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Nature Communications Nov 2023Genetic risks for schizophrenia are theoretically mediated by genetic effects on brain structure but it has been unclear which genes are associated with both...
Genetic risks for schizophrenia are theoretically mediated by genetic effects on brain structure but it has been unclear which genes are associated with both schizophrenia and cortical phenotypes. We accessed genome-wide association studies (GWAS) of schizophrenia (N = 69,369 cases; 236,642 controls), and of three magnetic resonance imaging (MRI) metrics (surface area, cortical thickness, neurite density index) measured at 180 cortical areas (N = 36,843, UK Biobank). Using Hi-C-coupled MAGMA, 61 genes were significantly associated with both schizophrenia and one or more MRI metrics. Whole genome analysis with partial least squares demonstrated significant genetic covariation between schizophrenia and area or thickness of most cortical regions. Genetic similarity between cortical areas was strongly coupled to their phenotypic covariance, and genetic covariation between schizophrenia and brain phenotypes was strongest in the hubs of structural covariance networks. Pleiotropically associated genes were enriched for neurodevelopmental processes and positionally concentrated in chromosomes 3p21, 17q21 and 11p11. Mendelian randomization analysis indicated that genetically determined variation in a posterior cingulate cortical area could be causal for schizophrenia. Parallel analyses of GWAS on bipolar disorder, Alzheimer's disease and height showed that pleiotropic association with MRI metrics was stronger for schizophrenia compared to other disorders.
Topics: Humans; Bipolar Disorder; Brain; Genome-Wide Association Study; Magnetic Resonance Imaging; Phenotype; Schizophrenia; Mendelian Randomization Analysis
PubMed: 38016951
DOI: 10.1038/s41467-023-43567-7 -
Science (New York, N.Y.) May 2024Last week, , , and published an extensive set of papers from the PsychENCODE Consortium, a multi-institutional collaboration whose aim is to study the genetics of...
Last week, , , and published an extensive set of papers from the PsychENCODE Consortium, a multi-institutional collaboration whose aim is to study the genetics of neuropsychiatric disorders such as bipolar disorder, autism spectrum disorder, and schizophrenia. The papers, collectively called PsychENCODE2, apply advances in single-cell and multi-omic technologies to postmortem brain tissue to elucidate factors that may help explain and develop treatments for neuropsychiatric conditions. The new insights gained from these considerable data will hopefully inspire new ways in which the clinical community can find common ground with researchers, something that is not always guaranteed in the contentious mental health field.
Topics: Humans; Autism Spectrum Disorder; Brain; Schizophrenia; Single-Cell Analysis; Autistic Disorder; Bipolar Disorder
PubMed: 38815019
DOI: 10.1126/science.adq6625 -
The Journal of the Royal College of... Sep 2023Bipolar disorder is a relatively common mental illness, characterised by recurrent episodes of mania (or hypomania) and major depression, and associated with a... (Review)
Review
Bipolar disorder is a relatively common mental illness, characterised by recurrent episodes of mania (or hypomania) and major depression, and associated with a significant burden of morbidity and premature mortality. Physicians across all specialities are likely to encounter individuals with the condition within their clinical practice. This short review provides an up-to-date overview of the clinical features, epidemiology, pathophysiology, evidence-based management, prognosis and future directions for treatment and research in bipolar disorder. Aspects of cross-specialty relevance are highlighted, including the physical health burden associated with the condition, and the side effects and safety considerations of medication regimes used in bipolar disorder.
Topics: Humans; Bipolar Disorder; Medicine; Physicians
PubMed: 37649414
DOI: 10.1177/14782715231197577 -
Psychiatria Danubina Oct 2023Bipolar disorder and Parkinson's disease are two distinct neurological conditions that share common features related to dopaminergic dysfunction. This article presents a... (Review)
Review
Bipolar disorder and Parkinson's disease are two distinct neurological conditions that share common features related to dopaminergic dysfunction. This article presents a comprehensive review of the existing literature to investigate the association between bipolar disorder and Parkinson's disease, focusing on the dopaminergic hypothesis and potential therapeutic options. The dopaminergic hypothesis suggests that both bipolar disorder and Parkinson's disease involve impairments in the nigrostriatal or mesolimbic dopaminergic pathways. Studies have demonstrated alterations in dopamine regulation during manic and depressive phases of bipolar disorder. Similarly, Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms. Recent analyses have highlighted a predisposition to Parkinson's disease in individuals with bipolar disorder. Longitudinal studies and meta-analyses have demonstrated an increased risk of developing Parkinson's disease in patients with bipolar disorder. However, differentiating idiopathic Parkinson's disease from parkinsonism induced by medications used in bipolar disorder can be challenging. Dopamine transporter (DAT) scans can aid in making a differential diagnosis. Treatment options for patients with both bipolar disorder and Parkinson's disease are limited. Neuroleptics, commonly used to manage psychotic symptoms in Parkinson's disease, may worsen motor symptoms and have limitations in bipolar disorder patients. Clozapine has shown efficacy in treating psychosis without worsening motor symptoms. Pimavanserin, an inverse agonist of the 5-HT2A receptor can offer new opportunities. However, its efficacy in bipolar disorder patients with Parkinson's disease remains unexplored. In conclusion, the association between bipolar disorder and Parkinson's disease is supported by the involvement of the dopaminergic system in both conditions. The identification of shared mechanisms opens new avenues for potential therapeutic interventions. Further research is needed to investigate the efficacy of pimavanserin and explore other treatment options for individuals with both bipolar disorder and Parkinson's disease.
Topics: Humans; Parkinson Disease; Bipolar Disorder; Drug Inverse Agonism; Piperidines; Dopamine
PubMed: 37800205
DOI: No ID Found -
Psychiatria Polska Oct 2023Bipolar affective illness (bipolar disorder - BD), also known as manic-depressive illness, is characterized by periodic opposite states of mood, activity, and motivation... (Review)
Review
Bipolar affective illness (bipolar disorder - BD), also known as manic-depressive illness, is characterized by periodic opposite states of mood, activity, and motivation (mania and depression) sometimes of extreme intensity. The development and maintenance of such states in evolution can betoken a possibility of their adaptive character, enabling adaptation to an unfavorable external situation (depression) and a mobilization to using resources when available (mania). In the article, the main focus is put on the evolutionary aspect of "bipolarity" and manic/hypomanic states. Molecular-genetic studies show that in evolution, the genes connected with a predisposition to BD have been conserved. In the paper, the evolutionary adaptive concepts connected with the functioning of Homo sapiens during the middle and late Pleistocene periods were discussed as well as the "mismatch" theories associated with not befitting brain functioning to contemporary conditions. The benefits of mania and hypomania, also in the context of their link to depression were delineated, indicating their relationship to the increase in reproductive success. They result from such features of mania/hypomania as increased exploratory, psychomotor and sexual activity, and prompt risk-taking. The reproductive success can be connected with hyperthymic and cyclothymic temperaments, most frequently occurring in subjects with BD. The hyperthymic temperament often leads to increased social status and a tendency to leadership, and the cyclothymic temperament can increase creativity. Examples of the relationship between manic/hypomanic states and the phenomenon of emigration as well as the advancement of American society are provided.
Topics: Humans; Bipolar Disorder; Mania; Temperament; Affect; Leadership
PubMed: 38345120
DOI: 10.12740/PP/159424 -
The British Journal of Psychiatry : the... Aug 2023The long-awaited 11th revision of the International Classification of Diseases (ICD-11) makes important advances but simultaneously compromises on some aspects, which...
The long-awaited 11th revision of the International Classification of Diseases (ICD-11) makes important advances but simultaneously compromises on some aspects, which may have a negative impact on clinical practice. This editorial illustrates the double-edged nature of some of the changes in ICD-11, focusing on mood disorders and specifically the subtyping of bipolar disorder.
Topics: Humans; Bipolar Disorder; International Classification of Diseases; Mood Disorders
PubMed: 37525999
DOI: 10.1192/bjp.2023.66 -
Journal of Affective Disorders Aug 2023Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the... (Review)
Review
BACKGROUND
Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the disease and its consequences, self-stigma can impact people with bipolar disorder. This review investigates the current state of research in self-stigma in bipolar disorder.
METHODS
An electronic search was carried out until February 2022. Three academic databases were systematically searched, and best-evidence synthesis was made.
RESULTS
Sixty-six articles were related to self-stigma in bipolar disorder. Seven key themes were extracted from these studies: 1/ Comparison of self-stigma in bipolar disorder and other mental illnesses, 2/ Sociocultural context and self-stigma, 3/ Correlates and predictors of self-stigma, 4/ Consequences of self-stigma, 5/ Treatments and self-stigma, 6/ Management of self-stigma, and 7/ Self-stigma and recovery in bipolar disorder.
LIMITATIONS
Firstly, a meta-analysis could not be performed due to the heterogeneity of the studies. Secondly, limiting the search to self-stigma has excluded other forms of stigma that also have an impact. Thirdly, the under-reporting of negative or nonsignificant results due to publication bias and unpublished studies might have limited the accuracy of this reviews' synthesis.
CONCLUSION
Research on self-stigma in persons with bipolar disorder has been the focused on different aspects, and interventions to reduce self-stigmatization have been developed, but evidence of their effectiveness is still sparse. Clinicians need to be attentive to self-stigma, its assessment, and its empowerment in their daily clinical practice. Future work is required to establish valid strategies to fight self-stigma.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Social Stigma; Mania
PubMed: 37207946
DOI: 10.1016/j.jad.2023.05.041 -
Molecular Psychiatry Dec 2023Across the major psychiatric disorders (MPDs), a shared disruption in brain physiology is suspected. Here we investigate the neural variability at rest, a...
Across the major psychiatric disorders (MPDs), a shared disruption in brain physiology is suspected. Here we investigate the neural variability at rest, a well-established behavior-relevant marker of brain function, and probe its basis in gene expression and neurotransmitter receptor profiles across the MPDs. We recruited 219 healthy controls and 279 patients with schizophrenia, major depressive disorder, or bipolar disorders (manic or depressive state). The standard deviation of blood oxygenation level-dependent signal (SD) obtained from resting-state fMRI was used to characterize neural variability. Transdiagnostic disruptions in SD patterns and their relationships with clinical symptoms and cognitive functions were tested by partial least-squares correlation. Moving beyond the clinical sample, spatial correlations between the observed patterns of SD disruption and postmortem gene expressions, Neurosynth meta-analytic cognitive functions, and neurotransmitter receptor profiles were estimated. Two transdiagnostic patterns of disrupted SD were discovered. Pattern 1 is exhibited in all diagnostic groups and is most pronounced in schizophrenia, characterized by higher SD in the language/auditory networks but lower SD in the default mode/sensorimotor networks. In comparison, pattern 2 is only exhibited in unipolar and bipolar depression, characterized by higher SD in the default mode/salience networks but lower SD in the sensorimotor network. The expression of pattern 1 related to the severity of clinical symptoms and cognitive deficits across MPDs. The two disrupted patterns had distinct spatial correlations with gene expressions (e.g., neuronal projections/cellular processes), meta-analytic cognitive functions (e.g., language/memory), and neurotransmitter receptor expression profiles (e.g., D2/serotonin/opioid receptors). In conclusion, neural variability is a potential transdiagnostic biomarker of MPDs with a substantial amount of its spatial distribution explained by gene expressions and neurotransmitter receptor profiles. The pathophysiology of MPDs can be traced through the measures of neural variability at rest, with varying clinical-cognitive profiles arising from differential spatial patterns of aberrant variability.
Topics: Humans; Depressive Disorder, Major; Female; Bipolar Disorder; Male; Schizophrenia; Adult; Magnetic Resonance Imaging; Brain; Middle Aged; Cognition; Mental Disorders; Oxygen
PubMed: 37443193
DOI: 10.1038/s41380-023-02164-2 -
JAMA Mar 2024
Topics: Humans; Bipolar Disorder; Prognosis
PubMed: 38363576
DOI: 10.1001/jama.2023.24844 -
CNS Neuroscience & Therapeutics Dec 2023Mania is a prevalent psychiatric disorder with undefined pathological mechanism. Here, we reviewed current knowledge indicating the potential involvement of autophagy... (Review)
Review
AIMS
Mania is a prevalent psychiatric disorder with undefined pathological mechanism. Here, we reviewed current knowledge indicating the potential involvement of autophagy dysregulation in mania and further discussed whether targeting autophagy could be a promising strategy for mania therapy.
DISCUSSIONS
Accumulating evidence indicated the involvement of autophagy in the pathology of mania. One of the most well-accepted mechanisms underlying mania, circadian dysregulation, showed mutual interaction with autophagy dysfunction. In addition, several first-line drugs for mania therapy were found to regulate neuronal autophagy. Besides, deficiencies in mitochondrial quality control, neurotransmission, and ion channel, which showed causal links to mania, were intimately associated with autophagy dysfunction.
CONCLUSIONS
Although more efforts should be made to either identify the key pathology of mania, the current evidence supported that autophagy dysregulation may act as a possible mechanism involved in the onset of mania-like symptoms. It is therefore a potential strategy to treat manic disorder by correting autophagy.
Topics: Humans; Mania; Bipolar Disorder
PubMed: 37438945
DOI: 10.1111/cns.14353