Social Cognition in Schizophrenia and Autism Spectrum Disorders: A Systematic Review and Meta-Analysis of Direct Comparisons

Background: Deficits in social cognition are well-recognized in both schizophrenia and autism spectrum disorders (ASD). However, it is less clear how social cognition deficits differ between both disorders and what distinct mechanisms may underlie such differences. We aimed at reviewing available evidence from studies directly comparing social cognitive performance between individuals with schizophrenia and ASD.Methods: We performed a systematic review of literature up to May 22, 2018 on Pubmed, Web of Science, and Scopus. Search terms included combinations of the keywords “social cognition,” “theory of mind,” “autism,” “Asperger,” “psychosis,” and “schizophrenia.” Two researchers independently selected and extracted data according to PRISMA guidelines. Random-effects meta-analyses were conducted for performance on social cognitive tasks evaluating: (1) emotion perception; (2) theory of mind (ToM); (3) emotional intelligence (managing emotions score of the Mayer-Salovey-Caruso Emotional Intelligence Test); and (4) social skills.Results: We identified 19 eligible studies for meta-analysis including a total of 1,040 patients (558 with schizophrenia and 482 with ASD). Eight studies provided data on facial emotion perception that evidenced a better performance by participants with schizophrenia compared to those with ASD (Hedges' g = 0.43; p = 0.031). No significant differences were found between groups in the Reading the Mind in the Eyes Test (8 studies; Hedges' g = 0.22; p = 0.351), other ToM tasks (9 studies; Hedges' g = −0.03; p = 0.903), emotional intelligence (3 studies; Hedges' g = −0.17; p = 0.490), and social skills (3 studies; Hedges' g = 0.86; p = 0.056). Participants' age was a significant moderator of effect size in emotion perception and RMET analyzes, with larger differences favoring patients with schizophrenia being observed in studies with younger participants.Conclusions: The instruments that are currently available to evaluate social cognition poorly differentiate between individuals with schizophrenia and ASD. Combining behavioral tasks with neurophysiologic assessments may better characterize the differences in social cognition between both disorders

Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD.Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed.Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time.Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD

A Systematic Review and Meta-Analysis

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD. Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed. Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time. Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.publishersversionpublishe

How the interplay between neuroscience and phenomenology changed our understanding of obsessive-compulsive disorder

The understanding of obsessive-compulsive disorder (OCD) has evolved with the knowledge of behavior, the brain, and their relationship. Modern views of OCD as a neuropsychiatric disorder originated from early lesion studies, with more recent models incorporating detailed neuropsychological findings, such as perseveration in set-shifting tasks, and findings of altered brain structure and function, namely of orbitofrontal corticostriatal circuits and their limbic connections. Interestingly, as neurobiological models of OCD evolved from cortical and cognitive to sub-cortical and behavioral, the focus of OCD phenomenology also moved from thought control and contents to new concepts rooted in animal models of action control. Most recently, the proposed analogy between habitual action control and compulsive behavior has led to the hypothesis that individuals suffering from OCD may be predisposed to rely excessively on habitual rather than on goal-directed behavioral strategies. Alternatively, compulsions have been proposed to result either from hyper-valuation of certain actions and/or their outcomes, or from excessive uncertainty in the monitoring of action performance, both leading to perseveration in prepotent actions such as washing or checking. In short, the last decades have witnessed a formidable renovation in the pathophysiology, phenomenology, and even semantics, of OCD. Nevertheless, such progress is challenged by several caveats, not least psychopathological oversimplification and overgeneralization of animal to human extrapolations. Here we present an historical overview of the understanding of OCD, highlighting converging studies and trends in neuroscience, psychiatry and neuropsychology, and how they influenced current perspectives on the nosology and phenomenology of this disorder.publishersversionpublishe

Criterion Validity of the Yale-Brown Obsessive-Compulsive Scale Second Edition for Diagnosis of Obsessive-Compulsive Disorder in Adults

Background: While the Yale-Brown Obsessive-Compulsive Scale Second Edition (Y-BOCS-II) is the gold-standard for measurement of obsessive-compulsive (OC) symptom severity, its factor structure is still a matter of debate and, most importantly, criterion validity for diagnosis of OC disorder (OCD) has not been tested. This study aimed to clarify factor structure and criterion validity of the Y-BOCS-II.Methods: We first validated and quantified the psychometric properties of a culturally adapted Portuguese translation of the Y-BOCS-II (PY-BOCS-II). The PY-BOCS-II and other psychometric instruments, including the OCD subscale of the Structured Clinical Interview for the DSM-IV, used to define OCD diagnosis, were administered to 187 participants (52 patients with OCD, 18 with other mood and anxiety disorders and 117 healthy subjects). In a subsample of 20 OCD patients and the 18 patients with other diagnoses, PY-BOCS-II was applied by clinicians blinded to diagnosis.Results: PY-BOCS-II had excellent internal consistency (Cronbach's α = 0.96) and very good test-retest reliability (Pearson's r = 0.94). Exploratory factor analysis revealed a two-factor structure with loadings consistent with the Obsessions and Compulsions subscales, and there was good to acceptable convergent and divergent validity. Importantly, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve suggested elevated accuracy in discriminating between patients with OCD and control subjects (AUC = 0.96; 95% confidence interval [CI]: 0.92–0.99), that was retained in comparisons with age, gender and education matched controls (AUC = 0.95; 95% CI: 0.91–0.99), as well as with patients with other mood and anxiety disorders (AUC = 0.93; 95% CI: 0.84–1). Additionally, a cut-off score of 13 had optimal discriminatory ability for the diagnosis of OCD, with sensitivity ranging between 85 and 90%, and specificity between 94 and 97%, respectively when all samples or only the clinical samples were considered.Conclusion: The PY-BOCS-II has excellent psychometric properties to assess the severity of obsessive-compulsive symptoms, reflecting obsessive, and compulsive dimensions, compatible with currently defined subscales. Furthermore, we found that a cut-off of 13 for the Y-BOCS-II total score has good to excellent sensitivity and specificity for the diagnosis of OCD

Relato de um caso clínico

Neuroleptic malignant syndrome is a neurological emergency caused by dysregulation of dopaminergic neurotransmission. While it is typically characterized by muscle rigidity, fever and altered mental status, it may have a heterogeneous and non-specific presentation, leading to delays in diagnosis and treatment. Treatment involves cessation of dopamine-receptor antagonists and supportive measures, but in more severe cases, bromocriptine, dantrolene, benzodiazepines and/or electroconvulsive therapy should be considered. We present the case of a 66-year-old man with severe neuroleptic malignant syndrome, diagnosed due to need for continuous invasive ventilation in an Intensive Care Unit, after successful treatment for respiratory sepsis. The patient recovered after electroconvulsive therapy and administration of bromocriptine. This unusually severe case illustrates the need for a high level of suspicion for neuroleptic malignant syndrome in critically ill patients with malignant catatonic syndromes, allowing for an early diagnosis and potentially lifesaving treatment.publishersversionpublishe

Motor cortical inhibitory deficits in patients with obsessive-compulsive disorder–A systematic review and meta-analysis of transcranial magnetic stimulation literature

Funding Information: DR was supported by H2020-SC1-DTH-2019-875358-FAITH. AM and GC are supported by Fundação para a Ciência e Tecnologia (FCT) through Ph.D. Scholarships (respectively, SFRH/BD/144508/2019 and SFRH/BD/130210/2017). GC and AO-M are supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. AO-M was funded by a Starting Grant from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 950357). JB-C and AO-M were supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020–Programa Operacional Regional de Lisboa. JO was supported by BBRF-27595-2018 NARSAD. None of the agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. Publisher Copyright: Copyright © 2022 Rodrigues da Silva, Maia, Cotovio, Oliveira, Oliveira-Maia and Barahona-Corrêa.Introduction: Obsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a non-invasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for in vivo assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures. Methods: We conducted a systematic review and meta-analysis of case-control studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we meta-analyzed motor cortical excitability changes after rTMS treatment. Results: From 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported. Discussion: Our work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABAB receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, in vivo. The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201764], identifier [CRD42020201764].publishersversionpublishe

Hypomania Symptoms Across Psychiatric Disorders: Screening Use of the Hypomania Check-List 32 at Admission to an Outpatient Psychiatry Clinic

Introduction: Hypomania symptoms are best described as a continuum, ranging beyond Bipolar Spectrum Disorders (BSD). Other nosological entities, such as major depressive disorder, schizoaffective disorder, or borderline personality disorder, may also share symptoms with BSD, raising challenges for differential diagnosis. While the Hypomania Checklist-32 is one of the most widely used tools for screening hypomania, there is limited evidence describing its use in a real-world outpatient psychiatric clinical setting.Methods: Here we tested the psychometric properties of a European Portuguese adaptation of the HCL-32, establishing its factor structure, reliability and construct validity. Furthermore, we analyzed differences in hypomanic symptoms among several clinical groups and in a non-clinical sample. Data was obtained retrospectively in an ecological setting from a clinical sample of an outpatient psychiatry and psychology clinic, comprising 463 Portuguese individuals, 326 of whom had a psychiatric diagnosis, namely BSD (n = 66), major depressive disorder (n = 116), or other psychiatric disorders (n = 144). A separate non-clinical sample was also collected among healthy volunteers (n = 62). A battery of self-report measures of affective symptoms was applied, and in a subset of patients, diagnosis was established using a structured diagnostic interview.Results: Psychometric properties of the HCL-32 were adequate, with good internal consistency (Cronbach's α = 0.86) and test-retest stability (ICC = 0.86), and two subscores (“active/elated” and “risk-taking/irritable”) defined by Principal Component Analysis. Receiver Operating Characteristic curve analysis demonstrated that the test score discriminated moderately between patients with BSD and other clinical samples as well as healthy volunteers, with a cut-off score of 17 for the total score of the HCL-32 rendering the best combination of sensitivity and specificity. When compared to the HCL-32 total score, the risk-taking/irritable subscore seems to provide additional benefit in discriminating between different clinical groups, namely regarding specificity in the discrimination from patients with a diagnosis of major depressive disorder that was low for the full scale and the alternate subscale.Conclusions: HCL-32 can be used as a screening tool for BSD among adult patients presenting in an outpatient psychiatric clinical setting

evidence from a systematic review and pooled lesion analysis

Despite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated. Here, we aimed to test whether focal brain lesions in lesional mania are more often right- than left-sided, and if lesions converge on areas relevant to mood regulation. We thus performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflect diagnoses and structures of interest, as well as lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, selecting reports of adult-onset hypomania, mania or mixed state following a focal brain lesion, for pooled-analyses of individual patient data. Eligible lesion images were manually traced onto the corresponding MNI space slices, and lesion topography analyzed using standard brain atlases. Using this approach, data from 211 lesional mania patients was extracted from 114 reports. Among 201 cases with focal lesions, more patients had lesions involving exclusively the right (60.7%) than exclusively the left (11.4%) hemisphere. In further analyses of 56 eligible lesion images, while findings should be considered cautiously given the potential for selection bias of published lesion images, right-sided predominance of lesions was confirmed across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, and several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions. Such pooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.publishersversionpublishe

The contribution of somatic items

Funding Information: JO is supported by the NARSAD 2018 Young Investigator Award from the Brain & Behavior Research Foundation , (Grant ID: 27595 ). RL is supported by the 2018 Scientific Employment Stimulus from Fundação para a Ciência e Tecnologia, Portugal (CEECIND/04157/2018). DF, BS and AJO-M are supported by the BOUNCE project (grant agreement number 777167 ), and RL and AJO-M are supported by the FAITH project (grant agreement number 875358 ), both funded by the European Union's Horizon 2020 research and innovation programme. JBB-C and AJO-M are supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. AJO-M is supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2022 The AuthorsBackground/Objective: Screening for depression in patients with cancer can be difficult due to overlap between symptoms of depression and cancer. We assessed validity of the Beck Depression Inventory (BDI-II) in this population. Method: Data was obtained in an outpatient neuropsychiatry unit treating patients with and without cancer. Psychometric properties of the BDI-II Portuguese version were assessed separately in 202 patients with cancer, and 376 outpatients with mental health complaints but without cancer. Results: Confirmatory factor analysis suggested a three-factor structure model (cognitive, affective and somatic) provided best fit to data in both samples. Criterion validity was good for detecting depression in oncological patients, with an area under the ROC curve (AUC) of 0.85 (95% confidence interval [CI], 0.76–0.91). A cut-off score of 14 had sensitivity of 87% and specificity of 73%. Excluding somatic items did not significantly change the ROC curve for BDI-II (difference AUCs = 0.002, p=0.9). A good criterion validity for BDI-II was also obtained in the non-oncological population (AUC = 0.87; 95% CI 0.81–0.91), with a cut-off of 18 (sensitivity=84%; specificity=73%). Conclusions: The BDI-II demonstrated good psychometric properties in patients with cancer, comparable to a population without cancer. Exclusion of somatic items did not affect screening accuracy.publishersversionpublishe