Temporal Structure of Mixed States: Does Sensitization Link Life Course to Episodes?

Susceptibility to combined depressive and manic syndromes correlates strongly with arousal-related symptoms including impulsivity, anxiety and agitation. This relationship to a driven, "mixed" activation-depression state, generated by a life-long process, was described in classical times. Course of illness in mixed states includes increased episode frequency, duration, earlier onset, and association with addiction- and trauma/stress-related disorders. Mixed episodes have catecholamine and hypothalamic-pituitary-adrenocortical activity increased beyond nonmixed states of similar symptom severity. These properties resemble behavioral sensitization, where salient, survival-related stimuli (traumatic or rewarding) can generate persistently exaggerated responses with disrupted arousal and reward, with potential for suicide and other severe consequences.