In this article, we present and review the evidence for two major biopsychosocial theories of the onset and course of bipolar spectrum disorders (BSDs) that integrate behavioral, environmental, and neurobiological mechanisms: the reward hypersensitivity and the social and circadian rhythm disruption models. We describe the clinical features, spectrum, age of onset, and course of BSDs. We then discuss research designs relevant to demonstrating whether a hypothesized mechanism represents a correlate, vulnerability, or predictor of the course of BSDs, as well as important methodological issues. We next present the reward hypersensitivity model of BSD, followed by the social/circadian rhythm disruption model of BSD. For each model, we review evidence regarding whether the proposed underlying mechanism is associated with BSDs, provides vulnerability to the onset of BSDs, and predicts the course of BSDs. We then present a new integrated reward/circadian rhythm (RCR) dysregulation model of BSD and discuss how the RCR model explains the symptoms, onset, and course of BSDs. We end with recommendations for future research directions.

Objective We examined the concurrent associations between multiple cognitive vulnerabilities to depression featured in Hopelessness Theory, Beck’s Theory, and Response Styles Theory and depressive symptoms and diagnoses in a sample of early adolescents. We also examined the specificity of these cognitive vulnerabilities to depression versus anxiety and externalizing psychopathology, controlling for co-occurring symptoms and diagnoses. Method Male and female, Caucasian and African-American, 12–13 year old adolescents were assessed in a cross-sectional design. Cognitive vulnerabilities of hopelessness, inferential style, rumination, and self-referent information processing were assessed with self-reports and behavioral tasks. Symptoms and diagnoses of depressive, anxiety, and externalizing disorders were assessed with self-report questionnaires and diagnostic interviews. Results Hopelessness exhibited the greatest specificity to depressive symptoms and diagnoses, whereas negative inferential styles, rumination, and negative self-referent information processing were associated with both depressive and anxiety symptoms and diagnoses and, in some cases, with externalizing disorders. Conclusions Consistent with cognitive theories of depression, hopelessness, negative inferential styles, rumination, and negative self-referent information processing were associated with depressive symptoms and diagnoses. However, with the exception of hopelessness, most of the remaining cognitive vulnerabilities were not specific to depression. With further maturation of our sample, these cognitive vulnerabilities may become more specific to depression as cognitive styles further develop and consolidate, the rates of depression increase, and individuals’ presentations of psychopathology become more differentiated.

These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.

Relative circadian phase delay (e.g., later melatonin peak, evening chronotype) is associated with BSD, particularly in the depressive phase. More consistent evidence supports irregularity of social rhythms, sleep/wake and activity patterns, and disruptions of social rhythms by life events, as stable trait markers of BSD and potential vulnerabilities for BSD onset. Growing research supports an integrative reward/circadian model. Both endogenous abnormalities in the biological clock pacemaking function and disruptions in the external entrainment of circadian rhythms by physical and social cues are involved in BSDs. Circadian dysregulation may provide vulnerability to BSD onset.