Adolescent residential mobility, genetic liability and risk of schizophrenia, bipolar disorder and major depression

BackgroundResidential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear.AimsWe used a population-based case–cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10–14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder.MethodInformation on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981–1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses.ResultsPRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00–1.16; and odds ratio 1.10, 95% CI 1.04–1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5–11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08–1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92–4.86; three or more moves and bipolar disorder).ConclusionsAssociations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.

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A population-based study of the risk of schizophrenia and bipolar disorder associated with parent–child separation during development

Psychological Medicine ◽

10.1017/s0033291715000781 ◽

2015 ◽

Vol 45 (13) ◽

pp. 2825-2837 ◽

Cited By ~ 23

Author(s):

D. Paksarian ◽

W. W. Eaton ◽

P. B. Mortensen ◽

K. R. Merikangas ◽

C. B. Pedersen

Keyword(s):

Bipolar Disorder ◽

Mental Disorder ◽

Psychotic Disorders ◽

Childhood Adversity ◽

Population Based ◽

Family Characteristics ◽

Parental Separation ◽

Parental History ◽

First Occurrence ◽

History Of

BackgroundThere is growing interest in the role of childhood adversities, including parental death and separation, in the etiology of psychotic disorders. However, few studies have used prospectively collected data to specifically investigate parental separation across development, or assessed the importance of duration of separation, and family characteristics.MethodWe measured three types of separation not due to death: maternal, paternal, and from both parents, across the ages of 1–15 years among a cohort of 985 058 individuals born in Denmark 1971–1991 and followed to 2011. Associations with narrowly and broadly defined schizophrenia and bipolar disorder in the psychiatric register were assessed in terms of separation occurrence, age of separation, and number of years separated. Interactions with parental history of mental disorder were assessed.ResultsEach type of separation was associated with all three outcomes, adjusting for age, sex, birth period, calendar year, family history of mental disorder, urbanicity at birth and parental age. Number of years of paternal separation was positively associated with both schizophrenia and bipolar disorder. Associations between separation from both parents and schizophrenia were stronger when separation occurred at later ages, while those with bipolar disorder remained stable across development. The first occurrence of paternal separation appeared to increase risk more when it occurred earlier in childhood. Associations differed according to parental history of mental disorder, although in no situation was separation protective.ConclusionsEffects of parental separation may differ by type, developmental timing and family characteristics. These findings highlight the importance of considering such factors in studies of childhood adversity.

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The association between school exam grades and subsequent development of bipolar disorder

Acta Neuropsychiatrica ◽

10.1017/neu.2018.3 ◽

2018 ◽

Vol 30 (4) ◽

pp. 209-217 ◽

Cited By ~ 2

Author(s):

Steffie Damgaard Pedersen ◽

Søren Dinesen Østergaard ◽

Liselotte Petersen

Keyword(s):

Bipolar Disorder ◽

Mental Disorder ◽

Cox Model ◽

Subsequent Development ◽

Parental History ◽

School Grades ◽

Increased Risk ◽

History Of ◽

Very High

AbstractObjectivePrior studies have indicated that both high and low school grades are associated with development of bipolar disorder (BD), but these studies have not adjusted for parental history of mental disorder, which is a likely confounder. Furthermore, the association between school grades and bipolar I disorder (BD-I) has not been studied. Therefore, we aimed to study the association between school exam grades and subsequent development of BD and BD-I while adjusting for parental history of mental disorder.MethodsWe conducted a register-based nationwide cohort study following 505 688 individuals born in Denmark between 1987 and 1995. We investigated the association between school exam grades and development of BD or BD-I with a Cox model adjusting for family history of mental disorder and other potential confounders.ResultsDuring follow-up, 900 individuals were diagnosed with BD and 277 of these with BD-I. The risk for BD and BD-I was significantly increased for individuals not having completed the exams at term [adjusted hazard ratio (aHR) for BD (aHR=1.71, 95% CI: 1.43–2.04) and for BD-I (aHR=1.57, 95% CI: 1.13–2.19)]. Also, having low exam grades in mathematics was associated with increased risk of both BD (aHR=2.41, 95% CI: 1.27–4.59) and BD-I (aHR=2.71, 95% CI: 1.41–5.21). Females with very high exam grades in Danish (percentile group>97.7) had a significantly increased risk of BD-I (aHR=2.49, 95% CI: 1.19–5.23).ConclusionsThe potential to develop BD seems to affect the school results of individuals negatively even before BD is diagnosed – with females having the potential to develop BD-I as a possible exception.

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Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression

American Journal of Medical Genetics Part B Neuropsychiatric Genetics ◽

10.1002/ajmg.b.32868 ◽

2021 ◽

Author(s):

Murray B. Stein ◽

Sonia Jain ◽

Laura Campbell‐Sills ◽

Erin B. Ware ◽

Karmel W. Choi ◽

...

Keyword(s):

Major Depression ◽

Suicide Attempt ◽

Parental History ◽

Polygenic Risk ◽

History Of

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Latent profiles of early developmental vulnerabilities in a New South Wales child population at age 5 years

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867417740208 ◽

2017 ◽

Vol 52 (6) ◽

pp. 530-541 ◽

Cited By ~ 6

Author(s):

Melissa J Green ◽

Stacy Tzoumakis ◽

Kristin R Laurens ◽

Kimberlie Dean ◽

Maina Kariuki ◽

...

Keyword(s):

Mental Illness ◽

Mental Disorders ◽

Mental Disorder ◽

Early Development ◽

Latent Class ◽

New South ◽

Criminal Offending ◽

Parental History ◽

South Wales ◽

History Of

Objective: Detecting the early emergence of childhood risk for adult mental disorders may lead to interventions for reducing subsequent burden of these disorders. We set out to determine classes of children who may be at risk for later mental disorder on the basis of early patterns of development in a population cohort, and associated exposures gleaned from linked administrative records obtained within the New South Wales Child Development Study. Methods: Intergenerational records from government departments of health, education, justice and child protection were linked with the Australian Early Development Census for a state population cohort of 67,353 children approximately 5 years of age. We used binary data from 16 subdomains of the Australian Early Development Census to determine classes of children with shared patterns of Australian Early Development Census–defined vulnerability using latent class analysis. Covariates, which included demographic features (sex, socioeconomic status) and exposure to child maltreatment, parental mental illness, parental criminal offending and perinatal adversities (i.e. birth complications, smoking during pregnancy, low birth weight), were examined hierarchically within latent class analysis models. Results: Four classes were identified, reflecting putative risk states for mental disorders: (1) disrespectful and aggressive/hyperactive behaviour, labelled ‘misconduct risk’ ( N = 4368; 6.5%); (2) ‘pervasive risk’ ( N = 2668; 4.0%); (3) ‘mild generalised risk’ ( N = 7822; 11.6%); and (4) ‘no risk’ ( N = 52,495; 77.9%). The odds of membership in putative risk groups (relative to the no risk group) were greater among children from backgrounds of child maltreatment, parental history of mental illness, parental history of criminal offending, socioeconomic disadvantage and perinatal adversities, with distinguishable patterns of association for some covariates. Conclusion: Patterns of early childhood developmental vulnerabilities may provide useful indicators for particular mental disorder outcomes in later life, although their predictive utility in this respect remains to be established in longitudinal follow-up of the cohort.

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Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores

10.1101/2020.03.31.20044800 ◽

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.

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Intellectual disability and mental disorders in a US population representative sample of adolescents

Psychological Medicine ◽

10.1017/s0033291718001605 ◽

2018 ◽

Vol 49 (6) ◽

pp. 952-961 ◽

Cited By ~ 9

Author(s):

Jonathan M. Platt ◽

Katherine M. Keyes ◽

Katie A. McLaughlin ◽

Alan S. Kaufman

Keyword(s):

Bipolar Disorder ◽

Intellectual Disability ◽

Mental Disorders ◽

Mental Disorder ◽

Behavioral Problems ◽

Behavior Disorders ◽

Representative Sample ◽

Age Of Onset ◽

Population Sample ◽

Clinical Samples

AbstractBackgroundMost research on the prevalence, distribution, and psychiatric comorbidity of intellectual disability (ID) relies on clinical samples, limiting the generalizability and utility of ID assessment in a legal context. This study assessed ID prevalence in a population-representative sample of US adolescents and examined associations of ID with socio-demographic factors and mental disorders.MethodsData were drawn from the National Comorbidity Survey Adolescent Supplement (N= 6256). ID was defined as: (1) IQ ⩽ 76, measured using the Kaufman Brief Intelligence Test; (2) an adaptive behavior score ⩽76, and (3) age of onset ⩽18 measured using a validated scale. The Composite International Diagnostic Interview assessed 15 lifetime mental disorders. The Sheehan disability scale assessed disorder severity. We used logistic regression models to estimate differences in lifetime disorders for adolescents with and without ID.ResultsID prevalence was 3.2%. Among adolescents with ID, 65.1% met lifetime criteria for a mental disorder. ID status was associated with specific phobia, agoraphobia, and bipolar disorder, but not behavior disorders after adjustment for socio-demographics. Adolescents with ID and mental disorders were significantly more likely to exhibit severe impairment than those without ID.ConclusionsThese findings highlight how sample selection and overlap between ID and psychopathology symptoms might bias understanding of the mental health consequences of ID. For example, associations between ID and behavior disorders widely reported in clinical samples were not observed in a population-representative sample after adjustment for socio-demographic confounders. Valid assessment and understanding of these constructs may prove influential in the legal system by influencing treatment referrals and capital punishment decisions.General Scientific SummaryCurrent definitions of intellectual disability (ID) are based on three criteria: formal designation of low intelligence through artificial problem-solving tasks, impairment in one's ability to function in his/her social environment, and early age of onset. In a national population sample of adolescents, the majority of those with ID met criteria for a lifetime mental disorder. Phobias and bipolar disorder, but not behavior disorders, were elevated in adolescents with ID. Findings highlight the need to consider how behavioral problems are conceptualized and classified in people with ID.

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Insights into the genomics of affective disorders

Medizinische Genetik ◽

10.1515/medgen-2020-2003 ◽

2020 ◽

Vol 32 (1) ◽

pp. 9-18

Author(s):

Andreas J. Forstner ◽

Per Hoffmann ◽

Markus M. Nöthen ◽

Sven Cichon

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Affective Disorders ◽

Association Studies ◽

Phenotypic Variability ◽

Genetic Research ◽

Autism Spectrum ◽

Risk Scores ◽

Depression Symptoms ◽

Genome Wide Association Studies

Abstract Affective disorders, or mood disorders, are a group of neuropsychiatric illnesses that are characterized by a disturbance of mood or affect. Most genetic research in this field to date has focused on bipolar disorder and major depression. Symptoms of major depression include a depressed mood, reduced energy, and a loss of interest and enjoyment. Bipolar disorder is characterized by the occurrence of (hypo)manic episodes, which generally alternate with periods of depression. Formal and molecular genetic studies have demonstrated that affective disorders are multifactorial diseases, in which both genetic and environmental factors contribute to disease development. Twin and family studies have generated heritability estimates of 58–85 % for bipolar disorder and 40 % for major depression. Large genome-wide association studies have provided important insights into the genetics of affective disorders via the identification of a number of common genetic risk factors. Based on these studies, the estimated overall contribution of common variants to the phenotypic variability (single-nucleotide polymorphism [SNP]-based heritability) is 17–23 % for bipolar disorder and 9 % for major depression. Bioinformatic analyses suggest that the associated loci and implicated genes converge into specific pathways, including calcium signaling. Research suggests that rare copy number variants make a lower contribution to the development of affective disorders than to other psychiatric diseases, such as schizophrenia or the autism spectrum disorders, which would be compatible with their less pronounced negative impact on reproduction. However, the identification of rare sequence variants remains in its infancy, as available next-generation sequencing studies have been conducted in limited samples. Future research strategies will include the enlargement of genomic data sets via innovative recruitment strategies; functional analyses of known associated loci; and the development of new, etiologically based disease models. Researchers hope that deeper insights into the biological causes of affective disorders will eventually lead to improved diagnostics and disease prediction, as well as to the development of new preventative, diagnostic, and therapeutic strategies. Pharmacogenetics and the application of polygenic risk scores represent promising initial approaches to the future translation of genomic findings into psychiatric clinical practice.

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Earlier Contact with Child Protection Services Among Children of Parents With Criminal Convictions and Mental Disorders

Child Maltreatment ◽

10.1177/1077559520935204 ◽

2020 ◽

pp. 107755952093520

Author(s):

Tyson Whitten ◽

Kimberlie Dean ◽

Rebecca Li ◽

Kristin R. Laurens ◽

Felicity Harris ◽

...

Keyword(s):

Risk Factors ◽

Mental Disorder ◽

Child Protection ◽

Mental Health Problems ◽

Population Sample ◽

Independent Effect ◽

Parental History ◽

Child Protection Services ◽

Criminal Convictions ◽

Mental Disorder Diagnosis

Parental history of offending and/or mental illness are risk factors for child maltreatment. However, limited research has directly contrasted the role of maternal versus paternal criminal offending or mental health problems in contributing to earlier contact with the child protection system. In this study we examined the relative contributions of these risk factors in relation to the time to the offspring’s first report to child protection services, or first placement in out of home care (OOHC), using administrative records for a population sample of 71,661 children. Prior paternal offending had a greater independent effect on time to the offspring’s first contact with child protection services (HR = 2.27 [95% CI = 2.14-2.40]) than maternal offending (HR = 1.75 [95% CI = 1.63 -1.87]) or maternal mental disorder diagnosis (HR = 1.66 [95% CI = 1.57 -1.77]). By contrast, prior maternal offending (HR = 2.58 [95% CI = 2.26-2.95]) and mental disorder diagnosis (HR = 2.33 [95% CI = 2.05-2.63]) had a greater effect on earlier placement in OOHC, relative to prior paternal offending (HR = 1.59 [95% CI = 1.35 -1.88]) and mental disorder diagnosis (HR = 1.06 [95% CI = 0.94 -1.19]). These findings demonstrate the potential benefits of coordinated government responses across multiple agencies to identify vulnerable children and families who might benefit from early interventions or support services.

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