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      Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia

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          Abstract

          Background

          Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.

          Methods

          Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.

          Results

          Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.

          Conclusions

          Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

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          Most cited references22

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          Temperamental origins of child and adolescent behavior problems: from age three to age fifteen.

          We assessed relations between early temperament and behavior problems across 12 years in an unselected sample of over 800 children. Temperament measures were drawn from behavior ratings made by examiners who observed children at ages 3, 5, 7, and 9. Factor analyses revealed 3 dimensions at each age: Lack of Control, Approach, and Sluggishness. Temperament dimensions at ages 3 and 5 were correlated in theoretically coherent ways with behavior problems that were independently evaluated by parents and teachers at ages 9 and 11, and by parents at ages 13 and 15. Lack of Control was more strongly associated with later externalizing behavior problems than with internalizing problems; Approach was associated with fewer internalizing problems among boys; and Sluggishness was weakly associated with both anxiety and inattention, especially among girls. Lack of Control and Sluggishness were also associated with fewer adolescent competencies. These results suggest that early temperament may have predictive specificity for the development of later psychopathology.
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            Is Open Access

            GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

            The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10−8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.
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              Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study.

              Whether offspring of parents with bipolar disorder (BP) are at specifically high risk to develop BP and other psychiatric disorders has not been adequately studied. To evaluate lifetime prevalence and specificity of psychiatric disorders in offspring of parents with BP-I and BP-II. Offspring aged 6 to 18 years who have parents with BP and community control subjects were interviewed with standardized instruments. All research staff except the statistician were blind to parental diagnoses. Parents with BP were recruited primarily through advertisement and outpatient clinics. Control parents were ascertained by random-digit dialing and were group matched for age, sex, and neighborhood to parents with BP. Three hundred eighty-eight offspring of 233 parents with BP and 251 offspring of 143 demographically matched control parents. Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) Axis I disorders. Adjusting for demographic factors, living with 1 vs both biological parents, both biological parents' non-BP psychopathology, and within-family correlations, offspring of parents with BP showed high risk for BP spectrum disorders (odds ratio [OR] = 13.4; 95% confidence interval [CI], 2.9-61.6) and any mood (OR = 5.2; 95% CI, 2.3-11.4), anxiety (OR = 2.3; 95% CI, 1.3-4.0), and Axis I (OR = 2.2; 95% CI, 1.5-3.3) disorders. Offspring of parents with BP with high socioeconomic status showed more disruptive behavior disorders and any Axis I disorders than offspring of control parents with high socioeconomic status. Families in which both parents had BP had more offspring with BP than families with only 1 parent with BP (OR = 3.6; 95% CI, 1.1-12.2). More than 75.0% of offspring who developed BP had their first mood episode before age 12 years, with most of these episodes meeting criteria for BP not otherwise specified and, to a lesser degree, major depression. Offspring of parents with BP are at high risk for psychiatric disorders and specifically for early-onset BP spectrum disorders. These findings further support the familiality and validity of BP in youth and indicate a need for early identification and treatment.
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                Author and article information

                Journal
                applab
                Psychological Medicine
                Psychol. Med.
                Cambridge University Press (CUP)
                0033-2917
                1469-8978
                May 23 2019
                : 1-7
                Article
                10.1017/S0033291719001089
                31120010
                d25d249c-5651-476c-bea0-166028354715
                © 2019

                https://www.cambridge.org/core/terms

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