A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium

Schizophrenia is associated with widespread alterations in subcortical brain structure.While analytic methods have enabled more detailed morphometric characterization,findings are often equivocal. In this meta-analysis, we employed the harmonizedENIGMA shape analysis protocols to collaboratively investigate subcortical brainstructure shape differences between individuals with schizophrenia and healthy con-trol participants. The study analyzed data from 2,833 individuals with schizophreniaand 3,929 healthy control participants contributed by 21 worldwide research groupsparticipating in the ENIGMA Schizophrenia Working Group. Harmonized shape analy-sis protocols were applied to each site's data independently for bilateral hippocam-pus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained fromT1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens,and thalamus in individuals with schizophrenia compared with control participants,more-convex-than-concave shape differences in the putamen and pallidum, and bothconcave and convex shape differences in the caudate. Patterns of exaggerated asym-metry were observed across the hippocampus, amygdala, and thalamus in individualswith schizophrenia compared to control participants, while diminished asymmetryencompassed ventral striatum and ventral and dorsal thalamus. Our analyses also rev-ealed that higher chlorpromazine dose equivalents and increased positive symptomlevels were associated with patterns of contiguous convex shape differences acrossmultiple subcortical structures. Findings from our shape meta-analysis suggest thatcommon neurobiological mechanisms may contribute to gray matter reduction acrossmultiple subcortical regions, thus enhancing our understanding of the nature of net-work disorganization in schizophrenia

Exploring the relationship between deficits in social cognition and neurodegenerative dementia: a systematic review

Background: Neurodegenerative diseases might affect social cognition in various ways depending on their components (theory of mind, emotional processing, attribution bias, and social perception) and the subtype of dementia they cause. This review aims to explore this difference in cognitive function among individuals with different aetiologies of dementia. Methods: The following databases were explored: MEDLINE via PubMed, Cochrane Library, Lilacs, Web of Science, and PsycINFO. We selected studies examining social cognition in individuals with neurodegenerative diseases in which dementia was the primary symptom that was studied. The neurodegenerative diseases included Alzheimer's disease, Lewy body disease and frontotemporal lobar degeneration. The search yielded 2,803 articles. Results: One hundred twenty-two articles were included in the present review. The summarised results indicate that people with neurodegenerative diseases indeed have deficits in social cognitive performance. Both in populations with Alzheimer's disease and in populations with frontotemporal dementia, we found that emotional processing was strongly affected. However, although theory of mind impairment could also be observed in the initial stages of frontotemporal dementia, in Alzheimer's disease it was only appreciated when performing highly complex task or in advanced stages of the disease. Conclusions: Each type of dementia has a differential profile of social cognition deterioration. This review could provide a useful reference for clinicians to improve detection and diagnosis, which would undoubtedly guarantee better interventions.FUNDING: This work was supported by a Juan de la Cierva-Formación contract (ESS) from the Spanish Ministry of Science and Innovation (FJC2019-042390-I/AEI/10.13039/501100011033) and a Miguel Servet contract (RAA) from the Carlos III Health Institute (CP18/00003)

Homocysteine and cognition: A systematic review of 111 studies

BACKGROUND: Elevated plasma homocysteine ??(Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected. METHODS: We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed. RESULTS: We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline. DISCUSSION: Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone

Background: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. Method: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n=55), risperidone (n=63), haloperidol (n=56), aripiprazole (n=78), ziprasidone (n=62), or quetiapine (n=62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. Results: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine=69.09, risperidone=71.43, aripiprazole=73.08%, ziprasidone=79.03%, haloperidol=89.28%, and quetiapine=95.53%) (x2=79.86; P=.000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank=92.240; P=.000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. Conclusions: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis

Intelligence quotient changes over 10 years: Diversity of cognitive profiles in first episode of psychosis and healthy controls

Objective: This study aimed to analyse whether intelligence quotient (IQ) improves, declines, or remains stable over 10 years among FEP patients and healthy subjects. Methods: A group of FEP patients enrolled in a Program of First Episode Psychosis in Spain called PAFIP, and a sample of Healthy Controls (HC) completed the same neuropsychological battery at baseline and approximately 10 years later, which included the WAIS vocabulary subtest to estimate premorbid IQ and 10-year IQ. Cluster analysis was performed separately in the patient group and the HC group to determine their profiles of intellectual change. Results: One hundred and thirty-seven FEP patients were grouped into five clusters: "Improved low IQ" (9.49 % of patients), "Improved average IQ" (14.6 %), "Preserved low IQ" (17.52 %), "Preserved average IQ" (43.06 %), and "Preserved high IQ" (15.33 %). Ninety HC were grouped into three clusters: "Preserved low IQ" (32.22 % of the HC), "Preserved average IQ" (44.44 %), and "Preserved high IQ" (23.33 %). The first two clusters of FEP patients, characterized by a low IQ, earlier age at illness onset, and lower educational attainment, showed a substantial cognitive improvement. The remaining clusters demonstrated cognitive stability. Conclusions: The FEP patients showed intellectual improvement or stability, but no decline post-onset of psychosis. However, their profiles of intellectual change are more heterogeneous than that of HC over 10 years. Particularly, there is a subgroup of FEP patients with a significant potential for long-term cognitive enhancementFunding: This work was supported by a Miguel Servet contract (Dr. Rosa Ayesa-Arriola) from the Carlos III Health Institute (CP18/00003); a “Juan de la Cierva-Formación” contract (Dr. Esther Setién-Suero) from the Spanish Ministry of Science and Innovation (FJC2019-042390-I/AEI/10.13039/501100011033); and a predoctoral contract (Nancy Murillo-Garcia) from the Valdecilla Biomedical Research Institute and the University of Cantabria (BOC49, REF. IDI-13). Acknowledgements: We acknowledge the collaboration of all members of the PAFIP team and thank the patients and their families for their participation in the stud

Understanding the Influence of Personality Traits on Risk of Suicidal Behaviour in Schizophrenia Spectrum Disorders: A Systematic Review

Risk of suicidal behaviour (SB) in schizophrenia spectrum disorders (SSD) is a major concern, particularly in early stages of the illness, when suicide accounts for a high number of premature deaths. Although some risk factors for SB in SSD are well understood, the extent to which personality traits may affect this risk remains unclear, which may have implications for prevention. We conducted a systematic review of previous studies indexed in MEDLINE, PsycINFO and Embase examining the relationship between personality traits and SB in samples of patients with SSD. Seven studies fulfilled predetermined selection criteria. Harm avoidance, passive-dependent, schizoid and schizotypal personality traits increased the risk of SB, while self-directedness, cooperativeness, excluding persistence and self-transcendence acted as protective factors. Although only seven studies were retrieved from three major databases after applying predetermined selection criteria, we found some evidence to support that personality issues may contribute to SB in patients with SSD. Personality traits may therefore become part of routine suicide risk assessment and interventions targeting these personality-related factors may contribute to prevention of SB in SSD

Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients

INTRODUCTION: Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. MATERIAL AND METHODS: A total of 390 patients were evaluated at baseline and after 3?years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). RESULTS: At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F?=?13.874; p?<?.001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2?=?7.97, p?=?.019). Longitudinally, patients maintaining cannabis consumption after 3?years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p?=?.022) and never-users (p?=?.016). No differences were seen in fibrosis scores associated with cannabis. CONCLUSIONS: Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.Funding sources: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Next-Val 2017 (ref.: NVAL17/24) and Inn-Val 2018 (ref.: INNVAL18/30) IDIVAL grants; Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005–0308007; and Fundación Marqués de Valdecilla API07/011

Data regarding the effect of cannabis consumption on liver function in the prospective PAFIP cohort of first episode psychosis

The presented article describes data from secondary analyses, related to the research article entitled ?Cannabis consumption and Non-Alcoholic Fatty Liver Disease. A three years longitudinal study in first episode non-affective psychosis patients? [1]. We present detailed data regarding the socio-demographic and baseline clinical characteristics of a sample of 390 drug-naïve patients with a first episode of non-affective psychosis, and the differences between cannabis users and non-users in those characteristics. Tables also show the results from cross-sectional and longitudinal statistical analyses exploring the relation between cannabis consumption and liver function, after excluding those patients with hazardous alcohol drinking

Pattern of long-Term weight and metabolic changes after a first-episode of psychosis: Results from a 10-years prospective follow-up of the PAFIP cohort

Background: People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. Methods: Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. Results: People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (?15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (?2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. Conclusions: This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances

Understanding sex differences in long-term outcomes after a first episode of psychosis

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions