Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis

Abstract

Antidepressants are widely used in clinical practice for the treatment of depression and other mood disorders. Numerous neuroimaging studies have recently examined how antidepressants influence emotional processes. However, both clinical trials and neuroimaging studies have reported inconsistent responses to antidepressants. Moreover, the neuropsychological mechanisms by which antidepressants act to improve depressive features remain underspecified. This systematic meta-analysis summarizes pharmacological neuroimaging studies (before February 2013) and the antidepressant effects on human brain activity underlying emotional processes. Sixty fMRI studies (involving 1569 subjects) applying antidepressants vs control were included in the current quantitative Activation Likelihood Estimation (ALE) meta-analysis. Pooling of results by ALE meta-analyses was stratified for population (mood disorder patients/healthy volunteers), emotional valence (positive/negative emotions) and treatment effects (increased/decreased brain activity). For both patients and healthy volunteers, the medial prefrontal and core limbic parts of the emotional network (for example, anterior cingulate, amygdala and thalamus) were increased in response to positive emotions but decreased to negative emotions by repeated antidepressant administration. Moreover, selective antidepressant effects were uncovered in patients and healthy volunteers, respectively. Antidepressants increased activity in the dorsolateral prefrontal (dlPFC), a key region mediating emotion regulation, during both negative and positive emotions in patients. Repeated antidepressant administration decreased brain responses to positive emotions in the nucleus accumbens, putamen, medial prefrontal and midbrain in healthy volunteers. Antidepressants act to normalize abnormal neural responses in depressed patients by increasing brain activity to positive stimuli and decreasing activity to negative stimuli in the emotional network, and increasing engagement of the regulatory mechanism in dlPFC.

Psychobiology of threat appraisal in the context of psychotic experiences: A selective review

“…Notably some patients may also be on anxiolytic or antidepressant medication, likely to alter affective processing [70].…”

Opposing Oxytocin Effects on Intergroup Cooperative Behavior in Intuitive and Reflective Minds

“…This has critical implications in the translation of the oxytocin effect from animal models to clinical populations, and draws caution to map animal findings directly on to human neurobiology. In addition, our previous work has documented genetic modulation on pharmacological challenge (ie, serotonin transporter gene modulated the efficiency of serotonergic drugs; Ma, 2015;Ma et al, 2015); therefore, it is of critical interest for future research to further test how psychological and biological factors influence the effects of oxytocin.…”

A neurocognitive model for understanding treatment action in depression

“…B 370: 20140213 also found decreased amygdala response to fearful faces [30,39,41,42]. However, other studies have found increased amygdala response [43], and a recent meta-analysis showed that the direction of effects in this network of structures varies between studies [46]. Future work should attempt to establish the reason behind these discrepancies, including a focus on dose-response relationships and the basal characteristics of the volunteers included in the studies.…”

“…These patterns of neural activity, restricted to areas involved in relatively low-level processing of emotional stimuli, suggest that early effects of antidepressants may be working in a 'bottom-up' fashion, affecting the automatic evaluation of emotional stimuli [45]. Indeed, a recent meta-analysis found that across a range of different cognitive tasks, short-term antidepressant treatment increased activation to positive emotional information, and decreased activation to negative information, across a network including the amygdala, putamen, ACC, parahippocampal gyrus and medial prefrontal cortex [46]. These limbic and paralimbic structures are involved in detecting and responding to salient emotional information, supporting this 'bottom-up' interpretation of early antidepressant effects.…”