Materiały źródłowe

• #1 Pathogenesis of depression: insights from human and rodent studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4664582/

  Major depressive disorder (MDD) will affect one out of every five people in their lifetime and is the leading cause of disability worldwide. Nevertheless, mechanisms associated with the pathogenesis of MDD have yet to be completely understood and current treatments remain ineffective in a large subset of patients. […] These mechanisms range from synaptic plasticity mechanisms to epigenetics and the immune system where there is strong evidence to support a functional role in the development of specific depression symptomology. Ultimately we conclude by discussing how novel therapeutic strategies targeting central and peripheral processes might ultimately aid in the development of effective new treatments for MDD and related stress disorders. […] MDD is characterized by symptoms of emotional, motivational, cognitive and physiological domains making it a complex disease to treat. […] In fact, it is estimated that only 50% of depressed patients are responsive to currently available antidepressant treatments. This may reflect the fact that depression diagnosis is based solely on behavioral symptoms and the drugs used to treat these symptoms are not specific to the underlying disease pathology.

• #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. Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses. […] Because all theories of depression apply to only some types of depressed patients but not others, and because depressive pathophysiology may vary considerably across the course of illness, the current extant knowledge argues against a unified hypothesis of depression. […] Individual depression hypotheses based on neurobiological knowledge are discussed in terms of their interest to both clinicians in daily practice and clinical researchers developing novel therapies. […] 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. […] Non-genetic factors, explaining the remaining 60-70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions).

• #3 Exploring New Mechanism of Depression from the Effects of Virus on Nerve Cells

  https://www.mdpi.com/2073-4409/12/13/1767

  Depression is a common neuropsychiatric disorder with long-term recurrent depressed mood, pain and despair, pessimism and anxiety, and even suicidal tendencies as the main symptoms. […] Current studies have shown the key role of glial cells in the development of depression, and it is noteworthy that some recent evidence suggests that the development of depression may be closely related to viral infections, such as SARS-CoV-2, BoDV-1, ZIKV, HIV, and HHV6, which infect the organism and cause some degree of glial cells, such as astrocytes, oligodendrocytes, and microglia. This can affect the transmission of related proteins, neurotransmitters, and cytokines, which in turn leads to neuroinflammation and depression. […] At present, the mechanism of depression is not clear, but many studies have shown that it is closely related to glial cells.

• #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. Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses. […] Because all theories of depression apply to only some types of depressed patients but not others, and because depressive pathophysiology may vary considerably across the course of illness, the current extant knowledge argues against a unified hypothesis of depression. […] Individual depression hypotheses based on neurobiological knowledge are discussed in terms of their interest to both clinicians in daily practice and clinical researchers developing novel therapies. […] 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. […] Non-genetic factors, explaining the remaining 60-70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions).

• #5

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

  Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. […] 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. […] Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients. […] 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.

• #6 Biology of depression – Wikipedia

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

  The observation of this efficacy led to the monoamine hypothesis of depression, which postulates that the deficit of certain neurotransmitters is responsible for depression, and even that certain neurotransmitters are linked to specific symptoms. […] The main limitation for the monoamine hypothesis of depression is the therapeutic lag between initiation of antidepressant treatment and perceived improvement of symptoms. […] One explanation for this therapeutic lag is that the initial increase in synaptic serotonin is only temporary, as firing of serotonergic neurons in the dorsal raphe adapt via the activity of 5-HT1A autoreceptors. […] The therapeutic effect of antidepressants is thought to arise from autoreceptor desensitization over a period of time, eventually elevating firing of serotonergic neurons.

• #7

  https://drpress.org/ojs/index.php/HSET/article/view/1120

  Depression is a serious mental disorder that influence about 280 million people around the world. […] Although the underlying pathophysiology of depression is remained unclear, neurotransmitters, including serotonin, dopamine, and norepinephrine, are proved to be related to the symptoms of depression by clinical experiments. […] The first two antidepressants were iproniazid (classified as a monoamine-oxidase inhibitor), and imipramine (classified as a tricyclic antidepressant) in 1950s. […] More antidepressants using different mechanisms and with fewer side-effect and safety concerns were developed later. […] Due to immature technology, drugs in the first-generation generally have more serious side-effect, more safety concerns, and more restrictions. […] Thus, second-generation antidepressants, which typically have less side-effect, are now more common in controlling the symptoms of depression. […] The third-generation antidepressants are still in development, but designed to be more effective with less side-effect.

• #8 Depression Epidemiology and Its Treatment Evolution

  https://www.psychiatrist.com/jcp/depression-epidemiology-treatment-evolution/

  The presumed mechanism of action of the tricyclics and of the MAOIs led scientists to develop a comprehensive theory of the pathophysiology of depression—the catecholamine hypothesis. Simply put, this hypothesis states that depression results from a deficiency of catecholamines (particularly serotonin and norepinephrine) in synapses in the brain. Elation results from an excess of such amines. […] The mechanism of action of the TCAs was to block the reuptake of specific neurotransmitters in the synapse—serotonin and norepinephrine—which produced an antidepressant effect. […] The MAOIs increase synaptic catecholamines by inhibiting the enzyme monoamine oxidase, which metabolizes them. Currently, MAOIs may be the most effective medications available to treat depression, but their widespread use has been limited by dietary restrictions and the potential for serious adverse events through drug-drug interactions.

• #9 Neuroprogression: the hidden mechanism of depression | NDT

  https://www.dovepress.com/neuroprogression-the-hidden-mechanism-of-depression-peer-reviewed-fulltext-article-NDT

  The negative impact of the hypercortisolemia in the monoaminergic transmission of 5-HT, NA, and DA is due to the disruption of their receptors located in the limbic regions (prefrontal cortex, amygdala, hippocampus, and hypothalamus) that are extremely sensitive to the hormones released during stress. […] The relevance of these neurotransmitters is based on the success obtained from the tricyclic drugs and the MAO inhibitors used in the treatment of DD. […] The findings have shown allelic variants in the genes encoding the serotonin receptors called s and l alleles (s for short and l for long) that represent the short and long versions of the gene. […] The serotonergic system, in particular, seems to have a more active participation in the neuroprogressive process because it usually acts like neurogenesis-stimulating factor by the expression of BDNF.

• #10 Biology of depression – Wikipedia

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

  The observation of this efficacy led to the monoamine hypothesis of depression, which postulates that the deficit of certain neurotransmitters is responsible for depression, and even that certain neurotransmitters are linked to specific symptoms. […] The main limitation for the monoamine hypothesis of depression is the therapeutic lag between initiation of antidepressant treatment and perceived improvement of symptoms. […] One explanation for this therapeutic lag is that the initial increase in synaptic serotonin is only temporary, as firing of serotonergic neurons in the dorsal raphe adapt via the activity of 5-HT1A autoreceptors. […] The therapeutic effect of antidepressants is thought to arise from autoreceptor desensitization over a period of time, eventually elevating firing of serotonergic neurons.

• #11 Biology of depression – Wikipedia

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

  The serotonin „chemical imbalance” theory of depression, proposed in the 1960s, is not supported by the available scientific evidence. […] SSRIs alter the balance of serotonin inside and outside of neurons: their clinical antidepressant effect is likely due to more complex changes in neuronal functioning which occur as a downstream consequence of this. […] The amygdala, a structure involved in emotional processing appears to be hyperactive in those with major depressive disorder. […] Atrophy of the hippocampus has been observed during depression, consistent with animal models of stress and neurogenesis. […] Stress can cause depression and depression-like symptoms through monoaminergic changes in several key brain regions as well as suppression in hippocampal neurogenesis. […] This leads to alteration in emotion and cognition related brain regions as well as HPA axis dysfunction.

• #12 Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications | Molecular Psychiatry

  https://www.nature.com/articles/s41380-022-01520-y

  Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. […] More recently, however, there has been a paradigm shift toward a neuroplasticity hypothesis of depression in which downstream effects of antidepressants, such as increased neurogenesis, contribute to improvements in cognition and mood. […] We conclude with a discussion of how antidepressant treatments share a common effect in modulating neuroplasticity and consider outstanding questions and future perspectives.

• #13 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Some studies have shown that inflammation and abnormal activity of the immune system may be associated with depression, and inflammatory responses and immune molecules may play a role in the pathophysiology of depression. […] Acupuncture, as an ancient and unique non-pharmacological treatment, stimulates the nervous system of the human body by inserting and rotating needles at specific acupoints and exerts analgesic, muscle relaxation, anti-inflammatory, mild anxiolytic, and antidepressant effects. […] Acupuncture is thought to affect the levels of some major neurotransmitters in the brain. […] Acupuncture exerts its antidepressant effect by regulating the neuroendocrine axis in the body, particularly the hypothalamic-pituitary-adrenal (HPA) axis. […] Neuroplasticity refers to the ability of the nervous system to adapt to environmental changes during life, including the strengthening or weakening of neural synapses, the formation of new neural synapses, or the disappearance of existing synapses.

• #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 inflammation theory has also been linked to depression, which surprises many people. It acts as a key point regarding treatment direction for depression cases. […] The neurotrophin hypothesis also has a vital role in the pathophysiology of depression. […] Changes in BDNF levels in the central nervous system disrupt the entire signaling pathway, which can lead to various psychological disorders, including depression. […] The immune system is very sensitive to oxidative stress and with moderate exercise, immune functionality can be enhanced. […] Recent studies on treatment resistance in depressed patients have related the condition to inflammation.

• #15 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  By influencing brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, kynurenine pathway metabolism, and neuroinflammation, exercise promotes neural plasticity and improves cognitive functions in depressed patients. BDNF is a pivotal neuronal plasticity factor that facilitates axon extension and the formation of new branches within the brain’s motor units. It also enhances neuronal connectivity and synaptic plasticity, thereby improving memory and cognitive function in depression patients. […] Exercise and the immune system. Chronic stress from environmental and psychological factors disrupts homeostasis and activates the sympathetic nervous system as well as the hypothalamic-pituitary-adrenal (HPA) axis and modifies the levels of neurotransmitters, neurochemicals, and hormones. Major depressive disorder can induce systemic immune activation, evidenced by differences in inflammatory markers, immune cell counts, and antibody titers. Increased pro-inflammatory cytokine and stress hormone levels cause behavioral changes in depression.

• #16 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.

• #17 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. […] 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.

• #18 So depression is an inflammatory disease, but where does the inflammation come from? | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-200

  We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. […] New evidence shows that clinical depression is accompanied by increased oxidative and nitrosative stress (ONS) and autoimmune responses directed against ONS modified neoepitopes. […] Not only is depression present in acute illness, but higher levels of inflammation appear to increase the risk for the development of de novo depression. […] Indeed, cytokines induce depressive-like behaviors; in studies where healthy participants are given endotoxin infusions to trigger cytokines release, classical depressive symptoms emerge. […] Exogenous cytokine infusions also cause the classical phenotypic behavioral and cognitive features of depression.

• #19

  https://www.jpccr.eu/Occurrence-of-depression-in-patients-with-psoriasis-the-role-of-inflammation-stress,122221,0,2.html

  The correlation between depression, psoriasis and inflammation is a subject of many publications. […] The study demonstrated that the link between psoriasis and depression is bi-directional. The pro-inflammatory cytokine, such as IL-6, TNF-, CRP and IL-17, are elevated in both cases, which provokes the exacerbation of sickness symptoms. The inflammation dangerously disturbs the functioning of neuronal system and human homeostasis. […] Inflammation plays an essential role by being a peculiar connector between psoriasis and depression. Stress and inflammation are crucial factors in pathogenesis of those two disorders and triggers the pathological mechanisms.

• #20 Novel treatments of depression: bridging the gap in current therapeutic approaches

  https://www.explorationpub.com/Journals/en/Article/100649

  Depression is no longer viewed solely through the lens of neurotransmitter imbalances; the immune systems involvement, particularly the inflammatory response, has gained prominence. […] Elevated levels of cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-), and C-reactive protein (CRP), have been consistently observed in individuals with depression. […] In depression, there is evidence to suggest that there may be alterations in the GABAergic system, leading to an imbalance in excitatory and inhibitory neurotransmission. […] The primary inhibitory neurotransmitter in the central nervous system, GABA, plays a crucial role in regulating neuronal excitability. […] Psychedelics exert their effects primarily through the modulation of serotonin receptors, particularly the 5-HT2A receptor.

• #21 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Depression is often associated with an increased inflammatory response. Chronic inflammation is now thought to be associated with depression. […] Acupuncture is considered to have anti-inflammatory effects and is able to reduce the production and release of inflammatory factors (eg, TNF-, IL-1, IL-6, etc.). […] Acupuncture treatment for depression is an ancient and effective method, and its mechanism involves multiple biological pathways. Acupuncture plays an antidepressant role by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammation, and other effects, and improving the emotional state.

• #22 Association between red blood cell distribution width-to-albumin ratio and depression: a cross-sectional analysis among US adults, 2011–2018 | BMC Psychiatry | Full Text

  https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06907-z

  RAR was positively associated with depression in 18,150 participants aged 20 years. In fully adjusted models, each one-unit increase in RAR was associated with a 22% increase in the likelihood of depression [1.22 (1.05, 1.41)]. Participants in the highest quartile of RAR had a 30% higher risk of depression than those in the lowest quartile of RAR [1.30 (1.04, 1.63)]. […] Higher baseline RAR was associated with an increased risk of depression in US adults and was more informative than RDW, albumin, and hemoglobin-to-RDW ratio (HRR). […] Existing evidence supports the association of inflammation with the pathophysiology of depression. […] Patients with depression tend to have higher levels of serum biomarkers associated with inflammation, including high-sensitivity c-reactive protein (hs-CRP), interleukin (IL)6, IL-12, IL-18, and TNF-.

• #23 KBS_Icon_questionmark

  https://www.kcl.ac.uk/a-key-biological-mechanism-linked-to-depression-risk-and-recovery-in-teenage-girls-a-new-path-to-prevention-and-treatment

  Depression is a mental health condition that affects millions, often beginning in adolescence or early adulthood. […] While scientists have studied depression in adults, they know much less about how biological processes drive depression in adolescents, particularly across sexes. […] The kynurenine pathway is a series of chemical reactions that processes tryptophan, an amino acid found in foods and the building block for serotonin, the feel-good neurotransmitter that regulates our mood. […] When the body experiences inflammation, an immune response that occurs during infection, stress, or illness, the kynurenine pathway is pushed towards producing more neurotoxic chemicals. […] In adults with depression, research has shown an imbalance in this pathway, with more neurotoxic than neuroprotective chemicals being produced.

• #24 KBS_Icon_questionmark

  https://www.kcl.ac.uk/a-key-biological-mechanism-linked-to-depression-risk-and-recovery-in-teenage-girls-a-new-path-to-prevention-and-treatment

  Measuring kynurenine pathway products, we found that adolescents with a higher risk for depression or a current diagnosis of depression had lower levels of kynurenic acid, the neuroprotective compound. […] This reduction was most evident in female adolescents, suggesting that females might be more vulnerable to the harmful effects of an imbalanced kynurenine pathway during adolescence, potentially explaining why females experience depression at higher rates, especially during adolescence when hormonal changes may further intensify these effects. […] This suggests that inflammation might drive the kynurenine pathway toward producing neurotoxic chemicals, increasing the risk of depression. […] Therefore, measuring kynurenine pathway chemicals in adolescence could potentially help identify those at risk of persistent depression, particularly in females.

• #25 Depression in Dialysis: A Poor Prognostic Factor and the Mechanism behind It

  https://clinmedjournals.org/articles/ijda/international-journal-of-depression-and-anxiety-ijda-3-019.php?jid=ijda

  Major Depressive Disorder (MDD) is one of the most common psychiatric illnesses. […] The article explains a myriad of biologic, behavioral, genetic and social factors underlying the association of depression and adverse medical outcomes in patients with CKD and ESRD. […] There are several potential biologic mechanisms that can explain the association between depression and poorer medical outcomes in patients with CKD and ESRD. Depression can increase inflammation, which in turn can accelerate atherosclerosis and potentially lead to cardiovascular events. […] Depression is also related to delay health care-seeking behaviors, difficulties in patient-physician communications, and possibly medical errors leading to Acute Kidney Injury (AKI). […] Depression predicts subsequent rapid decline in kidney function, in new onset clinically severe kidney disease (or end-stage renal disease), and hospitalizations that are complicated by acute kidney injury.

• #26 Frequency and predictors of depression and anxiety in chronic illnesses: A multi disease study across non-communicable and communicable diseases | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0323126

  Chronic diseases and mental health disorders such as depression and anxiety are interconnected through shared inflammatory pathways that significantly impact both physical and psychological well-being. Pro-inflammatory cytokines affect critical biological systems associated with the pathophysiology of depression. […] The prevalence of depression and anxiety is not only rising in the general population but is also alarmingly high among individuals with chronic illnesses. Genetic factors, inflammatory pathways, social factors, health behaviors, financial costs and the psychological stress of managing persistent symptoms among patients with chronic diseases contribute to this heightened vulnerability. […] Our study highlights the significant mental health burden among individuals with chronic diseases, demonstrating a contrast in the prevalence of depression and anxiety between those with chronic conditions and healthy controls. The frequency of depression was significantly higher among cases than controls (31% vs. 11%, p0.001), and a similar trend was observed for anxiety (13.25% vs. 6%, p=0.021).

• #27

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

  Stress sensitivity in depression is partly gender-specific. […] 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. […] 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.

• #28 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. […] 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. […] 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. […] These hypotheses are supported by many systemic reviews that have similarly reported the impact of physical activity on the serotonergic system and HPA axis.

• #29

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

  Stress sensitivity in depression is partly gender-specific. […] 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. […] 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.

• #30 Pathophysiology of Depression: Causes and Mechanisms

  https://desklib.com/study-documents/pathophysiology-depression-overview/

  According to Keller et al., (2017), the pathophysiology of depression has been associated with changes in the HPA axis in situations of excessive and chronic stress, which is a characteristic resultant of traumatic life events. […] Exposure to chronic stress in the form of challenging or traumatic life events, has been associated hyperactivity of the HPA axis. […] Steroidal hormones such as corticosteroids pose direct associations with the pathology of depression, where high levels of the same have been shown to result in reductions in the secretion of neurotransmitter dopamine as well as decreases in the size of the hippocampus. […] Hence, as researched by Dwivedi et al., (2015), stress and corticosteroid induced hippocampal reduction results in lack of regulation of the HPA axis, further leading to uncontrolled secretion of corticosteroids.

• #31 Neuroprogression: the hidden mechanism of depression | NDT

  https://www.dovepress.com/neuroprogression-the-hidden-mechanism-of-depression-peer-reviewed-fulltext-article-NDT

  The negative impact of the hypercortisolemia in the monoaminergic transmission of 5-HT, NA, and DA is due to the disruption of their receptors located in the limbic regions (prefrontal cortex, amygdala, hippocampus, and hypothalamus) that are extremely sensitive to the hormones released during stress. […] The relevance of these neurotransmitters is based on the success obtained from the tricyclic drugs and the MAO inhibitors used in the treatment of DD. […] The findings have shown allelic variants in the genes encoding the serotonin receptors called s and l alleles (s for short and l for long) that represent the short and long versions of the gene. […] The serotonergic system, in particular, seems to have a more active participation in the neuroprogressive process because it usually acts like neurogenesis-stimulating factor by the expression of BDNF.

• #32 Pathophysiology of Depression: Causes and Mechanisms

  https://desklib.com/study-documents/pathophysiology-depression-overview/

  Excessive corticosteroids have been implicated to yield depression like symptoms and alterations in emotion and further has been associated with reducing the size of the amygdala, the primary limbic center associated with memory, mood and reward perceptions. […] Hence, as researched by Grace (2015), hindrances to the dopamine system, exerted by corticosteroids results in alterations of the ventral tegmental area and nucleus accumbens – cerebral amygdala areas concerned with perception of reward responses leading to reductions in the sensation of pleasure and malfunctioning brain reward circuit. […] Hence, considering the above pathological processes, depression emerges due to a loss of neurotransmitter and adrenal homeostasis resulting in inhibited HPA hippocampus and elevated amygdala functioning further leading increased perceptions of negativity and brooding over past memories.

• #33 Biology of depression – Wikipedia

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

  Regions involved in the generation of emotion and reward such as the amygdala, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and striatum are frequently implicated as well. […] These regions are innervated by a monoaminergic nuclei, and tentative evidence suggests a potential role for abnormal monoaminergic activity. […] Depression may be related to abnormalities in the circadian rhythm, or biological clock. […] A well synchronized circadian rhythm is critical for maintaining optimal health. […] Adverse changes and alterations in the circadian rhythm have been associated with various neurological disorders and mood disorders including depression. […] Sleep disturbance is the most prominent symptom in depressive patients. […] Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep.

• #34 Biology of depression – Wikipedia

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

  Regions involved in the generation of emotion and reward such as the amygdala, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and striatum are frequently implicated as well. […] These regions are innervated by a monoaminergic nuclei, and tentative evidence suggests a potential role for abnormal monoaminergic activity. […] Depression may be related to abnormalities in the circadian rhythm, or biological clock. […] A well synchronized circadian rhythm is critical for maintaining optimal health. […] Adverse changes and alterations in the circadian rhythm have been associated with various neurological disorders and mood disorders including depression. […] Sleep disturbance is the most prominent symptom in depressive patients. […] Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep.

• #35

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

  The first depressive episode is usually reactive, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly endogenous, i.e., triggered by minor stressors or occurring spontaneously. […] 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 many theories of depression and the relatively low response rate of all available antidepressant treatments clearly argue against a unified hypothesis of depression and suggest that depression is a clinically and etiologically heterogeneous disorder.

• #36 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  One major pathogenesis of depression involves an imbalance of neurotransmitters. Neurotransmitters are chemical messengers in the brain that transmit signals between nerve cells and affect various functions of the brain, including mood regulation, stress response, sleep, and appetite. […] Serotonin is a neurotransmitter that plays an important role in emotional regulation and emotional stability in the brain, especially in inhibiting negative emotions and enhancing positive emotions. […] Dopamine (DA) is another neurotransmitter that is associated with reward, motivation, and affect. DA neurons are one of the crucial neurons involved in the pathogenesis of depression. […] Depression is associated with abnormalities in specific neural circuits in the brain. […] Genetic factors play an important role in the pathogenesis of depression. Family studies and twin studies suggest that genetic factors contribute to susceptibility to depression.

• #37 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  One major pathogenesis of depression involves an imbalance of neurotransmitters. Neurotransmitters are chemical messengers in the brain that transmit signals between nerve cells and affect various functions of the brain, including mood regulation, stress response, sleep, and appetite. […] Serotonin is a neurotransmitter that plays an important role in emotional regulation and emotional stability in the brain, especially in inhibiting negative emotions and enhancing positive emotions. […] Dopamine (DA) is another neurotransmitter that is associated with reward, motivation, and affect. DA neurons are one of the crucial neurons involved in the pathogenesis of depression. […] Depression is associated with abnormalities in specific neural circuits in the brain. […] Genetic factors play an important role in the pathogenesis of depression. Family studies and twin studies suggest that genetic factors contribute to susceptibility to depression.

• #38 Serotonin: What Is It, Function & Levels

  https://my.clevelandclinic.org/health/articles/22572-serotonin

  Low levels of serotonin are associated with depression and other mood problems. […] Lack of enough serotonin is thought to play a role in depression, anxiety, mania and other health conditions. […] Many medications used to treat anxiety, depression and other mood disorders often target ways to increase the level of serotonin in your brain. […] Scientists still have a lot to learn about the role of serotonin in the body and in disease. […] Serotonin plays a key role in such bodily functions as mood, sleep, appetite, anxiety, digestion, blood clotting and sexual desire.

• #39 Serotonin: What Is It, Function & Levels

  https://my.clevelandclinic.org/health/articles/22572-serotonin

  Low levels of serotonin are associated with depression and other mood problems. […] Lack of enough serotonin is thought to play a role in depression, anxiety, mania and other health conditions. […] Many medications used to treat anxiety, depression and other mood disorders often target ways to increase the level of serotonin in your brain. […] Scientists still have a lot to learn about the role of serotonin in the body and in disease. […] Serotonin plays a key role in such bodily functions as mood, sleep, appetite, anxiety, digestion, blood clotting and sexual desire.

• #40 Neuroprogression: the hidden mechanism of depression | NDT

  https://www.dovepress.com/neuroprogression-the-hidden-mechanism-of-depression-peer-reviewed-fulltext-article-NDT

  The negative impact of the hypercortisolemia in the monoaminergic transmission of 5-HT, NA, and DA is due to the disruption of their receptors located in the limbic regions (prefrontal cortex, amygdala, hippocampus, and hypothalamus) that are extremely sensitive to the hormones released during stress. […] The relevance of these neurotransmitters is based on the success obtained from the tricyclic drugs and the MAO inhibitors used in the treatment of DD. […] The findings have shown allelic variants in the genes encoding the serotonin receptors called s and l alleles (s for short and l for long) that represent the short and long versions of the gene. […] The serotonergic system, in particular, seems to have a more active participation in the neuroprogressive process because it usually acts like neurogenesis-stimulating factor by the expression of BDNF.

• #41

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

  Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. […] 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. […] Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients. […] 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.

• #42 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  Exercise and neurotransmitters. According to depression’s clinical pre-chronic stress model, depression is associated with reduced 5-hydroxy tryptamine (5-HT) levels in the hippocampus (HPC), prefrontal cortex (PFC), and striatum, as well as decreased norepinephrine (NE) levels in PFC and HPC. Reduced dopamine (DA) metabolism and activity in individuals with depression correlate with a decrease in reward anticipation within the striatum, culminating in anhedonia. Physical activity enhances the 5-HT and NE concentrations in the brain, thereby facilitating synaptic transmission, and reducing depressive-like behaviors. Moreover, aerobic exercise can acutely affect serotonergic and noradrenergic activities in depression patients. […] Exercise and neuroplasticity. Chronic physical activity induces structural and functional plasticity, leading to the benefits of exercise. Both low-intensity and high-intensity aerobic and resistance training positively influence cognitive function, brain activation, and structure as well as neuroplasticity neurochemical markers and their associations in healthy young and older individuals, as well as neurological disorder patients.

• #43 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  One major pathogenesis of depression involves an imbalance of neurotransmitters. Neurotransmitters are chemical messengers in the brain that transmit signals between nerve cells and affect various functions of the brain, including mood regulation, stress response, sleep, and appetite. […] Serotonin is a neurotransmitter that plays an important role in emotional regulation and emotional stability in the brain, especially in inhibiting negative emotions and enhancing positive emotions. […] Dopamine (DA) is another neurotransmitter that is associated with reward, motivation, and affect. DA neurons are one of the crucial neurons involved in the pathogenesis of depression. […] Depression is associated with abnormalities in specific neural circuits in the brain. […] Genetic factors play an important role in the pathogenesis of depression. Family studies and twin studies suggest that genetic factors contribute to susceptibility to depression.

• #44 Pathophysiology of Depression: Causes and Mechanisms

  https://desklib.com/study-documents/pathophysiology-depression-overview/

  Depression is known as a chronic psychological mood disorder which is characterized by detrimental changes in an individuals regulation of moods, emotions, thoughts and attitudes towards daily life. […] At present, the defects in the neurotransmission and signaling of dopamine has been associated as the primary pathophysiology underlying depression. Such disruptive changes can be attributed to the reductions in the number of receptors, decreases in the release of dopamine from presynaptic neurons, alterations in signal processing at the cellular level and impairments in the transduction of nervous signals. […] The mesolimbic dopamine system is of major concern in the pathophysiology of depression and is associated with neural connections from the midbrain dopamine system to the cerebral limbic and nucleus accumbens areas.

• #45 Pathophysiology of Depression: Causes and Mechanisms

  https://desklib.com/study-documents/pathophysiology-depression-overview/

  Depression is known as a chronic psychological mood disorder which is characterized by detrimental changes in an individuals regulation of moods, emotions, thoughts and attitudes towards daily life. […] At present, the defects in the neurotransmission and signaling of dopamine has been associated as the primary pathophysiology underlying depression. Such disruptive changes can be attributed to the reductions in the number of receptors, decreases in the release of dopamine from presynaptic neurons, alterations in signal processing at the cellular level and impairments in the transduction of nervous signals. […] The mesolimbic dopamine system is of major concern in the pathophysiology of depression and is associated with neural connections from the midbrain dopamine system to the cerebral limbic and nucleus accumbens areas.

• #46 Pathophysiology of Depression: Causes and Mechanisms

  https://desklib.com/study-documents/pathophysiology-depression-overview/

  Depression is known as a chronic psychological mood disorder which is characterized by detrimental changes in an individuals regulation of moods, emotions, thoughts and attitudes towards daily life. […] At present, the defects in the neurotransmission and signaling of dopamine has been associated as the primary pathophysiology underlying depression. Such disruptive changes can be attributed to the reductions in the number of receptors, decreases in the release of dopamine from presynaptic neurons, alterations in signal processing at the cellular level and impairments in the transduction of nervous signals. […] The mesolimbic dopamine system is of major concern in the pathophysiology of depression and is associated with neural connections from the midbrain dopamine system to the cerebral limbic and nucleus accumbens areas.

• #47 Pathophysiology of Depression: Causes and Mechanisms

  https://desklib.com/study-documents/pathophysiology-depression-overview/

  Excessive corticosteroids have been implicated to yield depression like symptoms and alterations in emotion and further has been associated with reducing the size of the amygdala, the primary limbic center associated with memory, mood and reward perceptions. […] Hence, as researched by Grace (2015), hindrances to the dopamine system, exerted by corticosteroids results in alterations of the ventral tegmental area and nucleus accumbens – cerebral amygdala areas concerned with perception of reward responses leading to reductions in the sensation of pleasure and malfunctioning brain reward circuit. […] Hence, considering the above pathological processes, depression emerges due to a loss of neurotransmitter and adrenal homeostasis resulting in inhibited HPA hippocampus and elevated amygdala functioning further leading increased perceptions of negativity and brooding over past memories.

• #48 Novel treatments of depression: bridging the gap in current therapeutic approaches

  https://www.explorationpub.com/Journals/en/Article/100649

  Depression poses a significant global health burden, yet current therapeutic approaches focusing on monoaminergic neurotransmission often fall short of achieving full remission and managing acute episodes effectively. […] The conventional understanding of depression, as posited by the monoamine hypothesis, has long shaped the landscape of antidepressant pharmacotherapy. This theory implicates imbalances in neurotransmitters, particularly serotonin, norepinephrine, and dopamine, as the primary culprits in the pathophysiology of depression. […] Glutamatergic dysfunction is increasingly being implicated in the pathophysiology of depression. […] Changes in the function or expression of these receptors may disrupt these processes and contribute to depressive symptoms. […] The success of ketamine in rapidly alleviating depressive symptoms is thought to be related to its modulation of the glutamatergic system through NMDA antagonism and activation of AMPA receptors.

• #49 Molecular Pathogenesis for Schizophrenia and Major Depression | SpringerLink

  https://link.springer.com/chapter/10.1007/978-0-387-72573-4_36

  In major depression, in contrast, glutamatergic hyperfunction seems to be closely related to the lack of serotonergic and noradrenergic neurotransmission and to the core symptoms of major depression. […] Therefore, glutamatergic dysfunction seems to be a common pathway in the neurobiology of schizophrenia and depression. […] The function of the glutamatergic system is closely related to the immune system and to the tryptophankynurenine metabolism, which both seem to play a key role in the pathophysiology of schizophrenia and major depression.

• #50 Novel treatments of depression: bridging the gap in current therapeutic approaches

  https://www.explorationpub.com/Journals/en/Article/100649

  Depression is no longer viewed solely through the lens of neurotransmitter imbalances; the immune systems involvement, particularly the inflammatory response, has gained prominence. […] Elevated levels of cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-), and C-reactive protein (CRP), have been consistently observed in individuals with depression. […] In depression, there is evidence to suggest that there may be alterations in the GABAergic system, leading to an imbalance in excitatory and inhibitory neurotransmission. […] The primary inhibitory neurotransmitter in the central nervous system, GABA, plays a crucial role in regulating neuronal excitability. […] Psychedelics exert their effects primarily through the modulation of serotonin receptors, particularly the 5-HT2A receptor.

• #51

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

  The first depressive episode is usually reactive, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly endogenous, i.e., triggered by minor stressors or occurring spontaneously. […] 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 many theories of depression and the relatively low response rate of all available antidepressant treatments clearly argue against a unified hypothesis of depression and suggest that depression is a clinically and etiologically heterogeneous disorder.

• #52 Novel treatments of depression: bridging the gap in current therapeutic approaches

  https://www.explorationpub.com/Journals/en/Article/100649

  Depression poses a significant global health burden, yet current therapeutic approaches focusing on monoaminergic neurotransmission often fall short of achieving full remission and managing acute episodes effectively. […] The conventional understanding of depression, as posited by the monoamine hypothesis, has long shaped the landscape of antidepressant pharmacotherapy. This theory implicates imbalances in neurotransmitters, particularly serotonin, norepinephrine, and dopamine, as the primary culprits in the pathophysiology of depression. […] Glutamatergic dysfunction is increasingly being implicated in the pathophysiology of depression. […] Changes in the function or expression of these receptors may disrupt these processes and contribute to depressive symptoms. […] The success of ketamine in rapidly alleviating depressive symptoms is thought to be related to its modulation of the glutamatergic system through NMDA antagonism and activation of AMPA receptors.

• #53 Biology of depression – Wikipedia

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

  The biology of depression is the attempt to identify a biochemical origin of depression, as opposed to theories that emphasize psychological or situational causes. […] Scientific studies have found that different brain areas show altered activity in humans with major depressive disorder (MDD). […] Several theories concerning the biologically based cause of depression have been suggested over the years, including theories revolving around monoamine neurotransmitters, neuroplasticity, neurogenesis, inflammation and the circadian rhythm. […] Neural circuits implicated in depression include those involved in the generation and regulation of emotion, as well as in reward. […] Abnormalities are commonly found in the lateral prefrontal cortex whose putative function is generally considered to involve regulation of emotion.

• #54 Neuroprogression: the hidden mechanism of depression | NDT

  https://www.dovepress.com/neuroprogression-the-hidden-mechanism-of-depression-peer-reviewed-fulltext-article-NDT

  The most obvious structural changes in the brain of depressed patients are a decrease in the integrity of the white matter and frontal cortex, reduction in the volume of the frontal lobe, prefrontal orbital lobe, circumvolution of the frontal corpus callosum, as well as in the complex set of structures and neuronal circuits of the limbic system involved in the control of reactions to stress, memory, attention, sexual instincts, and to the construction of emotions such as pleasure, fear, aggressiveness, personality, and behavior. […] The initial physiologic explanation of this condition has been attributed to endocrine desynchronization involving the following mechanism: After a stressful stimulus, the neuropeptides, corticotropin-releasing factor (CRF), and arginine-vasopressin (AVP) activate the hypothalamopituitaryadrenal (HPA) axis to produce and release adrenocorticotropic hormone (ACTH).

• #55 Biology of depression – Wikipedia

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

  Regions involved in the generation of emotion and reward such as the amygdala, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and striatum are frequently implicated as well. […] These regions are innervated by a monoaminergic nuclei, and tentative evidence suggests a potential role for abnormal monoaminergic activity. […] Depression may be related to abnormalities in the circadian rhythm, or biological clock. […] A well synchronized circadian rhythm is critical for maintaining optimal health. […] Adverse changes and alterations in the circadian rhythm have been associated with various neurological disorders and mood disorders including depression. […] Sleep disturbance is the most prominent symptom in depressive patients. […] Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep.

• #56 Biology of depression – Wikipedia

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

  The serotonin „chemical imbalance” theory of depression, proposed in the 1960s, is not supported by the available scientific evidence. […] SSRIs alter the balance of serotonin inside and outside of neurons: their clinical antidepressant effect is likely due to more complex changes in neuronal functioning which occur as a downstream consequence of this. […] The amygdala, a structure involved in emotional processing appears to be hyperactive in those with major depressive disorder. […] Atrophy of the hippocampus has been observed during depression, consistent with animal models of stress and neurogenesis. […] Stress can cause depression and depression-like symptoms through monoaminergic changes in several key brain regions as well as suppression in hippocampal neurogenesis. […] This leads to alteration in emotion and cognition related brain regions as well as HPA axis dysfunction.

• #57 Biology of depression – Wikipedia

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

  The serotonin „chemical imbalance” theory of depression, proposed in the 1960s, is not supported by the available scientific evidence. […] SSRIs alter the balance of serotonin inside and outside of neurons: their clinical antidepressant effect is likely due to more complex changes in neuronal functioning which occur as a downstream consequence of this. […] The amygdala, a structure involved in emotional processing appears to be hyperactive in those with major depressive disorder. […] Atrophy of the hippocampus has been observed during depression, consistent with animal models of stress and neurogenesis. […] Stress can cause depression and depression-like symptoms through monoaminergic changes in several key brain regions as well as suppression in hippocampal neurogenesis. […] This leads to alteration in emotion and cognition related brain regions as well as HPA axis dysfunction.

• #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

  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.

• #60 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. […] 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.

• #61 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  Exercise and neurotransmitters. According to depression’s clinical pre-chronic stress model, depression is associated with reduced 5-hydroxy tryptamine (5-HT) levels in the hippocampus (HPC), prefrontal cortex (PFC), and striatum, as well as decreased norepinephrine (NE) levels in PFC and HPC. Reduced dopamine (DA) metabolism and activity in individuals with depression correlate with a decrease in reward anticipation within the striatum, culminating in anhedonia. Physical activity enhances the 5-HT and NE concentrations in the brain, thereby facilitating synaptic transmission, and reducing depressive-like behaviors. Moreover, aerobic exercise can acutely affect serotonergic and noradrenergic activities in depression patients. […] Exercise and neuroplasticity. Chronic physical activity induces structural and functional plasticity, leading to the benefits of exercise. Both low-intensity and high-intensity aerobic and resistance training positively influence cognitive function, brain activation, and structure as well as neuroplasticity neurochemical markers and their associations in healthy young and older individuals, as well as neurological disorder patients.

• #62 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  By influencing brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, kynurenine pathway metabolism, and neuroinflammation, exercise promotes neural plasticity and improves cognitive functions in depressed patients. BDNF is a pivotal neuronal plasticity factor that facilitates axon extension and the formation of new branches within the brain’s motor units. It also enhances neuronal connectivity and synaptic plasticity, thereby improving memory and cognitive function in depression patients. […] Exercise and the immune system. Chronic stress from environmental and psychological factors disrupts homeostasis and activates the sympathetic nervous system as well as the hypothalamic-pituitary-adrenal (HPA) axis and modifies the levels of neurotransmitters, neurochemicals, and hormones. Major depressive disorder can induce systemic immune activation, evidenced by differences in inflammatory markers, immune cell counts, and antibody titers. Increased pro-inflammatory cytokine and stress hormone levels cause behavioral changes in depression.

• #63 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/htmls/JPBS_1256_Detail.html

  Depression is associated with a broad range of cognitive deficits, including processing speed (PS) and executive functioning (EF). […] The existence and severity of the cognitive deficits are the strongest predictors of functional and treatment outcomes in depression. […] The two most commonly and deleteriously impacted cognitive areas in depression are processing speed (PS) and executive functioning (EF). […] Existing treatments, such as antidepressants and psychotherapy, do not directly target these cognitive processes. […] This is important because targeting cognition may enable individuals to better benefit from interventions that target affective symptoms. […] Computerized cognitive training (CCT) is an intervention that directly targets cognitive functions as a means to mitigate both the affective and cognitive symptoms associated with depression.

• #64 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Depression is associated with a broad range of cognitive deficits, including processing speed (PS) and executive functioning (EF). […] The existence and severity of the cognitive deficits are the strongest predictors of functional and treatment outcomes in depression. […] The two most commonly and deleteriously impacted cognitive areas in depression are processing speed (PS) and executive functioning (EF). […] Indeed, emerging adults with depression score significantly worse on tests of EF and PS than controls. […] Processing speed is a lower-level, or fundamental cognitive resource, that facilitates the operations of higher-level (including executive) functions. […] Existing treatments, such as antidepressants and psychotherapy, do not directly target these cognitive processes. […] This is important because targeting cognition may enable individuals to better benefit from interventions that target affective symptoms.

• #65 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/htmls/JPBS_1256_Detail.html

  Depression is associated with a broad range of cognitive deficits, including processing speed (PS) and executive functioning (EF). […] The existence and severity of the cognitive deficits are the strongest predictors of functional and treatment outcomes in depression. […] The two most commonly and deleteriously impacted cognitive areas in depression are processing speed (PS) and executive functioning (EF). […] Existing treatments, such as antidepressants and psychotherapy, do not directly target these cognitive processes. […] This is important because targeting cognition may enable individuals to better benefit from interventions that target affective symptoms. […] Computerized cognitive training (CCT) is an intervention that directly targets cognitive functions as a means to mitigate both the affective and cognitive symptoms associated with depression.

• #66 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Depression is associated with a broad range of cognitive deficits, including processing speed (PS) and executive functioning (EF). […] The existence and severity of the cognitive deficits are the strongest predictors of functional and treatment outcomes in depression. […] The two most commonly and deleteriously impacted cognitive areas in depression are processing speed (PS) and executive functioning (EF). […] Indeed, emerging adults with depression score significantly worse on tests of EF and PS than controls. […] Processing speed is a lower-level, or fundamental cognitive resource, that facilitates the operations of higher-level (including executive) functions. […] Existing treatments, such as antidepressants and psychotherapy, do not directly target these cognitive processes. […] This is important because targeting cognition may enable individuals to better benefit from interventions that target affective symptoms.

• #67 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Computerized cognitive training (CCT) is an intervention that directly targets cognitive functions as a means to mitigate both the affective and cognitive symptoms associated with depression. […] CCT specifically targeting processing speed (PS) may have particular benefits. […] PS is of particular importance because decreased PS might prevent higher order mental operations from being executed properly. […] In depressed populations, previous research has found that PS mediates performance on tasks of executive function. […] Given the relevance of PS in depressed populations, we propose a model of cognitive influence on mood regulation that places processing speed at the center, mediating the relationship between executive dysfunction and mood dysregulation. […] The CCN is ordinarily activated when engaged in a purposeful, goal-oriented task.

• #68 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/htmls/JPBS_1256_Detail.html

  CCT specifically targeting processing speed (PS) may have particular benefits. […] PS is of particular importance because decreased PS might prevent higher order mental operations from being executed properly. […] Given the relevance of PS in depressed populations, we propose a model of cognitive influence on mood regulation that places processing speed at the center, mediating the relationship between executive dysfunction and mood dysregulation. […] The CCN is connected structurally and functionally to other limbic areas (such as the amygdala, hippocampus, and dentate gyrus) acting as a regulator of affective states. […] Disruption in this cortico-limbic connection is thought to be central to mood dysregulation in young adults with depression. […] The relationship between lack of response to antidepressant treatment and executive dysfunction is likely mediated by CCN integrity.

• #69 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Computerized cognitive training (CCT) is an intervention that directly targets cognitive functions as a means to mitigate both the affective and cognitive symptoms associated with depression. […] CCT specifically targeting processing speed (PS) may have particular benefits. […] PS is of particular importance because decreased PS might prevent higher order mental operations from being executed properly. […] In depressed populations, previous research has found that PS mediates performance on tasks of executive function. […] Given the relevance of PS in depressed populations, we propose a model of cognitive influence on mood regulation that places processing speed at the center, mediating the relationship between executive dysfunction and mood dysregulation. […] The CCN is ordinarily activated when engaged in a purposeful, goal-oriented task.

• #70 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Additionally, the CCN is involved in error detection and resolution, emotional processing, and information processing. […] In young adults with depression, however, the CCN fails to come online when performing an executive task, and conversely, has greater functional connectivity at rest, indicating a failure of deactivation in the absence of cognitive effort. […] This results in difficulties with attention, inhibitory control, novel generativity, planning, and working memory in individuals with depression. […] The CCN is also related to antidepressant treatment response. […] Thus, the relationship between lack of response to antidepressant treatment and executive dysfunction is likely mediated by CCN integrity. […] PS/EF training may result in greater and more efficient improvement by directly targeting the CCN, with improvements in cognitive control and emotional processing corresponding to restorations of the dysfunctional network in depression.

• #71 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Additionally, the CCN is involved in error detection and resolution, emotional processing, and information processing. […] In young adults with depression, however, the CCN fails to come online when performing an executive task, and conversely, has greater functional connectivity at rest, indicating a failure of deactivation in the absence of cognitive effort. […] This results in difficulties with attention, inhibitory control, novel generativity, planning, and working memory in individuals with depression. […] The CCN is also related to antidepressant treatment response. […] Thus, the relationship between lack of response to antidepressant treatment and executive dysfunction is likely mediated by CCN integrity. […] PS/EF training may result in greater and more efficient improvement by directly targeting the CCN, with improvements in cognitive control and emotional processing corresponding to restorations of the dysfunctional network in depression.

• #72

  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. Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses. […] Because all theories of depression apply to only some types of depressed patients but not others, and because depressive pathophysiology may vary considerably across the course of illness, the current extant knowledge argues against a unified hypothesis of depression. […] Individual depression hypotheses based on neurobiological knowledge are discussed in terms of their interest to both clinicians in daily practice and clinical researchers developing novel therapies. […] 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. […] Non-genetic factors, explaining the remaining 60-70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions).

• #73 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  One major pathogenesis of depression involves an imbalance of neurotransmitters. Neurotransmitters are chemical messengers in the brain that transmit signals between nerve cells and affect various functions of the brain, including mood regulation, stress response, sleep, and appetite. […] Serotonin is a neurotransmitter that plays an important role in emotional regulation and emotional stability in the brain, especially in inhibiting negative emotions and enhancing positive emotions. […] Dopamine (DA) is another neurotransmitter that is associated with reward, motivation, and affect. DA neurons are one of the crucial neurons involved in the pathogenesis of depression. […] Depression is associated with abnormalities in specific neural circuits in the brain. […] Genetic factors play an important role in the pathogenesis of depression. Family studies and twin studies suggest that genetic factors contribute to susceptibility to depression.

• #74 Neuroprogression: the hidden mechanism of depression | NDT

  https://www.dovepress.com/neuroprogression-the-hidden-mechanism-of-depression-peer-reviewed-fulltext-article-NDT

  The negative impact of the hypercortisolemia in the monoaminergic transmission of 5-HT, NA, and DA is due to the disruption of their receptors located in the limbic regions (prefrontal cortex, amygdala, hippocampus, and hypothalamus) that are extremely sensitive to the hormones released during stress. […] The relevance of these neurotransmitters is based on the success obtained from the tricyclic drugs and the MAO inhibitors used in the treatment of DD. […] The findings have shown allelic variants in the genes encoding the serotonin receptors called s and l alleles (s for short and l for long) that represent the short and long versions of the gene. […] The serotonergic system, in particular, seems to have a more active participation in the neuroprogressive process because it usually acts like neurogenesis-stimulating factor by the expression of BDNF.

• #75

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

  Stress sensitivity in depression is partly gender-specific. […] 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. […] 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.

• #76 Pathogenesis of depression: insights from human and rodent studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4664582/

  Early life traumatic events contribute to the development of individual differences in the ability to react and cope with subsequent stressful events. […] Rodent models of maternal separation suggest that offspring of separated pups are more submissive and generally adopt a more passive coping strategy in response to stress throughout life. […] These early life events permanently alter endocrine responses to stress and confer vulnerability to drug abuse in adulthood. […] In humans and rodents, learned helplessness (LH) is defined as a deficit to escape an aversive stimulus induced by prior exposure to uncontrollable stress. […] Helpless rats are characterized by a broad range of behavioral, physiological and hormonal changes reversed only by chronic antidepressant treatments. […] On the other hand, female rodents never develop traditional LH, hence the importance to keep gender in mind when looking for insights from animal models to develop novel, efficient drugs.

• #77

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

  The first depressive episode is usually reactive, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly endogenous, i.e., triggered by minor stressors or occurring spontaneously. […] 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 many theories of depression and the relatively low response rate of all available antidepressant treatments clearly argue against a unified hypothesis of depression and suggest that depression is a clinically and etiologically heterogeneous disorder.

• #78 So depression is an inflammatory disease, but where does the inflammation come from? | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-200

  This resistance to the immunosuppressive effects of antidepressants in depressed patients may be explained by chronic inflammatory processes, chronic damage by ONS and the onset of autoimmune responses. […] The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. […] The aim of this review was, therefore, to collate extant data on the role of inflammation and ONS as possible mediators of known environmental risk factors in depression. […] Psychosocial stressors, including acute psychological trauma or more sub-chronic stressors, and early exposure to childhood trauma robustly increase the risk of developing clinical depression and mood symptoms, while impacting neuro-immune circuits. […] There is now evidence that in experimental animals, different types of psychosocial stressors increase systemic and CNS levels of pro-inflammatory cytokines, including IL-1 and IL-6.

• #79 So depression is an inflammatory disease, but where does the inflammation come from? | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-200

  Clinical depression has recently been shown to be accompanied by increased plasma levels of immunoglobulin (Ig) A and/or IgM directed against a number of gram negative bacteria. […] Elevated plasma levels of IgA and IgM levels directed against the LPS of gram negative commensals indirectly indicate increased bacterial translocation and thus increased gut permeability. […] Thus, increased bacterial translocation may be a primary factor in the onset of clinical depression and may be a secondary factor further aggravating inflammatory and ONS pathways, leading to a vicious cycle between loosening of the tight junction barrier and activation of inflammatory and ONS pathways. […] The association between childhood adversity and vulnerability to inflammatory disease cannot fully be explained by a prolonged period of stress initiated by such an event.

• #80 So depression is an inflammatory disease, but where does the inflammation come from? | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-200

  Clinical depression has recently been shown to be accompanied by increased plasma levels of immunoglobulin (Ig) A and/or IgM directed against a number of gram negative bacteria. […] Elevated plasma levels of IgA and IgM levels directed against the LPS of gram negative commensals indirectly indicate increased bacterial translocation and thus increased gut permeability. […] Thus, increased bacterial translocation may be a primary factor in the onset of clinical depression and may be a secondary factor further aggravating inflammatory and ONS pathways, leading to a vicious cycle between loosening of the tight junction barrier and activation of inflammatory and ONS pathways. […] The association between childhood adversity and vulnerability to inflammatory disease cannot fully be explained by a prolonged period of stress initiated by such an event.

• #81

  https://journals.lww.com/md-journal/fulltext/2025/05020/association_between_tg_hdl_c_and_depression_in_us.50.aspx

  Lipid profile disturbances are frequently observed in depressive patients. Triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) can be reflective of the level of blood lipids. However, it remains unclear whether higher TG/HDL-C increases the risk of depression. This study aimed to investigate the association between TG/HDL-C and depression. […] Participants with depression had higher TG/HDL-C than those without depression (0.97 [0.541.64] vs 0.82 [0.501.38], P.001). TG/HDL-C was associated with an increased risk of depression after adjusting for all covariates (in model 3: odds ratio (OR)=1.31, 95% confidence interval (CI): 1.041.64, P=.02). Moreover, a nonlinear J-shaped relationship was observed between TG/HDL-C ratio and the risk of depression, with an inflection point of 0.402 by threshold effect analysis. These findings indicate that TG/HDL-C has a J-shaped association with the risk of depression (P for non-linearity=.008).

• #82

  https://journals.lww.com/md-journal/fulltext/2025/05020/association_between_tg_hdl_c_and_depression_in_us.50.aspx

  Lipid profile disturbances are frequently observed in depressive patients. Triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) can be reflective of the level of blood lipids. However, it remains unclear whether higher TG/HDL-C increases the risk of depression. This study aimed to investigate the association between TG/HDL-C and depression. […] Participants with depression had higher TG/HDL-C than those without depression (0.97 [0.541.64] vs 0.82 [0.501.38], P.001). TG/HDL-C was associated with an increased risk of depression after adjusting for all covariates (in model 3: odds ratio (OR)=1.31, 95% confidence interval (CI): 1.041.64, P=.02). Moreover, a nonlinear J-shaped relationship was observed between TG/HDL-C ratio and the risk of depression, with an inflection point of 0.402 by threshold effect analysis. These findings indicate that TG/HDL-C has a J-shaped association with the risk of depression (P for non-linearity=.008).

• #83

  https://journals.lww.com/md-journal/fulltext/2025/05020/association_between_tg_hdl_c_and_depression_in_us.50.aspx

  Accumulating evidence indicated a close relationship between depression and levels of lipids. […] In our study, serum lipid profiles were compared between participants with depressive disorder and without depressive disorder. The findings demonstrated significantly higher TG concentrations and lower HDL-C levels among patients meeting diagnostic criteria for depression. […] These findings suggest that disturbance in serum lipid homeostasis may contribute significantly to the pathogenesis of depressive disorder. […] The results demonstrated a significant association between an elevated TG/HDL-C and depression risk. After accounting for potential confounding variables, the TG/HDL-C remained significantly elevated in patients with depression compared to those without depression. […] When the log10-transformed TG/HDL-C was higher than 0.395 (TG/HDL-C=0.402), the risk of developing depression increased significantly. These findings suggest that an elevated TG/HDL-C may represent a potential biomarker for early detection of depressive disorders.

• #84 Association between red blood cell distribution width-to-albumin ratio and depression: a cross-sectional analysis among US adults, 2011–2018 | BMC Psychiatry | Full Text

  https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06907-z

  RAR was positively associated with depression in 18,150 participants aged 20 years. In fully adjusted models, each one-unit increase in RAR was associated with a 22% increase in the likelihood of depression [1.22 (1.05, 1.41)]. Participants in the highest quartile of RAR had a 30% higher risk of depression than those in the lowest quartile of RAR [1.30 (1.04, 1.63)]. […] Higher baseline RAR was associated with an increased risk of depression in US adults and was more informative than RDW, albumin, and hemoglobin-to-RDW ratio (HRR). […] Existing evidence supports the association of inflammation with the pathophysiology of depression. […] Patients with depression tend to have higher levels of serum biomarkers associated with inflammation, including high-sensitivity c-reactive protein (hs-CRP), interleukin (IL)6, IL-12, IL-18, and TNF-.

• #85 Association between red blood cell distribution width-to-albumin ratio and depression: a cross-sectional analysis among US adults, 2011–2018 | BMC Psychiatry | Full Text

  https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06907-z

  The presence of a chronic inflammatory cellular environment contributes to an increase in apoptosis at the molecular level, leading to dysregulation of red blood cell (RBC) homeostasis and even inducing inflammatory anemia. […] Depression is a common and difficult-to-treat condition associated with a chronic low-grade inflammatory response, cell-mediated immune activation, and activation of the compensatory anti-inflammatory reflex system (CIRS), accompanied by increased oxidative and nitrosative stress (ONS). […] Although the exact mechanisms underlying the association between elevated RAR levels and the risk of depression are not yet fully understood, the relationship between RDW and inflammation, as well as the findings of RAR and inflammation-related diseases, may at least in part explain the associations we found between depression and RAR. […] Our study demonstrated a positive correlation between higher RAR and higher prevalence of depression in US adults.

• #86 Novel treatments of depression: bridging the gap in current therapeutic approaches

  https://www.explorationpub.com/Journals/en/Article/100649

  These neurobiological changes are hypothesized to underlie the therapeutic effects of psychedelics in depression. […] The precise mechanisms underlying rTMS’s antidepressant effects are still under investigation, but evidence supports its ability to induce neuroplastic changes in the brain. […] The exact mechanisms underlying the antidepressant effects of DBS are not fully understood, but research suggests that it may influence neurotransmitter systems, neural connectivity, and neuroplasticity. […] The stimulation is typically delivered via a surgically implanted device that intermittently activates the vagus nerve in the neck, influencing various neurotransmitter systems, including serotonin and norepinephrine. […] Innovative therapies targeting glutamatergic modulation, GABA modulation, anti-inflammatory pathways, interactions within the gut-brain axis, brain stimulation techniques, and psychedelic-assisted therapy offer promising avenues for addressing the multifaceted nature of depression.

• #87

  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. […] 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. […] 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.

• #88

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

  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.

• #89

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

  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.

• #90 Study examines how laughing gas could treat depression | University of Chicago News

  https://news.uchicago.edu/story/study-examines-how-laughing-gas-could-treat-depression

  Although many therapies and medications now exist for major depression, roughly one in three diagnosed patients still suffer from treatment-resistant depressiona form of the disorder that does not respond to first-line antidepressants. […] In response to this need, scientists have recently begun investigating whether fast-acting agents with different neurological effects could serve as alternative antidepressants. […] Early clinical studies showed promise, so Nagele and his collaborators wanted to understand more about what exactly happens inside the brain during and after laughing gas treatment. […] Figuring out how the observed antidepressant effects work at a neuronal and molecular level is an important step toward clinical acceptance and implementation, said Nagele, the senior author of the new paper.

• #91 Study examines how laughing gas could treat depression | University of Chicago News

  https://news.uchicago.edu/story/study-examines-how-laughing-gas-could-treat-depression

  The results were striking, Nagele said. We saw people who had been struggling for years experience meaningful improvement within hours that lasted for weeks. It made us wonder what, exactly, was happening in the brain to cause this. […] More importantly, it didnt fully explain why nitrous oxide, which leaves the brain and body very quickly, could produce lasting effects. […] Particularly in stress-related depression, we usually see that these L5 neurons are underactive, Nagele said. […] This disinhibition effectwhere the brain becomes less suppressed and more engagedlooks to be a crucial reason for the drugs antidepressant benefits, Nagele explained. It helps reactivate neural circuits dulled by stress and depression without needing to form entirely new brain connections. […] These results show us there might be more than one path to the desired outcome in depression treatment, Nagele said. NMDA receptors matter, but what were seeing with nitrous oxide suggests theres another way to spark the brains circuitry back into action.

• #92 Study examines how laughing gas could treat depression | University of Chicago News

  https://news.uchicago.edu/story/study-examines-how-laughing-gas-could-treat-depression

  The results were striking, Nagele said. We saw people who had been struggling for years experience meaningful improvement within hours that lasted for weeks. It made us wonder what, exactly, was happening in the brain to cause this. […] More importantly, it didnt fully explain why nitrous oxide, which leaves the brain and body very quickly, could produce lasting effects. […] Particularly in stress-related depression, we usually see that these L5 neurons are underactive, Nagele said. […] This disinhibition effectwhere the brain becomes less suppressed and more engagedlooks to be a crucial reason for the drugs antidepressant benefits, Nagele explained. It helps reactivate neural circuits dulled by stress and depression without needing to form entirely new brain connections. […] These results show us there might be more than one path to the desired outcome in depression treatment, Nagele said. NMDA receptors matter, but what were seeing with nitrous oxide suggests theres another way to spark the brains circuitry back into action.

• #93 Study examines how laughing gas could treat depression | University of Chicago News

  https://news.uchicago.edu/story/study-examines-how-laughing-gas-could-treat-depression

  The results were striking, Nagele said. We saw people who had been struggling for years experience meaningful improvement within hours that lasted for weeks. It made us wonder what, exactly, was happening in the brain to cause this. […] More importantly, it didnt fully explain why nitrous oxide, which leaves the brain and body very quickly, could produce lasting effects. […] Particularly in stress-related depression, we usually see that these L5 neurons are underactive, Nagele said. […] This disinhibition effectwhere the brain becomes less suppressed and more engagedlooks to be a crucial reason for the drugs antidepressant benefits, Nagele explained. It helps reactivate neural circuits dulled by stress and depression without needing to form entirely new brain connections. […] These results show us there might be more than one path to the desired outcome in depression treatment, Nagele said. NMDA receptors matter, but what were seeing with nitrous oxide suggests theres another way to spark the brains circuitry back into action.

• #94 Pathogenesis of depression: insights from human and rodent studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4664582/

  The neurotrophic theory of depression and antidepressant responses argues that low levels of neurotrophic factors, such as BDNF, increase stress vulnerability through their effects on nerve cells within forebrain structures. […] Interestingly, desipramine has antidepressant effects in these same mice suggesting that this polymorphism could influence individual response to drug treatment. […] Alterations within the peripheral immune system and subsequent over activation of pro-inflammatory cytokines has long been associated with mood disorders leading to the proposal of a macrophage theory of depression. […] There is also increasing evidence that anti-inflammatory drugs may have antidepressant effects in MDD patients. […] Histopathological studies showed that glial cell density is reduced in the PFC, hippocampus and amygdala of MDD patients. […] Chronic stress seems to disrupt the GFAP+ astrocytic network leading to structural atrophy but maybe not loss of the astrocytes themselves as assessed with S100 and Nissl staining.

• #95 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  Currently, first-line antidepressant medications are ineffective in treating one-third to one-half of depression patients. These medications have several side effects, like headaches, gastrointestinal symptoms, anxiety, and sleep disturbances. Antidepressants side effects, poor therapeutic efficacy, and slow onset of action highlight the need for alternative and adjunctive treatment options. Additionally, exercise therapy has been a major non-pharmacological intervention in recent years for depression treatment, demonstrating high safety and superior antidepressant effects. […] Exercise is an effective treatment for depression. In order to minimize residual confounding and reverse causation issues in observational studies, a study used Mendelian randomization methods to assess the potential causal relationship between physical activity and depression risk. The results suggested that replacing sedentary behavior with 15 minutes of vigorous activity or 1 hour of moderate activity daily can reduce depression by 26%. This result strongly supports the hypothesis that increased physical activity can effectively prevent depression.

• #96 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  Regulation of hormone levels by exercise. The chronic stress coexisting with depression significantly enhances CORT levels. This damages hippocampal neurons and elevates corticosterone and ACTH levels on the HPA axis. This process is responsible for the physiological and biochemical mechanisms of stress-induced depression. Elevated CORT levels cause chronic stress-induced cognitive impairment, inhibition of brain structural and functional plasticity, and depression. […] Exercise is an effective alternative treatment option because of antidepressants limited acute and long-term efficacy as well as the frequent treatment resistance and side effects in patients. Acute exercise transiently modulates circulating 5-HT, NE, and BDNF levels as well as various immune-inflammatory mechanisms in depressions clinical cohorts. Additionally, exercise activates the HPA axis, increases CORT levels, prevents/reverses depression, improves cognition, and promotes plasticity of the brain structure and function.

• #97 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  In summary, exercise is an effective alternative therapy for depression and can be included in clinical treatment plans. However, there are several challenges in implementing it. Because of the diversity in assessment methods and inconsistencies in exercise prescription parameters, precise analysis of the dose-response relationship between physical activity and health outcomes is difficult.

• #98 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Computerized cognitive training (CCT) is an intervention that directly targets cognitive functions as a means to mitigate both the affective and cognitive symptoms associated with depression. […] CCT specifically targeting processing speed (PS) may have particular benefits. […] PS is of particular importance because decreased PS might prevent higher order mental operations from being executed properly. […] In depressed populations, previous research has found that PS mediates performance on tasks of executive function. […] Given the relevance of PS in depressed populations, we propose a model of cognitive influence on mood regulation that places processing speed at the center, mediating the relationship between executive dysfunction and mood dysregulation. […] The CCN is ordinarily activated when engaged in a purposeful, goal-oriented task.

• #99 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/htmls/JPBS_1256_Detail.html

  PS/EF training may result in greater and more efficient improvement by directly targeting the CCN, with improvements in cognitive control and emotional processing corresponding to restorations of the dysfunctional network in depression. […] This study is innovative in that it will include both active and waitlist control conditions and will explore changes in neural activation. Identifying the neural networks associated with improvements following CCT will allow for the development of more precise and effective interventions.

• #100 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/SwitchArticles.aspx?cid=1252&direction=right

  Additionally, the CCN is involved in error detection and resolution, emotional processing, and information processing. […] In young adults with depression, however, the CCN fails to come online when performing an executive task, and conversely, has greater functional connectivity at rest, indicating a failure of deactivation in the absence of cognitive effort. […] This results in difficulties with attention, inhibitory control, novel generativity, planning, and working memory in individuals with depression. […] The CCN is also related to antidepressant treatment response. […] Thus, the relationship between lack of response to antidepressant treatment and executive dysfunction is likely mediated by CCN integrity. […] PS/EF training may result in greater and more efficient improvement by directly targeting the CCN, with improvements in cognitive control and emotional processing corresponding to restorations of the dysfunctional network in depression.

• #101 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Some studies have shown that inflammation and abnormal activity of the immune system may be associated with depression, and inflammatory responses and immune molecules may play a role in the pathophysiology of depression. […] Acupuncture, as an ancient and unique non-pharmacological treatment, stimulates the nervous system of the human body by inserting and rotating needles at specific acupoints and exerts analgesic, muscle relaxation, anti-inflammatory, mild anxiolytic, and antidepressant effects. […] Acupuncture is thought to affect the levels of some major neurotransmitters in the brain. […] Acupuncture exerts its antidepressant effect by regulating the neuroendocrine axis in the body, particularly the hypothalamic-pituitary-adrenal (HPA) axis. […] Neuroplasticity refers to the ability of the nervous system to adapt to environmental changes during life, including the strengthening or weakening of neural synapses, the formation of new neural synapses, or the disappearance of existing synapses.

• #102 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Some studies have shown that inflammation and abnormal activity of the immune system may be associated with depression, and inflammatory responses and immune molecules may play a role in the pathophysiology of depression. […] Acupuncture, as an ancient and unique non-pharmacological treatment, stimulates the nervous system of the human body by inserting and rotating needles at specific acupoints and exerts analgesic, muscle relaxation, anti-inflammatory, mild anxiolytic, and antidepressant effects. […] Acupuncture is thought to affect the levels of some major neurotransmitters in the brain. […] Acupuncture exerts its antidepressant effect by regulating the neuroendocrine axis in the body, particularly the hypothalamic-pituitary-adrenal (HPA) axis. […] Neuroplasticity refers to the ability of the nervous system to adapt to environmental changes during life, including the strengthening or weakening of neural synapses, the formation of new neural synapses, or the disappearance of existing synapses.

• #103 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Depression is often associated with an increased inflammatory response. Chronic inflammation is now thought to be associated with depression. […] Acupuncture is considered to have anti-inflammatory effects and is able to reduce the production and release of inflammatory factors (eg, TNF-, IL-1, IL-6, etc.). […] Acupuncture treatment for depression is an ancient and effective method, and its mechanism involves multiple biological pathways. Acupuncture plays an antidepressant role by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammation, and other effects, and improving the emotional state.

• #104 Pathogenesis of depression: insights from human and rodent studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4664582/

  Major depressive disorder (MDD) will affect one out of every five people in their lifetime and is the leading cause of disability worldwide. Nevertheless, mechanisms associated with the pathogenesis of MDD have yet to be completely understood and current treatments remain ineffective in a large subset of patients. […] These mechanisms range from synaptic plasticity mechanisms to epigenetics and the immune system where there is strong evidence to support a functional role in the development of specific depression symptomology. Ultimately we conclude by discussing how novel therapeutic strategies targeting central and peripheral processes might ultimately aid in the development of effective new treatments for MDD and related stress disorders. […] MDD is characterized by symptoms of emotional, motivational, cognitive and physiological domains making it a complex disease to treat. […] In fact, it is estimated that only 50% of depressed patients are responsive to currently available antidepressant treatments. This may reflect the fact that depression diagnosis is based solely on behavioral symptoms and the drugs used to treat these symptoms are not specific to the underlying disease pathology.

• #105

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

  The first depressive episode is usually reactive, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly endogenous, i.e., triggered by minor stressors or occurring spontaneously. […] 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 many theories of depression and the relatively low response rate of all available antidepressant treatments clearly argue against a unified hypothesis of depression and suggest that depression is a clinically and etiologically heterogeneous disorder.

• #106 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Depression is often associated with an increased inflammatory response. Chronic inflammation is now thought to be associated with depression. […] Acupuncture is considered to have anti-inflammatory effects and is able to reduce the production and release of inflammatory factors (eg, TNF-, IL-1, IL-6, etc.). […] Acupuncture treatment for depression is an ancient and effective method, and its mechanism involves multiple biological pathways. Acupuncture plays an antidepressant role by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammation, and other effects, and improving the emotional state.

• #107 Novel treatments of depression: bridging the gap in current therapeutic approaches

  https://www.explorationpub.com/Journals/en/Article/100649

  These neurobiological changes are hypothesized to underlie the therapeutic effects of psychedelics in depression. […] The precise mechanisms underlying rTMS’s antidepressant effects are still under investigation, but evidence supports its ability to induce neuroplastic changes in the brain. […] The exact mechanisms underlying the antidepressant effects of DBS are not fully understood, but research suggests that it may influence neurotransmitter systems, neural connectivity, and neuroplasticity. […] The stimulation is typically delivered via a surgically implanted device that intermittently activates the vagus nerve in the neck, influencing various neurotransmitter systems, including serotonin and norepinephrine. […] Innovative therapies targeting glutamatergic modulation, GABA modulation, anti-inflammatory pathways, interactions within the gut-brain axis, brain stimulation techniques, and psychedelic-assisted therapy offer promising avenues for addressing the multifaceted nature of depression.

• #108 Research progress on the mechanism of exercise against depression

  https://www.wjgnet.com/2220-3206/full/v14/i11/1611.htm

  Regulation of hormone levels by exercise. The chronic stress coexisting with depression significantly enhances CORT levels. This damages hippocampal neurons and elevates corticosterone and ACTH levels on the HPA axis. This process is responsible for the physiological and biochemical mechanisms of stress-induced depression. Elevated CORT levels cause chronic stress-induced cognitive impairment, inhibition of brain structural and functional plasticity, and depression. […] Exercise is an effective alternative treatment option because of antidepressants limited acute and long-term efficacy as well as the frequent treatment resistance and side effects in patients. Acute exercise transiently modulates circulating 5-HT, NE, and BDNF levels as well as various immune-inflammatory mechanisms in depressions clinical cohorts. Additionally, exercise activates the HPA axis, increases CORT levels, prevents/reverses depression, improves cognition, and promotes plasticity of the brain structure and function.

• #109 Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial †

  https://jpbs.hapres.com/htmls/JPBS_1256_Detail.html

  PS/EF training may result in greater and more efficient improvement by directly targeting the CCN, with improvements in cognitive control and emotional processing corresponding to restorations of the dysfunctional network in depression. […] This study is innovative in that it will include both active and waitlist control conditions and will explore changes in neural activation. Identifying the neural networks associated with improvements following CCT will allow for the development of more precise and effective interventions.

• #110 Treatment of Depression with Acupuncture | IJGM

  https://www.dovepress.com/treatment-of-depression-with-acupuncture-based-on-pathophysiological-m-peer-reviewed-fulltext-article-IJGM

  Depression is often associated with an increased inflammatory response. Chronic inflammation is now thought to be associated with depression. […] Acupuncture is considered to have anti-inflammatory effects and is able to reduce the production and release of inflammatory factors (eg, TNF-, IL-1, IL-6, etc.). […] Acupuncture treatment for depression is an ancient and effective method, and its mechanism involves multiple biological pathways. Acupuncture plays an antidepressant role by regulating neurotransmitter levels, regulating the neuroendocrine axis, improving neuroplasticity, anti-inflammation, and other effects, and improving the emotional state.

• #111

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

  The first depressive episode is usually reactive, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly endogenous, i.e., triggered by minor stressors or occurring spontaneously. […] 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 many theories of depression and the relatively low response rate of all available antidepressant treatments clearly argue against a unified hypothesis of depression and suggest that depression is a clinically and etiologically heterogeneous disorder.

• #112 KBS_Icon_questionmark

  https://www.kcl.ac.uk/a-key-biological-mechanism-linked-to-depression-risk-and-recovery-in-teenage-girls-a-new-path-to-prevention-and-treatment

  The findings from this study suggest that targeting the kynurenine pathway could provide a more personalized treatment for female adolescents struggling with depression. […] By identifying the kynurenine pathway as one of the key mechanisms in adolescent depression, especially among females, this study points to the potential of developing sex-specific treatments that could intervene early and opens doors for personalised preventive approaches.

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