Brain plasticity and the course of mood disorders: Possible implications for secondary prevention

All recent publications agree that the natural course of mood disorders is progressive and that the frequency increases with time. Unfortunately, the higher frequency of relapses is associated with poorer outcome of prophylactic treatments. Any approach to the neural mechanism underlying the course of affective illness, seems to be based upon the understanding of different forms of brain plasticity, such as long-term potentiation (LTP), behavioral sensitization and kindling. Experimental evidence shows that LTP may be involved in the formation of emotional memories of past traumatic stress in a circuit which amygdala plays a central role.
 
Behavioral sensitization is defined as the progressive increase in behavioral responses (euphoria, aggressiveness, motor activity, etc) to the repeated administration of psychostimulants, such as cocaine and amphetamine. Most relevant to the psychiatric disorders, is the fact that repeated or prolonged stress sensitizes to psychostimulants, while sensitization to stress and to psychostimulants may be crossed. Moreover, chronic treatment with different classes of antidepressants has been shown to potentiate the psychostimulant effect of dopamine agonists. The clinical relevance of the above neural plasticity models is obvious. A number of depressed patients and particularly those suffering from bipolar type of mood disorders, treated with anti-depressants switch from depression to mania. Furthermore, repeated stress or repeated cocaine or amphetamine absorption, can precipitate manic stress and increase the probability of relapses in patients who are in remission. The understanding of the mechanisms underlying these forms of neural plasticity, may contribute to the development of more meaningful and evidence-based therapeutic and especially preventive strategies.