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

Altrecht Institute for Mental Health Care, Utrecht, The Netherlands.
Bipolar Disorders (Impact Factor: 4.89). 09/2005; 7(4):344-50. DOI: 10.1111/j.1399-5618.2005.00215.x
Source: PubMed

ABSTRACT 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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    ABSTRACT: Objectives There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder.Methods Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls.ResultsDuring adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages.Conclusions This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value.
    Bipolar Disorders 07/2014; · 4.62 Impact Factor
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    ABSTRACT: Background Severe mental illness (SMI), including schizophrenia, bipolar disorder and severe depression, is responsible for a substantial proportion of disability in the population. This article describes the aims and design of a research study that takes a novel approach to targeted prevention of SMI. It is based on the rationale that early developmental antecedents to SMI are likely to be more malleable than fully developed mood or psychotic disorders and that low-risk interventions targeting antecedents may reduce the risk of SMI.Methods/DesignFamilies Overcoming Risks and Building Opportunities for Well-being (FORBOW) is an accelerated cohort study that includes a large proportion of offspring of parents with SMI and embeds intervention trials in a cohort multiple randomized controlled trial (cmRCT) design. Antecedents are conditions of the individual that are distressing but not severely impairing, predict SMI with moderate-to-large effect sizes and precede the onset of SMI by at least several years. FORBOW focuses on the following antecedents: affective lability, anxiety, psychotic-like experiences, basic symptoms, sleep problems, somatic symptoms, cannabis use and cognitive delay. Enrolment of offspring over a broad age range (0 to 21 years) will allow researchers to draw conclusions on a longer developmental period from a study of shorter duration. Annual assessments cover a full range of psychopathology, cognitive abilities, eligibility criteria for interventions and outcomes. Pre-emptive early interventions (PEI) will include skill training for parents of younger children and courses in emotional well-being skills based on cognitive behavioural therapy for older children and youth. A sample enriched for familial risk of SMI will enhance statistical power for testing the efficacy of PEI.DiscussionFORBOW offers a platform for efficient and unbiased testing of interventions selected according to best available evidence. Since few differences exist between familial and ¿sporadic¿ SMI, the same interventions are likely to be effective in the general population. Comparison of short-term efficacy of PEI on antecedents and the long term efficacy for preventing the onset of SMI will provide an experimental test of the etiological role of antecedents in the development of SMI.
    BMC Psychiatry 12/2014; 14(1):344. · 2.24 Impact Factor
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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. · 3.71 Impact Factor


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