Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls

Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence

Cognitive Biases Questionnaire for Psychosis (CBQp): Spanish Validation and Relationship With Cognitive Insight in Psychotic Patients

Introduction: Cognitive biases are key factors in the development and persistence of delusions in psychosis. The Cognitive Biases Questionnaire for Psychosis (CBQp) is a new self-reported questionnaire of 30 relevant situations to evaluate five types of cognitive biases in psychosis. In the context of the validation of the Spanish version of the CBQp, our objectives were to (1) analyze the factorial structure of the questionnaire with a confirmatory factor analysis (CFA), (2) relate cognitive biases with a widely used scale in the field of delusion cognitive therapies for assessing metacognition, specifically, Beck's Cognitive Insight Scale (BCIS) (1), and, finally, (3) associate cognitive biases with delusional experiences, evaluated with the Peters Delusions Inventory (PDI) (2). Materials and Methods: An authorized Spanish version of the CBQp, by a translation and back-translation procedure, was obtained. A sample of 171 patients with different diagnoses of psychoses was included. A CFA was used to test three different construct models. Associations between CBQp biases, the BCIS, and the PDI were made by correlation and mean differences. Comparisons of the CBQp scores between a control group and patients with psychosis were analyzed. Results: The CFA showed comparative fit index (CFI) values of 0.94 and 0.95 for the models with one, two, and five factors, with root mean square error of approximation values of 0.031 and 0.029. The CBQp reliability was 0.87. Associations between cognitive biases, self-certainty, and cognitive insight subscales of the BCIS were found. Similarly, associations between total punctuation, conviction, distress, and concern subscales of the PDI were also found. When compared with the group of healthy subjects, patients with psychoses scored significantly higher in several cognitive biases. Conclusion: Given the correlation between biases, a one-factor model might be more appropriate to explain the scale's underlying construct. Biases were associated with a greater frequency of delusions, distress, conviction, and concern as well as worse cognitive insight in patients with psychosis

Prevalença i correlats clínics de la conducta suïcida i la seva relació amb la dimensió afectiva en primers episodis psicòtics d’inici precoç

[cat] INTRODUCCIÓ: El suïcidi és la principal causa de mort prematura entre les persones amb trastorns psicòtics. Entre el 20% i el 40% dels pacients psicòtics intenten suïcidar-se al llarg de la seva vida i entre el 5 i 10% moriran per suïcidi. El risc de suïcidi és més alt en les fases primerenques de la malaltia, poc abans o poc després del primer contacte per tractament. Per tant, els pacients amb psicosi d’inici recent és un grup de risc per suïcidi. Estudis prospectius de primers episodis psicòtics (PEP) en mostres adultes han informat d’unes taxes d’intents de suïcidi (IS) fins a 11% durant els dos primers anys de seguiment, essent la història prèvia de conducta suïcida i la simptomatologia depressiva els factors de risc que hi ha més consens. Malgrat això, els criteris restrictius categorials del DSM-IV han dificultat la investigació sobre la prevalença , rellevància clínica i pronòstic de la dimensió afectiva i com a conseqüència l’estudi de la mania i dels estats mixtes, ha estat confinat al Trastorn Bipolar. A més, hi ha pocs estudis de PEP d’inici precoç i no hi ha cap estudi previ amb un disseny prospectiu que hagi investigat els objectius d’aquesta tesi. Els objectius generals són: Ampliar el coneixement sobre els factors de risc de suïcidi sobre la dimensió afectiva en PEP d’inici precoç, així com la relació entre ambdós. METODOLOGIA: Cent deu nens i adolescents entre 9 i 17 anys que presentaven el seu primer episodi psicòtic seguint criteris DSM-IV es van incloure en l’estudi. La conducta suïcida va ser mesurada amb la “Clinical Global Impression for Severity of Suicidality” i els símptomes afectius amb la “Hamilton Depression Rating Scale” i la “Young Mania Rating Scale”. Es van realitzar anàlisis de regressió logística per investigar la magnitud e independència de les associacions. RESULTATS: Aproximadament el 83% dels subjectes presentaven símptomes afectius durant les fases primerenques de la malaltia, essent els depressius els més freqüents en la fase prodròmica (27,4%) i els mixtes en la fase aguda (41,1%) La proporció de subjectes que van realitzar IS al llarg dels 24 mesos va ser del 12,2% , el 10,9% durant els primers 12 mesos. La conducta suïcida durant el seguiment va estar relacionada amb la simptomatologia depressiva a les fases primerenques (OR= 4,75; 95% CI, 1,59-15,13, p=0,005). La prevalença o tipus de simptomatologia afectiva durant l’episodi agut no va predir de forma significativa el diagnòstic als 12 mesos de Trastorn Bipolar o Esquizofrènia. En canvi els subjectes amb Trastorn Bipolar presentaven més símptomes subllindar afectius tan del pol maníac com depressiu en la fase prodròmica. CONCLUSIONS: PEP d’inici precoç presenten elevades taxes de simptomatologia afectiva i de conducta suïcida durant les fases primerenques de la malaltia. La relació trobada entre simptomatologia depressiva i risc suïcida indica la importància en la pràctica clínica d’una acurada avaluació d’aquesta simptomatologia en mostres adolescents, així com una monitorització estreta durant el primer any, indiferentment de la categorització de psicosi afectiva o no afectiva. Els nostres resultats suggereixen per tant, que una aproximació dimensional seria més apropiada per la avaluació i tractament de la heterogeneïtat dels símptomes d’un PEP d’inici precoç.[eng] INTRODUCTION: Between 20% and 40% of psychotic patients will attempt suicide during their lifetime illness, the risk being particularly high during the early stages of the disorder. The most robust risk factors for attempting suicide are history of suicide behaviour and depression. However, the affective dimension and its relation with suicide has been scarcely studied in adult first-episode psychosis (FEP) and no prospective studies of suicidal behaviour in early –onset FEP have been published to date. The general aims of this thesis were : to increase the knowledge about risk factors of suicide and about the affective dimension of psychosis and the relationship between them. METHODS: Participants were 110 youths aged 9 to 17 years experiencing a FEP according to DSM-IV criteria. Suicidal behaviour was evaluated using the Clinical Global Impression for Severity of Suicidality, affective symptoms were assessed by means of the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Logistic regression analyses were performed to investigate the magnitude of relationships. RESULTS: Nearly 83% of subjects experienced affective symptoms during the early phases, with depressive symptoms being the most frequently reported during the prodrome and mixed symptoms during the acute episode. The 24-month prevalence of suicide attempters was 12.4%, 10.9% during first 12 months. Suicidality during follow-up was associated with depressive symptoms at early stage (OR= 4,75; 95% CI, 1,59-15,13, p=0,005). Presence or type of affective symptoms during the FEP did not significantly predict a later diagnosis of bipolar disorder or schizophrenia; however, bipolar subjects were more likely to manifest depressive and manic symptoms during the prodromal phase. CONCLUSIONS: Early-onset FEP subjects present high rates of affective symptoms and suicidality during early stages. The relationship of depressive symptoms with suicide risk highlights the importance of accurately assessing these symptoms in adolescent samples and to monitor them closely during first 12 months, regardless of DSM categories of affective and non-affective psychoses. Our findings therefore suggest that a dimensional diagnostic approach might be more appropriate for addressing the heterogeneous clinical presentation of a FEP

Increased levels of serum leptin in the early stages of psychosis

[Background] Studies evaluating leptin levels in patients with first-episode psychoses (FEP) have been inconclusive, and apparently, the high levels of leptin reported in patients with schizophrenia may be associated with weight gain. The aim of this study was to evaluate leptin levels at the early stages of the disease and the relationship between leptin and lifestyle habits, stress-related variables and metabolic parameters.[Methods] In total, 14 at-risk mental state (ARMS) patients, 39 FEP patients, 32 psychotic patients in the critical period (CP) and 21 healthy controls (HCs) were assessed. Anthropometric and biochemical parameters, as well as dietary intake, physical activity, stress-related variables and symptomatology, were collected.[Results] Leptin levels were higher in the ARMS, FEP and CP patients than in the HCs. After controlling for age, sex, BMI, physical exercise, tobacco use and dietary intake, the highest differences in leptin levels were observed between the ARMS patients and HCs (p = 0.025). In the whole sample, leptin levels were positively correlated with BMI (p < 0.001), waist circumference (p < 0.001), insulin levels (p = 0.020), levels of the inflammatory marker IL-6 (p = 0.007) and energy intake (p = 0.043) and negatively correlated with HDL cholesterol (p = 0.018). Interestingly, energy intake and food craving scores were positively correlated with levels of leptin only in females (p = 0.022 and p = 0.036, respectively).[Discussion] The present study detected increased leptin levels in the early stages of psychosis and significant correlations between leptin levels and anthropometric, lipid, hormone, and cytokine parameters. We found higher leptin levels in women, and we identified dietary intake habits associated with leptin exclusively in females that advocate considering sex in future studies.Funding for this study was provided by Fundació la Marató de TV3 (grants numbers 092230, 092231) and from the Instituto de Salud Carlos III (grant number PI10/01607). GM was the recipient of a BP-DGR scholarship from the Generalitat de Catalunya. LO and JL have received a personal grant to support their research activity (SLT002/16/0125 and SLT006/17/00012, respectively). The Health Department of the Generalitat de Catalunya also supported this study

Incidence rate and distinctive characteristics of first episode psychosis during the COVID-19 pandemic: A multicenter observational study

The COVID-19 pandemic has affected the mental health of people around the world. However, its impact on first-episode psychosis (FEP) remains unclear. The aim of this study was to determine the incidence rate (IR) and the clinical and sociodemographic characteristics of patients who developed FEP during the nine-month period following the COVID-19 outbreak in Spain and to compare these data to the corresponding period in the previous year. We included all patients (n = 220) treated for the first time during these two time periods at three FEP programs in Spain. The IR was 0.42/100,000 person-years during the pandemic vs. 0.54/100,000 in the prior year (p = 0.057). Compared to prior year, women accounted for a significantly higher proportion of FEP patients (46.3% vs. 28%; p = 0.005) during the COVID-19 period. This association was significant on the logistic regression analysis (odds ratio, female: 2.12 [confidence interval 1.17-3.82]; p = 0.014). These data reveal a non-significant trend towards a lower incidence of FEP during the pandemic period. Female sex was associated with a greater risk of developing FEP during the pandemic period, perhaps due to differences between males and females in the susceptibility and expression of psychosis. The findings of this study contribute to a better understanding of stress-related disorders

Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls

Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence