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Background: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. Methods: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. Results: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. Conclusion: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response. [ABSTRACT FROM AUTHOR]

The approach--withdrawal model posits 2 neural systems of motivation and emotion and hypothesizes that these systems are responsible for individual differences in emotional reactivity, or affective styles. The model also proposes that depression is characterized by a deficit in reward-seeking behavior (i.e., approach motivation) and is associated with a relative decrease in left frontal brain activity. The authors tested aspects of this model by comparing the electroencephalogram alpha power of depressed and nondepressed individuals during a task that manipulated approach motivation. The study found that control participants and individuals with late-onset depression exhibited the hypothesized increase in left frontal activity during the approach task but individuals with early-onset depression did not. This suggests that early-onset depression may be associated with a deficit in the hypothesized approach motivation system. Keywords: EEG asymmetry, early-onset depression, approach motivation, personality

Illness course separates patients with atypical depression into tricyclic responders and nonresponders as does perceptual asymmetry. The authors therefore investigated whether the course-of-illness parameters would define groups within atypical depression differing in brain laterality. Patients with atypical depression were assessed for illness course and brain laterality. Two patient groups were defined, I with onset prior to age 20 plus a very chronic course, and a 2nd group having later onset or less chronic illness. Patients reporting early onset of very chronic dysphoria showed significantly less right-ear (left-hemisphere) accuracy and also differed in characteristic perceptual asymmetry when compared to patients with later onset or less chronicity. Course of illness may usefully define more homogeneous depressive subgroups within atypical depression.

Two studies compared hemispatial bias for perceiving chimeric faces in patients having either atypical or typical depression and healthy controls. A total of 245 patients having major depressive disorder (MDD) or dysthymia (164 with atypical features) and 115 controls were tested on the Chimeric Faces Test. Atypical depression differed from typical depression and controls in showing abnormally large right hemisphere bias. This was present in patients having either MDD or dysthymia and was not related to anxiety, physical anhedonia, or vegetative symptoms. In contrast, patients having MDD with melancholia showed essentially no right hemisphere bias. This is further evidence that atypical depression is a biologically distinct subtype and underscores the importance of this diagnostic distinction for neurophysiologic studies.

A previous study showed that depressed patients who improved with tricyclic antidepressant medication had dichotic complex tones test results suggesting right-hemisphere dysfunction relative to nonresponders and controls (G. E. Bruder et al., 1990). A new sample of 68 depressed patients completed dichotic consonant-vowel (CV) and complex tones (CT) tests and then were treated with imipramine or placebo. A significant Ear X Test X Treatment X Response interaction was accounted for by significantly poorer left-ear accuracy for CVs among imipramine responders compared with nonresponders, placebo responders, and controis. CV left-ear accuracy was also significantly greater among placebo responders than placebo nonresponders and controls. The results only partially replicate the prior study in that evidence of right-hemisphere dysfunction in tricyclic responders was seen for the CV test but not the CT test.

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry.

Analysis of dichotic syllable and complex tone listening among 35 manic patients and 26 nonpsychiatric controls shows that manic patients were on the whole worse listeners, specifically for complex tones fed to the left ear. Patients in the euthymic mood displayed almost normal listening abilities and patients helped by lithium and neuroleptics did not have the normal left-ear asymmetry. It is likely that mania and malfunctioning of the brain's right hemisphere are related.