ABSTRACT
OBJECTIVES: Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) has antidepressant effects in patients suffering from treatment-resistant depression (TRD). However, limited information exists regarding the impact of NAcc-DBS on cognitive functioning. The aim of this study was to examine whether NAcc-DBS in patients with TRD has any cognitive effects. METHODS: A comprehensive neuropsychological battery was administered to 10 patients with TRD before onset of bilateral NAcc-DBS and after 1 year of DBS stimulation. Neuropsychological testing covered the domains of attention, learning and memory, executive functions, visual perception, and language. Performance was analyzed at baseline and after 1 year of continuous DBS. RESULTS: No evidence was found for cognitive decline following NAcc-DBS comparing test results after 1 year of NAcc-DBS with baseline. However, significantly improved cognitive performance on tests of attention, learning and memory, executive functions and visual perception was found. In addition, there was a general trend towards cognitive enhancement from below average to average performance. These procognitive effects were independent of the antidepressant effects of NAcc-DBS or changes in NAcc-DBS parameters. CONCLUSIONS: These results not only support cognitive safety of NAcc-DBS but also stress its beneficial role in augmenting cognitive performance in patients with TRD.
Subject(s)
Cognition/physiology , Deep Brain Stimulation/psychology , Depressive Disorder, Major/therapy , Depressive Disorder, Treatment-Resistant/therapy , Nucleus Accumbens/physiology , Adult , Aged , Deep Brain Stimulation/adverse effects , Deep Brain Stimulation/methods , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Time Factors , Treatment OutcomeABSTRACT
Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy. Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist. Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials.
Subject(s)
Depression/therapy , Electroconvulsive Therapy/methods , Magnetics/methods , Seizures/therapy , Adult , Aged , Analysis of Variance , Biophysics , Cognition Disorders/etiology , Depression/complications , Female , Humans , Male , Memory , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Retrospective Studies , Seizures/etiology , Treatment Outcome , Verbal LearningABSTRACT
BACKGROUND: While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising. METHODS: Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (+/-SD) length of the current episode was 10.8 (+/-7.5) years; the number of past treatment courses was 20.8 (+/-8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (+/-5.3). RESULTS: Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [+/-2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala. CONCLUSIONS: We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.
