RESUMEN

OBJECTIVES: The extent to which heterogeneity in childhood risk trajectories may underlie later heterogeneity in schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) remains a chief question. Answers may optimally be found by studying the longitudinal trajectories of children born to an affected parent. We aimed to differentiate trajectories of global functioning and their sensitive periods from the age of 6 to 17 years in children at familial risk (FHRs). METHODS: First, a latent class mixed model analysis (LCMM) was applied to yearly ratings of the Children's Global Assessment Scale (CGAS) from the age of 6 to 17 years in 170 FHRs born to a parent affected by DSM-IV SZ (N = 37), BP (N = 82) or MDD (N = 51). Then, we compared the obtained Classes or trajectories of FHRs in terms of sex, parental diagnosis, IQ, child clinical status, childhood trauma, polygenic risk score (PRS), and outcome in transition to illness. RESULTS: The LCMM on yearly CGAS trajectories identified a 4-class solution showing markedly different childhood and adolescence dynamic courses and temporal vulnerability windows marked by a functioning decline and a degree of specificity in parental diagnosis. Moreover, IQ, trauma exposure, PRS level, and timing of later transition to illness differentiated the trajectories. Almost half (46%) of the FHRs exhibited a good and stable global functioning trajectory. CONCLUSIONS: FHRs of major psychiatric disorders show heterogeneous functional decline during development associated with parental diagnosis, polygenic risk loading, and childhood trauma.

RESUMEN

With the cost-effectiveness technology in whole-genome sequencing, more sophisticated statistical methods for testing genetic association with both rare and common variants are being investigated to identify the genetic variation between individuals. Several methods which group variants, also called gene-based approaches, are developed. For instance, advanced extensions of the sequence kernel association test, which is a widely used variant-set test, have been proposed for unrelated samples and extended for family data. Family data have been shown to be powerful when analyzing rare variants. However, most of such methods capture familial relatedness using a random effect component within the generalized linear mixed model framework. Therefore, there is a need to develop unified and flexible methods to study the association between a set of genetic variants and a trait, especially for a binary outcome. Copulas are multivariate distribution functions with uniform margins on the [0,1] interval and they provide suitable models to capture familial dependence structure. In this work, we propose a flexible family-based association test for both rare and common variants in the presence of binary traits. The method, termed novel rare variant association test (NRVAT), uses a marginal logistic model and a Gaussian Copula. The latter is employed to model the dependence between relatives. An analytic score-type test is derived. Through simulations, we show that our method can achieve greater power than existing approaches. The proposed model is applied to investigate the association between schizophrenia and bipolar disorder in a family-based cohort consisting of 17 extended families from Eastern Quebec.

Asunto(s)

Variación Genética , Modelos Genéticos , Humanos , Simulación por Computador , Estudios de Asociación Genética , Fenotipo , Modelos Lineales

RESUMEN

Genetic correlations between human traits and disorders such as schizophrenia (SZ) and bipolar disorder (BD) diagnoses are well established. Improved prediction of individual traits has been obtained by combining predictors of multiple genetically correlated traits derived from summary statistics produced by genome-wide association studies, compared with single trait predictors. We extend this idea to penalized regression on summary statistics in Multivariate Lassosum, expressing regression coefficients for the multiple traits on single nucleotide polymorphisms (SNPs) as correlated random effects, similarly to multi-trait summary statistic best linear unbiased predictors (MT-SBLUPs). We also allow the SNP contributions to genetic covariance and heritability to depend on genomic annotations. We conducted simulations with two dichotomous traits having polygenic architecture similar to SZ and BD, using genotypes from 29,330 subjects from the CARTaGENE cohort. Multivariate Lassosum produced polygenic risk scores (PRSs) more strongly correlated with the true genetic risk predictor and had better discrimination power between affected and non-affected subjects than previously published sparse multi-trait (PANPRS) and univariate (Lassosum, sparse LDpred2, and the standard clumping and thresholding) methods in most simulation settings. Application of Multivariate Lassosum to predict SZ, BD, and related psychiatric traits in the Eastern Quebec SZ and BD kindred study revealed associations with every trait stronger than those obtained with univariate sparse PRSs, particularly when heritability and genetic covariance depended on genomic annotations. Multivariate Lassosum thus appears promising to improve prediction of genetically correlated traits with summary statistics for a selected subset of SNPs.

Asunto(s)

Estudio de Asociación del Genoma Completo , Esquizofrenia , Humanos , Estudio de Asociación del Genoma Completo/métodos , Fenotipo , Genotipo , Factores de Riesgo , Esquizofrenia/diagnóstico

RESUMEN

We previously proposed the electroretinogram (ERG) as a promising biomarker of major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP), given that we found anomalies in the ERG parameters of patients with these diagnoses as well as in their children who are at high risk (HR) of developing such disorders. The aim of the present study is to investigate the usefulness of the ERG for individual detection, among HR children, of an ERG profile resembling that of a SZ patient, as this may indicate a stronger likelihood of transition to psychosis. Using a logistic regression model previously derived from the ERG assessments of SZ patients and control (CT) subjects, individual risk scores were obtained for 61 HR and 80 CT youth. Those with a very high individual risk score were classified as "schizophrenia-like" (SZ-like). We found that the HR subjects were 3.5 times more likely to be classified as SZ-like than the CT subjects (95% CI [1.1-11.8]). Furthermore, among the HR subjects, we studied the relationship between the SZ-like classification and psychotic-like experiences and found that HR subjects classified as SZ-like were 2.7 times more likely than all remaining HR subjects to have experienced psychotic-like symptoms (95% CI [1.3-4.6]), and 6.8 times more likely than those with a very low individual risk score (95% CI [1.4-40.4]). Our results suggest that a model previously derived from ERG data on SZ patients could be a potential tool for early detection of the susceptibility to a psychotic-like disorder among familial HR children.

RESUMEN

Background: Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk. Methods: We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring. Results: Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58). Conclusion: Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders.

RESUMEN

OBJECTIVES: Previous studies have indicated that schizophrenia (SCZ) is linked to abnormal phospholipid and fatty acid metabolism. However, comprehensive analysis of phospholipids and free fatty acids (FFAs) for SCZ is very limited. Herein, we sought to compare serum levels of phospholipids and FFAs between patients with SCZ and healthy controls (HCs). METHODS: One hundred and nineteen SCZ patients and 109 HCs were enrolled in the study. The levels of 177 phospholipids and FFAs were measured in serum samples using a targeted liquid chromatography-mass spectrometry (LC-MS)-based platform. RESULTS: One hundred and ten metabolites, including 16 FFAs, 25 phosphatidylcholines, 23 lysophosphatidylcholines, 11 phosphatidylcholine plasmalogens, 7 phosphatidylethanolamines, 9 lysophosphatidylethanolamines, 6 phosphatidylethanolamine plasmalogens, and 13 sphingomyelins, were observed to be significantly altered in SCZ patients compared to HCs. These disturbances may represent underlying pathophysiology, including but not limited to altered activity of phospholipases and acyltransferases, increased oxidative stress, dysfunctional oligodendrocyte glycosynapses, and elevated lipid mobilisation and ß-oxidation. CONCLUSIONS: Our findings suggest that complex lipid profile abnormalities are associated with SCZ. This study may contribute to investigating the role of phospholipid and FFA alterations in the pathoetiology of SCZ.

Asunto(s)

Ácidos Grasos no Esterificados , Esquizofrenia , Estudios de Casos y Controles , Cromatografía Liquida , Humanos , Metabolismo de los Lípidos

RESUMEN

INTRODUCTION: Almost a third of the offspring of parents diagnosed with schizophrenia or bipolar disorder could develop a mental disorder or related symptoms. The objectives of this study were to test the existence of two distinct subgroups of youth at-risk, according to their retinal response to luminance measured with electroretinography (ERG), and to relate the resulting cluster memberships with the cognitive clusters previously reported. METHODOLOGY: A clustering analysis was performed with ERG measurements in 107 at-risk offspring. Each subgroup was compared to a healthy control group of 203 individuals. The ERG subgroup memberships were then associated with the cognitive clusters. RESULTS: A two-cluster solution was obtained: HR-Cluster1 (n=53) showed a control-like ERG profile and HR-Cluster2 (n=54) showed reduced rod amplitudes and prolonged cone latencies of the b-wave. Subjects in the HR-Cluster2 were 2.7 times more likely to belong to the most detrimental cognitive subgroup than subjects in the HR-Cluster1 (49% Vs 18%). CONCLUSION: At-risk offspring showed two distinct ERG profiles: a control-like and an altered profile. A higher risk of impaired cognitive function was observed in subjects with the altered ERG profile, suggesting the ERG as a potential biomarker of susceptibility to mental illness among youth at risk.

Asunto(s)

Trastorno Bipolar/fisiopatología , Disfunción Cognitiva/fisiopatología , Electrorretinografía/métodos , Retina/fisiopatología , Esquizofrenia/fisiopatología , Adolescente , Adulto , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Niño , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Estudios de Cohortes , Femenino , Humanos , Masculino , Factores de Riesgo , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto Joven

RESUMEN

INTRODUCTION: Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development, and later psychopathologies. The study aimed to determine the extent to which the coronavirus disease 2019 (COVID-19) pandemic may aggravate the prenatal distress and psychiatric symptomatology of pregnant women. MATERIAL AND METHODS: Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n = 496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n = 1258) was recruited online during the pandemic from 2 April to 13 April 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II), and Positive and Negative Affect Schedule (PANAS). RESULTS: The 1754 pregnant women (Mage  = 29.27, SD = 4.23) were between 4 and 41 gestational weeks (M = 24.80, SD = 9.42), were generally educated (91.3% had post-high-school training), and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education, and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' λ = 0.68, F6,1400  = 108.50, P < .001, partial η2  = 0.32). According to post-hoc analyses of covariance, the COVID-19 women reported higher levels of depressive and anxiety symptoms (ES = 0.57), dissociative symptoms (ES = 0.22 and ES = 0.25), symptoms of post-traumatic stress disorder (ES = 0.19), and negative affectivity (ES = 0.96), and less positive affectivity (ES = 0.95) than the pre-COVID-19 cohort. Women from the COVID-19 cohort were more likely than pre-COVID-19 women to present clinically significant levels of depressive and anxiety symptoms (OR = 1.94, χ2 [1] = 10.05, P = .002). Multiple regression analyses indicated that pregnant women in the COVID-19 cohort having a previous psychiatric diagnosis or low income would be more prone to elevated distress and psychiatric symptoms. CONCLUSIONS: Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.

Asunto(s)

Ansiedad , Infecciones por Coronavirus , Depresión , Pandemias , Neumonía Viral , Complicaciones del Embarazo , Mujeres Embarazadas/psicología , Estrés Psicológico , Adulto , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/etiología , Ansiedad/fisiopatología , Betacoronavirus/aislamiento & purificación , COVID-19 , Canadá/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/psicología , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Depresión/fisiopatología , Femenino , Humanos , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/psicología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/fisiopatología , Complicaciones del Embarazo/psicología , Escalas de Valoración Psiquiátrica , SARS-CoV-2 , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/prevención & control , Estrés Psicológico/diagnóstico , Estrés Psicológico/epidemiología , Estrés Psicológico/etiología , Estrés Psicológico/fisiopatología

Asunto(s)

Trastornos Mentales , Psiquiatría , Humanos , Neurobiología , Retina

RESUMEN

The complexity of schizophrenia (SZ) and bipolar disorder (BD) has slowed down progress in understanding their genetic roots. Alternative genomic approaches are needed to bypass these difficulties. We attempted a multimodal approach to follow-up on reported linkage findings in SZ and BD from the Eastern Quebec kindreds in chromosomes 3q21, 4p34, 6p22, 8p21, 8p11, 13q11-q14, 15q13, 16p12, and 18q21. First, in 498 subjects, we measured RNA expression (47 K Illumina chips) in SZ and BD patients that we compared with their non-affected relatives (NARs) to identify, for each chromosomal region, genes showing the most significant differences in expression. Second, we performed SNP genotyping (700 K Illumina chips) and cis-eQTN analysis. Third, we measured DNA methylation on genes with RNA expression differences or eQTNs. We found a significant overexpression of the gene ITGB5 at 3q25 in SZ and BD after multiple testing p value adjustment. SPCS3 gene at 4q34, and FZD3 gene at 8p21, contained significant eQTNs after multiple testing corrections, while ITGB5 provided suggestive results. Methylation in associated genes did not explain the expression differences between patients and NARs. Our multimodal approach involving RNA expression, dense SNP genotyping and eQTN analyses, restricted to chromosomal regions having shown linkage, lowered the multiple testing burden and allowed for a deeper examination of candidate genes in SZ or BD.

Asunto(s)

Trastorno Bipolar/genética , Metilación de ADN , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Esquizofrenia/genética , Transcriptoma , Línea Celular , Cromosomas/genética , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Técnicas de Genotipaje/métodos , Humanos , Cadenas beta de Integrinas/genética , Cadenas beta de Integrinas/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo

RESUMEN

BACKGROUND: The retina is recognized as an approachable part of the brain owing to their common embryonic origin. The electroretinogram (ERG) has proved to be a valuable tool to investigate psychiatric disorders. We therefore investigated its accuracy as a tool to differentiate schizophrenia (SZ) from bipolar disorder (BP) even after balancing patients for their main antipsychotic medication. METHODS: ERG cone and rod luminance response functions were recorded in 150 patients with SZ and 151 patients with BP and compared with 200 control subjects. We created a subgroup of subjects-45 with SZ and 45 with BP-balanced for their main antipsychotic medication. RESULTS: A reduced cone a-wave amplitude and a prolonged b-wave latency were observed in both disorders, whereas a reduced cone b-wave amplitude was present in SZ only. Reduced mixed rod-cone a- and b-wave amplitudes were observed in both disorders. Patients with SZ were distinguishable from control subjects with 0.91 accuracy, 77% sensitivity, and 91% specificity with similar numbers for patients with BP (0.89, 76%, and 88%, respectively). Patients with SZ and patients with BP could be differentiated with an accuracy of 0.86 (whole sample) and 0.83 (subsamples of 45 patients with 80% sensitivity and 82% specificity). Antipsychotic dosages were not correlated with ERG parameters. CONCLUSIONS: The ERG waveform parameters used in this study provided a very accurate distinction between the two disorders when using a logistic regression model. This supports the ERG as a tool that could aid the clinician in the differential diagnosis of SZ and BP in stabilized medicated patients.

Asunto(s)

Trastorno Bipolar , Esquizofrenia , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Encéfalo , Electrorretinografía , Humanos , Retina , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico

RESUMEN

BACKGROUND: Visual defects are documented in psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder. One of the most consistent alterations in patients is a change in cone and rod electroretinographic (ERG) responses. We previously showed a reduced rod b-wave amplitude in a small sample of young offspring born to an affected parent. A confirmation of the patients ERG anomalies in young offspring at high genetic risk would offer a new approach to the neurodevelopmental investigation of the illness. We thus investigated cone and rod responses in a larger sample of young healthy high-risk offspring. METHODS: The ERG was recorded in 99 offspring of patients having DMS-IV schizophrenia, bipolar or major depressive disorder (mean age 16.03; SD 6.14) and in 223 healthy controls balanced for sex and age. The a- and b-wave latency and amplitude of cones and rods were recorded. RESULTS: Cone b-wave latency was increased in offspring (ES = 0.31; P = 0.006) whereas rod b-wave amplitude was decreased (ES = -0.37; P = 0.001) and rod latency was increased (ES = 0.35; P = 0.002). CONCLUSIONS: The ERG rod and cone abnormal response previously reported in adult patients having schizophrenia, bipolar disorder or major depressive disorder are detectable in genetically high-risk offspring as early as in childhood and adolescence. Moreover, a gradient of effect sizes among offspring and the three adult diagnoses was found in the cone response. This suggests that ERG waveform as a risk endophenotype might become part of the definition of a "childhood risk syndrome".

Asunto(s)

Trastorno Bipolar , Trastorno Depresivo Mayor , Esquizofrenia , Adolescente , Adulto , Trastorno Bipolar/genética , Trastorno Depresivo Mayor/genética , Electrorretinografía , Humanos , Retina , Esquizofrenia/genética

RESUMEN

Recent studies have used results on SNP association with schizophrenia (SZ) and bipolar disorder (BD) to create polygenic risk scores (PRS) discriminating non-familial unrelated patients from controls. Little is known about the role of PRS in densely affected multigenerational families. We tested PRS differences between affected SZ and BD family members from their non-affected adult relatives (NAARs) in Eastern Quebec Kindreds and from controls. We examined 1227 subjects: from 17 SZ and BD kindreds, we studied 153 patients (57 SZ, 13 schizoaffective, and 83 BD) and 180 NAARs, and 894 unrelated controls from the Eastern Quebec population. PRS were derived from published case-control association studies of SZ and BD. We also constructed a combined SZ and BD PRS by using SNPs from both SZ and BD PRS. SZ patients had higher SZ PRS than controls (p = 0.0039, R2 = 0.027) and BD patients had higher BD PRS than controls (p = 0.013, R2 = 0.027). Differences between affected subjects and NAARs and controls were significant with both SZ and BD PRS. Moreover, a combined SZ-BD PRS was also significantly associated with SZ and BD when compared to NAARs (p = 0.0019, R2 = 0.010) and controls (p = 0.0025, R2 = 0.028), revealing a SZ-BD commonality effect in PRS at the diagnosis level. The SZ and the BD PRS, however, showed a degree of specificity regarding thought disorder symptoms. Overall, our report would confirm the usefulness of PRS in capturing the contribution of common genetic variants to the risk of SZ and BD in densely affected families.

Asunto(s)

Trastorno Bipolar/genética , Esquizofrenia/genética , Adulto , Trastorno Bipolar/psicología , Estudios de Casos y Controles , Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Herencia Multifactorial/genética , Polimorfismo de Nucleótido Simple/genética , Quebec , Factores de Riesgo , Psicología del Esquizofrénico

Asunto(s)

Trastornos del Humor/genética , Esquizofrenia/genética , Endofenotipos , Humanos , Trastornos del Humor/fisiopatología , Esquizofrenia/fisiopatología

Asunto(s)

Trastornos Mentales/diagnóstico , Padres , Atención Primaria de Salud/normas , Psiquiatría/normas , Adulto , Niño , Femenino , Humanos , Masculino , Trastornos Mentales/genética , Trastornos del Humor , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Esquizofrenia

RESUMEN

BACKGROUND: Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset. METHODS: Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model. RESULTS: In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11% of mania variance and 5% of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A. LIMITATIONS: Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample. CONCLUSIONS: We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.

Asunto(s)

Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/psicología , Glucógeno Sintasa Quinasa 3 beta/genética , Trastornos del Humor/genética , Trastornos del Humor/psicología , Polimorfismo Genético , Proteínas de Unión al ARN/genética , Adulto , Edad de Inicio , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Genotipo , Humanos , Litio/uso terapéutico , Masculino , Persona de Mediana Edad , Prevalencia

RESUMEN

Schizophrenia is associated with deficits in theory of mind (ToM) (i.e., the ability to infer the mental states of others) and cognition. Associations have often been reported between cognition and ToM, and ToM mediates the relationship between impaired cognition and impaired functioning in schizophrenia. Given that cognitive deficits could act as a limiting factor for ToM, this study investigated whether a cognitive remediation therapy (CRT) that targets nonsocial cognition and metacognition could improve ToM in schizophrenia. Four men with schizophrenia received CRT. Assessments of ToM, cognition, and metacognition were conducted at baseline and posttreatment as well as three months and 1 year later. Two patients reached a significant improvement in ToM immediately after treatment whereas at three months after treatment all four cases reached a significant improvement, which was maintained through 1 year after treatment for all three cases that remained in the study. Improvements in ToM were accompanied by significant improvements in the most severely impaired cognitive functions at baseline or by improvements in metacognition. This study establishes that a CRT program that does not explicitly target social abilities can improve ToM.

RESUMEN

The retina is tagged as an approachable part of the brain due to its common embryonic origin and appears as a promising site of investigation for psychiatric disorders. Retinal function is assessed best with the electroretinogram (ERG), which was obtained in a large sample of patients with major depressive disorder and matched controls. ERG cone and rod luminance response functions were recorded in non-dilated eyes in 100 major depressive disorder patients (MDD) and 100 controls, (mean age of 42.8 and 40.9y. o. respectively). Amongst MDD patients, 17 were drug free (mean age 41.2y. o). In medicated patients, at the cone level, a prolonged b-wave was observed (p≤0.01). In drug free patients a prolonged b-wave was discovered only when averaging the implicit time of the 3 highest b-wave amplitudes of the photopic hill. For the medicated patients, the mixed rods/cones a-wave was reduced (p=0.01) whereas a trend (p=0.06) was observed for the pure rod b-wave (reduced) and the mixed rods/cones (reduced and prolonged; p=0.05). In drug free patients, a similar pattern could be observed in terms of effect sizes. Overall, medicated and drug free MDD patients shared some deficits suggesting that some anomalies are present above and beyond the effect of medication. Of interest, the prolonged cone and reduced rod amplitude were reported by our group in schizophrenia patients, suggesting a common neurodevelopmental root of major psychiatric disorders.

Asunto(s)

Trastorno Depresivo Mayor/patología , Electrorretinografía , Retina/fisiopatología , Adulto , Análisis de Varianza , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Biofisica , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Escalas de Valoración Psiquiátrica , Retina/efectos de los fármacos , Adulto Joven

RESUMEN

Objectives: Offspring born to patients with affective and non-affective psychoses display indicators of brain dysfunctions that affected parents carry. Such indicators may help understand the risk trajectory. Methods: We followed up the clinical/developmental trajectories of 84 young offspring born to affected parents descending from the Quebec kindreds affected by schizophrenia or bipolar disorder. We longitudinally characterized childhood trajectories using 5 established risk indicators: cognitive impairments, psychotic-like experiences, non-psychotic DSM diagnosis and episodes of poor functioning, trauma and drug use. Results: Overall, offspring individually presented a high rate of risk indicators with 39% having 3 or more indicators. Thirty-three offspring progressed to an axis 1 DSM-IV disorder, 15 of whom transitioned to a major affective or non-affective disorder. The relative risks for each risk indicator were low in these vulnerable offspring (RR = 1.92 to 2.99). Remarkably, transitioners accumulated more risk indicators in childhood-adolescence than non-transitioners (Wilcoxon rank test; Z = 2.64, p = 0.008). Heterogeneity in the risk trajectories was observed. Outcome was not specific to parent's diagnosis. Conclusion: Young offspring descending from kindreds affected by major psychoses would accumulate risk indicators many years before transition. A clustering of risk factors has also been observed in children at risk of metabolic-cardiovascular disorders and influences practice guidelines in this field. Our findings may be significant for the primary care surveillance of millions of children born to affected parents in the G7 nations. Future longitudinal risk research of children at genetic risk should explore concurrently several intrinsic and environmental risk modalities to increase predictivity.

Asunto(s)

Trastorno Bipolar/genética , Hijo de Padres Discapacitados , Predisposición Genética a la Enfermedad , Esquizofrenia/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Trastornos Psicóticos , Quebec , Factores de Riesgo , Adulto Joven