Objectives:
This study had 2 objectives: First, to explore the gender-related differences in emotional processing (EP) and theory of mind—both cognitive (CToM) and affective (AToM)—in patients with ...schizophrenia and in a control group of healthy subjects; and, second, to examine, from a gender perspective, the possible association between EP and CToM in the AToM performance.
Methods:
Forty patients with schizophrenia/schizoaffective disorder were recruited and matched by gender, age and years of education with 40 healthy subjects. EP was measured by the pictures of facial affect (POFA) test. CToM was measured using first- and second-order false-belief (FB) stories. AToM was measured by the reading the mind in the eyes test (RMET). Group and gender differences in CToM were analysed using the X2
test, whereas EP and AToM were analysed using the non-parametric Mann–Whitney U Test and a general linear model. Results were adjusted by intelligence quotient and negative symptomatology.
Results:
Patients with schizophrenia underperformed against healthy subjects in the POFA test, second-order FB, and RMET, but not in first-order FB. No significant gender differences were found. However, there was a trend showing that females outperformed males in the POFA (P = 0.056). Group (P < 0.001), POFA (P < 0.001) and second-order FB (P = 0.022) were the best factors predicting RMET performance (adjusted R2
= 0.584).
Conclusions:
Our results suggest that the illness is the main factor related to the deficit in social cognition, except for the basic aspects of the CToM that were unimpaired in most patients. Nevertheless, the influence of female gender in EP should not be neglected in any group. Finally, the hierarchal interaction between these domains is discussed.
Background
The aims of the present multicenter pilot study were to examine the feasibility and usability of two different smartphone-based monitoring systems (the Pulso system and the ...Trilogis-Monsenso system) from two IT companies in patients with bipolar disorder, developed and selected to be testes as a part of a European Union funded Pre-Commercial Procurement (the NYMPHA-MD project).
Methods
Patients with bipolar disorder (ICD-10), > 18 years of age during a remitted, partial remitted or mild to moderate depressive state (HDRS-17 < 25) from Italy, Spain and Denmark were included. Patients were randomized 1:1 to the use of one of two smartphone-based monitoring systems. The randomization was stratified according to study location (Italy, Spain, Denmark) and all patients were followed for a 4 weeks study period. Usability and feasibility were evaluated using the Computer System Usability Questionnaire, and the Usefulness, Satisfaction, and Ease of use Questionnaire.
Results
A total of 60 patients aged 18–69 years with bipolar disorder (ICD-10) recruited from Italy, Spain, Denmark were included—59 patients completed the study. In Denmark, the patients evaluated the Trilogis-Monsenso system with a statistically significant higher usability compared with the Pulso system. In Italy and Spain, the patients evaluated no statistically significant difference between the two systems in any of the categories, except for the usefulness category favoring the Trilogis-Monsenso system (z = 2.68, p < 0.01).
Conclusions
Both monitoring systems showed acceptable usability and feasibility. There were differences in patient-based evaluations of the two monitoring systems related to the country of the study. Studies investigating the usability and feasibility during longer follow-up periods could perhaps reveal different findings. Future randomized controlled trials investigating the possible positive and negative effects of smartphone-based monitoring systems are needed.
•Reports a set of meta-analyses of human fMRI fear extinction studies involving over 1300 participants.•Human fear extinction learning and extinction recall are consistently distinct in their neural ...correlates.•The contribution of prefrontal cortical subregions to extinction appears to be more nuanced than what is currently suggested.
The study of fear extinction represents an important example of translational neuroscience in psychiatry and promises to improve the understanding and treatment of anxiety and fear-related disorders. We present the results of a set of meta-analyses of human fear extinction studies in healthy participants, conducted with functional magnetic resonance imaging (fMRI) and reporting whole-brain results. Meta-analyses of fear extinction learning primarily implicate consistent activation of brain regions linked to threat appraisal and experience, including the dorsal anterior cingulate and anterior insular cortices. An overlapping anatomical result was obtained from the meta-analysis of extinction recall studies, except when studies directly compared an extinguished threat stimulus to an unextinguished threat stimulus (instead of a safety stimulus). In this latter instance, more consistent activation was observed in dorsolateral and ventromedial prefrontal cortex regions, together with other areas including the hippocampus. While our results partially support the notion of a shared neuroanatomy between human and rodent models of extinction processes, they also encourage an expanded account of the neural basis of human fear extinction.
Electroconvulsive therapy (ECT) is considered the most effective treatment for major depressive disorder (MDD). In recent years, the pursuit of the neurobiological mechanisms of ECT action has ...generated a significant amount of functional magnetic resonance imaging (fMRI) research.
In this systematic review, we integrated all fMRI research in patients with MDD receiving ECT and, importantly, evaluated the level of convergence and replicability across multiple fMRI metrics.
While according to most studies changes in patients with MDD after ECT appear to be widely distributed across the brain, our multimetric review revealed specific changes involving functional connectivity increases in the superior and middle frontal gyri as the most replicated and across-modality convergent findings. Although this modulation of prefrontal connectivity was associated to ECT outcome, we also identified fMRI measurements of the subgenual anterior cingulate cortex as the fMRI signals most significantly linked to clinical response.
We identified specific prefrontal and cingulate territories which activity and connectivity with other brain regions is modulated by ECT, critically accounting for its mechanism of action.
•Multimetric reviews are the optimal approach for detecting neurofunctional findings.•Electroconvulsive therapy consistently modulates prefrontal functional connectivity.•Cingulate function is the best electroconvulsive therapy response biomarker.
Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs ...represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap.
To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals.
This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage.
Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs.
The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 79.9%; Swedish cohort: 5839 of 7458 78.3%). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 95% CI, 1.04-1.24; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 95% CI, 1.28-1.92). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries.
RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs.
Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are effective neuromodulation therapies for treatment-resistant depression (TRD). While ECT is generally ...considered the most effective antidepressant, rTMS is less invasive, better tolerated and leads to more durable therapeutic benefits. Both interventions are established device antidepressants, but it remains unknown if they share a common mechanism of action. Here we aimed to compare the brain volumetric changes in patients with TRD after right unilateral (RUL) ECT versus left dorsolateral prefrontal cortex (lDLPFC) rTMS.
We assessed 32 patients with TRD before the first treatment session and after treatment completion using structural magnetic resonance imaging. Fifteen patients were treated with RUL ECT and seventeen patients received lDLPFC rTMS.
Patients receiving RUL ECT, in comparison with patients treated with lDLPFC rTMS, showed a greater volumetric increase in the right striatum, pallidum, medial temporal lobe, anterior insular cortex, anterior midbrain, and subgenual anterior cingulate cortex. However, ECT- or rTMS-induced brain volumetric changes were not associated with the clinical improvement.
We evaluated a modest sample size with concurrent pharmacological treatment and without neuromodulation therapies randomization.
Our findings suggest that despite comparable clinical outcomes, only RUL ECT is associated with structural change, while rTMS is not. We hypothesize that structural neuroplasticity and/or neuroinflammation may explain the larger structural changes observed after ECT, whereas neurophysiological plasticity may underlie the rTMS effects. More broadly, our results support the notion that there are multiple therapeutic strategies to move patients from depression to euthymia.
•RUL 0.3-0.5 ms pulse width ECT and 10 Hz lDLPFC rTMS may have comparable clinical antidepressant efficacy.•ECT and rTMS induce different patterns of structural change: rTMS did not induce significant changes, while RUL ECT did.•Temporal, subcortical and cingulate volume increases are greater after ECT than rTMS.•Generally, results suggest there are multiple circuit-level antidepressant strategies.
Posttraumatic stress disorder (PTSD) is a highly disabling psychiatric condition that may arise after exposure to acute and severe trauma. It is a highly prevalent mental disorder worldwide, and the ...current treatment options for these patients remain limited due to low effectiveness. The time window right after traumatic events provides clinicians with a unique opportunity for preventive interventions against potential deleterious alterations in brain function that lead to PTSD. Some studies pointed out that PTSD patients present an abnormal function of the hypothalamic-pituitary-adrenal axis that may contribute to a vulnerability toward PTSD. Moreover, glucocorticoids have arisen as a promising option for preventing the disorder's development when administered in the aftermath of trauma. The present work compiles the recent findings of glucocorticoid administration for the prevention of a PTSD phenotype, from human studies to animal models of PTSD. Overall, glucocorticoid-based therapies for preventing PTSD demonstrated moderate evidence in terms of efficacy in both clinical and preclinical studies. Although clinical studies point out that glucocorticoids may not be effective for all patients' subpopulations, those with adequate traits might greatly benefit from them. Preclinical studies provide precise insight into the mechanisms mediating this preventive effect, showing glucocorticoid-based prevention to reduce long-lasting behavioral and neurobiological abnormalities caused by traumatic stress. However, further research is needed to delineate the precise mechanisms and the extent to which these interventions can translate into lower PTSD rates and morbidity.
This article is part of the Special Issue on 'Fear, Anxiety and PTSD'.
•PTSD may be prevented by interventions implemented immediately after a trauma.•Vulnerable individuals may benefit from glucocorticoid-based prevention of PTSD.•Glucocorticoids prevent behavioral and biological effects induced in animal models.•Larger studies are necessary for glucocorticoid prevention of PTSD.
Background
BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, ...with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities.
Methods
The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology.
Discussion
BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases.
Trial registration
: ISRCTN68010602 at
https://www.isrctn.com/ISRCTN68010602
. Registration date: 18/04/2023.
PDF
