Publications by authors named "Joaquim Radua"

188 Publications

Functional brain network dysfunctions in subjects at high-risk for psychosis: A meta-analysis of resting-state functional connectivity.

Neurosci Biobehav Rev 2021 Jun 10;128:90-101. Epub 2021 Jun 10.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Although emerging evidence suggests that altered functional connectivity (FC) of large-scale neural networks is associated with disturbances in individuals at high-risk for psychosis, the findings are still far to be conclusive. We conducted a meta-analysis of seed-based resting-state functional magnetic resonance imaging studies that compared individuals at clinical high-risk for psychosis (CHR), first-degree relatives of patients with schizophrenia, or subjects who reported psychotic-like experiences with healthy controls. Twenty-nine studies met the inclusion criteria. The MetaNSUE method was used to analyze connectivity comparisons and symptom correlations. Our results showed a significant hypo-connectivity within the salience network (p = 0.012, uncorrected) in the sample of CHR individuals (n = 810). Additionally, we found a positive correlation between negative symptom severity and FC between the default mode network and both the salience network (p < 0.001, r = 0.298) and the central executive network (p = 0.003, r = 0.23) in the CHR group. This meta-analysis lends support for the hypothesis that large-scale network dysfunctions represent a core neural deficit underlying psychosis development.
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http://dx.doi.org/10.1016/j.neubiorev.2021.06.020DOI Listing
June 2021

Route map for machine learning in psychiatry: Absence of bias, reproducibility, and utility.

Eur Neuropsychopharmacol 2021 Jun 8;50:115-117. Epub 2021 Jun 8.

IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.

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http://dx.doi.org/10.1016/j.euroneuro.2021.05.006DOI Listing
June 2021

Biased accuracy in multisite machine-learning studies due to incomplete removal of the effects of the site.

Psychiatry Res Neuroimaging 2021 May 29;314:111313. Epub 2021 May 29.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom; Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Brain MRI researchers conducting multisite studies, such as within the ENIGMA Consortium, are very aware of the importance of controlling the effects of the site (EoS) in the statistical analysis. Conversely, authors of the novel machine-learning MRI studies may remove the EoS when training the machine-learning models but not control them when estimating the models' accuracy, potentially leading to severely biased estimates. We show examples from a toy simulation study and real MRI data in which we remove the EoS from both the "training set" and the "test set" during the training and application of the model. However, the accuracy is still inflated (or occasionally shrunk) unless we further control the EoS during the estimation of the accuracy. We also provide several methods for controlling the EoS during the estimation of the accuracy, and a simple R package ("multisite.accuracy") that smoothly does this task for several accuracy estimates (e.g., sensitivity/specificity, area under the curve, correlation, hazard ratio, etc.).
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http://dx.doi.org/10.1016/j.pscychresns.2021.111313DOI Listing
May 2021

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Mol Psychiatry 2021 Jun 2. Epub 2021 Jun 2.

Department of Psychosis Studies, Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
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http://dx.doi.org/10.1038/s41380-021-01161-7DOI Listing
June 2021

Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis.

Transl Psychiatry 2021 May 24;11(1):312. Epub 2021 May 24.

Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.

Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models' ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40-64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
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http://dx.doi.org/10.1038/s41398-021-01409-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144430PMC
May 2021

Cortical gray matter reduction precedes transition to psychosis in individuals at clinical high-risk for psychosis: A voxel-based meta-analysis.

Schizophr Res 2021 May 21;232:98-106. Epub 2021 May 21.

Department of Child and Adolescent Psychiatry and Psychology, 2017SGR881, Institute of Neuroscience, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica (FCRB), Esther Koplowitz Centre, Rosselló 153, 08036 Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain. Electronic address:

Gray matter and cortical thickness reductions have been documented in individuals at clinical high-risk for psychosis and may be more pronounced in those who transition to psychosis. However, these findings rely on small samples and are inconsistent across studies. In this review and meta-analysis we aimed to investigate neuroanatomical correlates of clinical high-risk for psychosis and potential predictors of transition, using a novel meta-analytic method (Seed-based d Mapping with Permutation of Subject Images) and cortical mask, combining data from surface-based and voxel-based morphometry studies. Individuals at clinical high-risk for psychosis who later transitioned to psychosis were compared to those who did not and to controls, and included three statistical maps. Overall, individuals at clinical high-risk for psychosis did not differ from controls, however, within the clinical high-risk for psychosis group, transition to psychosis was associated with less cortical gray matter in the right temporal lobe (Hedges' g = -0.377), anterior cingulate and paracingulate (Hedges' g = -0.391). These findings have the potential to help refine prognostic and etiopathological research in early psychosis.
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http://dx.doi.org/10.1016/j.schres.2021.05.008DOI Listing
May 2021

What is the actual accuracy of clinical prediction models? The case of transition to psychosis.

Authors:
Joaquim Radua

Neurosci Biobehav Rev 2021 May 12;127:502-503. Epub 2021 May 12.

Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.neubiorev.2021.05.007DOI Listing
May 2021

Universal and Selective Interventions to Prevent Poor Mental Health Outcomes in Young People: Systematic Review and Meta-analysis.

Harv Rev Psychiatry 2021 May-Jun 01;29(3):196-215

From the Early Psychosis: Interventions and Clinical-Detection (EPIC) Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London (Drs. Salazar de Pablo, De Micheli, Catalan, Verdino, Di Maggio, Radua, Provenzani, Montealegre, Signorini, and Fusar-Poli, and Mr. Oliver); Departments of Child and Adolescent Psychiatry (Dr. Salazar de Pablo) and of Psychosis Studies (Drs. Bonoldi and Baccaredda Boy), Institute of Psychiatry, Psychology & Neuroscience, King's College London; Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid (Drs. Salazar de Pablo and Arango); National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London (Drs. De Micheli and Fusar-Poli); Department of Brain and Behavioral Sciences, University of Pavia (Drs. Di Maggio, Provenzani, Ruzzi, Calorio, Nosari, Di Marco, Famularo, Molteni, Filosi, Mensi, Balottin, Politi, and Fusar-Poli); Neurosciences Department, University of Padova (Dr. Solmi); Mental Health Department, Biocruces Bizkaia Health Research Institute, Basurto University Hospital, Facultad de Medicina y Odontología, Campus de Leioa, University of the Basque Country, UPV/EHU, Barakaldo, Bizkaia, Spain (Dr. Catalan); Department of Molecular and Developmental Medicine, Division of Psychiatry, University of Siena (Dr. Verdino); Imaging of Mood- and Anxiety-Related Disorders (IMARD) group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona (Dr. Radua); Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm (Dr. Radua); Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Mondino Foundation, Child and Adolescent Neuropsychiatric Unit (Dr. Mensi); Department of Paediatrics, Yonsei University College of Medicine, Seoul (Dr. Shin); Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY (Dr. Correll); Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY (Dr. Correll); Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY (Dr. Correll); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin (Dr. Correll); OASIS service, South London and Maudsley NHS Foundation Trust, London (Dr. Fusar-Poli).

Background: Much is not known about the efficacy of interventions to prevent poor mental health outcomes in young people by targeting either the general population (universal prevention) or asymptomatic individuals with high risk of developing a mental disorder (selective prevention).

Methods: We conducted a PRISMA/MOOSE-compliant systematic review and meta-analysis of Web of Science to identify studies comparing post-test efficacy (effect size [ES]; Hedges' g) of universal or selective interventions for poor mental health outcomes versus control groups, in samples with mean age <35 years (PROSPERO: CRD42018102143). Measurements included random-effects models, I2 statistics, publication bias, meta-regression, sensitivity analyses, quality assessments, number needed to treat, and population impact number.

Results: 295 articles (447,206 individuals; mean age = 15.4) appraising 17 poor mental health outcomes were included. Compared to control conditions, universal and selective interventions improved (in descending magnitude order) interpersonal violence, general psychological distress, alcohol use, anxiety features, affective symptoms, other emotional and behavioral problems, consequences of alcohol use, posttraumatic stress disorder features, conduct problems, tobacco use, externalizing behaviors, attention-deficit/hyperactivity disorder features, and cannabis use, but not eating-related problems, impaired functioning, internalizing behavior, or sleep-related problems. Psychoeducation had the highest effect size for ADHD features, affective symptoms, and interpersonal violence. Psychotherapy had the highest effect size for anxiety features.

Conclusion: Universal and selective preventive interventions for young individuals are feasible and can improve poor mental health outcomes.
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http://dx.doi.org/10.1097/HRP.0000000000000294DOI Listing
May 2021

PRimary carE digital Support ToOl in mental health (PRESTO): Design, development and study protocols.

Rev Psiquiatr Salud Ment 2021 Apr 29. Epub 2021 Apr 29.

Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic de Barcelona, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain; Digital Innovation Group, Bipolar and Depressive Disorders Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; University of Barcelona, Barcelona, Catalonia, Spain; Mental Health Research Networking Center (CIBERSAM), Madrid, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Electronic address:

Background: About 30-50% of Primary Care (PC) users in Spain suffer mental health problems, mostly mild to moderate anxious and depressive symptoms, which account for 2% of Spain's total Gross domestic product and 50% of the costs associated to all mental disorders. Mobile health tools have demonstrated to cost-effectively reduce anxious and depressive symptoms while machine learning (ML) techniques have shown to accurately detect severe cases. The main aim of this project is to develop a comprehensive ML digital support platform (PRESTO) to cost-effectively screen, assess, triage, and provide personalized treatments for anxious and depressive symptoms in PC.

Methods: The project will be carried out in 3 complementary phases: First, a ML predictive severity model will be built based on all the cases referred to the PC mental health support programme during the last 5 years in Catalonia. Simultaneously, a smartphone app to monitor and deliver psychological interventions for anxiety and depressive symptoms will be developed and tested in a clinical trial. Finally, the ML models and the app will be integrated in a comprehensive decision-support platform (PRESTO) which will triage and assign to each patient a specific intervention based on individual personal and clinical characteristics. The effectiveness of PRESTO to reduce waiting times in receiving mental healthcare will be tested in a stepped-wedge cluster randomized controlled trial in 5 PC centres.

Discussion: PRESTO will offer timely and personalized cost-effective mental health treatment to people with mild to moderate anxious and depressive symptoms. This will result in a reduction of the burden of mental health problems in PC and on society as a whole.

Trial Registration: The project and their clinical trials were registered in Clinical Trials.gov: NCT04559360 (September 2020).
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http://dx.doi.org/10.1016/j.rpsm.2021.04.003DOI Listing
April 2021

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Mol Psychiatry 2021 Apr 16. Epub 2021 Apr 16.

Unit for Psychosomatics / CL Outpatient Clinic for Adults, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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http://dx.doi.org/10.1038/s41380-021-01098-xDOI Listing
April 2021

Risk of cancer in bipolar disorder and the potential role of lithium: International collaborative systematic review and meta-analyses.

Neurosci Biobehav Rev 2021 Jul 5;126:529-541. Epub 2021 Apr 5.

Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, and the Department of Psychiatry, The University of Melbourne, Parkville, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia. Electronic address:

We examined bipolar disorder (BD) as a risk factor for developing cancer and the role of lithium on cancer incidence. We conducted two systematic review and meta-analyses of population-based studies providing data on these associations. We screened articles indexed in MEDLINE, Scopus, Embase, and PsycINFO up to August 2020. The first random-effects meta-analysis, based on 4,910,661 individuals from nine studies estimated an increased risk of cancer of any kind [RR = 1.24 (1.05-1.46); p < 0.01], especially breast cancer [RR = 1.33 (1.15-1.55); p < 0.01] in BD. The second random-effects meta-analysis, based on 2,606,187 individuals from five studies did not show increased risk of cancer in people with BD using lithium, and even suggested a small protective effect both in overall [RR = 0.94 (0.72-1.22); p = 0.66] and urinary cancer [RR = 0.93 (0.75-1.14); p = 0.48] although these findings did not reach statistical significance. The current evidence highlights that cancer risk is increased in individuals with BD, particularly breast cancer in women. Lithium may have a potential protective effect on cancer, including urinary cancer. The role of lithium as a mainstay of treatment for BD is reinforced by this study.
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http://dx.doi.org/10.1016/j.neubiorev.2021.03.034DOI Listing
July 2021

Risk and protective factors for cannabis, cocaine, and opioid use disorders: An umbrella review of meta-analyses of observational studies.

Neurosci Biobehav Rev 2021 Jul 15;126:243-251. Epub 2021 Mar 15.

Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology, London, UK; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Outreach and Support in South London (OASIS) Service, South London and Maudsley NHS Foundation Trust, London, UK.

Several meta-analyses of observational studies have addressed the association between risk and protective factors and cannabis/cocaine/opioid use disorders, but results are conflicting. No umbrella review has ever graded the credibility of this evidence (not significant/weak/suggestive/highly suggestive/convincing). We searched Pubmed-MEDLINE/PsycInfo, last search September 21, 2020. We assessed the quality of meta-analyses with the AMSTAR-2 tool. Out of 3,072 initial references, five were included, providing 19 associations between 12 putative risk/protective factors and cannabis/cocaine/opioid use disorders (cases: 4539; N = 1,118,872,721). While 84 % of the associations were statistically significant, none was convincing. One risk factor (smoking) had highly suggestive evidence for association with nonmedical use of prescription opioid medicines (OR = 3.07, 95 %CI:2.27 to 4.14). Convincing evidence emerged in sensitivity analyses on antisocial behavior and cannabis use disoder (OR 3.34, 95 %CI 2.53-4.41). Remaining associations had weak evidence. The quality of meta-analyses was rated as moderate in two (40 %), low in one (20 %), and critically low in two (40 %). Future research is needed to better profile risk/protective factors for cannabis/cocaine/opioid use disorders disorders informing preventive approaches.
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http://dx.doi.org/10.1016/j.neubiorev.2021.03.014DOI Listing
July 2021

Predicting pulmonary embolism in patients infected with COVID-19 based on D-dimer levels and days between diagnosis of the infection and D-dimer determination.

Monaldi Arch Chest Dis 2021 Mar 11;91(2). Epub 2021 Mar 11.

Department of Respiratory Medicine.

Ruling out pulmonary embolism (PE) can be challenging in a situation of elevated D-dimer values such as in a case of COVID-19 infection. Our objective was to evaluate the difference in D-dimer values of subjects infected with COVID-19 in those with PE and those without and to analyze the predictive value of D-dimer for PE in these subjects based on the day of D-dimer determination. This was an observational, retrospective study, conducted at a tertiary hospital. All subjects with PCR-confirmed COVID-19 infection requiring hospital admission at our institution between the months of March and April 2020 were included in the study. We compared D-dimer levels in subjects who went on to develop a PE and those who did not. We then created a model to predict the subsequent development of a PE with the current D-dimer levels of the subject. D-dimer levels changed over time from COVID-19 diagnosis, but were always higher in subjects who went on to develop a PE. Regarding the predictive model created, the area under the curve of the ROC analyses of the cross-validation predictions was 0.72. The risk of pulmonary embolism for the same D-dimer levels varied depending on the number of days elapsed since COVID-19 diagnosis and D-dimer determination. To conclude, D-dimer levels were elevated in subjects with a COVID-19 infection, especially in those with PE. D-dimer levels increased during the first 10 days after the diagnosis of the infection and can be used to predict the risk of PE in COVID-19 subjects.
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http://dx.doi.org/10.4081/monaldi.2021.1622DOI Listing
March 2021

Corrigendum to 'Voxel-based meta-analysis via permutation of subject images (PSI): Theory and implementation for SDM' [Neuroimage 186 (2019) 174-184/YNIMG_15396].

Neuroimage 2021 May 17;231:117859. Epub 2021 Feb 17.

FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Mental Health Research Networking Center (CIBERSAM), Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.neuroimage.2021.117859DOI Listing
May 2021

PRISMA 2020 - An updated checklist for systematic reviews and meta-analyses.

Authors:
Joaquim Radua

Neurosci Biobehav Rev 2021 May 14;124:324-325. Epub 2021 Feb 14.

Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.neubiorev.2021.02.016DOI Listing
May 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Resilience and mental health during the COVID-19 pandemic.

J Affect Disord 2021 03 29;283:156-164. Epub 2021 Jan 29.

Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Institute of Neuroscience, IDIBAPS, CIBERSAM, 170, Villarroel St., 08037, Barcelona, Catalonia, Spain.

Background: Resilience is a process that allows recovery from or adaptation to adversities. The aim of this study was to evaluate state resilience during the COVID-19 pandemic in psychiatric patients (PP), unaffected relatives (UR) and community controls (CC).

Methods: This study is part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Logistic regression models were performed to identify mental health outcomes associated with bad state resilience and predictors of good state resilience. The association between state resilience and specific affective temperaments as well as their influence on the association between depressive symptoms and state resilience were verified.

Results: The study recruited 898 participants that took part in the survey. The presence of depressive symptoms was a predictor of bad state resilience in PP (β=0.110, OR=1.117, p=0.028). No specific mental health outcome was associated with bad state resilience in UR and CC. Predictors of good state resilience in PP were having pursued hobbies/conducted home tasks (β=1.261, OR=3.528, p=0.044) and level of organization in the family (β=0.986, OR=2.682, p=0.008). Having a controlling family was inversely associated with good state resilience in CC (β=-1.004, OR=0.367, p=0.012). The association between bad state resilience and depressive symptoms was partially mediated by affective temperaments.

Limitations: Participants self-reported their psychiatric diagnoses, their relatives' diagnoses or the absence of a psychiatric disorder, as well as their psychiatric symptoms.

Conclusions: Enhancing resilience and coping strategies in the face of the COVID-19 pandemic might have important implications in terms of mental health outcomes.
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http://dx.doi.org/10.1016/j.jad.2021.01.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845537PMC
March 2021

Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder.

Sci Rep 2021 Jan 27;11(1):2373. Epub 2021 Jan 27.

FIDMAG Research Foundation, C/. Dr. Antoni Pujadas, 38, Sant Boi de Llobregat, 08830, Barcelona, Spain.

Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene's relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.
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http://dx.doi.org/10.1038/s41598-021-81915-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840726PMC
January 2021

Cortical thickness in Parkinson's disease: a coordinate-based meta-analysis.

Aging (Albany NY) 2021 01 10;13(3):4007-4023. Epub 2021 Jan 10.

Department of Neurology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng, PR China.

Parkinson's disease (PD) is a common age-related neurodegenerative disease that affects the structural architecture of the cerebral cortex. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis is a popular measure to assess brain structural alterations in the gray matter in PD. However, the results of CTh analysis in PD lack consistency and have not been systematically reviewed. We conducted a comprehensive coordinate-based meta-analysis (CBMA) of 38 CTh studies (57 comparison datasets) in 1,843 patients with PD using the latest seed-based d mapping software. Compared with 1,172 healthy controls, no significantly consistent CTh alterations were found in patients with PD, suggesting CTh as an unreliable neuroimaging marker for PD. The lack of consistent CTh alterations in PD could be ascribed to the heterogeneity in clinical populations, variations in imaging methods, and underpowered small sample sizes. These results highlight the need to control for potential confounding factors to produce robust and reproducible CTh results in PD.
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http://dx.doi.org/10.18632/aging.202368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906199PMC
January 2021

Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of , , and clinical trials.

Theranostics 2021 1;11(3):1207-1231. Epub 2021 Jan 1.

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of , , and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
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http://dx.doi.org/10.7150/thno.48342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738873PMC
January 2021

Cortical Gyrification Morphology in Individuals with ASD and ADHD across the Lifespan: A Systematic Review and Meta-Analysis.

Cereb Cortex 2021 Mar;31(5):2653-2669

Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.

Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are common neurodevelopmental disorders (NDDs) that may impact brain maturation. A number of studies have examined cortical gyrification morphology in both NDDs. Here we review and when possible pool their results to better understand the shared and potentially disorder-specific gyrification features. We searched MEDLINE, PsycINFO, and EMBASE databases, and 24 and 10 studies met the criteria to be included in the systematic review and meta-analysis portions, respectively. Meta-analysis of local Gyrification Index (lGI) findings across ASD studies was conducted with SDM software adapted for surface-based morphometry studies. Meta-regressions were used to explore effects of age, sex, and sample size on gyrification differences. There were no significant differences in gyrification across groups. Qualitative synthesis of remaining ASD studies highlighted heterogeneity in findings. Large-scale ADHD studies reported no differences in gyrification between cases and controls suggesting that, similar to ASD, there is currently no evidence of differences in gyrification morphology compared with controls. Larger, longitudinal studies are needed to further clarify the effects of age, sex, and IQ on cortical gyrification in these NDDs.
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http://dx.doi.org/10.1093/cercor/bhaa381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023842PMC
March 2021

Impact of simulation-based teamwork training on COVID-19 distress in healthcare professionals.

BMC Med Educ 2020 Dec 21;20(1):515. Epub 2020 Dec 21.

Vall Hebron centre Simulació Clínica Avançada (VHiSCA), Direcció Docència, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

Context: Non-technical skills such as leadership, communication, or situation awareness should lead to effective teamwork in a crisis. This study aimed to analyse the role of these skills in the emotional response of health professionals to the COVID-19 pandemic.

Methods: Before the COVID-19 outbreak, 48 doctors and 48 nurses participated in a simulation-based teamwork training program based on teaching non-technical skills through simulation. In May 2020, this group of professionals from a COVID-19 referral hospital was invited to participate in a survey exploring stress, anxiety, and depression, using the PSS-14 (Perceived Stress Scale) and the HADS (Hospital Anxiety and Depression Scale) measures. A control group that did not receive the training was included. We conducted a logistic regression to assess whether having attended a simulation-based teamwork training program modified the probability of presenting psychological distress (PSS-14 > 18 or HADS> 12).

Results: A total of 141 healthcare professionals were included, 77 in the intervention group and 64 in the control group. Based on the PSS-14, 70.1% of the intervention group and 75% of the control group (p = 0.342) had symptoms of stress. Having contact with COVID-19 patients [OR 4.16(1.64-10.52)]; having minors in charge [OR 2.75 (1.15-6.53)]; working as a doctor [0.39(0.16-0.95)], and being a woman [OR 2.94(1.09-7.91)] were related with PSS14 symptoms. Based on the HADS, 54.6% of the intervention group and 42.2% of the control group (p = 0.346) had symptoms of anxiety or depression. Having contact with COVID-19 patients [OR 2.17(1.05-4.48)] and having minors in charge [OR 2.14(1.06-4.32)] were related to HADS symptoms. Healthcare professionals who attended COVID-19 patients showed higher levels of anxiety and depression [OR 2.56(1.03-6.36) (p = 0.043)].

Conclusion: Healthcare professionals trained in non-technical skills through simulation tended towards higher levels of anxiety and depression and fewer levels of stress, during the COVID-19 pandemic.
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http://dx.doi.org/10.1186/s12909-020-02427-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751744PMC
December 2020

Risk and protective factors for alcohol and tobacco related disorders: An umbrella review of observational studies.

Neurosci Biobehav Rev 2021 02 25;121:20-28. Epub 2020 Nov 25.

IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia; Department of Psychiatry, University of Toronto, and the Centre for Addiction and Mental Health, Toronto, ON, Canada.

The credibility of evidence of various environmental risk factors for alcohol and tobacco use disorders (AUD/TUD) needs to be graded to identify groups to target with selective prevention. A systematic umbrella review was conducted (PubMed/PsycINFO), grading credibility of meta-analyses of prospective/retrospective observational cohort studies assessing risk/protective factors for AUD/TUD, applying established quantitative criteria. Sensitivity analyses were conducted. Quality of eligible meta-analyses was assessed with AMSTAR-2. Out of 8464 unique references, 80 full text articles were scrutinized, and 12 meta-analyses, corresponding to 21 individual estimates of 12 putative risk/protective factors (n = 241,300), were included. In main analyses no association had convincing nor highly suggestive evidence for AUD/TUD. Six associations had suggestive evidence for AUD, two for TUD. Among these, in sensitivity analyses without >1000 cases criterion, convincing evidence emerged for parental alcohol supply, and impulsivity traits in college students for AUD, and attention-deficit/hyperactivity disorder for TUD. Other associations were supported by weak evidence/were not nominally significant. Few risk factors identified at-risk groups where selective preventative strategies could be developed to prevent AUD/TUD.
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http://dx.doi.org/10.1016/j.neubiorev.2020.11.010DOI Listing
February 2021

Impact of Cognitive Reserve and Structural Connectivity on Cognitive Performance in Multiple Sclerosis.

Front Neurol 2020 30;11:581700. Epub 2020 Oct 30.

Laboratory of Advanced Imaging in Neuroimmunological Diseases, Center of Neuroimmunology, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic Barcelona, Universitat de Barcelona, Barcelona, Spain.

Cognitive reserve (CR) could attenuate the impact of the brain burden on the cognition in people with multiple sclerosis (PwMS). To explore the relationship between CR and structural brain connectivity and investigate their role on cognition in PwMS cognitively impaired (PwMS-CI) and cognitively preserved (PwMS-CP). In this study, 181 PwMS (71% female; 42.9 ± 10.0 years) were evaluated using the Cognitive Reserve Questionnaire (CRQ), Brief Repeatable Battery of Neuropsychological tests, and MRI. Brain lesion and gray matter volumes were quantified, as was the structural network connectivity. Patients were classified as PwMS-CI ( scores = -1.5 SD in at least two tests) or PwMS-CP. Linear and multiple regression analyses were run to evaluate the association of CRQ and structural connectivity with cognition in each group. Hedges's effect size was used to compute the strength of associations. We found a very low association between CRQ scores and connectivity metrics in PwMS-CP, while in PwMS-CI, this relation was low to moderate. The multiple regression model, adjusted for age, gender, mood, lesion volume, and graph metrics (local and global efficiency, and transitivity), indicated that the CRQ (β = 0.26, 95% CI: 0.17-0.35) was associated with cognition (adj = 0.34) in PwMS-CP (55%). In PwMS-CI, CRQ (β = 0.18, 95% CI: 0.07-0.29), age, and network global efficiency were independently associated with cognition (adj = 0.55). The age- and gender-adjusted association between CRQ score and global efficiency on having an impaired cognitive status was -0.338 (OR: 0.71, = 0.036) and -0.531 (OR: 0.59, = 0.002), respectively. CR seems to have a marginally significant effect on brain structural connectivity, observed in patients with more severe clinical impairment. It protects PwMS from cognitive decline regardless of their cognitive status, yet once cognitive impairment has set in, brain damage and aging are also influencing cognitive performance.
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http://dx.doi.org/10.3389/fneur.2020.581700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662554PMC
October 2020

Can we increase the subjective well-being of the general population? An umbrella review of the evidence.

Rev Psiquiatr Salud Ment (Engl Ed) 2021 Jan-Mar;14(1):50-64. Epub 2020 Nov 5.

Imaging of Mood- and Anxiety-Related Disorders (IMARD) group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Mental Health Research Networking Center (CIBERSAM), Madrid, Spain; Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Introduction: Subjective well-being (SWB) refers to being satisfied with one's life, having positive affect and having little negative affect. We may understand it as a subjective definition of good life, or in colloquial terms "happiness", and it has been associated with several important benefits such as lower mortality. In the last decades, several randomized controlled trials (RCT) have investigated the efficacy of several interventions in increasing SWB in the general population but results from different disciplines have not been integrated.

Methods: We conducted an umbrella review of systematic reviews and meta-analyses of RCT that assess the efficacy of any kind of interventions in increasing SWB in the general population, including both positive psychology interventions (PPI) and other interventions. We (re)calculated the meta-analytic statistics needed to objectively assess the quality of the evidence of the efficacy of each type of intervention in improving each component of SWB according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results: There was moderate-quality evidence that PPI might induce small decreases of negative affect, and low-quality evidence that they might induce moderate increases of positive affect. We found similar results for those PPI specifically consisting in conducting acts of kindness (especially spending money on or giving items to others), for which there was low-quality evidence that they might induces small increases of life satisfaction, but not for PPI specifically consisting in practicing gratitude. Quality of the evidence of the efficacy for the other interventions included in the umbrella review (yoga, resilience training, physical activity, leisure, control enhancement, psychoeducation, and miscellaneous) was very low.

Conclusion: There is some evidence that PPI, and specially conducting acts of kindness such as spending money on others, may increase the SWB of the general population. The quality of the evidence of the efficacy for other interventions (e.g., yoga, physical activity, or leisure) is still very low. Registration number: PROSPERO CRD42020111681.
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http://dx.doi.org/10.1016/j.rpsm.2020.08.002DOI Listing
November 2020

Toward a hierarchical model of social cognition: A neuroimaging meta-analysis and integrative review of empathy and theory of mind.

Psychol Bull 2021 03 5;147(3):293-327. Epub 2020 Nov 5.

Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden.

Along with the increased interest in and volume of social cognition research, there has been higher awareness of a lack of agreement on the concepts and taxonomy used to study social processes. Two central concepts in the field, empathy and Theory of Mind (ToM), have been identified as overlapping umbrella terms for different processes of limited convergence. Here, we review and integrate evidence of brain activation, brain organization, and behavior into a coherent model of social-cognitive processes. We start with a meta-analytic clustering of neuroimaging data across different social-cognitive tasks. Results show that understanding others' mental states can be described by a multilevel model of hierarchical structure, similar to models in intelligence and personality research. A higher level describes more broad and abstract classes of functioning, whereas a lower one explains how functions are applied to concrete contexts given by particular stimulus and task formats. Specifically, the higher level of our model suggests 3 groups of neurocognitive processes: (a) predominantly cognitive processes, which are engaged when mentalizing requires self-generated cognition decoupled from the physical world; (b) more affective processes, which are engaged when we witness emotions in others based on shared emotional, motor, and somatosensory representations; (c) combined processes, which engage cognitive and affective functions in parallel. We discuss how these processes are explained by an underlying principal gradient of structural brain organization. Finally, we validate the model by a review of empathy and ToM task interrelations found in behavioral studies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/bul0000303DOI Listing
March 2021

In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

Hum Brain Mapp 2020 Oct 19. Epub 2020 Oct 19.

Department of Psychiatry, University of Münster, Münster, Germany.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.
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http://dx.doi.org/10.1002/hbm.25249DOI Listing
October 2020

Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review.

Lancet Psychiatry 2020 11;7(11):955-970

Early Psychosis: Interventions and Clinical-Detection Lab, Department of Psychosis Studies, King's College London, London, UK; Outreach and Support in South London (OASIS) Service, South London and Maudsley NHS Foundation Trust, London, UK; National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

Background: Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD.

Methods: In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032.

Findings: We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51).

Interpretation: Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality.

Funding: None.
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http://dx.doi.org/10.1016/S2215-0366(20)30312-6DOI Listing
November 2020

Greater male than female variability in regional brain structure across the lifespan.

Hum Brain Mapp 2020 Oct 12. Epub 2020 Oct 12.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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http://dx.doi.org/10.1002/hbm.25204DOI Listing
October 2020