Depression is one of the most debilitating disorders of our times. Antidepressant medication, one of the most
common (and often first-line) treatments to date, aim to alleviate symptoms, but finding which type of drug benefits
which patient remains a daunting task. The underlying mechanism that translates neurochemical effects to symptom
improvement is still far from precise. In this review we summarized the evidence on the effects of antidepressants on
brain systems and cognitive functioning, and examined the possible value of these correlates as predictors of response.
Studies using acute (or sub-chronic) antidepressant administrations in healthy subjects showed effects on affective
cognition. In depressed patients, neuroimaging studies examining the effects of antidepressants in pre-post designs have
shown changes in the activation of the anterior cingulate cortex and the limbic system after treatment. Increasing evidence
shows that baseline anterior cingulate cortex activation could be a possibly critical biomarker of treatment response. The
few studies performed to date also indicate potentially different pathways for antidepressants targeting the serotonergic
neurotransmitter system versus those targeting the noradrenergic one, but findings are not always consistent. More studies
are necessary to establish whether early cognitive effects of drugs are predictive of long-term efficacy in depressed
patients. Considering the heterogeneity of depression and in order to approach a more personalized treatment, future
studies should also elucidate the effects of antidepressants on different cognitive systems and subsequently on different
Keywords: Antidepressant response, behavior, cognition, depression, neuroimaging, neuropsychology.
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