Switching from risperidone to paliperidone palmitate in schizophrenia: Changes in social functioning and cognitive performance.

BACKGROUND: Previous studies suggest that paliperidone might show a better profile for social functioning and cognitive abilities than risperidone. We aimed to study whether switching from risperidone to paliperidone palmitate (PP) is associated with improved cognitive abilities at 3 or 6 months after the switch. METHODS: Thirty-eight patients with a DSM-IV diagnosis of schizophrenia were studied. All patients were treated with oral risperidone or risperidone long-acting injection (RLAI) and had an indication to be switched to PP by their psychiatrists. Statistical analyses were conducted in a final sample of 27 patients who completed the follow-up visits. Three assessments were completed: 1) baseline (preswitch), 2) 3 months postswitch, and 3) 6 months postswitch. Social functioning at each visit was assessed with the Personal and Social Performance Scale. Cognitive assessment was conducted at each visit with the MATRICS Consensus Cognitive Battery. Statistical analyses were performed with R. Linear mixed models were used to explore longitudinal changes in social functioning and cognitive outcomes. RESULTS: PSP scores significantly improved over time after the switch from risperidone to PP. A sensitivity analysis found a significant negative interaction between time and PP maintenance doses (greater improvement in those patients receiving lower doses when compared to higher doses). Regarding longitudinal changes in cognitive functioning, patients improved in 6 out of 10 cognitive tasks involving processing speed, working memory, visual memory, reasoning and problem solving, and attention and vigilance. CONCLUSIONS: Our study suggests that switching from risperidone to PP in patients with schizophrenia is associated with an improvement in social functioning and cognitive performance.

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.

Cognitive biases are associated with clinical and functional variables in psychosis: A comparison across schizophrenia, early psychosis and healthy individuals.

OBJECTIVE: We investigated the presence of cognitive biases in people with a recent-onset psychosis (ROP), schizophrenia and healthy adolescents and explored potential associations between these biases and psychopathology. METHODS: Three groups were studied: schizophrenia (N=63), ROP (N=43) and healthy adolescents (N=45). Cognitive biases were assessed with the Cognitive Biases Questionnaire for Psychosis (CBQ). Positive, negative and depressive symptoms were assessed with the PANSS and Calgary Depression Scale (ROP; schizophrenia) and with the CAPE-42 (healthy adolescents). Cannabis use was registered. The association between CBQ and psychopathology scales was tested with multiple linear regression analyses. RESULTS: People with schizophrenia reported more cognitive biases (46.1±9.0) than ROP (40±5.9), without statistically significant differences when compared to healthy adolescents (43.7±7.3). Cognitive biases were significantly associated with positive symptoms in both healthy adolescents (Standardized ß=0.365, p=0.018) and people with psychotic disorders (ß=0.258, p=0.011). Cognitive biases were significantly associated with depressive symptoms in healthy adolescents (ß=0.359, p=0.019) but in patients with psychotic disorders a significant interaction between schizophrenia diagnosis and CBQ was found (ß=1.804, p=0.011), which suggests that the pattern differs between ROP and schizophrenia groups (positive association only found in the schizophrenia group). Concerning CBQ domains, jumping to conclusions was associated with positive and depressive symptoms in people with schizophrenia and with cannabis use in ROP individuals. Dichotomous thinking was associated with positive and depressive symptoms in all groups. CONCLUSIONS: Cognitive biases contribute to the expression of positive and depressive symptoms in both people with psychotic disorders and healthy individuals.

Early intervention services, patterns of prescription and rates of discontinuation of antipsychotic treatment in first-episode psychosis.

AIMS: Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group. METHODS: We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded. RESULTS: A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs. CONCLUSIONS: Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.

Free Thyroxine Concentrations Moderate the Response to a Cognitive Remediation Therapy in People With Early Psychosis: A Pilot Randomized Clinical Trial.

INTRODUCTION: Cognitive deficits are a cause of functional disability in psychotic disorders. Cognitive remediation therapy (CRT) might be applied to improve these deficits. We conducted a pilot study to explore whether thyroid hormones might predict the response to CRT in patients with recent-onset psychosis (ROP). METHODS: Twenty-eight stable ROP outpatients (9 women) were randomized to receive computerized CRT (N=14) or treatment as usual (TAU) (N=14), over three months. Both cognitive and thyroid functions were assessed at the baseline and after those three months to all patients. A full cognitive battery (CANTAB) was administered before and after the treatment. Serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured. FT4 concentrations were recoded into a dichotomic variable (FT4 group) based on the median of the sample (1.2 ng/dL). Data were analyzed on an intention-to-treat basis with linear mixed models. Afterwards, we offered CRT to all participants from the TAU group and seven enrolled CRT, reassessing them when finished. Secondary analyses were repeated in a sample of 14 participants who completed the CRT (either from the beginning or after the TAU period) and attended at least one third of the sessions. RESULTS: The linear mixed models showed a significant time x CRT x FT4 group effect in two cognitive tasks dealing with executive functions and sustained attention (participants with higher FT4 concentrations worsened executive functions but improved sustained attention after CRT). In the secondary analysis including all patients assigned to CRT, higher FT4 concentrations were associated with a poorer response in verbal memory but a better response in spatial working memory. CONCLUSIONS: Free thyroxine concentrations moderate the response to a CRT in patients with early psychosis.

Targeting Hormones for Improving Cognition in Major Mood Disorders and Schizophrenia: Thyroid Hormones and Prolactin.

Cognitive deficits are a core feature of serious mental illnesses such as major depression, bipolar disorder and schizophrenia and are a common cause of functional disability. However, the efficacy of pharmacological interventions for improving the cognitive deficits in these disorders is limited. As pro-cognitive pharmacological treatments are lacking, we aimed to review whether thyroid hormones or drugs that target prolactin may become potential candidates for 'repurposing' trials aiming to improve cognition. We conducted a narrative review focused on thyroid hormones and prolactin as potential targets for improving cognition in major mood disorders or schizophrenia. The role of thyroid hormones and prolactin on cognitive processes in non-psychiatric populations was also reviewed. Although clinical trials regarding these hormones are lacking, particularly in patients with schizophrenia, bipolar disorder or major depression, there is evidence from observational studies for the contribution of these hormones to cognitive processes. Patients with bipolar disorder and subclinical hypothyroidism show poorer cognitive function than euthyroid patients. In patients with early psychosis, lower free thyroxine concentrations have been associated with poorer attention whereas increased prolactin levels have been associated with poorer speed of processing. Only two small clinical trials tested the potential pro-cognitive effects of thyroid hormones, with positive findings for triiodothyronine (T3) treatment in patients receiving lithium or electroconvulsive therapy. In sum, thyroid hormones and prolactin might contribute to the cognitive performance of patients with major mood disorders and psychotic disorders. Thyroid hormones and prolactin-lowering drugs (e.g. cabergoline, aripiprazole) are candidate drugs to be tested in repurposing clinical trials aiming to improve the cognitive abilities of patients with major mood disorder and schizophrenia.

Improvement in cognitive biases after group psychoeducation and metacognitive training in recent-onset psychosis: A randomized crossover clinical trial.

Metacognitive training (MCT) improves cognitive biases in psychosis. We aimed to explore whether the effectiveness of the combination of psychoeducation and MCT group treatments on cognitive biases differed if the combination was started by psychoeducation or by MCT. Fourty-nine stable patients with a recent-onset psychosis were randomized to two different sequences: MCT + psychoeducation vs psychoeducation + MCT. Cognitive biases, psychopathology symptoms, insight and functioning were assessed. Cognitive biases and depressive symptoms improved with both group interventions, without differential effects between both sequences. Our study suggests that MCT and psychoeducation are useful in improving cognitive biases and depressive symptoms in recent-onset psychosis.

Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: a systematic review and narrative synthesis.

Cognitive deficits are a core feature of serious mental illnesses such as schizophrenia, major depressive disorder (MDD) and bipolar disorder (BD) and are a common cause of functional disability. There is limited efficacy of pharmacological interventions for improving the cognitive deficits in these disorders. As pro-cognitive pharmacological treatments are lacking, hormones or drugs that target the endocrine system may become potential candidates for 'repurposing' trials aiming to improve cognition. We aimed to study whether treatment with drugs targeting the hypothalamic-pituitary-adrenal (HPA) axis and sex steroids can improve cognition in patients with schizophrenia, MDD or BD. A systematic search was performed using PubMed (Medline), PsychInfo and clinicaltrials.gov, and a narrative synthesis was included. The systematic review identified 12 studies dealing with HPA-related drugs (mifepristone [n = 3], cortisol synthesis inhibitors [ketoconazole, n = 2], dehydroepiandrosterone [n = 5], fludrocortisone [n = 2]) and 14 studies dealing with sex steroids (oestradiol [n = 2], selective oestrogen receptor modulators [raloxifene, n = 7], pregnenolone [n = 5]). Positive trials were found for BD (mifepristone), MDD (dehydroepiandrosterone and fludrocortisone) and schizophrenia (dehydroepiandrosterone, raloxifene and pregnenolone). A replication of positive findings by at least two clinical trials was found for mifepristone in BD and raloxifene and pregnenolone in schizophrenia. The use of drugs targeting hormones related to the HPA axis and sex steroids is a promising field of research that might help to improve the cognitive outcome of patients with schizophrenia, bipolar disorder and major depressive disorder in the near future.

Thyroglobulin antibodies and risk of readmission at one year in subjects with bipolar disorder.

Thyroid autoimmunity has been proposed as an endophenotype for Bipolar Disorder (BD), although its relationship with clinical outcomes remains unclear. We aimed to determine whether thyroid autoimmune status (thyroperoxidase antibodies [TPO-Abs] and thyroglobulin antibodies [TG-Abs]) in BD is associated with a greater risk for readmission at one year. We studied 77 inpatients with BD admitted for an index manic or mixed episode. Serum thyroid antibodies (TPO-Abs and TG-Abs) were determined at admission. We compared the readmission risk at 1 year, based on patients׳ thyroid autoimmunity profile using survival analyses. Cox regression was used to control covariates. TG-Abs+ but not TPO-Abs+ was associated with a lower risk of relapse. The Kaplan-Meier mean estimated survival times were 341.6 days (CI95% 316.4-366.8) for the TG-Abs+ group and 261.9 days (CI95%: 221.8 to 302.0) for the TG-Abs- group. Cox proportional hazards regression indicated that subjects with TG-Abs+ were 3.7 (1/OR=1/0.27) times less likely to get admitted during the follow-up period than those with TG-Abs-. Our study suggests that an autoimmune biomarker in patients with BD (i.e., the presence of TG-Abs) is associated with a lower risk of psychiatric readmission after an index hospitalization for a manic or mixed episode.