Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Neural correlates of prenatal stress in young women.

BACKGROUND: Prenatal stress is hypothesized to have a disruptive impact on neurodevelopmental trajectories, but few human studies have been conducted on the long-term neural correlates of prenatal exposure to stress. The aim of this study was to explore the relationship between prenatal stress exposure and gray-matter volume and resting-state functional connectivity in a sample of 35 healthy women aged 14-40 years. METHOD: Voxel-based morphometry and functional connectivity analyses were performed on the whole brain and in specific regions of interest (hippocampus and amygdala). Data about prenatal/postnatal stress and obstetric complications were obtained by interviewing participants and their mothers, and reviewing obstetric records. RESULTS: Higher prenatal stress was associated with decreased gray-matter volume in the left medial temporal lobe (MTL) and both amygdalae, but not the hippocampus. Variance in gray-matter volume of these brain areas significantly correlated with depressive symptoms, after statistically adjusting for the effects of age, postnatal stress and obstetric complications. Prenatal stress showed a positive linear relationship with functional connectivity between the left MTL and the pregenual cortex. Moreover, connectivity between the left MTL and the left medial-orbitofrontal cortex partially explained variance in the depressive symptoms of offspring. CONCLUSIONS: In young women, exposure to prenatal stress showed a relationship with the morphometry and functional connectivity of brain areas involved in the pathophysiology of depressive disorders. These data provide evidence in favor of the hypothesis that early exposure to stress affects brain development and identified the MTL and amygdalae as possible targets of such exposure.

In utero exposure to virus infections and the risk of developing anorexia nervosa.

BACKGROUND: The study aims to explore, using indirect ecological measures of exposure, the role of viral infections in the development of anorexia nervosa (AN). METHOD: The cohort of participants consisted of all female subjects born in the Veneto region in the period between 1970 and 1984, and residing in the urban and suburban area of Padua (27,682 female subjects in an area of 424 km2). The main outcome measure was the diagnosis of AN resulting from the Public Mental Health Database, the Register of Hospital Admissions, and the Register of the Eating Disorders Unit (n=402, 1.4%). The number of cases of rubella, chickenpox, influenza and measles was ascertained for each month for the 15-year period. RESULTS: Exposures during the sixth month of pregnancy to the peaks of chickenpox [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.0] and rubella infections (OR 1.5, 95% CI 1.1-2.0) were significantly associated with an increased risk of developing AN, even after controlling for socio-economic status, urbanization and month of birth. We found weak evidence of a season-of-birth bias. CONCLUSIONS: In utero exposure to viral infection could be a risk factor for developing AN. We need further epidemiological and serological studies to confirm this hypothesis.

The interaction between perinatal factors and childhood abuse in the risk of developing anorexia nervosa.

BACKGROUND: Perinatal factors seem to be implicated in the pathogenesis of anorexia nervosa (AN) and may be involved in the programming of stress response systems in humans. Our aim was to explore one of the possible pathways to explain the association between perinatal complications and a psychiatric disorder. In particular, we tested the hypothesis that neonatal immaturity may confer an enhanced vulnerability to AN after exposure to a severe stressful event, such as childhood abuse. METHOD: The sample was composed of subjects who took part in a prevalence study carried out on a representative sample of the general population and cases of AN referred to an out-patient specialist unit. All subjects (n=663) were born in the two obstetric wards of Padua Hospital between 1971 and 1979. We analysed data using both a case-control and a cohort design. RESULTS: We found that functional signs of neonatal dysmaturity, but not a low birthweight or prematurity, had a significant additive interaction with childhood abuse in determining the risk for this illness. In normal subjects, but not in subjects with AN, neonatal dysmaturity was associated with being small, short or thin for gestational age at birth. CONCLUSIONS: The synergistic effect of neonatal dysmaturity and childhood abuse in increasing the risk for AN provides evidence for the hypothesis that a prenatal programming of stress response systems can result in an impairment of the individual's resilience to severe stressful events.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies.

UNLABELLED: Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. - comparing low and high-functioning genotype and allele frequencies in ED vs. CONTROLS: Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. CONTROLS: Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias.