Neurocognitive Predictors of Response in Treatment Resistant Depression to Subcallosal Cingulate Gyrus Deep Brain Stimulation.

Background: Deep brain stimulation (DBS) is a neurosurgical intervention with demonstrated effectiveness for treatment resistant depression (TRD), but longitudinal studies on the stability of cognitive parameters following treatment are limited. The objectives of this study are to (i) identify baseline cognitive predictors of treatment response to subcallosal cingulate gyrus (SCG) DBS for unipolar TRD and (ii) compare neurocognitive performance prior to and 12 months after DBS implantation. Methods: Twenty unipolar TRD patients received SCG DBS for 12 months. A standardized neuropsychological battery was used to assess a range of neurocognitive abilities at baseline and after 12 months. Severity of depression was evaluated using the 17 item Hamilton Rating Scale for Depression. Results: Finger Tap-Dominant Hand Test and total number of errors made on the Wisconsin Card Sorting Test predicted classification of patients as treatment responders or non-responders, and were independent of improvement in mood. Change in verbal fluency was the only neuropsychological test that correlated with change in mood from baseline to the follow up period. None of the neuropsychological measures displayed deterioration in cognitive functioning from baseline to repeat testing at 12 months. Limitations: This was an open label study with a small sample size which limits predictive analysis. Practice effects of the neuropsychological testing could explain the improvement from baseline to follow up on some tasks. Replication using a larger sample of subjects who received neuropsychological testing before and at least 12 months after DBS surgery is required. Conclusion: These preliminary results (i) suggest that psychomotor speed may be a useful baseline predictor of response to SCG DBS treatment and (ii) support previous suggestions that SCG DBS has no deleterious effects on cognition.

Development and validation of the Dimensional Anhedonia Rating Scale (DARS) in a community sample and individuals with major depression.

Anhedonia, a core symptom of Major Depressive Disorder (MDD), is predictive of antidepressant non-response. In contrast to the definition of anhedonia as a "loss of pleasure", neuropsychological studies provide evidence for multiple facets of hedonic function. The aim of the current study was to develop and validate the Dimensional Anhedonia Rating Scale (DARS), a dynamic scale that measures desire, motivation, effort and consummatory pleasure across hedonic domains. Following item selection procedures and reliability testing using data from community participants (N=229) (Study 1), the 17-item scale was validated in an online study with community participants (N=150) (Study 2). The DARS was also validated in unipolar or bipolar depressed patients (n=52) and controls (n=50) (Study 3). Principal components analysis of the 17-item DARS revealed a 4-component structure mapping onto the domains of anhedonia: hobbies, food/drink, social activities, and sensory experience. Reliability of the DARS subscales was high across studies (Cronbach's α=0.75-0.92). The DARS also demonstrated good convergent and divergent validity. Hierarchical regression analysis revealed the DARS showed additional utility over the Snaith-Hamilton Pleasure Scale (SHAPS) in predicting reward function and distinguishing MDD subgroups. These studies provide support for the reliability and validity of the DARS.

Depression and employment status in primary and tertiary care settings.

OBJECTIVE: Major depressive disorder (MDD) is a leading cause of disability. Impairment in work function considerably adds to symptom burden and increases the economic impact of this disorder. Our study aimed to investigate the factors associated with work status in MDD within primary and tertiary care. METHOD: We used data from 2 large databases for our analysis--Study 1: the InSight database, a chart review of MDD patients treated by primary care physicians across Canada (n=986); and Study 2: the International Mood Disorders Collaborative Project, a cross-sectional study of mood disorder patients (Canadian data only: n=274). RESULTS: Both studies demonstrated high rates of unemployment and disability (30.3% to 42.1%). Quebec showed the highest rate of unemployment (21%) and British Columbia had the greatest percentage of patients on disability (15%). Employed and unemployed groups were similar based on clinical characteristics; however, unemployed people may have higher age, prevalence of medical comorbidity, and greater likelihood of receiving a benzodiazepine. Increased disability rates were associated with history of childhood abuse, duration of current major depressive episode, comorbidity, benzodiazepine use, as well as greater depression and anxiety severity. The unemployed-disability groups had greater somatic symptoms and anhedonia. In keeping with this, anhedonia was the strongest predictor of disability. Absenteeism was also high across both studies. CONCLUSIONS: Unemployment and disability rates in MDD are high. The presence of anhedonia and medical comorbidity significantly influenced work status, emphasizing the need for treatment strategies to alleviate the additional symptom burden in this subpopulation.

The effect of bupropion XL and escitalopram on memory and functional outcomes in adults with major depressive disorder: results from a randomized controlled trial.

Decrements in cognitive function are a common feature of Major Depressive Disorder (MDD), and whether distinct classes of antidepressants differentially affect memory in these individuals has not been sufficiently evaluated. In this study we sought to determine the effect of escitalopram and bupropion XL on memory and psychosocial function. Forty-one individuals (18-50 years) with MDD were enrolled in an 8-week, double-blind, double-dummy, randomized controlled comparative trial of bupropion XL and escitalopram. Thirty-six participants completed pre and post memory assessments. Verbal, non-verbal and working memory were evaluated with a comprehensive neuropsychological battery. Psychosocial function was assessed with the Sheehan Disability Scale and Endicott Work Productivity Scale. Escitalopram and bupropion XL significantly improved immediate as well as delayed verbal and nonverbal memory, global function (all p≤0.001), and work productivity (p=0.045), with no significant between-group differences. Improvement in immediate verbal memory exerted a direct influence on improvement in global function (p=0.006). Treatment with either escitalopram or bupropion XL was associated with improvement in memory and psychosocial function in adults with MDD.