Right ventrolateral and left dorsolateral 10 Hz transcranial magnetic stimulation as an add-on treatment for bipolar I and II depression: a double-blind, randomised, three-arm, sham-controlled study.

OBJECTIVES: Despite the clinical importance of bipolar depression (BDE), effective treatment options are still limited. Transcranial magnetic stimulation (rTMS) has proven of moderate efficacy in major depression, but the evidence remains inconclusive for BDE. METHODS: A 4-week, double-blind, randomised, parallel-group, sham-controlled study (trial ID ISRCTN77188420) explored the benefits of 10 Hz MRI-guided right ventrolateral (RVL) rTMS and left dorsolateral (LDL) rTMS as add-on treatments for BDE. Outcome measures included changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) score, self-assessment, response and remission rates, and side effects. RESULTS: Sixty patients were randomly assigned to study groups, and forty-six completed the double-blind phase. The mean change from baseline to Week 4 in MADRS was greater in both active groups compared to the sham, yet differences did not achieve significance (RVL vs sham: -4.50, 95%CI -10.63 to 1.64, p = 0.3; LDL vs sham: -4.07, 95%CI -10.24 to 2.10, p = 0.4). None of the other outcome measures yielded significant results. CONCLUSIONS: While not demonstrating the superiority of either 10 Hz rTMS over sham, with the limited sample size, we can not rule out a moderate yet clinically meaningful effect. Further well-powered studies are essential to elucidate the role of rTMS in managing BDE.

Cognitive profiles of healthy siblings of first-episode schizophrenia patients.

AIM: Cognitive deficit in psychotic illness is intensively studied, different cognitive subtypes have been suggested. In recent years, there has been an increase in the number of studies in patients with schizophrenia and their relatives searching for endophenotypes of the disease. The aim of our study was to investigate cognitive performance and cognitive subtypes in the siblings of the patients. METHODS: Four groups of subjects were included: patients with a first episode of psychotic illness, the siblings of these patients, and two control groups. All the study subjects (N = 84) had a battery of neuropsychological tests that measured basic cognitive domains - memory, executive functions, attention, visual-spatial skills, language skills and psychomotor speed - administered to them. The data were assessed with pairwise t-tests for group comparisons. The siblings were distributed into three groups according to their cognitive performance: non-deficit, partial deficit, and global deficit. Subsequently, the patients were assigned into three groups corresponding to their siblings' performance. RESULTS: Our results revealed attenuation of abstract thinking in the siblings compared to the controls. As expected, the patients showed impairment across all cognitive domains. The patients and siblings demonstrated similar profiles in each subtype, in the severity of their impairment, and in their patterns of cognitive performance. CONCLUSIONS: Our results suggest that the cognitive profile can be considered as an endophenotype of psychotic disorders.

Higher Body-Mass Index and Lower Gray Matter Volumes in First Episode of Psychosis.

BACKGROUND: Neurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP. METHOD: We analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses. RESULTS: In primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations. CONCLUSIONS: This study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our findings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP.