Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27). RESULTS: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function. CONCLUSION: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.

Antibodies to CRMP3-4 associated with limbic encephalitis and thymoma.

We present a case with subacute limbic encephalitis (LE) and thymoma. Neither classical onconeural antibodies nor antibodies to voltage gated potassium channels (VGKC) were detected, but the serum was positive for anti-glutamic acid decarboxylase (GAD). The patient serum also stained synaptic boutons of pyramidal cells and nuclei of granule cells of rat hippocampus. The objective of the study was to identify new antibodies associated with LE. Screening a cDNA expression library identified collapsin response mediator protein 3 (CRMP3), a protein involved in neurite outgrowth. The serum also reacted with both CRMP3 and CRMP4 by Western blot. Similar binding pattern of hippocampal granule cells was obtained with the patient serum and rabbit anti-serum against CRMP1-4. The CRMP1-4 antibodies stained neuronal nuclei of a biopsy from the patient's temporal lobe, but CRMP1-4 expression in thymoma could only be detected by immunoblotting. Absorption studies with recombinant GAD failed to abolish the staining of the hippocampal granule cells. Our findings illustrate that CRMP3-4 antibodies can be associated with LE and thymoma. This has previously been associated with CRMP5.

Sec6 is localized to the plasma membrane of mature synaptic terminals and is transported with secretogranin II-containing vesicles.

The sec6/8 (exocyst) complex is implicated in targeting of vesicles for regulated exocytosis in various cell types and is believed to play a role in synaptogenesis and brain development. We show that the subunits sec6 and sec8 are present at significant levels in neurons of adult rat brain, and that immunoreactivity for the two subunits has a differential subcellular distribution. We show that in developing as well as mature neurons sec6 is concentrated at the inside of the presynaptic plasma membrane, while sec8 immunoreactivity shows a diffuse cytoplasmic distribution. Among established, strongly synaptophysin-positive neuronal boutons, sec6 displays highly differential concentrations, indicating a role for the complex independent of the ongoing synaptic-vesicle release activity. Sec6 is transported along neurites on secretogranin II-positive vesicles, while sec6-negative/secretogranin II-positive vesicles stay in the cell body. In PC12 cells, sec6-positive vesicles accumulate at the plasma membrane at sites of cell-cell contact. Neuronal induction of the PC12 cells with nerve growth factor shows that sec8 is not freely soluble, but may probably interact with cytoskeletal elements. The complex may facilitate the targeting of membrane material to presynaptic sites and may possibly shuttle vesicles from the cytoskeletal transport machinery to presynaptic membrane sites. Thus, we suggest that the exocyst complex serves to modulate exocytotic activity, by targeting membrane material to its presynaptic destination.