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Bipolar disorder (BD) is a severe mood disorder characterized by episodes of depression and (hypo)mania. BD affects 1-2% of the population and is known for its recurrent, chronic display with high interpersonal and societal impact. With a diagnostic delay of 5-10 years, one of the key challenges in the field of BD is early identification and adequate treatment during adolescence and young adulthood - a crucial time window for interpersonal and psychosocial development. The strongest risk factor for BD is having a parent affected with BD. I will therefor study the development of BD in those with the highest risk by conducting the 20-year follow-up of the Dutch Bipolar Offspring cohort.

 

To date, longitudinal bipolar offspring studies have revealed important convergent insights on the risk and early trajectories of BD. Bipolar offspring are at high risk for BD (10-20%), mood disorders (>50%), and psychopathology in general (60-75%) and BD debuts in almost all cases with a (mild) depressive episode. However, none of these offspring studies thus far have had the opportunity to follow offspring beyond the age of 30 year. Middle adulthood is of particular interest for those bipolar offspring affected with unipolar depression (UD), as the risk for a switch to BD is potentially high and affects treatment options. At present we are unable to predict who are at high risk to switch from UD to BD; a better understanding is thus of clinical importance. Also, limited attention has been paid to functional outcomes within this vulnerable population (e.g. professional participation, family functioning and social functioning) while this is of great importance for the daily life of BD patients and their families. Both the focus on early identification of BD and functional outcome in bipolar offspring have been indicated as clinically very relevant by the patient association (VMDB), the knowledge center for Bipolar Disorders (kenniscentrum bipolaire stoornissen, KenBis) and consulted participants of the Dutch Bipolar Offspring Study.

 

With this project I aim to provide unique insights in 1) risk estimates of BD, switch rates from UD to BD and features of early trajectories in adult bipolar offspring, and 2) investigate the link between (early) psychopathology and functional outcome in adult bipolar offspring. In order to meet these aims, I will conduct the 20-years follow-up of the Dutch Bipolar Offspring Study. This unique study was established in 1997 and followed 140 children of 86 families from adolescence (mean age 16, range 12-21 years) into adulthood (mean age 28, 24-32 years). Assessments took place at baseline, 1- 5- and 12-year follow-up, 108 offspring are still participating and have in 2018 reached a mean age of 36 years. From prior assessments data on (dimensional) psychopathology, cognition, stressful life events, psychological aspects (e.g. coping), immunological and genetics are available. For the 20-year follow-up wave, I will collect phenotypical data on (dimensional) psychopathology, demographics and functioning through face to face semi-structured clinical interviews and questionnaires. Functional outcomes will focus on measures of professional participation, school achievements, family functioning, social network (romantic relationships, friends), self-suffiency and (mental) health care consumption gathered through interviews and self-report measures.

 

Apart from these well-established assessment methods, I will employ innovative methods using smartphone applications, in order to link this well-established panel study with new research paradigms in psychiatry (e.g., network models on intensive longitudinal data). I will use experience sampling, namely a structured diary technique to measure mood fluctuations in daily life (5 times a day, for 14 consecutive days, 1-2 minutes). For an example see figure 1. To study real-world functional outcome, I will use a passive behavioral monitoring smartphone application which passively collects in real time a longitudinal trace of (online) social and other aspects of behavior (e.g. diurnal rythms) with minimal awareness (e.g. BeHapp). These new methods will provide additional information on self-report and will provide a unique insight in daily behavior and enable us to study individual patterns in daily life and different contexts.

 

As the Dutch Bipolar Offspring Study does not include a control cohort a new control cohort of 50 individuals will be collected for the study of experience sampling. To further expand the control sample I will collaborate with the Netherlands Study for Depression and Anxiety (NESDA; PI Prof. Brenda Penninx).

 

In sum, extending one of the strongest bipolar offspring studies with an innovative 20-year follow-up and combining it with novel paradigms in psychiatry has the potential to identify targets for early detection and optimal treatment of UD and BD and contribute to the development ofpreventive strategies in a high risk population.

 

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