Efectos secundarios de tipo metabólico asociados al tratamiento con antipsicóticos de segunda generación en niños, adolescentes y adultos

Algunos estudios sugieren que el riesgo de experimentar efectos secundarios de tipo metabólico en pacientes tratados con antipsicóticos de segunda generación (ASG) puede estar incrementado en niños y adolescentes respecto a adultos. Hasta el momento, ningún estudio prospectivo ha explorado de forma específica el efecto de la edad sobre este tipo de efectos secundarios en pacientes pediátricos y adultos con mínima exposición previa a antipsicóticos, teniendo en cuenta los cambios antropométricos esperables por la edad en el grupo de pacientes pediátricos. Hipótesis: 1) El tratamiento con ASG durante 24 semanas estará asociado con aumento de peso y alteraciones metabólicas en pacientes pediátricos y adultos. 2) Existirá un perfil diferencial de efectos secundarios según el antipsicótico, con mayor aumento de peso en los pacientes tratados con olanzapina en ambos grupos de edad. 3) El tratamiento con ASG durante 24 semanas se asociará con mayores alteraciones en la composición corporal en los pacientes pediátricos que en adultos. 4) El efecto de los cambios en la composición corporal sobre el desarrollo de algunas alteraciones metabólicas será mayor en el grupo de pacientes pediátricos que en adultos. 5) Algunas variables demográficas y clínicas modularán las trayectorias individuales de cambio en las variables de riesgo metabólico durante el seguimiento en ambos grupos de edad..

Cognition and functionality in delusional disorder.

BACKGROUND: Even if neurocognition is known to affect functional outcomes in schizophrenia, no previous study has explored the impact of cognition on functionality in delusional disorder (DD). We aimed to assess the effect of clinical characteristics, symptom dimensions and neuropsychological performance on psychosocial functioning and self-perceived functional impairment in DD. METHODS: Seventy-five patients with a SCID-I confirmed diagnosis of DD underwent neurocognitive testing using a neuropsychological battery examining verbal memory, attention, working memory and executive functions. We assessed psychotic symptoms with the Positive and Negative Syndrome Scale, and calculated factor scores for four clinical dimensions: Paranoid, Cognitive, Affective and Schizoid. We conducted hierarchical linear regression models to identify predictors of psychosocial functioning, as measured with the Global Assessment of Functioning scale, and self-perceived functional impairment, as measured with the Sheehan's Disability Inventory. RESULTS: In the final linear regression models, higher scores in the Paranoid (β= 0.471, p < .001, r2 = 0.273) and Cognitive (β = 0.325, p < .001, r2 = 0.180) symptomatic dimensions and lower scores in verbal memory (β = -0.273, p < .05, r2 = 0.075) were significantly associated with poorer psychosocial functioning in patients with DD. Lower scores in verbal memory (β= -0.337, p < .01, r2 = 0.158) and executive functions (β= -0.323, p < .01, r2 = 0.094) were significantly associated with higher self-perceived disability. CONCLUSIONS: Impaired verbal memory and cognitive symptoms seem to affect functionality in DD, above and beyond the severity of the paranoid idea. This suggests a potential role for cognitive interventions in the management of DD

Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia

Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and positive covariance with mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, and autism. Conversely, genetic variation with discordant effects only contributes to schizophrenia risk in males and is negatively correlated with those disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia than vice versa. These results illustrate the genetic footprint of LNL-ISO on schizophrenia

Services for people at high risk improve outcomes in patients with first episode psychosis

OBJECTIVE: About one‐third of patients referred to services for people at high risk for psychosis may have already developed a first episode of psychosis (FEP). We compared clinical outcomes in FEP patients who presented to either high risk or conventional mental health services. METHOD: Retrospective study comparing duration of hospital admission, referral‐to‐diagnosis time, need for compulsory hospital admission and frequency of admission in patients with FEP who initially presented to a high‐risk service (n = 164) to patients with FEP who initially presented to conventional mental health services (n = 2779). Regression models were performed, controlling for several confounders. RESULTS: FEP patients who had presented to a high‐risk service spent 17 fewer days in hospital [95% CI: −33.7 to (−0.3)], had a shorter referral‐to‐diagnosis time [B coefficient −74.5 days, 95% CI: −101.9 to −(47.1)], a lower frequency of admission [IRR: 0.49 (95% CI: 0.39–0.61)] and a lower likelihood of compulsory admission [OR: 0.52 (95% CI: 0.34–0.81)] in the 24 months following referral, as compared to FEP patients who were first diagnosed at conventional services. CONCLUSION: Services for people at high risk for psychosis are associated with better clinical outcomes in patients who are already psychotic

Cognitive reserve and its correlates in child and adolescent offspring of patients diagnosed with schizophrenia or bipolar disorder

Aim: To analyze cognitive reserve (CR) in child and adolescent offspring of patients diagnosed with schizophrenia (SZ-off) or bipolar disorder (BD-off) and compare them with a group of community controls (CC-off). We also aimed to investigate whether there was an association between CR and clinical and neuropsychological variables according to group. Methods: The study included 46 SZ-off, 105 BD-off and 102 CC-off. All participants completed assessments regarding CR and clinical, neuropsychological and psychosocial functioning. CR was measured with a proxy based on premorbid intelligence, parental occupational level, educational attainment, developmental milestones and sociability. The clinical assessment included the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime, the Semi-structured Interview for Prodromal Syndromes, and the Global Assessment Functioning scale. The neuropsychological assessment included measures of executive functioning, attention, verbal memory, working memory and processing speed. Results: SZ-off showed a lower level of CR compared to BD-off and CC-off, while BD-off showed an intermediate level of CR between SZ-off and CC-off. Moreover, an association between higher CR and less lifetime psychopathology, fewer prodromal psychotic symptoms, higher psychosocial functioning, and a higher working memory score was observed in all groups, but it was stronger in SZ-off. Conclusions: CR seemed to be associated with psychopathology, clinical symptoms, psychosocial functioning, and some cognitive functions. SZ-off appeared to benefit more from a higher CR, therefore it could be considered a protective factor against the development of clinical symptomatology and cognitive impairment

Cortical thinning over two years after first-episode psychosis depends on age of onset.

[EN] First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15-35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d=0.54; p=002). In a post-hoc-analysis, adolescent-onset (≤19y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe.We are extremely grateful to all subjects who took part in this study. This work was supported by CIBERSAM; Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (PI081203, PI08/0208; PI11/00325; PI1101686, PI14/00612, PI17/01997, PI20/01342), co‐financed by the ERDF from the European Commission “A way of making Europe”, European Union Seventh Framework Program (FP7- HEALTH-2013-2.2.1-2-603196 [Project PSYSCAN]), EU H2020 (IMI‐2 Joint Undertaking under grant agreements 115916 (project PRISM) and 777394 (project AIMS‐2‐TRIALS)), Madrid Regional Government (S2017/BMD‐3740, and AGES-CM-2-CM) and European Union Structural Funds; Fundación Familia Alonso, Fundacion Mutua Madrileña, and Fundación Alicia Koplowitz

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15-35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients

Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia

Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and positive covariance with mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, and autism. Conversely, genetic variation with discordant effects only contributes to schizophrenia risk in males and is negatively correlated with those disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia than vice versa. These results illustrate the genetic footprint of LNL-ISO on schizophrenia