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BACKGROUND AND HYPOTHESIS: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. STUDY DESIGN: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group. STUDY RESULTS: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings. CONCLUSIONS: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders.
Subject(s)
Psychotic Disorders , Humans , Psychotic Disorders/epidemiology , Adult , Male , Female , Incidence , Young Adult , Adolescent , Middle Aged , Europe/epidemiology , Psychosocial Deprivation , Marijuana Use/epidemiologyABSTRACT
The DDR1 locus is associated with the diagnosis of schizophrenia and with processing speed in patients with schizophrenia and first-episode psychosis. Here, we investigated whether DDR1 variants are associated with bipolar disorder (BD) features. First, we performed a caseâcontrol association study comparing DDR1 variants between patients with BD and healthy controls. Second, we performed linear regression analyses to assess the associations of DDR1 variants with neurocognitive domains and psychosocial functioning. Third, we conducted a mediation analysis to explore whether neurocognitive impairment mediated the association between DDR1 variants and psychosocial functioning in patients with BD. Finally, we studied the association between DDR1 variants and white matter microstructure. We did not find any statistically significant associations in the caseâcontrol association study; however, we found that the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse neurocognitive performance in patients with BD with psychotic symptoms. In addition, the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse psychosocial functioning through processing speed. We did not find correlations between white matter microstructure abnormalities and the neurocognitive domains associated with the combined genotypes rs1264323AA-rs2267641AC/CC. Overall, the results suggest that DDR1 may be a marker of worse neurocognitive performance and psychosocial functioning in patients with BD, specifically those with psychotic symptoms.
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BACKGROUND: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. METHODS: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. RESULTS: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. CONCLUSIONS: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.
Subject(s)
Psychotic Disorders , Schizotypal Personality Disorder , Humans , Psychotic Disorders/epidemiology , Male , Female , Europe/epidemiology , Adult , Brazil/epidemiology , Young Adult , Adolescent , Schizotypal Personality Disorder/epidemiology , Incidence , Middle Aged , PhenotypeABSTRACT
BACKGROUND: Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. METHODS: A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. RESULTS: At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. CONCLUSIONS: Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.
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BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
Subject(s)
Adverse Childhood Experiences , Cannabis , Psychotic Disorders , Schizophrenia , Humans , Child , Cannabis/adverse effects , Case-Control Studies , Psychotic Disorders/epidemiology , Psychotic Disorders/etiology , Psychotic Disorders/psychology , Schizophrenia/epidemiology , Schizophrenia/complicationsABSTRACT
BACKGROUND: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. METHODS: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. FINDINGS: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. INTERPRETATION: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries.
Subject(s)
Cannabis , Central Nervous System Stimulants , Psychotic Disorders , Humans , Psychotic Disorders/epidemiology , Psychotic Disorders/psychology , Cannabis/adverse effects , Europe , Ethnicity , IncidenceABSTRACT
INTRODUCTION: Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. MATERIAL AND METHODS: We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. RESULTS: In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. CONCLUSIONS: We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.
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BACKGROUND: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. METHODS: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. RESULTS: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). CONCLUSIONS: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Subject(s)
Adverse Childhood Experiences , Psychotic Disorders , Humans , Psychotic Disorders/etiology , Psychotic Disorders/genetics , Genomics , Multifactorial Inheritance , Odds RatioABSTRACT
This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood.
Subject(s)
Child Abuse , Psychotic Disorders , Schizophrenia , Adult , Humans , Child , Case-Control Studies , Psychotic Disorders/genetics , Schizophrenia/epidemiology , Schizophrenia/genetics , CognitionABSTRACT
BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.
Subject(s)
Cannabis , Marijuana Smoking , Psychotic Disorders , Humans , Cannabis/adverse effects , Case-Control Studies , Marijuana Smoking/adverse effects , Psychotic Disorders/epidemiology , Risk FactorsABSTRACT
ABTRACT: Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = <0.001; abuse: OR = 2.16; p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 × 10-8). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 × 10-5) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.
Subject(s)
Adverse Childhood Experiences , Psychological Tests , Psychotic Disorders , Self Report , Humans , Child , DNA Methylation/genetics , Epigenome , Psychotic Disorders/geneticsABSTRACT
BACKGROUND: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. RESULTS: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. CONCLUSIONS: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.
Subject(s)
Cognition , Exposome , Schizophrenic Psychology , Adult , Humans , Cross-Sectional Studies , Schizophrenia/epidemiology , Siblings/psychology , Case-Control Studies , Cognition Disorders/epidemiology , Male , FemaleABSTRACT
Introduction: This systematic review aimed to answer whether we can predict subsequent social functioning in first episode psychosis (FEP) by means of an initial cognitive examination. In order to do this, we gathered longitudinal studies which evaluated neurocognition and/or social cognition regarding their impact on long-term social functioning of FEP patients. Methods: The MOOSE method was employed and 28 studies covering data from a total of 2572 patients with longitudinal trajectories from 2 months to 5 years were reviewed. Results: In general, cognitive deficits impacted on the social functioning of the FEP patients across the time. The neurocognitive domains which most closely predicted social functioning were processing speed, sustained attention and working memory. An overall cognitive dysfunction, low IQ and the academic trajectory were also found predictive. Regarding social cognition, the findings were not unanimous. Discussion: In addition of the impact of each variable, several of the articles found a complex relationship between social cognition, neurocognition, social functioning and negative symptoms, pointing social cognition as a modulator of neurocognition but being modulated as well by negative symptoms. The principal clinical implication of this review is that the initial assessment of FEP patients and their rehabilitation must take cognition into account.
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BACKGROUND: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status. METHODS: We included FEP patients aged 18-64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status. RESULTS: We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations. CONCLUSIONS: The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.
Subject(s)
Child Abuse , Psychotic Disorders , Transients and Migrants , Child , Humans , Psychotic Disorders/epidemiology , Ethnicity , IncidenceABSTRACT
Background and Hypothesis: It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. Study Design: We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. Study Results: Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROCâ =â 0.84-0.86). Specificity (rangeâ =â 73.9-78.0%) and sensitivity (rangeâ =â 75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. Conclusions: The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability.
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INTRODUCTION: An updated summary of the most used instruments assessing auditory hallucinations in population with psychosis, allows us to underline the scarceness and need of Spanish versions of important instruments. The aim of the study is to examine the psychometric characteristics of two different and complementary instruments for assessing auditory hallucinations, the Spanish version of the Auditory Vocal Hallucination Scale (AVHRS) and the Spanish version of the Positive and Useful Voices Inquiry (PUVI). MATERIALS AND METHODS: A sample of 68 patients from four different centres, with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder presenting with auditory hallucinations were included. Apart from the AVHRS and the PUVI, the Psychotic Symptom Rating Scales-Auditory Hallucinations subscale (PSYRATS-AH) and the Positive and Negative Syndrome Scale (PANSS) were also administered to all patients, plus an acceptability questionnaire. RESULTS: The Spanish version of the AVHRS showed a good internal consistency, a moderate to high inter-rater reliability, a medium to moderate test-retest reliability, and a good convergent and discriminant validity. The Spanish version of the PUVI showed a good internal consistency and a heterogeneous, but in general moderate, test-retest reliability. CONCLUSIONS: The Spanish versions of the AVHRS and the PUVI have good psychometric properties and are well accepted among patients.
Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Reproducibility of Results , Psychiatric Status Rating Scales , Hallucinations/diagnosis , Hallucinations/etiology , Hallucinations/epidemiology , Psychotic Disorders/complications , Psychotic Disorders/diagnosis , Psychotic Disorders/psychology , Schizophrenia/complications , Schizophrenia/diagnosisABSTRACT
BACKGROUND: To date, a large number of functional magnetic resonance imaging (fMRI) studies have been conducted on psychosis. However, little is known about changes in brain functioning in psychotic patients using an emotional auditory paradigm at different stages of the disease. Such knowledge is important for advancing our understanding of the disorder and thus creating more targeted interventions. This study aimed to investigate whether individuals with first-episode psychosis (FEP) and chronic schizophrenia show abnormal brain responses to emotional auditory processing and to compare the responses between FEP and chronic schizophrenia. METHODS: Patients with FEP (n = 31) or chronic schizophrenia (n = 23) and healthy controls (HCs, n = 31) underwent an fMRI scan while presented with both emotional and nonemotional words. RESULTS: Using HC as a reference, patients with FEP showed decreased right temporal activation, while patients with chronic schizophrenia showed increased bilateral temporal activation. When comparing the patient groups, individuals with FEP showed lower frontal lobe activation. CONCLUSION: To the best of our knowledge, this is the first study with an emotional auditory paradigm used in psychotic patients at different stages of the disease. Our results suggested that the temporal lobe might be a key issue in the physiopathology of psychosis, although abnormal activation could also be derived from a connectivity problem. There is lower activation in the early stage and evolution to greater activation when patients become chronic. This study highlights the relevance of using emotional paradigms to better understand brain activation at different stages of psychosis.
Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Psychotic Disorders/psychology , Schizophrenia/diagnostic imaging , Emotions/physiology , Brain/diagnostic imaging , Frontal Lobe , Magnetic Resonance ImagingSubject(s)
Magnetic Resonance Imaging , Voice , Humans , Follow-Up Studies , Brain/diagnostic imagingABSTRACT
Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples.
Subject(s)
Cannabis , Facial Recognition , Psychotic Disorders , Schizophrenia , Cannabinoid Receptor Agonists , Cross-Sectional Studies , Emotions , Humans , Psychotic Disorders/psychology , Schizophrenia/complications , Siblings/psychologyABSTRACT
INTRODUCTION: The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP. METHODS: Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines. RESULTS: Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum. CONCLUSIONS: While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation.