Materiały źródłowe

• #1

  https://www.alliedacademies.org/articles/pathogenesis-and-treatment-of-psychiatric-disorders-26882.html

  Psychiatric diseases, which include illnesses like schizophrenia, bipolar disorder, depression, and anxiety, among many others, pose a serious threat to global health. The pathophysiology of these ailments is complex and not entirely understood despite decades of research and clinical breakthroughs. […] Complex interactions among genetic, neurological, environmental, and psychological factors define the pathophysiology of psychiatric diseases. Emerging research emphasises the contributions of polygenic risk and epigenetic changes in addition to the significant influence played by hereditary predisposition. Various illnesses have been linked neurobiological to abnormalities in neurotransmitter systems, brain circuitry, and neuroinflammatory processes. […] The specific etiological mechanisms underlying psychiatric diseases are still being investigated, with an emphasis on genetic, neurobiological, and environmental factors.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/The-Genetics-of-Mental-Disorder.aspx

  Bipolar disorder is characterized by periods of depression followed by periods of abnormally elevated mood (mania/hypomania). Whilst environmental factors are known to be important causes of bipolar disorder, it is estimated that around 70-90% of all cases are attributed to genetic factors. […] Schizophrenia is thought to have up to 70-80% genetic heritability. Like bipolar disorder, having a first-degree relative with the disorder drastically increases the risk of developing schizophrenia later in life though environmental factors are also incredibly important. […] ASD is a neurodevelopmental disorder usually present from birth. Specific genes have been implicated in ASD including MECP2, SHANK1-3, CACN1E/B2, NRXN, SYNGAP1, UBE3A, KCNQ2/3/5, SCNA2 SYN1/3 to name a few common examples. […] In summary, mental (psychiatric) disorders such as bipolar disorder, schizophrenia and ASD have strong genetic bases (mutations, polymorphisms and epigenetic changes) that can be directly inherited from an affected parent, or for de novo during development. […] Thus, many of these disorders arise due to abnormal neurodevelopment which can either cause disorder from birth (ASD) or strongly predispose individuals to developing psychiatric conditions later in life especially in combination with additional environmental factors such as stress.

• #1 Causes of mental disorders – Wikipedia

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

  In February 2013, a study found genetic links between five major psychiatric disorders: autism, ADHD, bipolar disorder, major depressive disorder, and schizophrenia. Abnormal functioning of neurotransmitter systems is also responsible for some mental disorders, including serotonin, norepinephrine, dopamine, and glutamate system’s abnormal functioning. […] Psychological mechanisms have also been implicated, such as cognitive (e.g. reasoning) biases, emotional influences, personality dynamics, temperament, and coping style. […] Studies have indicated that variation in genes can play an important role in the evolution of mental disorders, although the reliable identification of connections between specific genes and specific disorders has proven more difficult. […] Environmental events surrounding pregnancy (such as maternal hypertension, preeclampsia, or infection) and birth have also been implicated.

• #1 Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models

  https://www.mdpi.com/2073-4425/12/7/1101

  The vast majority of heritability involves common variants that are often in non-coding areas, which cannot be directly mapped onto a gene network. […] To connect these loci with molecular networks in disease-relevant tissues, functional genomics serves as a bridge between genetics and other omics. […] The small number of core genes usually plays a large regulatory role in the network, thus having large effect sizes. On the other hand, the majority of genes are peripheral genes, which account for most of the heritability as a whole, yet each displays a small effect size. […] Network methodologies provide us with a perspective beyond the identified disorder-associated variants. […] Candidate genes in the network which show high connectivity to many previously identified genes can be prioritized as hub genes or driver genes.

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

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

  Pharmacological ablation of astrocytes in the medial prefrontal cortex (mPFC) causes depressive-like symptoms in experimental animals, and postmortem studies of patients with MDD have shown reduced densities of glial cells in the prefrontal cortex (PFC), hippocampus and amygdala. In addition, glial fibrillary acidic protein (GFAP), one of the markers of astrocytes, is expressed at various levels, and the levels of connexins, glutamine synthase (GS), glutamate transporter-1 (GLT-1), and aquaporin-4 (AQP4) are reduced in patients with MDD. […] The traditional monoamine theory contends that in addition to common pathogenic factors, deficiencies in monoamine neurotransmitters, such as serotonin (5-HT), dopamine (DA) and norepinephrine (NE), are the root cause of clinical depression. […] Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that have been proven to successfully treat clinical depression, were developed in response to this hypothesis, which was derived primarily on the basis of the pharmacological mechanism of drug that were accidentally discovered to act as antidepressants.

• #1 5 Powerful Insights Into The Pathogenesis Of Schizophrenia – Delhi Mind Clinic

  https://www.delhimindclinic.com/pathogenesis-of-schizophrenia/

  Genetic predisposition plays a pivotal role in the pathogenesis of schizophrenia. Research shows that individuals with a family history of schizophrenia have a significantly higher risk of developing the condition. Twin and adoption studies estimate that genetic factors account for up to 80% of the risk. […] Schizophrenia is often described as a neurodevelopmental disorder. Abnormalities during brain development, particularly in the prenatal and early postnatal stages, are critical to understanding the pathogenesis of schizophrenia. […] The dopamine hypothesis remains one of the most widely studied theories in schizophrenia research. According to this hypothesis, dysregulation of dopamine pathways in the brain contributes significantly to the symptoms of schizophrenia. […] Environmental factors can significantly influence the pathogenesis of schizophrenia, particularly when combined with genetic vulnerability.

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

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

  It is also crucial to note that astrocytes express NE transporter (NETT) and 5-HT transporter (SERT), which are the targets of some traditional antidepressants. […] A previous study suggested that the function of astrocytes can be directly regulated by SSRIs. […] Monoamine oxidase (MAO) activates the metabolism of adrenaline and triggers calcium signaling in astrocytes, which suggests that antidepressants may directly affect astrocytes by preventing them from reabsorbing monoamines. […] The HPA axis, a component of the neuroendocrine system, is commonly associated with the stress response. Hyperactivity of the HPA axis is thought to be an important pathophysiological mechanism underlying depression. High HPA activity is among the most typical neurobiological alterations in depressed individuals.

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

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

  Some data suggest that HPA axis imbalance and high levels of GCs play a core role in the pathogenesis of MDD and suggest that GR may serve as an important target for treating depression. […] MDD is accompanied by changes in the levels of proinflammatory cytokines and trophic factors, including BDNF, interleukins (IL-1β, IL-6), and tumor necrosis factor alpha (TNF-α). Increasing data suggest that the production of certain cytokines by brain astrocytes plays a significant role in the pathogenesis of MDD. […] Higher levels of inflammation increase the chance of developing new-onset depression. […] Evidence suggests that MDD is associated with the immune response, as shown by increased levels of IL-1β, TNF-α, and IL-6. […] Neuroinflammation is a central pathophysiological mechanism and defining characteristic of MDD.

• #1 The Role of Cytokines in the Pathogenesis of Schizophrenia

  https://www.mdpi.com/2077-0383/10/17/3849

  Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. […] Recent research indicates that subclinical inflammation in the CNS and immune dysregulation may play a role in the etiopathogenesis of schizophrenia, which is supported by immunogenetic evidence and a higher incidence of autoimmune diseases in patients with schizophrenia relative to the general population. Neuroinflammation can lead to white matter pathology, dysconnectivity, and thus to the onset of schizophrenia symptoms. […] Numerous studies, including many meta-analyses, demonstrate alterations in blood cytokine levels in schizophrenia patients compared to healthy controls.

• #1 Mind and body: Scientists identify immune system link to mental illness | University of Cambridge

  https://www.cam.ac.uk/research/news/mind-and-body-scientists-identify-immune-system-link-to-mental-illness

  Children with high everyday levels of a protein released into the blood in response to infection are at greater risk of developing depression and psychosis in adulthood, according to new research which suggests a role for the immune system in mental illness. […] The study, published today in JAMA Psychiatry, indicates that mental illness and chronic physical illness such as coronary heart disease and type 2 diabetes may share common biological mechanisms. […] The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. […] Inflammation may be a common mechanism that influences both our physical and mental health. […] It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.

• #1 Researchers discover a mechanism that impairs synaptic plasticity in the brains of schizophrenia patients

  https://medicalxpress.com/news/2024-09-mechanism-impairs-synaptic-plasticity-brains.html

  Synaptic plasticity—a cellular mechanism whereby the strength of synaptic connections between neurons strengthens or weakens over time—is crucial for learning and memory. Disruptions in this process are believed to contribute to the development of schizophrenia. […] „Our computational model demonstrates that specific alterations in the expression of genes associated with schizophrenia result in impairments in synaptic plasticity. This conclusion is supported by our subsequent analysis, where we adjusted polygenic risk scores from genome-wide association studies to measure the exclusive contribution of plasticity-related genes to the risk of developing schizophrenia,” says Academy Research Fellow Tuomo Mäki-Marttunen, the lead author of the research paper. […] The findings highlight three plasticity-related proteins that may significantly contribute to the schizophrenia-associated plasticity deficits. Mäki-Marttunen hopes that the findings will inspire new animal and cell culture studies to further elucidate the role of these proteins in the condition. This could pave the way for new treatments.

• #1 Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders? | Journal of Neuroscience

  https://www.jneurosci.org/content/36/45/11411

  Actin polymerization governs activity-dependent modulation of excitatory synapses, including their morphology and functionality. […] One such signaling pathway that is heavily implicated by candidate genes for psychiatric and neurodevelopmental disorders are regulators of signaling to the actin cytoskeleton, suggesting that its disruption and the ensuring abnormalities of spine structures and postsynaptic complexes is a commonly affected pathway in brain disorders. […] Consistent with the central role of actin remodeling in governing most spine functions, dysfunction of the signaling pathways that reorganize synaptic actin is associated with a diverse range of developmental brain disorders, including autism spectrum disorders (ASDs), schizophrenia, and intellectual disability. […] The hypothesis that disrupted regulation of Arp2/3 activity can underlie the synaptic and behavioral phenotypes associated with these developmental brain disorders has recently been tested.

• #1

  https://link.springer.com/article/10.1134/S0006297923040053

  Therefore, non-specific endogenous intoxication syndrome per se can be considered as an important component of pathogenesis in all diseases. […] Endogenous intoxication can be manifested at two levels metabolic and clinical. […] However, despite the importance of this topic, the mechanisms and metabolic hallmarks of developing endogenous intoxication syndrome in patients with mental disorders (as well as with other pathological conditions) have been poorly investigated. […] Oxidative stress is one of the factors contributing to the development of endogenous intoxication. […] Stress is a hosts response to potentially damaging insults. […] Chronic stress can elicit brain damage. […] Long-term stress plays an important role in pathogenetic mechanisms of mental disorders by suppressing cell proliferation and neurogenesis.

• #1

  https://www.alliedacademies.org/articles/pathogenesis-and-treatment-of-psychiatric-disorders-26882.html

  Environmental factors have a key role in vulnerability and the development of psychiatric illnesses. These factors range from early-life stresses and traumatic events to substance addiction and socioeconomic inequities. […] The onset, severity, and prognosis of psychiatric diseases are further influenced by psychosocial variables, which include social support, socioeconomic status, and stigma associated with mental illness. […] Research is still being done to determine the precise etiological causes of psychiatric diseases, with an emphasis on genetic, neurobiological, and environmental factors.

• #1 Impact of Early Life Stress on the Pathogenesis of Mental Disorders: Relation to Brain Oxidative Stress

  https://eurekaselect.com/public/article/64341

  Stress to some extent could be considered normal and even necessary for the survival and the regular psychological development during childhood or adolescence. […] However, exposure to prolonged stress could become harmful and strongly impact mental health increasing the risk of developing psychiatric disorders. […] Oxidative stress, defined as a disequilibrium between the oxidant generation and the antioxidant response, has been recently described as a candidate for most of the observed modifications. […] In this review, we will discuss how prolonged stressful events during childhood or adolescence (such as early maternal separation, parental divorce, physical violence, sexual or psychological abuses, or exposure to war events) can lead to increased oxidative stress in the CNS and enhance the risk to develop psychiatric diseases such as anxiety, depression, drug abuse or psychosis. […] Defining the sources of oxidative stress following exposure to early life stress might open new beneficial insights in therapeutic approaches to these mental disorders.

• #1 The Role of Cytokines in the Pathogenesis of Schizophrenia

  https://www.mdpi.com/2077-0383/10/17/3849

  The aim of this narrative review is to present the most valuable evidence on cytokine dysregulation in schizophrenia, the links between cytokine levels and psychopathological presentation, as well as their alterations in response to antipsychotics. We will also investigate the possible underpinnings of changes in the cytokine system. […] The role of immunological dysfunction in the etiopathogenesis of schizophrenia is also demonstrated by its association with disorders of known autoimmunological underpinnings. Schizophrenia has been shown to be associated with major histocompatibility complex A gene (MHC-A) polymorphisms, and with rheumatoid arthritis through major histocompatibility complex class II (MHC-II) or DRB1 chain gene (HLA-DRB1). […] Early childhood trauma has been associated with elevated peripheral levels of IL-6 and a faster elevation in IL-6 and IL-1β levels with age in healthy adults, which, in the case of IL-6, also seems to have an impact on neurophysiology, but not IQ.

• #1 Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models

  https://www.mdpi.com/2073-4425/12/7/1101

  Psychiatric disorders are complex brain disorders with a high degree of genetic heterogeneity, affecting millions of people worldwide. Despite advances in psychiatric genetics, the underlying pathogenic mechanisms of psychiatric disorders are still largely elusive, which impedes the development of novel rational therapies. […] There has been accumulating evidence suggesting that the genetics of complex disorders can be viewed through an omnigenic lens, which involves contextualizing genes in highly interconnected networks. Thus, applying network-based multi-omics integration methods could cast new light on the pathophysiology of psychiatric disorders. […] In this review, we first provide an overview of the recent advances in psychiatric genetics and highlight gaps in translating molecular associations into mechanistic insights.

• #1 Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models

  https://www.mdpi.com/2073-4425/12/7/1101

  We will present advances in multi-omics approaches and network methodologies that could address these challenges in the context of an omnigenic model. […] The assumption that rare variants are core genes in the network, which have larger effect sizes, account for a small percent of heritability, and are more phenotype-specific, is supported by existing studies. […] Thus, we believe that the omnigenic model is superior in reflecting the underlying pathogenic mechanisms of complex psychiatric disorders. […] Integrating and embedding multi-tissue, multi-omics data into network architectures offers unprecedented relational insights while anchored to physiologic contexts. […] Multi-omics approaches integrate genetics, functional genomics, transcriptomics, proteomics, and epigenetics. […] Integrating multiple levels of analysis in this manner can provide unique windows into key driving elements and hypothesized biological functions of genes that would otherwise be opaque to a single-level analysis.

• #1 Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models | JPN

  https://www.jpn.ca/content/49/2/E109

  The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. […] Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. […] Alterations at the embryonic and later neurodevelopmental stages leading to defects in neuronal differentiation, connectivity, and neurotransmission have been traced both in schizophrenia and bipolar disorder, with higher frequencies recorded in schizophrenia. […] Schizophrenia and bipolar disorder seem to share some identified genetic and environmental risk factors that seem to underpin the neurobiology of both disorders.

• #1 Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models | JPN

  https://www.jpn.ca/content/49/2/E109

  Overall, the current results of iPSC models of schizophrenia have shown how alterations traced in levels of Wnt, molecular signalling cascades, and the concentration of microRNAs might lead to defects in different neurodevelopmental processes such as neuronal proliferation, maturation, and migration. […] Overall, growing evidence indicates the presence of aberrations in several molecular mechanisms in neurodevelopment, rather than 1 mechanism, in iPSC models of bipolar disorder. […] Dysfunctions in neurotransmission have been regarded to play a primary role in the development of psychiatric disorders. […] Overall, these results suggest that alterations in both glutamate and GABA neurotransmission may contribute to the pathophysiology of schizophrenia. […] Overall, the evidence from iPSC studies of bipolar disorder on the dysfunctions linked to the glutamatergic, GABAergic and dopaminergic systems or on the excitatory-inhibitory imbalance is still scarce and further studies are required to improve knowledge on the topic.

• #1

  https://link.springer.com/article/10.1134/S0006297923040053

  It was confirmed that chronic stress contributes to the oxidative stress in the brain areas involved in the development of mental pathologies. […] Elevated levels of these molecules (in particular, MDA, which causes protein damage and generation of LPO terminal products with proinflammatory properties) serve as indirect markers of oxidative stress in patients with depression. […] The level of 8-OH-dG is increased in patients with depression. […] Various mental disorders, e.g., depression and schizophrenia, are characterized by excessive telomere shortening and decreased telomerase activity. […] The extent of telomere shortening was found to correlate with the oxidative stress level, suggesting a significant impact of oxidative stress on the telomere damage, a hallmark of cell aging, in patients with depression.

• #1

  https://link.springer.com/article/10.1134/S0006297923040053

  Impaired albumin function can profoundly impact the redox processes in vivo and increase the extent of endogenous intoxication. […] The disturbance in this arm of the redox processes in mentally ill subjects might play a role in the development of metabolic disorders earlier defined as endogenous intoxication syndrome. […] We believe that the proposed scheme not only allows us to interpret the mechanisms of endotoxicosis development, but also to suggest the approaches to break the vicious cycle and to ameliorate intoxication.

• #1 Genetic mechanism could lead to RNA therapies for mental health

  https://www.drugtargetreview.com/news/155157/genetic-mechanism-rna-mental-health/

  Researchers at the Medical University of South Carolina have discovered a key genetic mechanism that could lead to RNA-based therapies for psychiatric disorders triggered by emotional experiences. […] The discovery sheds light on the genetic processes that influence how emotional experiences can lead to lasting changes in behaviour, which can become problematic in conditions such as depression or substance abuse. […] Their findings suggest that a specific genetic structure, an RNA:DNA sandwich, plays a critical role in these adaptations. […] The team focused on the gene NPAS4, which plays a role in stress-induced anhedonia (the inability to experience pleasure) and drug-induced relapse. […] Their study reveals the first evidence that R-loops are critical in regulating genes like NPAS4 in response to emotional experiences, offering new insights into how these experiences influence behaviour.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240311/Researchers-explore-the-role-of-vitamin-A-in-pathogenesis-of-psychiatric-disorders.aspx

  A Newcastle research team has been exploring the role of vitamin A in the pathogenesis of psychiatric disorders. […] Our previous research suggests this could be to do with vitamin A levels or retinol levels, which are known to play an important role in the differentiation, maturation and synaptic function of brain cells. […] Beyond understanding the genetic architecture of retinol levels in humans, Professor Cairns says the real value of this research is to better understand its role in a range of complex health conditions. […] This is significant because we use synthetic retinoids as drugs and potentially guide their application through a genetically informed precision medicine approach. […] There’s a lot more work that needs to be done to fully understand how retinol impacts human health but we do know that it is very important and potent. […] Retinol is hugely important for many aspects of our development; brain, immune system, skin and vision.

• #1 Researchers uncover novel mechanism behind schizophrenia

  https://medicalxpress.com/news/2018-02-uncover-mechanism-schizophrenia.html

  An international team of researchers led by a Case Western Reserve University School of Medicine scientist has uncovered a novel mechanism in which a protein—neuregulin 3—controls how key neurotransmitters are released in the brain during schizophrenia. The protein is elevated in people with schizophrenia and other severe mental illnesses, but the study is the first to investigate how it causes such severe mental illness. […] Certain variations in the gene encoding neuregulin 3 are considered risk factors for schizophrenia. The new study helps explain why neuregulin 3 is central to the disease. „We have identified a novel function of a schizophrenia susceptibility gene, neuregulin 3, which provides insight into cellular mechanisms of this devastating disorder and could lead to new therapeutic targets,” said senior author Lin Mei, PhD.

• #1 FDA Approves Drug with New Mechanism of Action for Treatment of Schizophrenia | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia

  Schizophrenia is a leading cause of disability worldwide. It is a severe, chronic mental illness that is often damaging to a persons quality of life, said Tiffany Farchione, M.D., director of the Division of Psychiatry, Office of Neuroscience in the FDAs Center for Drug Evaluation and Research. This drug takes the first new approach to schizophrenia treatment in decades. This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed. […] Cobenfys effectiveness for the treatment of schizophrenia in adults was evaluated in two studies with identical designs. Study 1 and Study 2 were 5-week, randomized, double-blind, placebo-controlled, multi-center studies in adults with a diagnosis of schizophrenia according to DSM-5 criteria.

• #1 Feeling Lucky? Convergence Mental Health as a Mechanism for Serendipitous Innovation

  https://www.psychiatrictimes.com/view/feeling-lucky-convergence-mental-health-mechanism-serendipitous-innovation

  The world is in the throes of a global mental health crisis with severe physical, social, and economic ramifications. According to a recent World Health Organization (WHO) report, around 450 million individuals currently suffer from mental health conditions, marking mental health disorders among the leading causes of ill-health and disability worldwide. Mental disorders account for 5 out of the top 10 causes of global disability. […] The commission estimates more than 13 million lives could be saved every year if mental illness was treated properlyor at all. […] Convergence science is an approach to problem solving that cuts across disciplinary boundaries. It integrates knowledge, tools, and thought strategies from various fields for tackling challenges that exist at the interfaces of multiple fields. It can be a mechanism for serendipity through integration of knowledge, tools, and thought-strategies from various fields for tackling challenges that exist at the interface of multiple disciplines.

• #1 The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes | BMC Psychiatry | Full Text

  https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02541-z

  A major research finding in the field of Biological Psychiatry is that symptom-based categories of mental disorders map poorly onto dysfunctions in brain circuits or neurobiological pathways. […] The compromised biological validity of the current classification system for mental disorders impedes rather than supports the development of treatments that not only target symptoms but also the underlying pathophysiological mechanisms. […] The long-term aim of BeCOME is to contribute to a novel taxonomy of mental disorders that integrates the underlying pathomechanisms into diagnoses. […] Numerous biological correlates of mental disorders are now known, but symptom-based categories of mental disorders map poorly onto dysfunctions in brain circuits or neurobiological pathways. […] While the RDC aimed at overcoming the lack of reliability of mental diagnoses, the aim of RDoC-like approaches such as the Biological Classification of Mental Disorders (BeCOME) study is to identify biology-based disease categories.

• #1 The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes | BMC Psychiatry | Full Text

  https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02541-z

  Such differentiated patient profiles transport more information for an optimized treatment selection than the rather imprecise DSM-based diagnosis of major depression. […] The information collected in BeCOME spans many levels from omics, cellular and imaging data to psychophysiological parameters as well as self-reported symptoms of mental disorders, personality traits and lifetime exposure to trauma and other environmental risk factors.

• #1 Shared mechanisms across the major psychiatric and neurodegenerative diseases | Nature Communications

  https://www.nature.com/articles/s41467-022-31873-5

  Several common psychiatric and neurodegenerative diseases share epidemiologic risk; however, whether they share pathophysiology is unclear and is the focus of our investigation. […] Together, our findings suggest these psychiatric and neurodegenerative diseases have shared genetic and molecular pathophysiology, which has important ramifications for early treatment and therapeutic development. […] Insights into mechanisms shared among these psychiatric and neurodegenerative diseases could fuel the development of novel, effective therapeutics for both the psychiatric and neurodegenerative diseases and for the psychiatric symptoms that arise during the course of the neurodegenerative diseases. […] Given these connections, we hypothesized that there is a shared genetic and molecular basis among these psychiatric and neurodegenerative diseases.

• #1 Genetic mechanism could lead to RNA therapies for mental health

  https://www.drugtargetreview.com/news/155157/genetic-mechanism-rna-mental-health/

  These results suggest that R-loops at the NPAS4 gene are essential for the brains adaptation to emotional experiences, influencing behaviours linked to substance use and mood disorders. […] Their work suggests that R-loops might play a broader role in how neural circuits adapt to stimuli, similar to their function in the immune system, where they help develop immunity. […] The teams ultimate goal is to explore how widespread this genetic mechanism is across different brain regions, and whether disruptions to it could contribute to psychiatric disorders. […] This discovery not only enhances our understanding of the brains response to emotional experiences but also has the potential to inform the development of RNA-based therapies that could treat psychiatric disorders, offering hope for more targeted treatments in the future.

• #1

  https://www.alliedacademies.org/articles/pathogenesis-and-treatment-of-psychiatric-disorders-26882.html

  A complicated and diverse riddle, the pathogenesis of psychiatric illnesses is characterized by complex interactions among genetic, neurobiological, environmental, and behavioral factors. Heritability estimates emphasize how important genetic susceptibility is in many of these illnesses, where genetic predisposition plays a crucial role. Recent discoveries in genomics and molecular biology have shed light on the polygenic nature of psychiatric diseases and shown that many genetic risk variants and epigenetic changes contribute to the onset of these conditions. […] The crucial roles played by neurotransmitter systems, brain circuitry, and neuroinflammatory processes in the development of psychiatric diseases have been made clear by neurobiological research. The appearance of these illnesses’ symptoms and their course are both influenced by dysregulation in these neural systems.

• #2 Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models

  https://www.mdpi.com/2073-4425/12/7/1101

  Psychiatric disorders are complex brain disorders with a high degree of genetic heterogeneity, affecting millions of people worldwide. Despite advances in psychiatric genetics, the underlying pathogenic mechanisms of psychiatric disorders are still largely elusive, which impedes the development of novel rational therapies. […] There has been accumulating evidence suggesting that the genetics of complex disorders can be viewed through an omnigenic lens, which involves contextualizing genes in highly interconnected networks. Thus, applying network-based multi-omics integration methods could cast new light on the pathophysiology of psychiatric disorders. […] In this review, we first provide an overview of the recent advances in psychiatric genetics and highlight gaps in translating molecular associations into mechanistic insights.

• #2 Causes of mental disorders – Wikipedia

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

  In February 2013, a study found genetic links between five major psychiatric disorders: autism, ADHD, bipolar disorder, major depressive disorder, and schizophrenia. Abnormal functioning of neurotransmitter systems is also responsible for some mental disorders, including serotonin, norepinephrine, dopamine, and glutamate system’s abnormal functioning. […] Psychological mechanisms have also been implicated, such as cognitive (e.g. reasoning) biases, emotional influences, personality dynamics, temperament, and coping style. […] Studies have indicated that variation in genes can play an important role in the evolution of mental disorders, although the reliable identification of connections between specific genes and specific disorders has proven more difficult. […] Environmental events surrounding pregnancy (such as maternal hypertension, preeclampsia, or infection) and birth have also been implicated.

• #2 Shared mechanisms across the major psychiatric and neurodegenerative diseases | Nature Communications

  https://www.nature.com/articles/s41467-022-31873-5

  Our findings implicated several distinct and shared causal brain proteins and elucidated potential shared mechanisms among these psychiatric and neurodegenerative diseases, paving the way for precision medicine and therapeutic development. […] This striking percentage of shared causal proteins is supportive of the hypothesis of a shared genetic and molecular basis between the psychiatric and neurodegenerative groups. […] Together, these shared causal proteins underscore a shared genetic susceptibility among the psychiatric and neurodegenerative diseases. […] Our study has several strengths. First, we used the largest set of deep human brain proteomes to maximize the number of heritable proteins to be included in the PWAS, enabling examination of more proteins. […] In summary, we demonstrated here that the major psychiatric and neurodegenerative diseases have shared genetic susceptibility and pathophysiology and identified 13 shared causal proteins, 118 interacting causal proteins, and the central role of synaptic transmission, immune function, and mitochondrial processes in the shared pathogenesis.

• #2 Mental disorder – Genetics, Environment, Stress | Britannica

  https://www.britannica.com/science/mental-disorder/Theories-of-causation

  If a mental disease is caused by a biochemical abnormality, investigation of the brain at the site where the biochemical imbalance occurs should show neurochemical differences from normal. […] Despite these problems, progress has been made in unraveling the biochemistry of mood disorders, schizophrenia, and some of the dementias. […] Certain drugs have been demonstrated to have beneficial effects upon mental illnesses. Antidepressant, antipsychotic, and antianxiety drugs are thought to achieve their therapeutic results by the selective inhibition or enhancement of the quantities, action, or breakdown of neurotransmitters in the brain. […] Abnormally low or high concentrations of neurotransmitters at sites in the brain are thought to change the synaptic activities of neurons, thus ultimately leading to the disturbances of mood, emotion, or thought found in various mental disorders.

• #2 Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models | JPN

  https://www.jpn.ca/content/49/2/E109

  Overall, the current results of iPSC models of schizophrenia have shown how alterations traced in levels of Wnt, molecular signalling cascades, and the concentration of microRNAs might lead to defects in different neurodevelopmental processes such as neuronal proliferation, maturation, and migration. […] Overall, growing evidence indicates the presence of aberrations in several molecular mechanisms in neurodevelopment, rather than 1 mechanism, in iPSC models of bipolar disorder. […] Dysfunctions in neurotransmission have been regarded to play a primary role in the development of psychiatric disorders. […] Overall, these results suggest that alterations in both glutamate and GABA neurotransmission may contribute to the pathophysiology of schizophrenia. […] Overall, the evidence from iPSC studies of bipolar disorder on the dysfunctions linked to the glutamatergic, GABAergic and dopaminergic systems or on the excitatory-inhibitory imbalance is still scarce and further studies are required to improve knowledge on the topic.

• #2 The Role of Cytokines in the Pathogenesis of Schizophrenia

  https://www.mdpi.com/2077-0383/10/17/3849

  Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. […] Recent research indicates that subclinical inflammation in the CNS and immune dysregulation may play a role in the etiopathogenesis of schizophrenia, which is supported by immunogenetic evidence and a higher incidence of autoimmune diseases in patients with schizophrenia relative to the general population. Neuroinflammation can lead to white matter pathology, dysconnectivity, and thus to the onset of schizophrenia symptoms. […] Numerous studies, including many meta-analyses, demonstrate alterations in blood cytokine levels in schizophrenia patients compared to healthy controls.

• #2 Researchers discover a mechanism that impairs synaptic plasticity in the brains of schizophrenia patients | ScienceDaily

  https://www.sciencedaily.com/releases/2024/09/240904130930.htm

  A study mapped genes linked to schizophrenia and uncovered a mechanism that disrupts synaptic plasticity in affected individuals. The researchers showed the role of three proteins in mediating the impairments of plasticity in schizophrenia. […] Disruptions in this process are believed to contribute to the development of schizophrenia. […] Our computational model demonstrates that specific alterations in the expression of genes associated with schizophrenia result in impairments in synaptic plasticity. […] The findings highlight three plasticity-related proteins that may significantly contribute to the schizophrenia-associated plasticity deficits. […] Our study does not yet explain how the observed alterations in gene expression and the resulting changes in synaptic plasticity affect the symptoms of schizophrenia.

• #2 Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders? | Journal of Neuroscience

  https://www.jneurosci.org/content/36/45/11411

  The pathogenic processes and molecular mechanisms producing cell type-specific alterations in actin dynamics could produce cortical dendritic spine deficits as an upstream pathology that subsequently gives rise to excessive striatal dopamine function and the appearance of psychosis in schizophrenia. […] It is becoming clear from human genetic and brain tissue studies, and from mouse models, that dysfunction of the actin cytoskeleton at excitatory spine synapses is likely a shared molecular pathology across different neurodevelopmental and psychiatric disorders.

• #2

  https://link.springer.com/article/10.1134/S0006297923040053

  It was confirmed that chronic stress contributes to the oxidative stress in the brain areas involved in the development of mental pathologies. […] Elevated levels of these molecules (in particular, MDA, which causes protein damage and generation of LPO terminal products with proinflammatory properties) serve as indirect markers of oxidative stress in patients with depression. […] The level of 8-OH-dG is increased in patients with depression. […] Various mental disorders, e.g., depression and schizophrenia, are characterized by excessive telomere shortening and decreased telomerase activity. […] The extent of telomere shortening was found to correlate with the oxidative stress level, suggesting a significant impact of oxidative stress on the telomere damage, a hallmark of cell aging, in patients with depression.

• #2 Mental illness – types, causes and diagnosis of mental health issues | healthdirect

  https://www.healthdirect.gov.au/mental-illness

  Some examples of these factors include: […] Genetic factors having a close family member with a mental illness can increase the chance that you might get a mental illness. However, just because one family member has a mental illness doesn’t mean that others will. […] Drug and alcohol abuse illicit drug use can trigger a manic episode (bipolar disorder) or an episode of psychosis. Drugs such as cocaine, marijuana and amphetamines can cause paranoia. […] Other biological factors some medical conditions or hormonal changes can cause mental health problems. […] Early life environment negative childhood experiences can increase the risk of some mental illnesses. Examples of negative childhood experiences are abuse or neglect. […] Trauma and stress in adulthood, traumatic life events or ongoing stress can increase the risk of mental illness. Issues such as social isolation, domestic violence, relationship breakdown, financial or work problems can impact on mental health. Traumatic experiences such as living in a war zone can increase the risk of post-traumatic stress disorder (PTSD). […] Personality factors some traits such as perfectionism or low self-esteem can increase the risk of depression or anxiety.

• #2 Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models

  https://escholarship.org/uc/item/3g03w65s

  Psychiatric disorders are complex brain disorders with a high degree of genetic heterogeneity, affecting millions of people worldwide. […] Despite advances in psychiatric genetics, the underlying pathogenic mechanisms of psychiatric disorders are still largely elusive, which impedes the development of novel rational therapies. […] There has been accumulating evidence suggesting that the genetics of complex disorders can be viewed through an omnigenic lens, which involves contextualizing genes in highly interconnected networks. […] Thus, applying network-based multi-omics integration methods could cast new light on the pathophysiology of psychiatric disorders. […] We then present an overview of network methodologies and review previous applications of network methods in the study of psychiatric disorders. […] Lastly, we describe the potential of such methodologies within a multi-tissue, multi-omics approach, and summarize the future directions in adopting diverse network approaches.

• #2 Genetic mechanism could lead to RNA therapies for mental health

  https://www.drugtargetreview.com/news/155157/genetic-mechanism-rna-mental-health/

  These results suggest that R-loops at the NPAS4 gene are essential for the brains adaptation to emotional experiences, influencing behaviours linked to substance use and mood disorders. […] Their work suggests that R-loops might play a broader role in how neural circuits adapt to stimuli, similar to their function in the immune system, where they help develop immunity. […] The teams ultimate goal is to explore how widespread this genetic mechanism is across different brain regions, and whether disruptions to it could contribute to psychiatric disorders. […] This discovery not only enhances our understanding of the brains response to emotional experiences but also has the potential to inform the development of RNA-based therapies that could treat psychiatric disorders, offering hope for more targeted treatments in the future.

• #2 Researchers uncover novel mechanism behind schizophrenia

  https://medicalxpress.com/news/2018-02-uncover-mechanism-schizophrenia.html

  By studying brain samples from the mice, the researchers learned how neuregulin 3 works at the cellular level. They found it inhibits assembly of a complex of proteins at synapses, the place where adjacent nerve cells communicate. Neurons need the complex, called SNARE, to transmit certain neurotransmitters between each other. In particular, SNARE complex helps neurons transmit glutamate—the most common „excitatory” neurotransmitter in the brain. Glutamate helps activate neurons and is essential for learning. Glutamate imbalances can cause schizophrenic symptoms. […] People with severe mental illnesses like schizophrenia, bipolar disorder, and major depression, tend to have higher levels of neuregulin 3. The researchers mimicked protein levels found in the brains of schizophrenics by elevating neuregulin 3 in cultured neurons, and found higher levels of neuregulin 3 suppresses glutamate release.

• #2 Feeling Lucky? Convergence Mental Health as a Mechanism for Serendipitous Innovation

  https://www.psychiatrictimes.com/view/feeling-lucky-convergence-mental-health-mechanism-serendipitous-innovation

  In the context of mental health, convergence science involves the integration of scientists, clinicians, bioinformaticists, global health experts, social scientists, health economists, engineers, technology entrepreneurs, medical educators, caregivers, and patientswe call this Convergence Mental Health. […] Convergence Mental Health provides a historic opportunity to lead to a new era of innovation and progress, leading to improved outcomes for all people and preparing psychiatry to meet the unprecedented mental health challenges of the 21st century.

• #2

  https://www.alliedacademies.org/articles/pathogenesis-and-treatment-of-psychiatric-disorders-26882.html

  Psychiatric diseases, which include illnesses like schizophrenia, bipolar disorder, depression, and anxiety, among many others, pose a serious threat to global health. The pathophysiology of these ailments is complex and not entirely understood despite decades of research and clinical breakthroughs. […] Complex interactions among genetic, neurological, environmental, and psychological factors define the pathophysiology of psychiatric diseases. Emerging research emphasises the contributions of polygenic risk and epigenetic changes in addition to the significant influence played by hereditary predisposition. Various illnesses have been linked neurobiological to abnormalities in neurotransmitter systems, brain circuitry, and neuroinflammatory processes. […] The specific etiological mechanisms underlying psychiatric diseases are still being investigated, with an emphasis on genetic, neurobiological, and environmental factors.

• #2 Mind and body: Scientists identify immune system link to mental illness | University of Cambridge

  https://www.cam.ac.uk/research/news/mind-and-body-scientists-identify-immune-system-link-to-mental-illness

  Children with high everyday levels of a protein released into the blood in response to infection are at greater risk of developing depression and psychosis in adulthood, according to new research which suggests a role for the immune system in mental illness. […] The study, published today in JAMA Psychiatry, indicates that mental illness and chronic physical illness such as coronary heart disease and type 2 diabetes may share common biological mechanisms. […] The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. […] Inflammation may be a common mechanism that influences both our physical and mental health. […] It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.

• #2 Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders? | Journal of Neuroscience

  https://www.jneurosci.org/content/36/45/11411

  Actin polymerization governs activity-dependent modulation of excitatory synapses, including their morphology and functionality. […] One such signaling pathway that is heavily implicated by candidate genes for psychiatric and neurodevelopmental disorders are regulators of signaling to the actin cytoskeleton, suggesting that its disruption and the ensuring abnormalities of spine structures and postsynaptic complexes is a commonly affected pathway in brain disorders. […] Consistent with the central role of actin remodeling in governing most spine functions, dysfunction of the signaling pathways that reorganize synaptic actin is associated with a diverse range of developmental brain disorders, including autism spectrum disorders (ASDs), schizophrenia, and intellectual disability. […] The hypothesis that disrupted regulation of Arp2/3 activity can underlie the synaptic and behavioral phenotypes associated with these developmental brain disorders has recently been tested.

• #2 Researchers uncover novel mechanism behind schizophrenia

  https://medicalxpress.com/news/2018-02-uncover-mechanism-schizophrenia.html

  The findings suggest neuregulin 3 could serve as a new therapeutic target to help treat schizophrenia or other mental illnesses. Drugs that target neuregulin 3 could help restore glutamate levels in certain types of neurons—a novel approach to schizophrenia treatment. „Identifying a novel mechanism of action is a prerequisite to understanding a disorder, and to development of therapeutic interventions,” Mei said.

• #2 Biological mechanism study of meditation and its application in mental disorders | General Psychiatry

  https://gpsych.bmj.com/content/33/4/e100214

  Increasingly, meditation techniques are being applied to substance-related and addiction disorders, including alcohol use disorders, substance use disorders, tobacco use disorders, cannabis and stimulant use disorders. […] Meditation interventions may be an alternative therapy in the management of PTSD, including TM, sudarshan kriya yoga and MM as common techniques. […] Up to now, the efficacy of meditation intervention in adult patients diagnosed with ADHD is relatively manifest, prevailingly using MBIs. […] Meditation techniques have been tried for patients with schizophrenia over the years, with main techniques used being MBIs and ACT.

• #3

  https://apcz.umk.pl/JEHS/article/view/JEHS.2020.10.08.039

  Schizophrenia is one of the most serious and frightening of all mental illnesses. It affects almost 1% of the population worldwide. The main concept and treatment of schizophrenia are based on the dopaminergic hypothesis. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid signaling. […] There are evidence that pathogenesis of schizophrenia include dysfunction in dopaminergic, serotoninergic, GABAergic, glutamatergic systems. The use of drugs that act on any of these systems reduces the symptoms of the disease. Nicotinic receptors may also be the target for drugs in treatment of schizophrenia. Studies about the role of nicotinic receptors in pathogenesis of schizophrenia show that it normalize many of the sensory processing deficits found in schizophrenia.

• #3 Researchers uncover novel mechanism behind schizophrenia

  https://medicalxpress.com/news/2018-02-uncover-mechanism-schizophrenia.html

  The findings suggest neuregulin 3 could serve as a new therapeutic target to help treat schizophrenia or other mental illnesses. Drugs that target neuregulin 3 could help restore glutamate levels in certain types of neurons—a novel approach to schizophrenia treatment. „Identifying a novel mechanism of action is a prerequisite to understanding a disorder, and to development of therapeutic interventions,” Mei said.

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