The Genetics of Bipolar Disorder

1993 ◽  
Vol 27 (4) ◽  
pp. 560-580 ◽  
Author(s):  
Philip Mitchell ◽  
Andrew Mackinnon ◽  
Brent Waters
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Dna Markers ◽  
Major Gene ◽  
Adoption Studies ◽  
Polygenic Inheritance ◽  
Current State ◽  
Number Of Genes ◽  
Mode Of Transmission ◽  
Molecular Biological Techniques

Growing interest in the application of molecular biological techniques to psychiatric disorders has reinvigorated interest in the genetics of the psychoses. It is therefore timely to review the current state of knowledge of the genetics of bipolar disorder. Family, twin and adoption studies are all consistent in confirming the strongly heritable nature of this condition. As segregation analyses have been unable to determine the mode of transmission of bipolar disorder, ongoing linkage analyses using DNA markers will be crucial in determining whether this condition is due to a single major gene, a small number of genes, or multifactorial polygenic inheritance.

The Co-Occurrence of Mania with Medical and other Psychiatric Disorders

1994 ◽  
Vol 24 (4) ◽  
pp. 305-328 ◽  
Author(s):  
Stephen M. Strakowski ◽  
Susan L. McElroy ◽  
Paul W. Keck ◽  
Scott A. West
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Brain Structures ◽  
Future Research ◽  
Medical Illness ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Medical Disorders ◽  
Current State ◽  
Secondary Mania

Objective: The co-occurrence of mania with other medical and psychiatric disorders has been little studied. The authors reviewed the literature in order to clarify the current state of knowledge of this subject and to identify possible areas of future research. Methods: Published articles which specifically addressed associations of mania with medical disorders and other psychiatric syndromes were identified using the Paperchase® medical literature search system and by cross-referencing from other published work. The articles were then organized into three categories: 1) medical disorders associated with secondary mania; 2) medical comorbidity in bipolar disorder; and 3) psychiatric comorbidity in bipolar disorder. Results: The review of medical illness and secondary mania supports the hypothesis that injuries involving right-side and mid-line brain structures are associated with so-called secondary mania. Additionally, an association between bipolar disorder and migraine is identified. Several psychiatric disorders appear to occur with mania at rates higher than expected including obsessive-compulsive disorder, bulimia nervosa, panic disorder, impulse control disorders, and substance abuse. Conclusions: The authors discuss the potential implications of these findings and suggest research approaches to further examine the relationships between mania and other medical and psychiatric syndromes.

Genetic Linkage and Schizophrenia: Methods, Recent Findings and Future Directions

1993 ◽  
Vol 27 (2) ◽  
pp. 200-218 ◽  
Author(s):  
Bryan J. Mowry ◽  
Douglas F. Levinson
Keyword(s):  
Linkage Analysis ◽  
Genetic Linkage ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Genetic Linkage Analysis ◽  
Adoption Studies ◽  
Future Directions ◽  
Number Of Genes ◽  
Genetic Techniques ◽  
Mode Of Transmission

Family, twin and adoption studies have shown that familial clustering in schizophrenia is predominantly due to genetic factors. On the basis of segregation analyses of the illness distribution in relatives of patients, various models of the mode of transmission have been put forward but as yet there is no consensus. Linkage analysis based on molecular genetic techniques provides more direct approach to discovering precisely what is inherited (one gene, small number of genes or many genes?) that generates vulnerability to schizophrenia. To date there has been no sufficiently replicated finding of one or more linked genes and many methodological complexities remain. However, the rate of progress in addressing these issues gives hope that genetic linkage analysis of schizophrenia will provide some answers.

DSM Applications to Young Children: Are There Really Bipolar and Depressed Two-Year-Olds?

2017 ◽  
Author(s):  
Harold Kincaid
Keyword(s):  
Bipolar Disorder ◽  
Young Children ◽  
Psychiatric Disorders ◽  
Practical Importance ◽  
Empirical Support ◽  
Current Evidence ◽  
Psychiatric Diagnoses ◽  
Psychoactive Drugs ◽  
Small Children ◽  
Current State

Scientific commonsense would suggest that very young children cannot have psychiatric disorders such as bipolar disorder or major depression since they do not have the level of development to express the complex characteristics of these disorders. This chapter provides a detailed survey of current evidence supporting this common sense claim. The chapter first gives a general perspective on DSM that will be applied in looking at childhood psychiatric diagnoses and should be of some interest in its own right. I argue that there are some DSM based categorizations--those of major depressive disorder and bipolar disorder--that have substantial empirical support. I look at these two classifications as the best case for pediatric psychiatric disorders. I argue that this best case fails given our current state of knowledge, raising doubts in general about psychiatric diagnoses in small children. This conclusion has practical importance, since small children are increasingly being given powerful psychoactive drugs.

scholarly journals Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tempei Ikegame ◽  
Yosuke Hidaka ◽  
Yutaka Nakachi ◽  
Yui Murata ◽  
Risa Watanabe ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Serotonin Transporter ◽  
Tandem Repeats ◽  
Large Population ◽  
Functional Characterization ◽  
Luciferase Assay ◽  
Elderly Subjects ◽  
Polymorphic Region ◽  
Rare Alleles

AbstractSLC6A4, which encodes the serotonin transporter, has a functional polymorphism called the serotonin transporter-linked polymorphic region (5-HTTLPR). The 5-HTTLPR consists of short (S) and long (L) alleles, each of which has 14 or 16 tandem repeats. In addition, the extralong (XL) and other rare alleles have been reported in 5-HTTLPR. Although they are more frequent in Asian and African than in other populations, the extent of variations and allele frequencies (AFs) were not addressed in a large population. Here, we report the AFs of the rare alleles in a large number of Japanese subjects (N = 2894) consisting of two cohorts. The first cohort (case-control study set, CCSS) consisted of 1366 subjects, including 485 controls and 881 patients with psychosis (bipolar disorder or schizophrenia). The second cohort (the Arao cohort study set, ACSS) consisted of 1528 elderly subjects. During genotyping, we identified 11 novel 5-HTTLPR alleles, including 3 XL alleles. One novel allele had the longest subunit ever reported, consisting of 28 tandem repeats. We named this XL28-A. An in vitro luciferase assay revealed that XL28-A has no transcriptional activity. XL28-A was found in two unrelated patients with bipolar disorder in the CCSS and one healthy subject in the ACSS who did not show depressive symptoms or a decline in cognitive function. Therefore, it is unlikely that XL28-A is associated with psychiatric disorders, despite its apparent functional deficit. Our results suggest that unraveling the complex genetic variations of 5-HTTLPR will be important for further understanding its role in psychiatric disorders.

scholarly journals Molecular genetics of bipolar disorder

2001 ◽  
Vol 178 (S41) ◽  
pp. s128-s133 ◽  
Author(s):  
Nick Craddock ◽  
Ian Jones
Keyword(s):  
Bipolar Disorder ◽  
Candidate Gene ◽  
Molecular Genetics ◽  
Ethical Issues ◽  
Association Studies ◽  
Single Gene ◽  
Molecular Genetic ◽  
Genetic Dissection ◽  
Adoption Studies ◽  
Candidate Gene Association

BackgroundA robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.AimsTo present an overview for clinical psychiatrists.MethodReview of current molecular genetics approaches and emerging findings.ResultsOccasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.ConclusionIt is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.

scholarly journals Prediction of response to drug therapy in psychiatric disorders

Open Biology ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. 180031 ◽  
Author(s):  
Shani Stern ◽  
Sara Linker ◽  
Krishna C. Vadodaria ◽  
Maria C. Marchetto ◽  
Fred H. Gage
Keyword(s):  
Autism Spectrum Disorder ◽  
Bipolar Disorder ◽  
Major Depression ◽  
Personalized Medicine ◽  
Psychiatric Disorders ◽  
Association Studies ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Genome Wide Association Studies ◽  
Patient Reported

Personalized medicine has become increasingly relevant to many medical fields, promising more efficient drug therapies and earlier intervention. The development of personalized medicine is coupled with the identification of biomarkers and classification algorithms that help predict the responses of different patients to different drugs. In the last 10 years, the Food and Drug Administration (FDA) has approved several genetically pre-screened drugs labelled as pharmacogenomics in the fields of oncology, pulmonary medicine, gastroenterology, haematology, neurology, rheumatology and even psychiatry. Clinicians have long cautioned that what may appear to be similar patient-reported symptoms may actually arise from different biological causes. With growing populations being diagnosed with different psychiatric conditions, it is critical for scientists and clinicians to develop precision medication tailored to individual conditions. Genome-wide association studies have highlighted the complicated nature of psychiatric disorders such as schizophrenia, bipolar disorder, major depression and autism spectrum disorder. Following these studies, association studies are needed to look for genomic markers of responsiveness to available drugs of individual patients within the population of a specific disorder. In addition to GWAS, the advent of new technologies such as brain imaging, cell reprogramming, sequencing and gene editing has given us the opportunity to look for more biomarkers that characterize a therapeutic response to a drug and to use all these biomarkers for determining treatment options. In this review, we discuss studies that were performed to find biomarkers of responsiveness to different available drugs for four brain disorders: bipolar disorder, schizophrenia, major depression and autism spectrum disorder. We provide recommendations for using an integrated method that will use available techniques for a better prediction of the most suitable drug.

Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

2018 ◽  
Vol 49 (14) ◽  
pp. 2397-2404 ◽  
Author(s):  
Mu-Hong Chen ◽  
Ju-Wei Hsu ◽  
Kei-Lin Huang ◽  
Tung-Ping Su ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Population Based ◽  
Autism Spectrum ◽  
The Public ◽  
First Degree Relatives ◽  
Relative Risks ◽  
Dependent Relationship ◽  
Increased Risk ◽  
Bipolar Patients

AbstractBackgroundBipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.MethodsAmong the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.ResultsFDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.ConclusionsOur study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

scholarly journals Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores

2020 ◽  
Author(s):  
Brandon J. Coombes ◽  
Matej Markota ◽  
J. John Mann ◽  
Colin Colby ◽  
Eli Stahl ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Suicide Attempts ◽  
Risk Scores ◽  
Rapid Cycling ◽  
Clinical Heterogeneity ◽  
Polygenic Risk ◽  
Clinical Observations ◽  
History Of ◽  
Dsm Iv

AbstractBipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic PRS analysis using multiple polygenic risk scores (PRSs) from a range of psychiatric, personality, and lifestyle traits to dissect differences in BD sub-phenotypes in two BD cohorts: the Mayo Clinic BD Biobank (N = 968) and Genetic Association Information Network (N = 1001). Participants were assessed for history of psychosis, early-onset BD, rapid cycling (defined as four or more episodes in a year), and suicide attempts using questionnaires and the Structured Clinical Interview for DSM-IV. In a combined sample of 1969 bipolar cases (45.5% male), those with psychosis had higher PRS for SCZ (OR = 1.3 per S.D.; p = 3e-5) but lower PRSs for anhedonia (OR = 0.87; p = 0.003) and BMI (OR = 0.87; p = 0.003). Rapid cycling cases had higher PRS for ADHD (OR = 1.23; p = 7e-5) and MDD (OR = 1.23; p = 4e-5) and lower BD PRS (OR = 0.8; p = 0.004). Cases with a suicide attempt had higher PRS for MDD (OR = 1.26; p = 1e-6) and anhedonia (OR = 1.22; p = 2e-5) as well as lower PRS for educational attainment (OR = 0.87; p = 0.003). The observed novel PRS associations with sub-phenotypes align with clinical observations such as rapid cycling BD patients having a greater lifetime prevalence of ADHD. Our findings confirm that genetic heterogeneity underlies the clinical heterogeneity of BD and consideration of genetic contribution to psychopathologic components of psychiatric disorders may improve genetic prediction of complex psychiatric disorders.

scholarly journals Highly Predictive Transdiagnostic Features Shared across Schizophrenia, Bipolar Disorder, and ADHD Identified Using a Machine Learning Based Approach

2018 ◽  
Author(s):  
Yuelu Liu ◽  
Monika S. Mellem ◽  
Humberto Gonzalez ◽  
Matthew Kollada ◽  
Atul R. Mahableshwarkar ◽  
...  
Keyword(s):  
Machine Learning ◽  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Patient Group ◽  
Attention Deficit ◽  
The United States ◽  
Self Report ◽  
Healthy Controls ◽  
Cohen’S D ◽  
Cohen's D

AbstractThe Diagnostic and Statistical Manual of Mental Disorders (DSM) is the standard for diagnosing psychiatric disorders in the United States. However, evidence has suggested that symptoms in psychiatric disorders are not restricted to the boundaries between DSM categories, implying an underlying latent transdiagnostic structure of psychopathology. Here, we applied an importance-guided machine learning technique for model selection to item-level data from self-reported instruments contained within the Consortium for Neuropsychiatric Phenomics dataset. From 578 questionnaire items, we identified a set of features which consisted of 85 items that were shared across diagnoses of schizophrenia (SCZ), bipolar disorder (BD), and attention deficit/hyperactivity disorder (ADHD). A classifier trained on the transdiagnostic features reliably distinguished the patient group as a whole from healthy controls (classification AUC = 0.95) and only 10 items were needed to attain the performance level of AUC being 0.90. A sum score created from the items produced high separability between patients and healthy controls (Cohen’s d = 2.85), and it outperformed predefined sum scores and sub-scores within the instruments (Cohen’s d ranging between 0.13 and 1.21). The transdiagnostic features comprised both symptom domains (e.g. dysregulated mood, attention deficit, and anhedonia) and personality traits (e.g. neuroticism, impulsivity, and extraversion). Moreover, by comparing the features that were common across the three patient groups with those that were most predictive of a single patient category, we can describe the unique features for each patient group superimposed on the transdiagnostic feature structure. Overall, our results reveal a latent transdiagnostic symptom/behavioral phenotypic structure shared across SCZ, BD, and ADHD and present a new perspective to understand insights offered by self-report psychiatric instruments.

Whither Psychiatric Diagnosis

1999 ◽  
Vol 33 (2) ◽  
pp. 161-165 ◽  
Author(s):  
Allen J. Frances ◽  
Helen Link Egger
Keyword(s):  
Psychiatric Disorders ◽  
Psychiatric Illness ◽  
Biological Effects ◽  
Genetic Research ◽  
Explanatory Models ◽  
Psychiatric Research ◽  
Diagnostic And Statistical Manual ◽  
Current State ◽  
System Method ◽  
Dsm Iv

Objective: The aim of this paper is to describe the development of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), its purposes and limitations, and the psychiatric nosologies which may emerge from advances in psychiatric research and which may supersede the current classification system. Method: A review of the methodology used to develop DSM-IV, considered in the context of current and future psychiatric, neurobiological, and genetic research, was undertaken. Results: The DSM-IV is a descriptive nosology that has shaped psychiatric research and clinical practice by providing agreed-upon definitions of psychiatric disorders based on the current state of empirical data. Despite the critical importance of the DSM system of classification, this complex yet limited nosology will eventually be replaced by simpler, more incisive explanatory models of psychiatric illness that reflect the interplay of biological, psychological, environmental and social variables affecting the expression and treatment of psychiatric disorders. Conclusions: As we continue to understand the pathophysiology of brain disorders, as well as the biological effects of psychiatric interventions, we will be able to move from a descriptive model to an integrative, explanatory model of psychiatric illness.

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