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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.

Recent neurobiological models of obsessive-compulsive disorder (OCD) have highlighted the potential role of abnormalities in fear learning processes. We compared brain activation -as assessed with whole-brain functional magnetic resonance imaging- during fear conditioning, fear extinction learning, and fear extinction recall in patients with OCD (n = 18) and healthy controls (n = 18). We also investigated whether brain activation during any of these processes was associated with exposure-based cognitive-behavioral therapy (CBT) outcome in patients. Patients with OCD showed significantly lower brain activation in the right insulo-opercular region and the dorsal anterior cingulate cortex during fear conditioning in comparison to healthy controls. Moreover, brain activation in the right insula predicted CBT outcome, with lower activation predicting a better outcome. Brain activation during extinction learning or recall did not differ between patients and controls or predicted CBT outcome in patients. Our results suggest that neural activations during fear conditioning in patients with OCD are abnormal and predict CBT outcome.

BACKGROUND: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. METHODS: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. RESULTS: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). CONCLUSION: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.

Background: Neural correlates of psychotic disorders encompass multiple brain regions in multiple brain circuits, even at early stages. Previous research has characterized structural brain alterations in ¿rst-episode psychosis (FEP), but few studies have focused on the relationship between brain alterations and disease trajectories. First psychotic episodes typically evolve into a chronic course, affecting quality of life of patients and their families, with huge societal costs. Importantly, up to 80% of the patients relapse in the next five years after a first psychotic episode, with a significant risk of developing treatment resistance. Here, we investigated whether disease course may be predicted from brain structural assessments. Specifically, we measured structural covariance, a well-established approach to identify abnormal patterns of volumetric correlation across distant brain regions, which allows to incorporate network-level information to structural assessments. We performed a whole-brain structural covariance assessment of three bilateral regions form to three different cortical networks - dorsolateral prefrontal cortex (dlPFC) for the executive network, posterior cingulate cortex for the default mode network and insulae for the salience network - and subcortical structures (hippocampi, amygdalae and dorsomedial nucleus of the thalamus) that have shown to play a key role in schizophrenia. Methods: We assessed a sample of 74 subjects from a multicenter, naturalistic, prospective and longitudinal study designed to evaluate clinical, neuropsychological, neuroimaging, biochemical, environmental and pharmacogenetic variables in first episode psychotic patients (PEPs project). Magnetic resonance imaging (MRI) scans were acquired at baseline and at 2-year follow-up, as well as clinical assessments. Psychotic symptoms were assessed using the Positive and Negative Symptom Scale (PANSS) due its widespread use in clinical studies and its reliability in assessing psychopathology across a range of patient populations. The sample was split in two groups as a function of the clinical improvement at 2-year follow-up: responders (i.e. 40% reduction in PANSS global score from baseline; n=29) and non-responders (n=45). Results: Responder patients showed increase structural covariance between the left dlPFC and the left middle frontal gyrus, and between the right dlPFC and the right middle and superior gyrus, the left rectus and inferior frontal gyrus, the right hippocampus, and the vermis of the cerebellum. In addition, they showed increased structural covariance between the left anterior hippocampus and the ipsilateral middle occipital gyrus and the contralateral postcentral gyrus. Likewise, the structural covariance of right anterior hippocampus with right superior occipital gyrus and precentral gyrus was also increased in responder patients. Discussion: This study shows, for the first time in the literature, that increased structural covariance at baseline within the executive network and between the hippocampi and posterior brain regions was associated with a superior treatment response at two-year follow-up. These results indicate that the integrity of structural networks should be taken into account to predict treatment outcome in FEP patients.

Obsessive-compulsive disorder (OCD) has been associated with a wide range of biological and neurocognitive findings, which could assist in the search for biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses to assess and grade the strength of the evidence of the association between OCD and several potential diagnostic biomarkers while controlling for several potential biases. Twenty-four systematic reviews and meta-analyses were included, comprising 352 individual studies, more than 10,000 individuals with OCD, and covering 73 potential biomarkers. OCD was significantly associated with several neurocognitive biomarkers, with varying degrees of evidence, ranging from weak to convincing. A number of biochemical, neurophysiological, and neuroimaging biomarkers also showed statistically significant, albeit weak, associations with OCD. Analyses in unmedicated samples (123 studies) weakened the strength of the evidence for most biomarkers or rendered them non-significant. None of the biomarkers seem to have sufficient sensitivity and specificity to become a diagnostic biomarker. A more promising avenue for future biomarker research in OCD might be the prediction of clinical outcomes rather than diagnosis.