Essays on Science and SocietyNeuroscience

Jump-starting natural resilience reverses stress susceptibility

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Science  31 Oct 2014:
Vol. 346, Issue 6209, pp. 555
DOI: 10.1126/science.1260781


Major depressive disorder (MDD) is a severe mental disorder that affects more than 121 million people worldwide, according to the World Health Organization (1, 2). Despite the prevalence of this pathological syndrome, the most effective treatment currently for MDD is a combination of a limited variety of monoamine-based antidepressant medications and psychotherapy. Twenty percent of people with MDD are not helped by existing therapies (35), which have been targeting the same serotonin and norepinephrine systems for over 60 years (6). Most antidepressant treatments have multiple side effects and require weeks to take effect (7). Unfortunately, during this lag period, up to the onset of activation, there is considerable morbidity and a high risk of suicide (8, 9). Thus there is an imperative need for the development of naturally acting antidepressants. A possible reason for the ineffectual treatment of MDD so far has been the incomplete understanding of the nature of depression. Most work in the field, to date, has focused on the passive pathological mechanisms that contribute to the pathogenesis of depression. In contrast, my work focuses on understanding why some individuals are psychophysiologically normal in response to stress (i.e., resilient to depression), while others succumb to depression (1014). The majority of the population successfully employs active coping skills in response to stress, such as optimism, rationalization, wishful thinking, relaxation, and humor, which are linked to the function of the mesolimbic reward neural circuitry (15). Thus, current work has only recently begun to understand the neurobiological basis for these psychosocial coping skills (10, 14, 15).

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