6 These cortical regions—which are anatomically connected to the amygdala,

hypothalamus, and brain stem—are thought to be implicated in the integration of experiential stimuli with emotional salience.12,13 Furthermore, the orbital frontal cortex has been shown to be involved with emotional processing biases in depressed individuals.14,15 Response to CBT was also found to be associated with a reduction of glucose metabolic activity in the medial PFC.6,7 This cortical area, which seems to be implicated in self-referential processing of emotional stimuli, is activated during a wide variety of emotional tasks, including attention to subjective feeling,16 recollection of emotionally charged personal life events,17 Inhibitors,research,lifescience,medical and processing Inhibitors,research,lifescience,medical of emotion-related meanings.18 The fMRI activation studies conducted by Dichter et al8 and Buchheim et al9 indicate that BATD and long-term, psychodynamic therapy can also modulate the activity of brain regions and circuits implicated in various aspects of emotion processing. The reduced activation of the anterior hippocampus/amygdala complex detected after psychodynamic therapy,

in response to personally relevant Inhibitors,research,lifescience,medical material, is particularly interesting given that this cerebral structure displays enhanced reactivity in MDD.19,20,21 Along the same lines, a reduction in the reactivity of the subgenual Belinostat clinical trial cingulate cortex was also detected in the Buchheim et al study. Now this portion of the cingulate cortex appears to be critically involved in mood dysregulation and its resolution.22 It is important to recognize that the functional neuroimaging studies of psychotherapy for MDD do not always yield similar findings. Several potentially biasing factors may lead to contrasting results and render problematic a direct comparison between these studies. For example,

Inhibitors,research,lifescience,medical MDD may have many different causes that Inhibitors,research,lifescience,medical are difficult to differentiate clinically.23 This may lead to a variability in symptoms and regional brain abnormalities across depressed individuals. The differences in rationale, technique, and efficacy of the various psychotherapeutic PAK6 modalities investigated constitute another factor. Furthermore, inconsistencies in results can be produced by a more or less rigid adherence to a given framework,24 varying numbers of sessions, distinct milieus (eg, individual vs group therapy), and the use of single vs multiple therapists.25 Other methodological factors that vary between neuroimaging studies of psychotherapy include the phenomena measured (eg, “metabolic activity” vs “hemodynamic activity”), the sensitivity and spatial/temporal resolutions of the neuroimaging techniques used, and the methods for examining regional brain activity (eg, voxel-based techniques, region-of-interest-based approaches).1,25 The sample size, the type of control participants (eg, healthy, waitlist), and the point of the second scan within the treatment course, may also lead to divergent results.