Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents

Department of Psychiatry, University of Groningen, Groningen, Groningen, Netherlands
Bipolar Disorders (Impact Factor: 4.97). 09/2005; 7(4):344-50. DOI: 10.1111/j.1399-5618.2005.00215.x
Source: PubMed


For nearly 5 years a prospective high risk cohort study was carried out in the Netherlands among adolescent offspring of parents with bipolar disorder (BD). The purpose of this study was to determine the prevalence of psychopathology, specifically mood disorders, in adolescents and young adults with a bipolar parent.
At first and second measurement 140 and 132 children of bipolar parents, respectively, were psychiatrically evaluated with a semi-structured psychiatric interview (K-SADS-PL). At follow up (third measurement), nearly 5 years later, lifetime DSM IV diagnoses were obtained from the SCID interview for 129 subjects (aged 16--26 years).
Compared with the first measurement, the lifetime prevalence of BD increased from 3 to 10% at follow up. In addition, the lifetime prevalence of overall mood disorders increased to 40% and of overall psychopathology to 59%. All subjects except for one with BD, debuted with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to the first (hypo)manic episode.
At follow up, we noticed an increase in BD onset, while a further increase could be expected. In addition, we found that a unipolar depression in bipolar offspring is a risk factor for, and at the same time the first sign of, the development of BD.

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Available from: Johan Ormel, Dec 22, 2013
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    • "First, it remains unknown whether currently unaffected HR-well subjects may develop a mood disorder in the future. Second, previous longitudinal studies have reported that the majority of the high-risk subjects who developed BD themselves experienced depressive episodes years before conversion (Hillegers et al. 2005; Duffy, 2010) so that it appears likely that some of our HR-MDD subjects may develop BD in the future. The follow-up assessments of our study cohort will clarify if some of the HR-MDD participants will convert to BD and if some of our HR-well subjects go on to develop a mood disorder. "
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    ABSTRACT: Background. Neurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset. Method. A neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HRwell). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility. Results. Reduced long delay verbal memory and extradimensional set-shifting performance across both time Points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional setshifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups. Conclusions. Reduced verbal memory and cognitiveflexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.
    Psychological Medicine 07/2015; DOI:10.1017/S0033291715001324 · 5.94 Impact Factor
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    • "In contrast to studies of mental health in the OBD (i.e. Goldstein et al., 2010; Hillegers et al., 2005), the present study focused on non-psychiatric outcomes, in addition to the rates of affective and non-affective disorders among high-risk offspring. The objectives of the current investigation were twofold: (1) to examine differences in personality traits, coping style, and risk-taking behavior (smoking, anti-social behaviors, high risk sexual behaviors, selfinjury , and suicidality) between the OBD and controls, and (2) to compare these psychosocial profiles in offspring who have developed an affective disorder with those who have not, so as to tease apart prodromal markers from those that are present by virtue of having an affective disorder. "
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    ABSTRACT: Objectives It has been proposed that the offspring of parents with bipolar disorder (OBD), through genetic mechanisms and early family interactions, develop a heightened sensitivity to stress, maladaptive coping, and dysregulated behavior, which ultimately increases the risk for affective disorders. The current study tested certain predictions of this model by assessing different psychosocial and health-related outcomes in the OBD, including personality, coping style, smoking, suicidality, high-risk sexual behaviors, criminality, and mental health. Method The sample was composed of 74 OBD and 75 control offspring, who were between 14 and 27 years of age (mean: 19.38±3.56). Participants underwent a diagnostic interview and a structured interview to assess high-risk behavior and other maladaptive outcomes, and they completed the Revised NEO Personality Inventory and Coping in Stressful Situations questionnaire. Results The rates of affective (31.1%) and non-affective (56.8%) disorders were elevated in the OBD compared to controls (9.5% and 32.4%). Relative to controls, OBD endorsed fewer task-oriented and more distraction coping strategies [Wilk׳s λ=.83, F(1, 136) =6.92, p<.01], and were more likely to report engaging in high-risk sexual behavior (OR=2.37; Wald=4.13, 1 df, p<05). Importantly, OBD reported elevated high-risk sexual behavior relative to controls, irrespective of affective disorder diagnosis. Conclusion The results highlight a potential risk profile for the OBD, consisting of ineffective coping strategies and risky sexual behavior and are discussed in the context of current knowledge of stress and coping in this population. Limitations The present findings were based on cross-sectional data and relied on offspring self-report. It would be useful to corroborate these findings with biobehavioural and longitudinal measures.
    Journal of Affective Disorders 09/2014; 166:315–323. DOI:10.1016/j.jad.2014.04.047 · 3.38 Impact Factor
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    • "(iv) Two studies did not compare incidence of MDD or BD in FDRs and/or SDRs of probands affected by MDD or BD to population incidence rates or controls (Hillegers et al., 2005; Schreier et al., 2006). (v) Forty-one publications did not report data point estimates of the effect measure, or were reported without p values, CIs or raw data, from which the effect measure could be calculated (Andreasen et al., 1987; Brent et al., 2004; Chang et al., 2000; Dienes et al., 2002; Dierker et al., 1999; Eley et al., 2004; Ferro et al., 2000; Gershon, 1982; Giovanni et al., 2010; Grigoroiu- Serbanescu et al., 1989; Grove et al., 1987; Hillegers et al., 2005; Kaufman et al., 1998; Kendler et al., 1997; Kessler et al., 1998; Lavori et al., 1987; Levinson et al., 2003; Li et al., 2008; Lieb et al., 2002; Marazita et al., 1997; Martinez-Devesa et al., 2007; McGuffin et al., 1988; McMahon et al., 1995; Merikangas et al., 1988; Mitchell et al., 1989; Moberg, 1991; Mojtabai, 2005; Murray et al., 2011; Olino et al., 2008; Orvaschel, 1990; Peterson et al., 1982; Ryan et al., 1992; Singh et al., 2007; Stevenson et al., 2010; Thorndike et al., 1996; Todd et al., 1994; Tozzi et al., 2008; Wals et al., 2003; Wals et al., 2004; Weissman et al., 1984a; Wickramaratne and Weissman, 1998). (vi) Wickramaratne and Weissman (1998) duplicated cases reported in two later studies, respectively (Beardslee et al., 1996; Wickramaratne et al., 2000), which were subsequently excluded because they did not report the outcomes of interest. "
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    ABSTRACT: Background To conduct a meta-analysis to estimate the incidence of major depressive disorder (MDD) and bipolar disorder (BD) in first-degree relatives (FDRs) of probands affected by MDD or BD. The risk for MDD in FDR of BD probands and vice versa is also investigated. Methods A systematic review of case-control and cohort studies, which were published between 1977 and 2012; reported relative risks (RR) or odd ratios (OR) or equivalent raw data; made an explicit distinction between MDD and BD; used operational diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained by electronic MEDLINE and EMBASE searches and hand-searching. Estimates were derived from pooled data using random effects methods. Results Of an initial sample of 241 articles, 22 were eligible for inclusion. For FDRs of one proband with MDD compared to healthy control probands, estimates for MDD were OR=2.14 (95% CI 1.72–2.67), increasing to OR=3.23 (95% CI 2.11–4.94) for two MDD probands. For FDRs of one BD proband compared to healthy control probands, estimates for BD were OR=7.92 (95% CI 2.45–25.61), and OR=6.58 (95% CI 2.64–16.43) for FDRs of two BD probands. Conclusions These findings support previously published data indicating strong familiality for both MDD and BD. Data will be useful in providing individuals with a family history of MDD or BPD with tailored risk estimates.
    Journal of Affective Disorders 04/2014; 58:37-47. DOI:10.1016/j.jad.2014.01.014 · 3.38 Impact Factor
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