There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment out come remain to be determined in future studies.

The extent to which the second member of a pair of monotic clicks facilitates simple reaction time was examined for 35 psychiatric patients and 43 non-patient controls across 2 studies. Affective psychotic patients showed greater reaction time facilitation than did either schizophrenic patients or non-patient controls. Computer simulations of a ‘statistical facilitation’ model for these data are also presented.

The sensitivity in detecting a click was measured separately for the right and left ear of psychiatric patients and non-patient controls using a three-interval forced-choice staircase procedure. Patients with affective disorders showed reduced right ear sensitivity, while schizophrenic patients did not show reduced sensitivity. Lower sensitivity correlated with higher structured-interview ratings of speech retardation.

Patients diagnosed on the basis of structured interviews as having affective psychoses were less sensitive in detecting the presence of a transient auditory signal than were schizophrenic patients or non-patients. Patients with affective psychoses also benefited more (their reaction time was more reduced) than the other two groups from the presence of a second auditory transient.

Low positive emotionality (PE; e.g., listlessness, anhedonia, and lack of enthusiasm) has been hypothesized to be a temperamental precursor or risk factor for depression. The present study sought to evaluate the validity of this hypothesis by testing whether low PE children have similar external correlates as individuals with depression. This paper focused on the external correlate of EEG asymmetry. Previous studies have reported that individuals at risk for depression exhibited a frontal EEG asymmetry (greater right than left activity). Others have reported an association with posterior asymmetries (greater left than right activity). In the present study, children classified as having low PE at age 3 exhibited an overall asymmetry at age 5–6 with less relative activity in the right hemisphere. This asymmetry appeared to be largely due to a difference in the posterior region because children with low PE exhibited decreased right posterior activity whereas high PE children exhibited no posterior asymmetry. These findings support the construct validity of the hypothesis that low PE may be a temperamental precursor or risk factor for depression.

We gratefully acknowledge Jurgen Kayser's assistance and advice.

ERP topographies for 30 scalp electrodes were examined in 26 healthy right-handed volunteers during oddball tasks (20% targets) using binaurally presented consonant-vowel syllables or complex tones. Response hand was counterbalanced across participants. Both window averages and a principal components analysis (PCA) with Varimax rotation revealed task-related (tonal/phonetic) hemispheric asymmetries for N2, early P3, and particularly for N2-P3 amplitude. In the tonal task, N2 was maximal over right lateral-temporal regions, and early P3 over right medial-parietal regions. For the phonetic task, N2 was maximal over the left lateral-parietal regions, and late P3/N3 over left medial-parietal regions. A response-related frontal negativity (N3) interacted with task-related asymmetries in an unbalanced fashion. The distinct, asymmetric N2 and P3 topographies for tonal and phonetic tasks presumably reflect differential involvement of cortical structures in pitch (right frontotemporal) and phoneme (left parietotemporal) discrimination.

Event-related potentials to binaural complex tones were recorded from 40 depressed outpatients and 22 normal control participants at 30 electrode sites. Patients did not differ from control participants in N1 or P3 amplitude but showed greater N2. N2 was greater over right than over the left hemisphere at lateral sites in patients and control participants. A P3 asymmetry was found for control participants and patients with low scores on a physical anhedonia scale, but not for patients with high anhedonia scores. Topographic (local Laplacian) maps corresponding to P3 showed greater radial current flow over right than over left central regions in control participants. Patients with high anhedonia did not show this asymmetry, whereas patients with low anhedonia showed an intermediate asymmetry. These findings support the hypothesis that anhedonic depression is associated with dysfunction of right hemisphere mechanisms mediating the processing of complex pitch information.

The association between lateralized hemispheric dysfunction and psychiatric diagnosis was investigated with a measure of summation of dichotic clicks and with a dichotic competing message task. Ear asymmetries of affective psychotic patients were similar to those of right temporal lesioned controls and differed from those of schizophrenic patients and normal controls. In contrast, schizophrenic patients did not display abnormal auditory perceptual asymmetries.