sleep disturbances and daytime fatigue are diagnostic criteria for MDD, suggesting impaired sleep-wake regulation in depressed patients. […] Based on these findings, circadian abnormalities have been hypothesized to be etiologically associated with MDD. […] The main strengths and weaknesses of the various neurobiological hypotheses of depression are summarized in Table 1. […] The identification of reliable predictors of therapeutic outcomes will allow for the development of personalized medicine that has the potential to individually tailor interventions and to open up new pathways in the evaluation of novel therapeutic approaches.

• #109 Anhedonia and Depressive Disorders

  https://www.cpn.or.kr/view.html?uid=1533&vmd=Full

  In the context of mood disorders, convergent lines of evidence imply that anhedonia is linked with a more severe and recurrent disease. […] Higher levels of anhedonia in depression have been related with a larger number of preceding depressive episodes, longer depressive episode length, and greater overall disease severity. […] Anhedonia has often been associated with an increased risk for suicidal behavior. […] The relationship between anhedonia and inflammation may be bidirectional, meaning that inflammation may contribute to the physiopathology of anhedonia, and anhedonia may also influence inflammation by reducing engagement in anti-inflammatory behaviors, such as exercise and social interactions. […] Traditional antidepressants, such as selective serotonin reuptake inhibitors, showed a limited benefit on anhedonia, also considering their potential pro-anhedonic effect in some subjects.

• #110 Anhedonia and Depressive Disorders

  https://www.cpn.or.kr/view.html?uid=1533&vmd=Full

  However, some antidepressants may be more effective in treating anhedonia than others. […] Anhedonia may be more effectively treated with a variety of different antidepressants, such as bupropion, dextromethorphan combined with bupropion, agomelatine, ketamine and transcranial magnetic stimulation. […] In conclusion, a substantial body of data demonstrates that anhedonia is at least somewhat separate from depression.

• #111 Ethiopathogenesis of Depressive Disorders

  https://clinical-practice-and-epidemiology-in-mental-health.com/VOLUME/10/PAGE/166/FULLTEXT/

  The etiopathogenesis of depressive disorders is always complex and multifactorial. […] In conclusion, the currently available data seem to support the hypothesis that some people are biologically predisposed to depression (genetics that affects neurotransmitters, CNS disorders), but on this predisposition are engrafted temperamental, attachment styles and environmental factors.

• #112 Major depressive disorder – Wikipedia

  https://en.wikipedia.org/wiki/Major_depressive_disorder

  Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, with about 40% of the risk being genetic. […] The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA-axis dysfunction, and structural or functional abnormalities of emotional circuits. […] The monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. […] HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. […] Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior, creating a pro-inflammatory profile in MDD. […] The newer field of psychoneuroimmunology suggests that cytokines may impact depression.

• #113 Major Depressive Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559078/

  Major depressive disorder (MDD) has been ranked as the third cause of the burden of disease worldwide in 2008 by WHO, which has projected that this disease will rank first by 2030. […] The etiology of Major depressive disorder is believed to be multifactorial, including biological, genetic, environmental, and psychosocial factors. MDD was earlier considered to be mainly due to abnormalities in neurotransmitters, especially serotonin, norepinephrine, and dopamine. This has been evidenced by the use of different antidepressants such as selective serotonin receptor inhibitors, serotonin-norepinephrine receptor inhibitors, dopamine-norepinephrine receptor inhibitors in the treatment of depression. […] However, recent theories indicate that it is associated primarily with more complex neuroregulatory systems and neural circuits, causing secondary disturbances of neurotransmitter systems.

• #114 Major depressive disorder: hypothesis, mechanism, prevention and treatment | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01738-y

  Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear, and additional diagnostic and therapeutic strategies for MDD still are needed. The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis hypothesis, cytokine hypothesis, neuroplasticity hypothesis and systemic influence hypothesis, but these hypothesis cannot completely explain the pathological mechanism of MDD. […] Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD, thus in recent years, great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies, further revealing the disease features of MDD. Furthermore, some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention, some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms.

• #115 Pathogenesis of major depressive disorder | NDT

  https://www.dovepress.com/association-between-nr4a2-gene-polymorphism-and-depressive-symptoms-an-peer-reviewed-fulltext-article-NDT

  In our study, we investigated the association between NR4A2 gene polymorphisms and depressive symptoms and antidepressant efficacy. The results revealed that NR4A2 gene polymorphisms were associated with partial depressive symptoms, and NR4A2 rs3769340 was associated with the efficacy of antidepressant. […] The rs3769340 gene polymorphism was associated with weight loss in patients with MDD. […] In general, these findings demonstrate the significant association between NR4A2 gene polymorphisms and retardation: psychomotor, somatic general symptoms (gastro-intestinal), somatic anxiety symptoms, weight loss, and insight in patients with MDD. This suggests that phenotypic studies may be more suitable for molecular genetic studies of depression disorders, suggesting that we can further collect patients with different diagnoses of mental disorders in future studies, and further classify patients according to phenotypes, so as to study the genetic mechanism of a certain phenotype. NR4A2 gene polymorphism may be a predictor of antidepressant efficacy.

• #116

  https://apcz.umk.pl/JEHS/article/view/42852

  Depressive disorders are a significant problem. They lead to suffering, loss of interest and may contribute to suicide attempts. Despite the large number of available medications, 10-35% of patients fail to achieve remission. Therefore, for these ongoing researches are underway to thoroughly understand the pathophysiology of depression. […] The purpose of the study was to review the latest literature on the kynurenine pathway importance in depression, and to discover its links with theories relating to the pathogenesis of depression. […] Animal studies confirm the importance of the kynurenine pathway in animal models of depression. Peripherally directed inflammatory stimuli in humans lead to peripheral activation of the kynurenine pathway. The regulation of the kynurenine pathway in the brain is specific to a particular region as well as to a given type of depression. […] Understanding changes in kynurenine pathway transmission in a particular type of depression may be helpful in developing new, more effective drugs.

• #117 Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications | Neuroscience Bulletin

  https://link.springer.com/article/10.1007/s12264-021-00638-3

  Major depressive disorder (MDD), also referred to as depression, is one of the most common psychiatric disorders with a high economic burden. The etiology of depression is still not clear, but it is generally believed that MDD is a multifactorial disease caused by the interaction of social, psychological, and biological aspects. Therefore, there is no exact pathological theory that can independently explain its pathogenesis, involving genetics, neurobiology, and neuroimaging. […] The underlying pathogenesis of depression is far beyond the simple monoamine mechanism. Other hypotheses of depression have gradually received increasing attention because of biomarkers for depression and the effects pharmacological treatments, such as the stress-responsive hypothalamic pituitary adrenal (HPA) axis, neuroendocrine systems, the neurotrophic family of growth factors, and neuroinflammation.

• #118

  https://consensus.app/questions/major-depressive-disorder-vs-depression/

  Major depressive disorder (MDD) is a specific psychiatric condition characterized by a persistent and intense state of sadness or irritability, accompanied by various psychophysiological changes. These changes include disturbances in sleep, appetite, sexual desire, and energy levels, as well as cognitive impairments such as difficulty concentrating and making decisions. To be diagnosed with MDD, these symptoms must be present nearly every day for at least two weeks and significantly interfere with daily functioning. […] The etiology of MDD is multifactorial, involving genetic, neurobiological, and psychosocial factors. Research indicates that altered neurotransmission, chronic stress, inflammation, and reduced neuroplasticity are key mechanisms underlying MDD. […] Recent advances in neuroscience research have led to the development of new antidepressants, improving treatment for major depressive disorder.

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