Examining relations between alpha power as well as anterior cingulate cortex-localized theta activity and response to single or dual antidepressant pharmacotherapies.

Electrocortical indices may be useful in predicting antidepressant response. Greater pretreatment alpha power and high rostral anterior cingulate cortex (rACC) theta activity tend to index a favorable outcome. The predictive utility of alpha power asymmetry has been under-explored. Baseline alpha2 (10.5-13.0 Hz) power/asymmetry, rACC theta2 (6.0-8.0 Hz) activity and early (one week) changes in these measures were assessed in relation to antidepressant response by week 12 to three treatment regimens (escitalopram (ESC) + bupropion (BUP), ESC or BUP) in patients with major depressive disorder (N=51). No treatment differences in response existed at week 12. Overall, treatment responders exhibited high, and non-responders low, frontal baseline alpha2 power. Frontal alpha2 power weakly discriminated responders/non-responders overall while posterior alpha2 power and BA25-localized theta2 activity strongly discriminated ESC responders/non-responders. No associations with alpha2 asymmetry and response emerged. BUP responders exhibited high, and BUP non-responders low, baseline rACC theta2 activity. Greater early decreases in rACC theta2 activity existed in ESC+BUP non-responders versus ESC+BUP responders. BUP responders exhibited greater rACC theta2 activity decreases than ESC responders. These preliminary results indicate that baseline and early changes in alpha2 and rACC theta2 activity associate with response and have implications for tailoring antidepressant treatments.

Auditory P3 in antidepressant pharmacotherapy treatment responders, non-responders and controls.

Event-related potentials (ERPs), derived from electroencephalographic (EEG) recordings, can index electrocortical activity related to cognitive operations. The fronto-central P3a ERP is involved in involuntary processing of novel auditory information, whereas the parietal P3b indexes controlled attention processing. The amplitude of the auditory P3b has been found to be decreased in major depressive disorder (MDD). However, few studies have examined the relations between the P3b, the related P3a, and antidepressant treatment response. We tested 53 unmedicated individuals (25 females) with MDD, as well as 43 non-depressed controls (23 females) on the novelty oddball task, wherein infrequent deviant (target) and frequent standard (non-target) tones were presented, along with infrequent novel (non-target/distractor) sounds. The P3a and P3b ERPs were assessed to novel and target sounds, respectively, as were their accompanying behavioral performance measures. Depression ratings and the antidepressant response status were assessed following 12 weeks of pharmacotherapy with three different regimens. Antidepressant treatment non-responders had smaller baseline P3a/b amplitudes than responders and healthy controls. Baseline P3b amplitude also weakly predicted the extent of depression rating changes by week 12. Females exhibited larger P3a/b amplitudes than males. With respect to task performance, controls had more target hits than treatment non-responders. ERP measures correlated with clinical changes in males and with behavioral measures in females. These results suggest that greater (or control-like) baseline P3a/b amplitudes are associated with a positive antidepressant response, and that gender differences characterize the P3 and, by extension, basic attentive processes.

Response prediction to antidepressants using scalp and source-localized loudness dependence of auditory evoked potential (LDAEP) slopes.

The loudness-dependence of the auditory evoked potential (LDAEP) slope may be inversely related to serotonin (5-HT) neurotransmission. Thus, steep LDAEPs tend to predict a positive response to selective serotonin reuptake inhibitor (SSRI) antidepressants, which augment 5-HT. However, LDAEPs also predict outcome to antidepressants indirectly altering 5-HT (e.g. bupropion). Hence, the LDAEP's predicative specificity and sensitivity to antidepressant response/outcome remains elusive. Scalp N1, P2 and N1/P2 LDAEP slopes and standardized low resolution brain electromagnetic tomography (sLORETA)-localized N1 and P2 LDAEP slopes were assessed in depressed individuals (N=51) at baseline, 1 and 12 weeks post-treatment with one of three antidepressant regimens [escitalopram (ESC)+bupropion (BUP), ESC or BUP]. Clinical response was greatest with ESC+BUP at week 1. Treatment responders had steep N1 sLORETA-LDAEP baseline slopes while non-responders had shallow ones. P2 sLORETA-LDAEP slope increases at 1 week existed in responders; decreases were noted in non-responders. Exploratory analyses indicated that more BUP and ESC responders versus non-responders had steep baseline N1 sLORETA-LDAEP slopes. Additionally, slight decreases in scalp P2 LDAEP by week 1 existed for ESC treatment, while slope increases existed with ESC+BUP treatment. Only baseline N1 sLORETA-LDAEP discriminated treatment responders/non-responders. This work confirms that certain LDAEP measures are associated with treatment outcome and appear to be differentially modulated with varying antidepressant drug regimens, though this should be confirmed using larger samples.

α Power, α asymmetry and anterior cingulate cortex activity in depressed males and females.

Left fronto-cortical hypoactivity, thought to reflect reduced activity in approach-related systems, and right parietal hypoactivity, associated with emotional under-arousal, have been noted in major depressive disorder (MDD). Altered theta activity in the anterior cingulate cortex (ACC) has also been associated with the disorder. We assessed resting frontal and parietal alpha asymmetry and power in non-medicated MDD (N = 53; 29 females) and control (N = 43; 23 females) individuals. Theta activity was examined using standardized low-resolution electromagnetic tomography (sLORETA) in the ACC [BA24ab and BA32 comprising the rostral ACC and BA25/subgenual (sg) ACC]. The MDD group, and particularly depressed males, displayed increased overall frontal and parietal alpha power and left midfrontal hypoactivity (alpha(2)-indexed). They also exhibited increased sgACC theta(2) activity. MDD females had increased right parietal activity, suggesting increased emotive arousal. Thus, unmedicated depressed adults were characterized by lower activity in regions implicated in approach/positive affective tendencies as well as diffuse cortical hypoarousal, though sex specific modulations emerged. Altered theta in the sgACC may reflect emotion regulation abnormalities in MDD.

Scalp- and sLORETA-derived loudness dependence of auditory evoked potentials (LDAEPs) in unmedicated depressed males and females and healthy controls.

OBJECTIVE: As major depressive disorder (MDD) is associated with altered 5-HT activity, we probed intensity-dependent auditory evoked potentials (AEPs) and loudness dependence of the AEP (LDAEP) slopes, shown pre-clinically to be inversely related to 5-HT activity, in MDD. METHODS: AEPs and LDAEP slopes were measured in MDD (N=50; 27 females) and controls (N=43; 23 females). Correlations between scalp AEPs/LDAEPs and low-resolution electromagnetic tomography (sLORETA)-derived indices were assessed. RESULTS: Smaller scalp intensity-dependent N1 and N1/P2 amplitudes in MDD versus control males and longer P2 latencies in MDD versus control females were found; no LDAEP group differences existed. Females had greater scalp AEPs, steeper N1 and N1/P2 scalp LDAEPs as well as greater intensity-dependent primary auditory cortex activation during the N1 than males. Scalp LDAEPs correlated weak-moderately with sLORETA counterparts. P2 LDAEP-sLORETA correlated negatively with MADRS scores. Female P2 and N1/P2 LDAEP-sLORETA correlated negatively with HAMD-17 and MADRS scores. CONCLUSIONS: MDD was not associated with altered LDAEPs. Impaired processing or potentiated inhibition of auditory stimuli was found in MDD males; longer processing existed in MDD females. Inverse relationships between LDAEPs and clinical scores may be related to treatment history, personality and/or MDD features. SIGNIFICANCE: MDD was not associated with an altered LDAEP, though subtle AEPs alterations were noted in MDD.

The temporal electrocortical profile of emotive facial processing in depressed males and females and healthy controls.

BACKGROUND: Previous work indicates that emotive processing, such as of facial expressions, may be altered in major depressive disorder (MDD). Individuals with MDD tend to exhibit a mood-congruent processing bias, though MDD may also be characterized by blunted emotive processing in general. Females tend to exhibit enhanced facial emotive processing than males. Few groups have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles, spanning preconscious to sustained, conscious processing of facial expressions in MDD; systematic comparisons of ERPs to emotive stimuli between depressed males and females are also lacking. METHODS: This study examined the temporal ERP profile to a simple expression recognition task in depressed adult males and females (N=52; 29 females) and controls (N=43; 23 females). RESULTS: The MDD group rated facial expressions as sadder overall than controls. Females exhibited enhanced and speeded pre- and conscious face processing than males. Subtle group differences emerged to specific expressions at mid-latency ERPs (N2, P2) indicating both blunted late pre-conscious perceptual processing of expressions and prolonged processing of intensely sad faces. LIMITATIONS: A more involved emotive processing task, employing threatening faces, may have revealed more robust group ERP differences. Menstrual cycle should also be controlled for in future work. CONCLUSIONS: This is the first study to systematically assess the temporal ERP profile, including of ERPs preceding the face-sensitive N170/VPP, to expressions in MDD. Overall, early perceptual and late conscious expression processing did not differ fundamentally between groups. Altered emotive processing may be a candidate index for monitoring and predicting antidepressant treatment outcome.