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1.
Psychol Med ; : 1-16, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33557968

RESUMO

Anxiety disorders are among the most common psychiatric disorders worldwide. They often onset early in life, with symptoms and consequences that can persist for decades. This makes anxiety disorders some of the most debilitating and costly disorders of our time. Although much is known about the synaptic and circuit mechanisms of fear and anxiety, research on the underlying genetics has lagged behind that of other psychiatric disorders. However, alongside the formation of the Psychiatric Genomic Consortium Anxiety workgroup, progress is rapidly advancing, offering opportunities for future research.Here we review current knowledge about the genetics of anxiety across the lifespan from genetically informative designs (i.e. twin studies and molecular genetics). We include studies of specific anxiety disorders (e.g. panic disorder, generalised anxiety disorder) as well as those using dimensional measures of trait anxiety. We particularly address findings from large-scale genome-wide association studies and show how such discoveries may provide opportunities for translation into improved or new therapeutics for affected individuals. Finally, we describe how discoveries in anxiety genetics open the door to numerous new research possibilities, such as the investigation of specific gene-environment interactions and the disentangling of causal associations with related traits and disorders.We discuss how the field of anxiety genetics is expected to move forward. In addition to the obvious need for larger sample sizes in genome-wide studies, we highlight the need for studies among young people, focusing on specific underlying dimensional traits or components of anxiety.

2.
Psychol Med ; : 1-9, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33531098

RESUMO

BACKGROUND: A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE). METHODS: The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. RESULTS: When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, ß = 0.088, p = 0.02) but not for CE (R2 = 0.011, ß = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10). CONCLUSIONS: We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

3.
J Behav Ther Exp Psychiatry ; 70: 101618, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33039814

RESUMO

BACKGROUND AND OBJECTIVES: Fear conditioning paradigms use various measures to assess learned fear, including autonomic arousal responses like skin conductance, and self-reports of both associative (US-expectancies) and evaluative (affective ratings) learning. The present study uses a dimensional approach to examine associations among fear indices directly. METHODS: Seventy-three participants completed a differential fear conditioning experiment, during which a neutral stimulus (CS+) was paired with an electric shock (US), while another stimulus (CS-) was never paired with the shock (partially instructed fear acquisition). Ten minutes later, both stimuli were presented without any shocks (fear extinction). Skin conductance responses and US-expectancy ratings were recorded during each phase, while self-reported negative affect was assessed for each CS at the end of extinction. RESULTS: Results showed a positive association among US-expectancy ratings and skin conductance responses during acquisition and early extinction. US-expectancy ratings during overall extinction were positively associated with post-extinction negative affect. LIMITATIONS: The lack of affective ratings post-acquisition may have obscured associations between associative and evaluative learning indices. CONCLUSIONS: Results provide evidence for the expected correspondence among different indices of associative fear learning. Findings emphasize the need for incorporating both associative and evaluative learning measures in fear conditioning paradigms.

4.
Transl Psychiatry ; 10(1): 298, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839438

RESUMO

Bipolar disorder is often comorbid with anxiety, which is itself associated with poorer clinical outcomes, including suicide. A better etiologic understanding of this comorbidity could inform diagnosis and treatment. The present study aims to test whether comorbid anxiety in bipolar disorder reflects shared genetic risk factors. We also sought to assess the contribution of genetic risk for anxiety to suicide attempts in bipolar disorder. Polygenic risk scores (PRS) were calculated from published genome-wide association studies of samples of controls and cases with anxiety (n = 83,566) or bipolar disorder (n = 51,710), then scored in independent target samples (total n = 3369) of individuals with bipolar disorder who reported or denied lifetime anxiety disorders or suicidal attempts in research interviews. Participants were recruited from clinical and nonclinical settings and genotyped for common genetic variants. The results show that polygenic risk for anxiety was associated with comorbid anxiety disorders and suicide attempts in bipolar disorder, while polygenic risk for bipolar disorder was not associated with any of these variables. Our findings point out that comorbid anxiety disorders in bipolar disorder reflect a dual burden of bipolar and anxiety-related genes; the latter may also contribute to suicide attempts. Clinical care that recognizes and addresses this dual burden may help improve outcomes in people living with comorbid bipolar and anxiety disorders.

6.
Depress Anxiety ; 37(6): 512-520, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31951317

RESUMO

BACKGROUND: Anxiety and depressive disorders can be classified under a bidimensional model, where depression and generalized anxiety disorder are represented by distress and the other anxiety disorders, by fear. The phenotypic structure of this model has been validated, but twin studies only show partial evidence for genetic and environmental distinctions between distress and fear. Moreover, the effects of genetic variants are mostly shared between anxiety and depression, but the genome-wide genetic distinction between distress and fear remains unexplored. This study aimed to examine the degree of common genetic variation overlap between distress and fear, and their associations with the psychosocial risk factors of loneliness and social isolation. METHODS: We used genome-wide data from 157,366 individuals in the UK Biobank who answered a mental health questionnaire. RESULTS: Genetic correlations indicated that depression and generalized anxiety had a substantial genetic overlap, and that they were genetically partially distinct from fear disorders. Associations with loneliness, but not social isolation, showed that loneliness was more strongly associated with both distress disorders than with fear. CONCLUSIONS: Our findings shed light on genetic and environmental mechanisms that are common and unique to distress and fear and contribute to current knowledge on individuals' susceptibility to anxiety and depression.


Assuntos
Bancos de Espécimes Biológicos , Depressão , Ansiedade/genética , Transtornos de Ansiedade/genética , Depressão/genética , Humanos , Reino Unido
7.
Mol Psychiatry ; 25(7): 1430-1446, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31969693

RESUMO

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

8.
Biol Psychiatry ; 87(5): 419-430, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570195

RESUMO

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

9.
Mol Psychiatry ; 25(12): 3292-3303, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31748690

RESUMO

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (ncase = 25 453, ncontrol = 58 113) and an additional analysis of Current Anxiety Symptoms (ncase = 19 012, ncontrol = 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.

10.
Addiction ; 115(3): 482-492, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31833150

RESUMO

BACKGROUND AND AIMS: The use of cannabis has previously been linked to both depression and self-harm; however, the role of genetics in this relationship is unclear. This study aimed to estimate the phenotypic and genetic associations between cannabis use and depression and self-harm. DESIGN: Cross-sectional data collected through UK Biobank were used to test the phenotypic association between cannabis use, depression and self-harm. UK Biobank genetic data were then combined with consortia genome-wide association study summary statistics to further test the genetic relationships between these traits using LD score regression, polygenic risk scoring and Mendelian randomization methods. SETTING: United Kingdom, with additional international consortia data. PARTICIPANTS: A total of 126 291 British adults aged between 40 and 70 years, recruited into UK Biobank. MEASUREMENTS: Phenotypic outcomes were life-time history of cannabis use (including initial and continued cannabis use), depression (including single-episode and recurrent depression) and self-harm. Genome-wide genetic data were used and assessment centre, batch and the first six principal components were included as key covariates when handling genetic data. FINDINGS: In UK Biobank, cannabis use is associated with an increased likelihood of depression [odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.59-1.70] and self-harm (OR = 2.85, 95% CI = 2.69-3.01). The strength of this phenotypic association is stronger when more severe trait definitions of cannabis use and depression are considered. Using consortia genome-wide summary statistics, significant genetic correlations are seen between cannabis use and depression [rg = 0.289, standard error (SE) = 0.036]. Polygenic risk scores for cannabis use and depression explain a small but significant proportion of variance in cannabis use, depression and self-harm within a UK Biobank target sample. However, two-sample Mendelian randomization analyses were not significant. CONCLUSIONS: Cannabis use appeared to be both phenotypically and genetically associated with depression and self-harm. Limitations in statistical power mean that conclusions could not be made on the direction of causality between these traits.

11.
Behav Res Ther ; 121: 103413, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31491689

RESUMO

The majority of those who experience clinical anxiety and/or depressive symptoms in the population do not receive treatment. Studies investigating inequalities in treatment outcomes rarely consider that individuals respond differently to their experience of the environment. Much of our environment is under genetic influence, via our behaviour, whereby individuals actively select their experiences. If genes influence who seeks and receives treatment, selection bias will confound genomic studies of treatment response. Furthermore, if some individuals are at high genetic risk of needing but not commencing treatment, then greater efforts could be made to engage them. The role of common genetic variation on four lifetime treatment-seeking behaviours (treatment-seeking, treatment-receipt, self-help, self-medication with alcohol/drugs) was examined in participants of the UK Biobank (sample size range: 48,106 - 75,322). Treatment-related behaviours were only modestly heritable in these data. Nonetheless, genetic correlations reveal substantial genetic overlap between lifetime treatment-related behaviours and psychiatric disorders, symptoms and behavioural traits. To our knowledge, this is the first study to examine genetic influences on treatment-related behaviours. Further work is required to determine whether genetic factors could be used alongside clinical, social and demographic factors to identify at risk groups and inform strategies which target early intervention.


Assuntos
Ansiedade/genética , Depressão/genética , Transtornos Mentais/genética , Adulto , Ansiedade/terapia , Bancos de Espécimes Biológicos , Depressão/terapia , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Transtornos Mentais/terapia , Saúde Mental , Aceitação pelo Paciente de Cuidados de Saúde , Fenótipo , Fatores de Risco , Autogestão , Reino Unido
12.
Nat Genet ; 51(8): 1207-1214, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308545

RESUMO

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.


Assuntos
Anorexia Nervosa/etiologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica/métodos , Transtornos Mentais/complicações , Doenças Metabólicas/complicações , Locos de Características Quantitativas , Adulto , Anorexia Nervosa/genética , Anorexia Nervosa/patologia , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos Mentais/genética , Doenças Metabólicas/genética , Fenótipo , Prognóstico
13.
Transl Psychiatry ; 9(1): 150, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123309

RESUMO

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/estatística & dados numéricos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Criança , Humanos
14.
JAMA Psychiatry ; 76(9): 924-932, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116379

RESUMO

Importance: Anxiety and stress-related disorders are among the most common mental disorders. Although family and twin studies indicate that both genetic and environmental factors play an important role underlying their etiology, the genetic underpinnings of anxiety and stress-related disorders are poorly understood. Objectives: To estimate the single-nucleotide polymorphism-based heritability of anxiety and stress-related disorders; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to evaluate the association of psychiatric comorbidities with genetic findings. Design, Setting, Participants: This genome-wide association study included individuals with various anxiety and stress-related diagnoses and controls derived from the population-based Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) study. Lifetime diagnoses of anxiety and stress-related disorders were obtained through the national Danish registers. Genes of interest were further evaluated in mice exposed to chronic social defeat. The study was conducted between June 2016 and November 2018. Main Outcomes and Measures: Diagnoses of a relatively broad diagnostic spectrum of anxiety and stress-related disorders. Results: The study sample included 12 655 individuals with various anxiety and stress-related diagnoses and 19 225 controls. Overall, 17 740 study participants (55.6%) were women. A total of 7308 participants (22.9%) were born between 1981-1985, 8840 (27.7%) between 1986-1990, 8157 (25.6%) between 1991-1995, 5918 (18.6%) between 1996-2000, and 1657 (5.2%) between 2001-2005. Standard association analysis revealed variants in PDE4B to be associated with anxiety and stress-related disorder (rs7528604; P = 5.39 × 10-11; odds ratio = 0.89; 95% CI, 0.86-0.92). A framework of sensitivity analyses adjusting for mental comorbidity supported this result showing consistent association of PDE4B variants with anxiety and stress-related disorder across analytical scenarios. In mouse models, alterations in Pde4b expression were observed in those mice displaying anxiety-like behavior after exposure to chronic stress in the prefrontal cortex (P = .002; t = -3.33) and the hippocampus (P = .001; t = -3.72). We also found a single-nucleotide polymorphism heritability of 28% (standard error = 0.027) and that the genetic signature of anxiety and stress-related overlapped with psychiatric traits, educational outcomes, obesity-related phenotypes, smoking, and reproductive success. Conclusions and Relevance: This study highlights anxiety and stress-related disorders as complex heritable phenotypes with intriguing genetic correlations not only with psychiatric traits, but also with educational outcomes and multiple obesity-related phenotypes. Furthermore, we highlight the candidate gene PDE4B as a robust risk locus pointing to the potential of PDE4B inhibitors in treatment of these disorders.

15.
Am J Med Genet B Neuropsychiatr Genet ; 180(6): 428-438, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30593698

RESUMO

Anorexia nervosa (AN) occurs nine times more often in females than in males. Although environmental factors likely play a role, the reasons for this imbalanced sex ratio remain unresolved. AN displays high genetic correlations with anthropometric and metabolic traits. Given sex differences in body composition, we investigated the possible metabolic underpinnings of female propensity for AN. We conducted sex-specific GWAS in a healthy and medication-free subsample of the UK Biobank (n = 155,961), identifying 77 genome-wide significant loci associated with body fat percentage (BF%) and 174 with fat-free mass (FFM). Partitioned heritability analysis showed an enrichment for central nervous tissue-associated genes for BF%, which was more prominent in females than males. Genetic correlations of BF% and FFM with the largest GWAS of AN by the Psychiatric Genomics Consortium were estimated to explore shared genomics. The genetic correlations of BF%male and BF%female with AN differed significantly from each other (p < .0001, δ = -0.17), suggesting that the female preponderance in AN may, in part, be explained by sex-specific anthropometric and metabolic genetic factors increasing liability to AN.


Assuntos
Anorexia Nervosa/genética , Anorexia Nervosa/metabolismo , Composição Corporal/genética , Tecido Adiposo/metabolismo , Adulto , Anorexia Nervosa/fisiopatologia , Índice de Massa Corporal , Estudos de Casos e Controles , Bases de Dados Genéticas , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores Sexuais
16.
Transl Psychiatry ; 8(1): 223, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333497

RESUMO

Twin studies have shown that emotional problems (anxiety and depression) in childhood and adolescence are moderately heritable (~20-50%). In contrast, DNA-based 'SNP heritability' estimates are generally <15% and non-significant. One notable feature of emotional problems is that they can be somewhat transient, but the moderate stability seen across time and across raters is predominantly influenced by stable genetic influences. This suggests that by capturing what is in common across time and across raters, we might be more likely to tap into any underlying genetic vulnerability. We therefore hypothesised that a phenotype capturing the pervasive stability of emotional problems would show higher heritability. We fitted single-factor latent trait models using 12 emotional problems measures across ages 7, 12 and 16, rated by parents, teachers and children themselves in the Twins Early Development Study sample. Twin and SNP heritability estimates for stable emotional problems (N = 6110 pairs and 6110 unrelated individuals, respectively) were compared to those for individual measures. Twin heritability increased from 45% on average for individual measures to 76% (se = 0.023) by focusing on stable trait variance. SNP heritability rose from 5% on average (n.s.) to 14% (se = 0.049; p = 0.002). Heritability was also higher for stable within-rater composites. Polygenic scores for both adult anxiety and depression significantly explained variance in stable emotional problems (0.4%; p = 0.0001). The variance explained was more than in most individual measures. Stable emotional problems also showed significant genetic correlation with adult depression and anxiety (average = 52%). These results demonstrate the value of examining stable emotional problems in gene-finding and prediction studies.


Assuntos
Ansiedade/genética , Depressão/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Criança , Feminino , Humanos , Masculino , Herança Multifatorial , Gêmeos/genética
17.
Am J Psychiatry ; 174(7): 667-675, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28135845

RESUMO

OBJECTIVE: Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems. METHOD: The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. RESULTS: Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality. CONCLUSIONS: Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiopatologia , Imagem por Ressonância Magnética , Tentativa de Suicídio/psicologia , Adolescente , Tonsila do Cerebelo/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Dominância Cerebral/fisiologia , Substância Cinzenta/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Rede Nervosa/diagnóstico por imagem , Medição de Risco , Estatística como Assunto , Ideação Suicida , Tentativa de Suicídio/prevenção & controle , Substância Branca/diagnóstico por imagem , Adulto Jovem
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