Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

Abstract

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamD-percent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response.

A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial

“…The neurobiological basis of the placebo response is characterized by an increase in the metabolic activity of the frontal and striatal cortical regions [20] and increased endogenous opioid release in the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala [21,22]. The placebo response has also been linked to increased baseline resting state functional connectivity of the rostral anterior cingulate cortex (rACC) within the salience network [23] and to increased pretreatment rACC activity in 2 EEG studies [24,25]. Previous studies of neuroimaging biomarkers of placebo response have been limited by small sample sizes and a lack of comparison with other clinical and biobehavioral markers [21,23].…”

Salience Network Functional Connectivity Predicts Placebo Effects in Major Depression

“…Regions involved in these networks have emerged as biological markers of response to antidepressant treatments (8-13). Yet, the ability of these biomarkers to selectively distinguish drug-specific effects from other non-specific elements of the treatment response, such as the placebo effect, is still limited, with very few studies specifically addressing biomarkers of non-specific elements of antidepressant treatment response (14, 15). This is not a small concern, as placebo response rates in antidepressant clinical trials average 31-45% compared with response rates to antidepressants of ~50% and have increased at a rate of 7% per decade over the last 30 years (16, 17).…”

Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy

“…Other brain areas implicated in the mood and anxiety disorders are: the insula, linked to self-awareness and autonomic regulation of emotions (Craig, 2009;Paulus and Stein, 2006); the hippocampus, involved in memory formation, learning, sensitivity to context, and regulation of stress, as well as a major site of neurogenesis (Bellani et al, 2010;Brooks et al, 2012;den Heijer et al, 2012); the thalamus, a processing centre for sensation and motor regulation, which also plays a role in awareness, attention, memory, and language (Herrero et al, 2002;Matsumoto et al, 2001); the cingulate cortex, involved in the regulation of both cognitive and emotional processing with functions in directed attention and motivated behaviour (Amiez et al, 2012;Blair et al, 2012;Bush et al, 2000;Etkin et al, 2011); and the superior temporal gyrus (STG), implicated not only in auditory processes, but also in language processing, social cognition, and emotion perception in faces (Bigler et al, 2007;Domínguez-Borràs et al, 2009;Turk-Browne et al, 2010). Furthermore, research on the treatment of affective disorders has demonstrated that treatment restores the function of these regions (e.g., Arce et al, 2007;Korb et al, 2011).…”