Bipolar disorder and aggressive behaviors: literature insights and chrono-biological interventions

Bipolar disorder (BD) is a common psychiatric disorder characterized by recurrent episodes of mood disturbances and changes in energy level and behavior, including periods of depression, hypomania or mania, mixed states and euthymia. The World Health Organization ranks BD among the top ten disabling disorders in the world. Aggression and violence are major public health concerns, particularly in psychiatric populations. Bipolar disorder (BD) has been associated with aggressive behavior, especially during manic or mixed episodes, though evidence is inconsistent and often reinforces stigma. Standard management strategies for aggressive behaviors in BD (verbal de-escalation, restrictive interventions, and pharmacotherapy) present several limitations and side effects. Bright light therapy (BLT) is a chronobiologic therapy, widely used to treat depression, with strong evidence of efficacy and tolerability, whose impact on irritability and aggression related symptoms, has received limited attention so far. This thesis was aimed to better understand the relation between BD and aggressive behaviors (Paper 1 and 2), with a specific focus on the illness phase and sex differences and to evaluate the potential effects of bright light therapy in managing irritability, psychomotor agitation, and anger attacks in BD (Paper 3 and 4). Paper 1 aimed to investigate the presence of interpersonal violent behavior (IVB) in BD patients across different illness phases. The results tend to locate in active phases of illness the risk of IVB, but also acknowledge the significance of aggressive behavior in females, often understated. Moreover, our results underline the important role of alcohol abuse, substance abuse and personality disorders as important mediators of IVB. With our systematic review, Paper 2, we tried to summarize the existing literature data on the relationship between BD and hetero-aggressive behaviors with a sex-based perspective. Our results showed that aggression and violent behavior in BD result from a complex interaction of clinical, socio-demographic, and environmental factors, with sex playing a significant but nuanced role. Again, the risk of aggressive behaviors towards others seems to be limited to the active phases BD; moreover, comorbid cluster B personality disorder, substance and alcohol use disorder represent important aggression facilitating factors. Paper 3 addresses the symptom-complex irritability, a core feature of BD, an often-underestimated factor for a higher risk of violence and suicide attempts. In our study, we showed a potent effect of adjunct morning BLT in reducing irritability during a depressive episode in BD. Finally, in our Paper 4, BLT shows similar promising results for managing irritability, psychomotor agitation, and anger attacks in patients with bipolar depression comorbid with alcohol misuse.