Neurocognition in young offspring of individuals with bipolar disorder: The role of co-existing familial and clinical high-risk for bipolar disorder
Introduction
Bipolar disorder (BD) is associated with significant cognitive dysfunction that is present during episodes and persists in euthymia (Arts et al., 2008, Bora et al., 2009, Bora et al., 2016a; Man-Wrobel et al., 2011; Raucher-Chéné et al., 2017; Torres et al., 2007). Cognitive dysfunction in BD is evident in a wide range of domains including verbal memory, executive functions, verbal fluency, working memory, visual memory, attention, theory of mind and processing speed (Arts et al., 2008, Bora et al., 2009; Bora et al., 2016b). However, the timing of the emergence of cognitive dysfunction in BD is still unclear. Some authors argue that cognition in BD is preserved premorbidly and declines after the onset of the illness (Goodwin et al., 2008; Murray et al., 2004). However, other evidence suggests that cognitive deficits might be evident in first-episode BD (Bora and Pantelis, 2015; Lee et al., 2014) and remains largely unchanged thereafter (Bora and Özerdem, 2017a; Samame et al., 2014).
Studies of offspring of patients with BD (BDoff) can aid in disassociating the role of familial predisposition and mood symptoms on cognition. Most studies have investigated the cognitive performance of adult relatives of BD patients (Arts et al., 2008, Balanzá-Martínez et al., 2008; Bora and Özerdem, 2017b; Hıdıroğlu et al., 2015; Santos et al., 2017). Some authors suggest that there is no consistent evidence for global cognitive dysfunction in BDoff (Klimes-Dougan et al., 2017; Kumar and Frangou, 2010). However, recent years have witnessed increasing number of studies investigating cognitive deficits in offspring and young siblings of patients with BD (de la Serna et al., 2016; Klimes-Dougan et al., 2017; Maziade et al., 2009; Whitney et al., 2013). A recent meta-analysis of the relevant literature (Bora and Özerdem, 2017c) found that compared to controls, youth with positive family history for BD showed dysfunction in verbal and visual memory, attention and processing speed while planning/problem solving and working memory were preserved.
Some authors suggest that premorbid abnormalities in developmental processes may contribute to cognitive dysfunction in youth with familial predisposition to BD independent of current mood symptoms (Bombin et al., 2013; Bora, 2015; Diwadkar et al., 2011; Hanford et al., 2016; McIntyre et al., 2017; Parellada et al., 2017; Surganyes et al., 2017). An alternative explanation is that cognitive dysfunction in these youth might be linked to the history of subclinical mood syndromes particularly since persistent subthreshold manic and depressive symptoms are common among BDoff and might be associated with risk for emergence of BD (Axelson et al., 2015; Mesman et al., 2017). The history of subclinical manic syndromes are particularly essential in definition of Clinical-High-Risk (or Ultra-High-Risk) for BD (Bechdolf et al., 2014; Correll et al., 2014; Van Meter et al., 2016). Attenuated psychotic symptoms also precede BD in some individuals (Correll et al., 2008). The history of depressive symptoms in BDoff (which are also common in the general population) are less predictive in emergence manic symptoms but co-existence of depressive symptoms with subsyndromal manic symptoms, mood lability and attenuated psychotic symptoms might be related to higher risk. In the help-seeking populations, CHR for BD is associated with cognitive difficulties (Metzler et al., 2014) and individuals with attenuated psychotic symptoms who had developed BD at follow-up have also significant cognitive abnormalities (Olvet et al., 2010; Ratheesh et al., 2013). However, a few studies have investigated the potential role of Clinical-High-Risk (CHR) status on cognitive abnormalities in BDoff (Lin et al., 2015). Most notably, Lin and colleagues (Lin et al., 2017) found that visual memory, planning and working memory abnormalities were only evident in BDOff with CHR while only in verbal memory was affected in the offspring without CHR.
In this study, we assessed neurocognitive functioning in 75 BDoff and 50 demographically matched control participants. The BDoff were further categorized into individuals with clinical-high-risk (BDoff+CHR) and those without clinical-high-risk (BDoff-non-CHR). We tested the hypothesis that compared to youth without familial risk to BD, cognitive dysfunction would be present in BDoff irrespective of CHR status, but that the co-existence of familial and clinical high risk would be associated with greater cognitive abnormalities.
Section snippets
Participants
The study was conducted at Department of Neuroscience and Department of Psychiatry, Dokuz Eylul University. Offspring aged between 15 and 30 years were identified through patients with BD attending the Bipolar Disorders Outpatient Unit of the Department of Psychiatry. Healthy individuals, aged 15–30 years, without a personal history of psychiatric disorders and without a family history (up to 2nd degree relatives) of mood and psychotic disorders were recruited as controls through advertisements
Demographic and clinical data
As shown in Table 1, the groups were demographically matched except for the duration of education which differed significantly among the groups (p = 0.04) with the HCs having the longest duration of education (Table 2). Three groups were statistically matched for BMI. None of the BDoff-CHR and BDoff-non-CHR participants had current depressive and hypomanic symptoms (HDRS and YMRS≤8 in all). Only three offspring were on medication (antidepressant and mood stabilizers for depressive or anxiety
Discussion
The current study investigated neurocognitive function in BDoff-non-CHR and BDoff-CHR in comparison to healthy individuals without familial predisposition to BD. Cognitive abnormalities were evident in all BDoff irrespective of CHR status. Group differences in individual cognitive tasks were driven by deficits in global cognition and a selective deficit in fluency/central executive domains. There were no significant differences between BDoff+CHR and BDoff-non-CHR in any cognitive measure except
Funding body agreements and policies
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Declaration of Competing Interest
The authors have no conflicts of interest regarding subject of this manuscript.
Acknowledgements
Not relevant
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