Escitalopram but not placebo modulates brain rhythmic oscillatory activity in the first week of treatment of Major Depressive Disorder.

Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5-8 Hz) and the alpha (8-12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms. Prefrontal delta-theta and alpha power were calculated for 194 subjects with moderate MDD prior to and one week after start of treatment. Changes at one week in delta-theta and alpha power, as well as the delta-theta/alpha ratio, were examined in three cohorts: initial (N = 70) and replication (N = 76) cohorts treated with escitalopram, and a cohort treated with placebo (N = 48). Mean delta-theta power significantly increased and alpha power decreased after one week of escitalopram treatment, but did not significantly change with placebo treatment. The delta-theta/alpha ratio change was a specific predictor of the likelihood of remission after seven weeks of medication treatment: a large increase in this ratio was associated with non-remission in escitalopram-treated subjects, but not placebo-treated subjects. Escitalopram and placebo treatment have differential effects on delta-theta and alpha frequency oscillations. Early increase in delta-theta/alpha may constitute a replicable biomarker for non-remission during SSRI treatment of MDD.

Heart rate variability and treatment outcome in major depression: a pilot study.

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N=26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N=16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R2>.43 and p<0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker.

Focus on the positive: anxiety modulates the effects of emotional stimuli on hemispheric attention.

People with high levels of trait anxiety are said to orient attention selectively to threatening stimuli (Bradley, Mogg, White, Groom, & de Bono, 1999; MacLeod, Mathews, & Tata, 1986), but this effect is sometimes difficult to replicate. We suggest a reason for this difficulty is that typical tests of the spatial attention bias in anxiety failed to consider together: (1) the differential effects of positive and threatening stimuli on attention in anxiety, (2) the separate contributions of each hemisphere to the attention bias, and (3) whether the attention bias in anxiety is restricted to orienting or can be observed more strongly in the conflict or alerting networks of attention. We compared the effects of schematic angry, happy, and neutral face cues using a lateralized version of Posner's Attention Network Task (Lateralized Attention Network Test) which distinguishes spatial Orienting Cost (due to an invalid cue; disengagement) from spatial Orienting Benefit (due to a valid cue; hypervigilance), and which considers executive Conflict resolution and Alerting in addition to spatial Orienting in each hemisphere separately. We tested participants with high and low trait anxiety measured by the STAI-TA (Spielberger, Gorsuch, & Lushene, 1983). Surprisingly, happy face cues rather than angry face cues interacted with target visual field and participant level of anxiety. Happy face cues presented to participants with low anxiety elicited maximal Orienting Benefit and minimal Orienting Cost for targets presented to the left visual field. Anxious individuals failed to benefit from happy cues in the left visual field. We suggest that lateralized positive cues can provide a more sensitive index of attention changes in anxiety than is provided by centrally-presented threatening cues.