Effects of electroconvulsive therapy on amygdala function in major depression - a longitudinal functional magnetic resonance imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. METHOD: In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. RESULTS: Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. CONCLUSIONS: In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.

[Cognitive deficits in unipolar major depression]. / Kognitive Störungen bei unipolarer Depression.

Cognitive deficits are common symptom presentations in neurology and psychiatry. Cognitive symptoms during major depressive episodes cause subjective distress as well as difficulties during therapy and psychosocial reintegration. Depression-associated cognitive symptoms are characterized by a mood-congruent information processing bias as well as by cognitive performance deficits. A diagnostically relevant profile of neuropsychological impairments specific to depression has not yet been identified. Nevertheless, deficits of executive and declarative memory functions have repeatedly been reported. The time course of cognitive deficits after remission of mood is not entirely clear. Depending on the point of time of the reinvestigation, patients may still exhibit pronounced cognitive deficits. This article presents the current knowledge about cognitive symptoms in major depression, including the pathophysiology and treatment options.

Auditory processing in remitted major depression: a long-term follow-up investigation using 3T-fMRI.

Major depression is accompanied by cortical dysfunction including impaired auditory processing of non-speech stimuli. In a previous study, we could show that potent antidepressant treatment with electroconvulsive therapy (ECT) did not lead to full functional normalization of altered fMRI activation patterns in response to sine tones although depressive symptoms improved and remission was achieved in the majority of patients. In a next step, a longitudinal follow-up investigation was conducted looking on neuronal activation over time along with full remission in a subgroup of patients of the previous study in order to address the question whether changes in neuronal activation patterns reflect a more state- or trait-dependent characteristic. Results showed that although clinically remitted, patients still exhibited an increased activity of the secondary auditory cortex and multimodal recruitment of the left cuneus, an area of the visual system. However, activity of recruited secondary visual network had decreased over time. A positive correlation was observed between the number of hospital admissions during the follow-up period and activity of the secondary visual area of the left cuneus at baseline prior to ECT. Thus, although the persistence of differences in activation patterns after sine tone presentation in this follow-up investigation could argue for a potential trait marker of depression characterized by alterations in auditory processing, attenuation of neuronal activation in some areas over time suggests that changes might in part also be state-dependent.

Anxiolytic effects of transcranial magnetic stimulation--an alternative treatment option in anxiety disorders?

In contrast to major depression, only few studies are available so far on the effects of repetitive transcranial magnetic stimulation (rTMS) in anxiety disorders. In order to summarise available data concerning the putative anxiolytic action of repetitive rTMS, a systematic literature review was carried out. Although interpretation of the results is difficult because of a large variety of used treatment protocols and the lack of a placebo-controlled design in the majority of studies, there is evidence for anxiolytic action of rTMS both from preclinical trials and studies in humans. Based on the idea of interhemispheric imbalance and/or deficits in cortico-limbic control as a model for human anxiety, inhibitory rTMS of the prefrontal cortex has been shown to exert beneficial effects in a number of studies in healthy subjects, patients with PTSD and panic disorder. However, to further elucidate the putative anxiolytic action of rTMS in patients with anxiety disorders future studies have to be conducted addressing in particular the limitations of the studies mentioned above.

Influence of single-dose quetiapine on fear network activity - A pharmaco-imaging study.

OBJECTIVE: Anxiety disorders are among the most frequent psychiatric disorders. Current treatment guidelines recommend antidepressants, the calcium modulator gabapentin, and benzodiazepines as pharmacological treatments. However, delayed onset of action precludes the use of antidepressants as an acute treatment, while benzodiazepines can be recommended only as an emergency treatment due to their inherent risk of dependence. Therefore, an alternative pharmacological agent with acute efficacy is needed. Preliminary evidence points towards possible anxiolytic properties of the atypical antipsychotic quetiapine. The goals of this study were to test the acute anxiolytic properties of quetiapine in patients suffering from arachnophobia in a challenge paradigm, and to assess the effects of quetiapine on the central nervous fear network. METHODS: In a randomized, double-blind, placebo-controlled proof-of-concept study, n=58 arachnophobic patients underwent an fMRI scan while looking at phobia-related and neutral stimuli. Subjective anxiety was evaluated retrospectively in questionnaires. RESULTS: The functional imaging data revealed that patients showed stronger amygdala activation to phobia-related than to neutral stimuli. However, no effect of quetiapine on fear network activity was detected. Further, on questionnaire measures, quetiapine significantly reduced somatic anxiety symptoms, but had no effect on general psychological anxiety. CONCLUSION: Viewing phobic pictures resulted in a robust amygdala activation in arachnophobic patients. Quetiapine seems to have no influence on activation in anxiety-related brain areas but appears to reduce acute somatic anxiety symptoms in patients with specific phobia. The central nervous correlates of the anxiolytic effects of quetiapine remain to be clarified in future studies.