Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Long COVID 12 months after discharge: persistent symptoms in patients hospitalised due to COVID-19 and patients hospitalised due to other causes-a multicentre cohort study.

BACKGROUND: Long-term-specific sequelae or persistent symptoms (SPS) after hospitalisation due to COVID-19 are not known. The aim of this study was to explore the presence of SPS 12 months after discharge in survivors hospitalised due to COVID-19 and compare it with survivors hospitalised due to other causes. METHODS: Prospective cohort study, the Andalusian Cohort of Hospitalised patients for COVID-19 (ANCOHVID study), conducted in 4 hospitals and 29 primary care centres in Andalusia, Spain. The sample was composed of 906 adult patients; 453 patients hospitalised due to COVID-19 (exposed) and 453 hospitalised due to other causes (non-exposed) from March 1 to April 15, 2020, and discharged alive. The main outcomes were (1) the prevalence of SPS at 12 months after discharge and (2) the incidence of SPS after discharge. Outcome data at 12 months were compared between the exposed and non-exposed cohorts. Risk ratios were calculated, and bivariate analyses were performed. RESULTS: A total of 163 (36.1%) and 160 (35.3%) patients of the exposed and non-exposed cohorts, respectively, showed at least one SPS at 12 months after discharge. The SPS with higher prevalence in the subgroup of patients hospitalised due to COVID-19 12 months after discharge were persistent pharyngeal symptoms (p<0.001), neurological SPS (p=0.049), confusion or memory loss (p=0.043), thrombotic events (p=0.025) and anxiety (p=0.046). The incidence of SPS was higher for the exposed cohort regarding pharyngeal symptoms (risk ratio, 8.00; 95% CI, 1.85 to 36.12), confusion or memory loss (risk ratio, 3.50; 95% CI, 1.16 to 10.55) and anxiety symptoms (risk ratio, 2.36; 95% CI, 1.28 to 4.34). CONCLUSIONS: There was a similar frequency of long-term SPS after discharge at 12 months, regardless of the cause of admission (COVID-19 or other causes). Nevertheless, some symptoms that were found to be more associated with COVID-19, such as memory loss or anxiety, merit further investigation. These results should guide future follow-up of COVID-19 patients after hospital discharge.

The Affective Core of Delusional Disorder.

The aim of the present study is to investigate the relationship between personality, trait affectivity, and severity of delusions in patients with delusional disorder (DD). Thirty-two outpatients affected by DD were administered the Structured Interview for DSM-IV-TR Personality Disorders (SIDP-IV), the Pathological Narcissism Inventory (PNI), the Positive and Negative Affect Schedule (PANAS), and the Psychotic Symptom Rating Scale (PSYRATS). We analyzed the prevalence of personality disorder in our sample of patients with DD and studied the correlations between the severity of delusions and the different affective variables. Finally, we obtained a multivariate explanatory model of the severity of the delusions. The severity of delusions was directly associated with "grandiose fantasy" item of narcissistic personality and inversely related with the feelings of shame, fear, and guilt. In the multivariate model, the feeling of shame was the only independent variable capable of accounting for the severity of delusions that, in DD patients, would lie on an affective core of shame.

HEPATITIS C VIRUS SCREENING AND LINKAGE TO CARE IN MENTAL HEALTH UNITS: AN OPPORTUNITY FOR HCV ELIMINATION.

Hepatitis C Virus (HCV) affects approximately 71 million people infected, with 1.75 million people being diagnosed each year, according to the World Health Organization (WHO) estimates. HCV infection leads to cirrhosis, hepatocellular carcinoma (HCC), liver failure and death.

Current Evidences on Psychopharmacology of Schizoaffective Disorder.

Schizoaffective disorder (SAD) is a psychotic disorder which has presented a certain nosological controversy. Apart from these difficulties, very few studies focused in SAD as a distinct condition from schizophrenia have been found. This lack of specifical studies on SAD results in a lack of specific evidence about treatment. Currently, its treatment is based mainly on the use of antipsychotics, although there are no specific treatment guidelines for SAD. The objective of this review is to establish which are the most recommended treatments according to evidence available, considering clinical variables such as efficacy, safety, adherence, and tolerance as well as the role of these factors in different subtypes of SAD. This exhaustive review examines experimental and observational studies involving patients with a diagnosis of SAD. It was concluded that more clinical trials performed exclusively on patients affected by SAD are needed. Paliperidone, the only drug with authorized use in SAD, is the one that has the highest quality of studies to support its use. Risperidone, olanzapine, aripiprazole and ziprasidone also have randomized clinical trials supporting their efficacy and safety. In treatment-refractory patients, there are observational studies indicating the usefulness of clozapine. Likewise, there is evidence from observational studies showing the usefulness of lithium and carbamazepine during the treatment maintenance phase. It is necessary to establish the role of combined treatment with mood stabilizers and/or antidepressants.

A Psychopathological Comparison between Delusional Disorder and Schizophrenia.

OBJECTIVE: To contribute to a better differential clinical categorisation of delusional disorder (DD) versus schizophrenia (SZ) and to add and complete evidence from previous clinical studies of DD compared to schizophrenia. METHODS: A cross-sectional study using a clinical sample of 275 patients (132 patients with DD) was studied. Patients were consecutively attending public clinics located in urban and rural areas in both Andalusia and Catalonia (Spain). All participants met DSM-IV diagnostic criteria for either DD or SZ. Data were gathered on sociodemographics, illness duration, Barona-Index estimation of intelligence quotient (IQ), and global functioning, along with a thorough psychopathological assessment using the Positive and Negative Syndrome Scale (PANSS). Comparisons between both groups were calculated using χ2, Student t, and multivariate analysis of covariance tests. RESULTS: Patients with DD were older (mean [SD], 50.3 [14.6] years vs. 36.6 [11.1] years; t = 8.597; P ≤ 0.0001), were more frequently married (45.4% vs. 10.8%; χ2 = 38.569; P ≤ 0.0001), and had a higher mean estimated premorbid IQ (111.4 vs. 105.4; t = 2.609; P ≤ 0.01). On the other hand, SZ patients were predominantly male (71.4% vs. 48.9%; χ2 = 14.433; P ≤ 0.0001) and had greater work-related disability than DD patients (20.5% vs. 50.3%; χ2 = 19.564; P ≤ 0.001). Overall, the DD group showed a less severe PANSS psychopathology than SZ group. Thus, total mean (SD) PANSS scores for schizophrenia and delusional disorder, respectively, were 76.2 (22.4) versus 54.1 (18.4) ( t = -8.762; P ≤ 0.0001). Moreover, patients with DD showed a better global functioning than those with SZ (62.7 [13.2] vs. 51.9 [16.9]; F = 44.114; P ≤ 0.0001). CONCLUSIONS: DD is a milder and distinct disorder compared to SZ in terms of psychopathology and global functionality.

A Cross-Sectional Study on the Prevalence and Risk Correlates of Mental Disorders: The GRANADΣP Study.

This is a cross-sectional study of participants from a population census living in the province of Granada (Spain). A total of 1176 persons were contacted, 367 (31%) refused and 54 (6.7%) needed substitution. A final sample of 809 participants (response rate, 69.3%) were screened for mental disorder (MD) using the MINI International Neuropsychiatric Interview, a comprehensive interview validated to generate diagnoses compatible with ICD-10/DSM-4 criteria. Current (1-month) prevalence for any MD was 11.3% (95% confidence interval [CI], 9.7%-13.4%; affective 8.2%, anxiety 9.6%, psychotic 2.1%, addiction 1.8%, personality disorder 3.6%). Lifetime MD prevalence was 24.6% (95% CI, 21.6-27.6; affective 14.9%, anxiety 15.5%, psychotic 3.4%, addiction 4.4%, personality disorder 3.6%). Female sex was associated with MD, but this appeared partially due to higher levels of neuroticism among women. MD also correlated significantly with cannabis use, family history of MD, higher social adversity, higher suicide risk, poorer physical health, poorer cognitive performance, and personality problems.

A Systematic Review on the Pharmacological Treatment of Delusional Disorder.

BACKGROUND: Pharmacological treatment is the criterion standard in delusional disorder (DD). No second-generation antipsychotic (SGA) is specifically authorized for the treatment of DD. AIMS: To evaluate the evidence available on pharmacological treatments in adults with DD and to compare first-generation antipsychotics (FGA) versus SGA. METHODS: A systematic review on pharmacological treatment of DD following the PRISMA methodology was conducted. We selected the best evidence available and analyzed it critically assessing both, biases and quality, to finally perform a narrative and quantitative synthesis. RESULTS: The evidence available was mainly limited to observational studies and case series. There were no randomized clinical trials. Three hundred eighty-five DD cases were included (177 of which were on SGAs). Overall, antipsychotics achieved a good response in 33.6%% of the patients. As a group, FGAs showed significant superiority compared to SGAs (good response rates were 39% vs 28%, respectively). We did not find superiority of any specific antipsychotic over another. CONCLUSIONS: There is no strong evidence to make definite recommendations, although antipsychotics in general seem to be an effective treatment for DD with a slight superiority in favor of FGAs as compared with SGAs. Existent data are, albeit, scarce and specific clinical trials on DD, are strongly recommended.

Quality of care and its determinants in longer term mental health facilities across Europe; a cross-sectional analysis.

BACKGROUND: The Quality Indicator for Rehabilitative Care (QuIRC) is an international, standardised quality tool for the evaluation of mental health facilities that provide longer term care. Completed by the service manager, it comprises 145 items that assess seven domains of care: living environment; treatments and interventions; therapeutic environment; self-management and autonomy; social interface; human rights; and recovery based practice. We used the QuIRC to investigate associations between characteristics of longer term mental health facilities across Europe and the quality of care they delivered to service patients. METHODS: QuIRC assessments were completed for 213 longer term mental health units in ten countries that were at various stages of deinstitutionalisation of their mental health services. Associations between QuIRC domain scores and unit descriptive variables were explored using simple and multiple linear regression that took into account clustering at the unit and country level. RESULTS: We found wide variation in QuIRC domain scores between individual units, but across countries, fewer than a quarter scored below 50 % on any domains. The quality of care was higher in units that were smaller, of mixed sex, that had a defined expected maximum length of stay and in which not all patients were severely disabled. CONCLUSIONS: This is the first time longer term mental health units across a number of European countries have been compared using a standardised measure. Further use of the QuIRC will allow greater understanding of the quality of care in these units across Europe and provide an opportunity to monitor pan-European quality standards of care for this vulnerable patient group.

The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study.

BACKGROUND: There is limited evidence for a moderating role of both serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) genes on the risk for major depression (MD) developing after childhood maltreatment. However, research on this topic remains inconclusive, and there is a lack of data from longitudinal studies with large and representative population samples. Our study aimed to clarify whether, in the presence of previous childhood maltreatment, individuals carrying low functional alleles for both SERT 5-HTTLPR and BDNF Val66Met polymorphisms had a higher risk for MD. METHODS: We explored 2- and 3-way gene (SERT and BDNF) × environment (childhood maltreatment) interactions in a large sample of Spanish adults who were followed up over a 3-year period and assessed in person for both DSM-IV MD and exposure to childhood maltreatment. RESULTS: Our study included 2679 participants. Those with both the 5-HTTLPR s allele and the BDNF Met allele showed the highest risk of MD if they had previously experienced emotional (z = 2.08, p = 0.037), sexual (z = 2.19, p = 0.029) or any kind of childhood abuse (z = 2.37, p = 0.018). These 3-way interactions remained significant regardless of whether the 5-HTTLPR triallelic or the 5-HTTLPR biallelic polymorphisms were included in the analyses. LIMITATIONS: Retrospective assessment of childhood maltreatment may have resulted in a moderate degree of recall bias. CONCLUSION: Our results confirm that the risk of depression conferred by childhood maltreatment is modified by variation at both SERT and BDNF genes.

Do patient and ward-related characteristics influence the use of coercive measures? Results from the EUNOMIA international study.

PURPOSE: This study aims to identify whether selected patient and ward-related factors are associated with the use of coercive measures. Data were collected as part of the EUNOMIA international collaborative study on the use of coercive measures in ten European countries. METHODS: Involuntarily admitted patients (N = 2,027) were divided into two groups. The first group (N = 770) included patients that had been subject to at least one of these coercive measures during hospitalization: restraint, and/or seclusion, and/or forced medication; the other group (N = 1,257) included patients who had not received any coercive measure during hospitalization. To identify predictors of use of coercive measures, both patients' sociodemographic and clinical characteristics and centre-related characteristics were tested in a multivariate logistic regression model, controlled for countries' effect. RESULTS: The frequency of the use of coercive measures varied significantly across countries, being higher in Poland, Italy and Greece. Patients who received coercive measures were more frequently male and with a diagnosis of psychotic disorder (F20-F29). According to the regression model, patients with higher levels of psychotic and hostility symptoms, and of perceived coercion had a higher risk to be coerced at admission. Controlling for countries' effect, the risk of being coerced was higher in Poland. Patients' sociodemographic characteristics and ward-related factors were not identifying as possible predictors because they did not enter the model. CONCLUSIONS: The use of coercive measures varied significantly in the participating countries. Clinical factors, such as high levels of psychotic symptoms and high levels of perceived coercion at admission were associated with the use of coercive measures, when controlling for countries' effect. These factors should be taken into consideration by programs aimed at reducing the use of coercive measures in psychiatric wards.

Epidemiology of social phobia in Andalusia.

INTRODUCTION: Population studies on social anxiety disorder (SAD) are relatively scarce and there is no previous reported evidence on prevalence or correlates of SAD in an Andalusian general population sample. MATERIAL AND METHODS: We used a random representative sample previously identified via standard stratification procedures. Thus, a final sample of 4507 participants were included (response rate 83.7%). Interviewees were thoroughly assessed on sociodemographic, clinical and psychosocial factors, including: exposures to threatening life events (TLEs), childhood abuse, personality disorder and traits (neuroticism, impulsivity, paranoia), global functioning, physical health and toxics consumption. SAD diagnosis was ascertained using the Mini International Neuropsychiatric Interview. Both, pooled prevalences (with 95% confidence intervals) and risk correlates for SAD were estimated using binary logistic regression. RESULTS: Estimated prevalence for SAD was 1.1% (95% CI=0.8-1.4). Having a SAD diagnosis was independently and significantly associated with younger age, poorer global functioning, higher neuroticism and paranoia personality traits, having suffered childhood abuse and exposure to previous TLEs. Furthermore, SAD was significantly associated with comorbid personality disorder, major depression, panic disorder and alcohol abuse. CONCLUSIONS: Among this large Andalusian population sample, the prevalence of SAD and its associated factors are relatively similar to previously reported international studies, although no population study had previously reported such a strong association with paranoia.

An epidemiological survey on personality disorder in Andalusia (the PISMA-ep PD study).

BACKGROUND: Despite a significant clinical and social burden, there is a relative scarcity of epidemiological studies on Personality Disorder (PD). AIM: To determine the current prevalence of PD and the psychosocial correlates associated with this in the Andalusian population. METHOD: We carried out a cross-sectional population mental-health survey in Andalusia, southern Spain. Thus, 4,518 randomly selected participants were interviewed following sampling using different standard stratification levels. We used the Spanish version of the SAPAS to estimate PD prevalence. In addition, a full battery of other instruments was utilized to explore global functionality, childhood abuse, maltreatment, threatening life events, personality traits (neuroticism, impulsivity and paranoia), medical and psychiatric comorbidities, family history of psychological problems and other potential risk factors for PD. RESULTS: PD prevalence (10.8%; 95% CI [9.8, 11.7]) and ran two different multivariate models for PD. We obtained the highest PD prevalence in those affected by any mental disorder plus those reporting having suffered childhood abuse, particularly sexual abuse. Additional potential risk factors or correlates of PD identified were: younger age, lower levels of functioning, less social support, poorer general health, having suffered maltreatment, threatening life events, higher suicidal risk scores and higher levels of both neuroticism and impulsivity. CONCLUSIONS: This study reports PD prevalence and risk correlates in consonance with similar findings reported in other Western populations. However, longitudinal studies are needed to elicit a more thorough group of prospective determinants of PD.

Undiagnosed mood disorders and sleep disturbances in primary care patients with chronic musculoskeletal pain.

OBJECTIVE: The study aims to determine the prevalence of undiagnosed comorbid mood disorders in patients suffering chronic musculoskeletal pain in a primary care setting and to identify sleep disturbances and other associated factors in these patients, and to compare the use of health services by chronic musculoskeletal pain patients with and without comorbid mood disorders. DESIGN: Cross-sectional study. SUBJECTS: A total of 1,006 patients with chronic musculoskeletal pain from a representative sample of primary care centers were evaluated. OUTCOME MEASURES: Pain was measured using a visual analog scale and the Primary Care Evaluation of Mental Disorders questionnaire was used to measure mood disorders. RESULTS: We observed a high prevalence of undiagnosed mood disorders in chronic musculoskeletal pain patients (74.7%, 95% confidence interval [CI] 71.9-77.4%), with greater comorbidity in women (adjusted odds ratio [OR] = 1.91, 95% CI 1.37-2.66%) and widow(er)s (adjusted OR = 1.87, 95% CI 1.19-2.91%). Both sleep disturbances (adjusted OR = 1.60, 95% CI 1.17-2.19%) and pain intensity (adjusted OR = 1.02, 95% CI 1.01-1.02%) displayed a direct relationship with mood disorders. Moreover, we found that chronic musculoskeletal pain patients with comorbid mood disorders availed of health care services more frequently than those without (P < 0.001). CONCLUSIONS: The prevalence of undiagnosed mood disorders in patients with chronic musculoskeletal pain is very high in primary care settings. Our findings suggest that greater attention should be paid to this condition in general practice and that sleep disorders should be evaluated in greater detail to achieve accurate diagnoses and select the most appropriate treatment.

Factors associated with chronic pain in patients with bipolar depression: a cross-sectional study.

BACKGROUND: While pain is frequently associated with unipolar depression, few studies have investigated the link between pain and bipolar depression. In the present study we estimated the prevalence and characteristics of pain among patients with bipolar depression treated by psychiatrists in their regular clinical practice. The study was designed to identify factors associated with the manifestation of pain in these patients. METHODS: Patients diagnosed with bipolar disorder (n=121) were selected to participate in a cross-sectional study in which DSM-IV-TR criteria were employed to identify depressive episodes. The patients were asked to describe any pain experienced during the study, and in the 6 weeks beforehand, by means of a Visual Analogical Scale (VAS). RESULTS: Over half of the bipolar depressed patients (51.2%, 95% CI: 41.9%-60.6%), and 2/3 of the female experienced concomitant pain. The pain was of moderate to severe intensity and prolonged duration, and it occurred at multiple sites, significantly limiting the patient's everyday activities. The most important factors associated with the presence of pain were older age, sleep disorders and delayed diagnosis of bipolar disorder. CONCLUSIONS: Chronic pain is common in bipolar depressed patients, and it is related to sleep disorders and delayed diagnosis of their disorder. More attention should be paid to study the presence of pain in bipolar depressed patients, in order to achieve more accurate diagnoses and to provide better treatment options.

Empirical redefinition of delusional disorder and its phenomenology: the DELIREMP study.

AIMS: Since Kraepelin, the controversy has persisted surrounding the nature of delusional disorder (DD) as a separate nosological entity or its clinical subtypes. Nevertheless, there has been no systematic study of its psychopathological structure based on patient interviews. Our goal was to empirically explore syndromic subentities in DD. METHODS: A cross-sectional study was conducted in 86 outpatients with DSM-IV-confirmed DD using SCID-I. Psychopathological factors were identified by factor analysis of PANSS scores. The association between these factors and clinical variables (as per standardized instruments) was analyzed using uni- and multivariate techniques. RESULTS: PANSS symptoms were consistent with four factors (Paranoid, Cognitive, Schizoid, and Affective dimensions), accounting for 59.4% of the total variance. The Paranoid Dimension was associated with premorbid paranoid personality disorder, more adverse childhood experiences, chronic course, legal problems, worse global functioning, and poorer treatment adherence and response. The Cognitive Dimension was associated with poorer cognitive functioning, premorbid substance abuse, comorbid somatic diseases, mainly non-prominent visual hallucinations, fewer comorbid depressive disorders, and poorer global functioning. The Schizoid Dimension was associated with being single, a family history of schizophrenia, premorbid personality disorders (largely schizoid and schizotypal), non-prominent auditory hallucinations, and dysthymia. Finally, the Affective Dimension was associated with a family history of depression, premorbid obsessive personality, somatic delusions, absence of reference delusions, tactile and olfactory hallucinations, depressive and anxiety disorders, risk of suicide, and higher perceived stress. CONCLUSION: The identification and clinical validation of four separate psychopathological dimensions in DD provide evidence toward a more accurate conceptualization of DD and its types.

Spanish validation of the Premorbid Adjustment Scale (PAS-S).

BACKGROUND: The Premorbid Adjustment Scale (PAS) has been the most widely used scale to quantify premorbid status in schizophrenia, coming to be regarded as the gold standard of retrospective assessment instruments. AIMS: To examine the psychometric properties of the Spanish version of the PAS (PAS-S). METHOD: Retrospective study of 140 individuals experiencing a first episode of psychosis (n=77) and individuals who have schizophrenia (n=63), both adult and adolescent patients. Data were collected through a socio-demographic questionnaire and a battery of instruments which includes the following scales: PAS-S, PANSS, LSP, GAF and DAS-sv. The Cronbach's alpha was performed to assess the internal consistency of PAS-S. Pearson's correlations were performed to assess the convergent and discriminant validity. RESULTS: The Cronbach's alpha of the PAS-S scale was 0.85. The correlation between social PAS-S and total PAS-S was 0.85 (p<0.001); while for academic PAS-S and total PAS-S it was 0.53 (p<0.001). Significant correlations were observed between all the scores of each age period evaluated across the PAS-S scale, with a significance value less than 0.001. There was a relationship between negative symptoms and social PAS-S (0.20, p<0.05) and total PAS-S (0.22, p<0.05), but not with academic PAS-S. However, there was a correlation between academic PAS-S and general subscale of the PANSS (0.19, p<0.05). Social PAS-S was related to disability measures (DAS-sv); and academic PAS-S showed discriminant validity with most of the variables of social functioning. PAS-S did not show association with the total LSP scale (discriminant validity). CONCLUSION: The Spanish version of the Premorbid Adjustment Scale showed appropriate psychometric properties in patients experiencing a first episode of psychosis and who have a chronic evolution of the illness. Moreover, each domain of the PAS-S (social and academic premorbid functioning) showed a differential relationship to other characteristics such as psychotic symptoms, disability or social functioning after onset of illness.

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations.

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10-6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.

Neuropsychological research in delusional disorder: a comprehensive review.

In recent decades, there has been a growing interest in the field of delusions, and different aspects of delusional disorder (DD) have been investigated. However, DD is still one of the most underresearched psychiatric disorders. In this paper, we review the literature on DD and most of the theoretical approaches proposed to explain the development and maintenance of delusions. DD research is infrequent, and delusions in this disorder have been scarcely investigated. We aim to establish the state of the art of delusions research to date and point to the shortage of neuropsychological studies in patients with DD. We also justify the need for future research into the neuropsychological correlates of DD as measured in patients with this disorder given that most previous research has mainly focused on other psychotic conditions.

Psychotic symptoms associate inversely with social support, social autonomy and psychosocial functioning: A community-based study.

BACKGROUND: Population-based studies exploring psychotic symptoms (PS) show that their prevalence in the community is higher than previously thought. Psychosocial functioning and social support are poorer among people presenting clinical and subclinical PS. AIMS: We aimed to estimate the prevalence rate of PS in Andalusia and to explore the association between PS and psychosocial functioning, social support and social autonomy in a Southern European population. MATERIAL AND METHODS: This is a cross-sectional study. We undertook multi-stage sampling using different standard stratification techniques. Out of 5496 households approached, we interviewed 4507 (83.7%) randomly selected participants living in the autonomous region of Andalusia (Southern Spain). The Spanish version of the MINI International Neuropsychiatric Interview was used to elicit PS. We also gathered information on socio-demographic factors, suicidality risk, psychosocial functioning, social support and social autonomy. RESULTS: The overall prevalence of PS was 6.7% (95% CI: 5.99-6.45). PS were associated with lower age (OR 0.975; 95% CI (0.967-0.983); p < .0001), female gender (OR = 1.346; 95% CI (1.05-1.07) p = .018), not living in a rural area (OR = 0.677; 95% CI (0.50-0.90) p = 0.009), lower social support (OR = 0.898; 95% CI (0.85-0.94) p < .0001), lower scores on social autonomy (OR = 0.889; 95% CI (0.79-1.00) p = .050), having an increased suicidality risk score (OR = 1.038; 95% CI (1.005-1.07); p = .023) and having lower scores on psychosocial functioning (OR = 0.956; 95% CI (0.95-0.96); p < 0.0001). CONCLUSIONS: Social outcomes seem to be strongly inversely associated with PS in spite of presumed higher levels of social support among Southern European cultures.