This research aims to elucidate mechanisms through which change occurs during cognitive behavior therapy (CBT) for depression. Assessing meta-cognitive processes of self-knowledge (top-down), electrophysiological and behavioral correlates of emotion processing (bottom-up), and their relation to treatment outcome will provide new insights into the mechanisms of emotion regulation deficits in depression. It will also contribute toward the clinical goal of identifying patients who may benefit most from CBT for unipolar depression.
This R21 application aims to clarify the neurobiological mechanisms by which change occurs during cognitive behavior therapy (CBT) for major depressive disorder (MDD). This hypothesis-driven study will explore the association between the psychological constructs of psychological mindedness (PM) and mindfulness (M) during the time course of CBT for MDD, and its relationship to electrophysiological and behavioral measures of automatic (i.e. stimulus-driven or bottom-up) emotion processing. This objective is motivated by the following rationale: PM and M represent different meta-cognitive processes of self-knowledge deemed critical for emotion regulation (ER) and CBT success. Event-related potentials (ERPs) to salient affective pictures reflect different stages of motivated attention. Using advanced analytic EEG techniques, we have linked these stages to the hierarchical activation of 'emotional' brain regions along the occipitotemporal ventral stream, ranging from preconscious stimulus categorization (right secondary visual cortex, right temporoparietal junction) to conscious appraisal (posterior cingulate cortex, ventromedial cortex). Importantly, blunted ERP responses to emotionally-arousing stimuli have been observed in clinical depression, and hypoactivation of right temporoparietal and dorsolateral prefrontal regions normalize after successful antidepressant or electroconvulsive treatment. A dichotic emotion recognition test, which provides an auditory measure of bottom-up emotion processing in form of a left ear (right hemisphere) advantage for recognizing the emotional intonation of speech patterns, has revealed behavioral deficits in MDD patients. Moreover, an increased right ear advantage for verbal stimuli (left hemisphere) is seen in CBT responders. Employing a sample of 60 MDD patients randomly assigned to CBT or nonspecific supportive therapy (placebo), we will obtain psychological, electrophysiological, behavioral and clinical outcome measures of response to 12 weeks of CBT in a pre-post treatment design to determine: (1) when and where in the brain automatic emotion processing is altered by CBT; (2) if changes in emotional responding are moderated or mediated by meta-cognitive processes of self-knowledge; and, (3) if these measures, alone or in combination, have promise as markers of CBT treatment response. Existing ERP and behavioral data for healthy adults (HC) obtained using the same experimental protocols will provide normative (yardstick) data. This study brings together experienced clinical psychologists and psychiatrists doing treatment and research in depression with investigators having expertise in affective neuroscience and electrophysiological studies in MDD. It will provide a critical new step for outlining the affective-cognitive and neurophysiological mechanisms of ER by which change through CBT occurs. Apart from their theoretical relevance, the findings of this project will also aid in developing novel and more targeted interventions and in identifying patients who may benefit most from CBT for unipolar depression.
Following established procedures at the DES at NYSPI, 12 sessions of individual manual-driven CBT (Emery, 2000) will be conducted by highly trained master degree clinicians.
As a non-CBT intervention that includes warmth, genuineness and empathy (Linde et al., 2011), nonspecific supportive therapy (PBO) will be administered in a parallel format to CBT, also consisting of 12 individual sessions.
New York State Psychiatric Institute
New York, New York, United States
HRSD slope
17-item Hamilton Rating Scale for Depression (HRSD); standard clinical instrument (Hamilton, 1960) to assess symptom severity in major depressive disorder (MDD); interpretation: \< 7 = absence or remission of depression; 7-17 = mild depression; 18-24 = moderate depression; \> 25 = severe depression; HRSD rate of symptom change over time (slope); to obtain a continuous measure of treatment outcome, we will employ a mixed-effects model for all HRSD ratings to compute estimates of each patient's rate of symptom change over time (slope of HRSD scores; Petkova et al 2017)
Time frame: 12 weeks or up to 12 weeks
BDI slope
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression; interpretation: \< 14 = minimal range; 14-19 = mild depression; 20-28 = moderate depression; 29-63 = severe depression; BDI-II rate of symptom change over time (slope); To obtain a continuous measure of treatment outcome, we will employ a mixed-effects model for all BDI ratings to compute estimates of each patient's rate of symptom change over time (slope of BDI scores; Petkova et al 2017)
Time frame: 12 weeks or up to 12 weeks
N2 sink (pre)
N2 sink (ERP, Emotional Hemifield Task); early (212 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting asymmetrical neuronal sources involving striate and prestriate cortex in the occipital lobe, with a maximum activation in the right middle temporal gyrus
Time frame: pre-treatment, at baseline
N2 sink (post)
N2 sink (ERP, Emotional Hemifield Task); early (212 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting asymmetrical neuronal sources involving striate and prestriate cortex in the occipital lobe, with a maximum activation in the right middle temporal gyrus
Time frame: post-treatment, after about 12 weeks
P3 source (pre)
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Study Type
OBSERVATIONAL
Enrollment
41
P3 source (ERP, Emotional Hemifield Task); mid-latency (385 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting neuronal sources involving medial parietal lobe, with a maximum activation in the posterior cingulate cortex
Time frame: pre-treatment, at baseline
P3 source (post)
P3 source (ERP, Emotional Hemifield Task); mid-latency (385 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting neuronal sources involving medial parietal lobe, with a maximum activation in the posterior cingulate cortex
Time frame: post-treatment, after about 12 weeks
CP source (pre)
CP source (ERP, Emotional Hemifield Task); late (630 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting bilateral generator sources within the temporal lobe, with a maximum activations in uncus and the inferior temporal area
Time frame: pre-treatment, at baseline
CP source (post)
CP source (ERP, Emotional Hemifield Task); late (630 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting bilateral generator sources within the temporal lobe, with a maximum activations in uncus and the inferior temporal area
Time frame: post-treatment, after about 12 weeks
LEA ERT (pre)
LEA ERT (dichotic listing behavior, Emotional Recognition Task); measures extent of right hemisphere dominance or left ear advantage (LEA) for recognizing prosody during a dichotic emotional recognition task (Bruder et al 2016)
Time frame: pre-treatment, at baseline
LEA ERT (post)
LEA ERT (dichotic listing behavior, Emotional Recognition Task); measures extent of right hemisphere dominance or left ear advantage (LEA) for recognizing prosody during a dichotic emotional recognition task (Bruder et al 2016)
Time frame: post-treatment, after about 12 weeks
REA Fused Words (pre)
REA Fused Words (dichotic listing behavior); measures extent of left hemisphere dominance or right ear advantage (REA) for verbal processing (Bruder et al 1997, 2017)
Time frame: pre-treatment, at baseline
REA Fused Words (post)
REA Fused Words (dichotic listing behavior); measures extent of left hemisphere dominance or right ear advantage (REA) for verbal processing (Bruder et al 1997, 2017)
Time frame: post-treatment, after about 12 weeks