Childhood adversity in bipolar disorder

In this issue, Daglas and colleagues (2014) present a study examining the impact of early adversity on the 12-month outcome of patients managed in Melbourne who presented with first-episode psychotic mania. The data shows that patients who have reported early adversity fare worse and have higher scores on symptom rating scales and worse psychosocial functioning at 12-month follow-up. This study is unique because of the specificity of the population and the authors are to be congratulated for recruiting 65 participants. The study adds significantly to the literature in this area. Over the past few years it has become increasingly evident that childhood adversity is a major risk factor for bipolar disorder (indeed for all mood disorders) and is associated with a greater symptom burden and a worse prognosis.

There are a number of implications of this. First, it is incumbent upon us, as clinicians, to give our patients the opportunity to discuss childhood experiences – and here we need to be aware that the relevant experiences are not confined to intrusive and frightening incidents but include also factors such as the persistent absence of a loving and supportive parental relationship (Watson et al., 2013). We also need to reconsider our use of psychological therapies. Psychological treatment for bipolar disorder has tended to focus on psychoeducation, often with the intended outcome being increased compliance with medication (Crowe et al., 2012), and on ‘Social Rhythms’ focusing on regularising activity and sleep. Psychoeducation and Interpersonal Social Rhythms Therapy have proven benefit in clinical trials (Crowe et al., 2012). Daglas’ paper, however, and others in the field, in demonstrating the importance of early experiences raise the question of the extent to which it may also be helpful to develop therapeutic interventions which address the psychological consequences of upbringing and early experience. The potential value of this is highlighted by a study which demonstrated a greater benefit from psychotherapy compared with drug treatment in depressed patients who had experienced childhood abuse (Nemeroff et al., 2003). The natural tendency is for the intensity of therapeutic input to reduce when bipolar patients recover from acute episodes and are ‘stabilised’. This is the very time, we would argue, that bipolar patients are most able to make use of psychological therapies which may serve to improve prognosis by reducing the persistent burden of low mood or the likelihood, severity or duration of future relapse.

Daglas’ study also causes us to reflect on the biological substrates of mania and depression and on the mechanism by which events in childhood, or indeed in utero, can alter developmental trajectories and ultimately manifest such diverse psychopathology in adulthood. Exciting developments in the field of epigenetics shows us that genes relevant to the aetiology and maintenance of bipolar disorder can be persistently rendered more or less active by experiences during critical developmental periods. Such epigenetic scars, which are moderated by genetic factors (single nuclear polymorphisms, etc.) to determine the risk of developing a host of psychiatric disorders, including bipolar disorder, can be transmitted from generation to generation but, importantly, are reversible and thus may give a biological substrate for the beneficial effect of mindfulness and other therapies. The impact of epigenetic changes is likely mediated by an interacting network of structural and functional parameters. Hippocampal structure and function, the immune system and the hypothalamic-pituitary-adrenal axis appear particularly relevant at this stage; certainly the relationship of childhood adversity on the expression and function of the glucocorticoid receptor has been the focus of much scientific endeavour (Klengel et al., 2014).

In short, the paper by Daglas and colleagues in this month’s issue provides further support to the notion that upbringing affects the risk of developing psychosis and mania and engenders a poor prognosis. This finding reminds us of the value of seeking information about early experiences so that we can better advise about their expected health trajectories and optimise the use of, unfortunately scarce, psychotherapeutic resources. It raises questions about the biological and psychological mediation of the impact of early adversity. The emerging understanding of the epigenetic scars imposed by childhood stress and the knowledge that these scars are reversible is relevant here and, when considered alongside the Daglas study, will help us to better understand both the way that our earliest experiences alter developmental trajectories and also the biological underpinnings of bipolar disorder. It will also give hope that psychotherapeutic endeavours will make a real difference to our patients.