Relationship between hair cortisol concentrations and cognitive functioning in adolescents with ADHD.

Background: Our study aimed to explore whether the hair cortisol concentration (HCC), a measure of long-term cortisol output, is associated with poorer cognitive functioning in adolescents with attention deficit and hyperactivity disorder (ADHD). We further aimed to test the potential moderating effects of sex and childhood maltreatment.Methods: In this cross-sectional study, fifty-three adolescents with ADHD were studied. The ADHD Rating Scale (ADHD-RS) and Childhood Trauma Questionnaire (CTQ) were administered. Seven cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered, and two cognitive factors (attention and memory and executive functioning) were identified by confirmatory factor analysis. A 3-cm hair sample from the posterior vertex region of the head was obtained. HCCs were determined by a high-sensitivity enzyme immunoassay kit. Multiple linear regression analyses were used to explore the association between HCCs and either cognitive performance or ADHD severity while adjusting for sex, childhood maltreatment and the ADHD-RS total score.Results: Sex moderated the relationship between HCCs and attention/memory confirmatory factor analysis (CFA) scores, with better performance in boys with higher HCCs. HCCs were not associated with executive functioning or ADHD symptoms. Childhood maltreatment was associated with inattention symptoms in adolescents with ADHD.Conclusions: Our study suggests that HCCs are positively associated with attention and memory performance in adolescents with ADHD, with a moderating effect of sex (the relationship is strongest in boys).

We studied the relationship between cortisol and cognition in adolescents with ADHD.Hair cortisol concentrations (HCCs) were determined.We explored the moderating effects of sex and childhood trauma.Sex moderated the relationship between HCCs and attention and memory.Childhood trauma did not moderate the relationship between HCCs and cognition.

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.

Stress-related biomarkers and cognitive functioning in adolescents with ADHD: Effect of childhood maltreatment.

Our study aimed to explore whether stress-related hormones (hypothalamic-pituitary-adrenal [HPA] axis hormones and prolactin) are associated with poorer cognitive functioning in adolescents with attention deficit and hyperactivity disorder (ADHD) and to test the potential moderating effect of childhood maltreatment. Seventy-six adolescents with ADHD were studied. The ADHD rating scale (ADHD-RS) and Childhood Trauma Questionnaire (CTQ) were administered. Seven cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered, and two cognitive factors (attention and memory as well as executive functioning) were identified by confirmatory factor analysis. Stress-related hormone levels were assessed at the clinic (plasma prolactin and cortisol levels and salivary cortisol levels) before cognitive testing and at home for two consecutive days (cortisol awakening response [CAR] and diurnal cortisol slope). Multiple linear regression analyses were used to explore the association between hormone levels and ADHD severity or cognitive functioning while adjusting for sex and childhood maltreatment. Regarding hormonal measurements obtained at the clinic, female sex moderated the relationship between salivary cortisol levels and executive functioning, whereas childhood maltreatment moderated the relationship between salivary cortisol levels and inattention symptoms of patients with ADHD. Prolactin levels were not associated with cognitive functioning or the severity of ADHD. Regarding HPA axis measurements performed at home, lower cortisol levels at awakening were associated with poorer executive functioning. Neither CAR nor the cortisol diurnal slope were associated with cognitive functioning or ADHD severity. Our study suggests that HPA axis hormone levels are associated with the severity of cognitive and inattention symptoms of patients with ADHD and that childhood maltreatment and sex exert distinct moderating effects depending on the symptom type.

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.MethodsThree 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.ResultsPeople 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 β=0.365, p=0.018) and people with psychotic disorders (β=0.258, p=0.011). Cognitive biases were significantly associated with depressive symptoms in healthy adolescents (β=0.359, p=0.019) but in patients with psychotic disorders a significant interaction between schizophrenia diagnosis and CBQ was found (β=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.ConclusionsCognitive biases contribute to the expression of positive and depressive symptoms in both people with psychotic disorders and healthy individuals. (AU)

Objetivo: Investigamos la presencia de sesgos cognitivos en personas con psicosis de reciente comienzo (ROP), esquizofrenia y adolescentes sanos, y exploramos las asociaciones potenciales entre estos sesgos y la psicopatología.MétodosSe estudiaron tres grupos: esquizofrenia (N=63), ROP (N=43) y adolescentes sanos (N=45). Los sesgos cognitivos se evaluaron utilizando Cognitive Biases Questionnaire for Psychosis (CBQ). Los síntomas positivos, negativos y depresivos se evaluaron utilizando las escalas PANSS and Calgary Depression Scale (ROP; esquizofrenia) y CAPE-42 (adolescentes sanos). Se registró el consumo de cannabis. La asociación entre CBQ y las escalas de psicopatología se probó utilizando un análisis de regresión lineal múltiple.ResultadosLas personas esquizofrénicas reportaron más sesgos cognitivos (46,1±9) que las personas con ROP (40±5,9), sin diferencias estadísticamente significativas en la comparación con los adolescentes sanos (43,7±7,3). Los sesgos cognitivos se asociaron significativamente a los síntomas positivos, tanto en adolescentes sanos (β=0,365 estandarizada; p=0,018) como en personas con trastornos psicóticos (β=0,258; p=0,011). Los sesgos cognitivos se asociaron significativamente a síntomas depresivos en adolescentes sanos (β=0,359; p=0,019), pero en pacientes con trastornos psicóticos se encontró una interacción significativa entre diagnóstico de esquizofrenia y CBQ (β=1,804; p=0,011), lo cual sugiere que el patrón difiere entre los grupos de ROP y esquizofrenia (solo se encontró asociación positiva en el grupo de esquizofrenia). En cuanto a los dominios de CBQ, el adoptar conclusiones se asoció a síntomas positivos y depresivos en las personas esquizofrénicas y que consumen cannabis en los individuos con ROP. El pensamiento dicótomo se asoció a síntomas positivos y depresivos en todos los grupos. (AU)

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.

Perceived stress, social functioning and quality of life in first-episode psychosis: A 1-year follow-up study.

AIM: Quality of life (QoL) has been widely studied in people with schizophrenia. In the early phases of psychosis, it remains often impaired even after the remission of psychotic symptoms. The aim of this study was to explore QoL and social functioning during the first year after a first-episode psychosis (FEP), and to study potential moderating effects of stress measures. METHODS: Here, 61 FEP subjects and 55 healthy controls (HCs) were included. Sociodemographic data and clinical variables were collected through a semi-structured interview. Stress measures, social functioning and QoL were assessed with the Holmes-Rahe Social Readjustment Rating Scale, the Perceived Stress Scale, the Social Adaptation Self-Scale and the Euro-QoL-5D, respectively. Analysis of variance was employed with repeated measures and a mediation analysis at baseline and at 1-year follow-up was carried out. RESULTS: Patients reported lower QoL, poorer social functioning and more stress than HC. FEP patients significantly improved in QoL and stress measures over time, but not in social functioning. Perceived stress mediated the association between poorer social functioning and lower QoL. CONCLUSIONS: Social functioning at baseline may determine QoL over a 1-year follow-up period. Despite the improvement in most measures, patients do not achieve the level of well-being as the healthy group.

Relación entre el maltrato infantil y la adaptación social en una muestra de jóvenes atendidos en un servicio de intervención precoz en psicosis / Relationship between childhood trauma and social adaptation in a sample of young people attending an early intervention service for psychosis

INTRODUCCIÓN: El maltrato infantil se ha asociado a un mayor riesgo de psicosis, a una mayor severidad en síntomas psicopatológicos y a un peor pronóstico funcional en pacientes con un trastorno psicótico. El presente estudio pretende evaluar la relación entre el maltrato infantil, psicopatología y la adaptación social en una muestra de primeros episodios psicóticos (PEP) y de estados mentales de alto riesgo (EMAR). MATERIAL Y MÉTODOS: La muestra incluyó 114 jóvenes (18-35 años, 81 PEP y 33 EMAR) atendidos en un Servicio de Intervención Precoz en Psicosis. Se evaluaron síntomas positivos, negativos y depresivos con las escalas PANSS y Calgary de Depresión; los antecedentes de maltrato infantil con el Childhood Trauma Questionnaire; la adaptación social con la Escala Autoaplicada de Adaptación Social (SASS). Se utilizó el modelo de ecuaciones estructurales (SEM) para explorar relaciones entre psicopatología, maltrato infantil y dimensiones de la SASS en toda la muestra (incluyendo PEP y EMAR). Se repitió un análisis SEM exploratorio en la submuestra de PEP. RESULTADOS: Los EMAR presentaron más negligencia emocional y peor adaptación social, comparados con los PEP. El SEM muestra que el maltrato se asocia con una peor adaptación social en todos los dominios, de forma directa en dominios que implican relaciones interpersonales, y por una vía mediada por síntomas depresivos en los dominios que implican ocio y trabajo e intereses socioculturales. CONCLUSIONES: El maltrato infantil tiene un efecto negativo sobre la adaptación social en jóvenes en fases tempranas de las psicosis. Los síntomas depresivos son mediadores de una peor adaptación en aspectos funcionales relacionados con el ocio y el trabajo

INTRODUCTION: Childhood trauma has been associated with an increased risk of psychosis, a greater severity of psychopathological symptoms, and a worse functional prognosis in patients with psychotic disorders. The current study aims to explore the relationship between childhood trauma, psychopathology and social adaptation in a sample of young people with first episode psychosis (FEP) or at-risk mental states (ARMS). MATERIAL AND METHODS: The sample included 114 young people (18-35 years old, 81 FEP and 33 ARMS) who were attending an Early Intervention Service for Psychosis. Positive, negative and depressive symptoms were assessed with the PANSS and the Calgary Depression Scale; history of childhood trauma was assessed with the Childhood Trauma Questionnaire; social adaptation was assessed with the Social Adaptation Self-evaluation Scale (SASS). Structural equation modeling (SEM) was used to explore the relationship between childhood trauma, psychopathology and SASS dimensions in the global sample (including FEP and ARMS). An exploratory SEM analysis was repeated in the subsample of FEP patients. RESULTS: ARMS individuals reported more emotional neglect and worse social adaptation compared to FEP. SEM analysis showed that childhood trauma is associated with a worse social adaptation, in a direct way with domains involving interpersonal relationships, and mediated by depressive symptoms with those domains involving leisure, work and socio-cultural interests. CONCLUSIONS: Childhood trauma has a negative effect on social adaptation in young people with early psychosis. Depressive symptoms play a mediation role in this association, especially in domains of leisure and work

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.

Data of a meta-analysis on pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia.

The data presented in this paper describe supplementary material to the article entitled "Pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia: a systematic review and meta-analysis" [1]. Although raw data was published on the original article, additional raw data has been included in the current paper (new tables with socio-demographic and clinical characteristics of the samples of the studies included in the systematic review). Supplementary data also include the PICO scheme of the systematic review, PRISMA checklist, flow diagram, an explanation of the method for obtaining prolactin concentrations from published figures when data was only available in figures, list of the selected studies, risk of bias summary of all five randomized clinical trials evaluating the addition of aripiprazole for lowering prolactin (included in the meta-analysis in the original article). Extra analyses, figures and R code of the meta-analysis have been also included. Meta-analysis of randomized clinical trials (RCTs) considering aripiprazole addition for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia were conducted with two softwares: 1) R and the metaphor package (for the meta-analysis of the primary outcome [prolactin reduction]); 2) MedCalc version 18.11 (for the meta-analysis of the secondary outcome [withdrawal rates]). Data from a sensitivity analysis (repeating the meta-analysis with only placebo-controlled RCTs) has been also included in the current article.

Relationship between childhood trauma and social adaptation in a sample of young people attending an early intervention service for psychosis. / Relación entre el maltrato infantil y la adaptación social en una muestra de jóvenes atendidos en un servicio de intervención precoz en psicosis.

INTRODUCTION: Childhood trauma has been associated with an increased risk of psychosis, a greater severity of psychopathological symptoms, and a worse functional prognosis in patients with psychotic disorders. The current study aims to explore the relationship between childhood trauma, psychopathology and social adaptation in a sample of young people with first episode psychosis (FEP) or at-risk mental states (ARMS). MATERIAL AND METHODS: The sample included 114 young people (18-35 years old, 81 FEP and 33 ARMS) who were attending an Early Intervention Service for Psychosis. Positive, negative and depressive symptoms were assessed with the PANSS and the Calgary Depression Scale; history of childhood trauma was assessed with the Childhood Trauma Questionnaire; social adaptation was assessed with the Social Adaptation Self-evaluation Scale (SASS). Structural equation modeling (SEM) was used to explore the relationship between childhood trauma, psychopathology and SASS dimensions in the global sample (including FEP and ARMS). An exploratory SEM analysis was repeated in the subsample of FEP patients. RESULTS: ARMS individuals reported more emotional neglect and worse social adaptation compared to FEP. SEM analysis showed that childhood trauma is associated with a worse social adaptation, in a direct way with domains involving interpersonal relationships, and mediated by depressive symptoms with those domains involving leisure, work and socio-cultural interests. CONCLUSIONS: Childhood trauma has a negative effect on social adaptation in young people with early psychosis. Depressive symptoms play a mediation role in this association, especially in domains of leisure and work.

Glycated Haemoglobin Is Associated With Poorer Cognitive Performance in Patients With Recent-Onset Psychosis.

BACKGROUND: Glucose abnormalities and cognitive alterations are present before the onset of schizophrenia. We aimed to study whether glucose metabolism parameters are associated with cognitive functioning in recent-onset psychosis (ROP) patients while adjusting for hypothalamic-pituitary adrenal (HPA) axis measures. METHODS: Sixty ROP outpatients and 50 healthy subjects (HS) were studied. Cognitive function was assessed with the MATRICS Consensus Cognitive Battery. Glycated haemoglobin (HbA1c), glucose, insulin, and C-peptide levels were determined in plasma. The HOMA-insulin resistance index was calculated. Salivary samples were obtained at home on another day to assess the cortisol awakening response and cortisol levels during the day. Univariate analyses were conducted to explore the association between glucose metabolism parameters and cognitive tasks. For those parameters that were more clearly associated with the cognitive outcome, multiple linear regression analyses were conducted to adjust for covariates. Each cognitive task was considered the dependent variable. Covariates were age, sex, education level, diagnosis, antipsychotic and benzodiazepine treatment, body mass index (BMI), smoking, and HPA axis measures. Potential interactions between diagnosis and glucose parameters were tested. RESULTS: There were no significant differences in HPA axis measures or glucose parameters, with the exception of C-peptide (that was higher in ROP patients), between groups. ROP patients had a lower performance than HS in all cognitive tasks (p < 0.01 for all tasks). Of all glucose metabolism parameters, HbA1c levels were more clearly associated with cognitive impairment in cognitive tasks dealing with executive functions and visual memory in both ROP patients and HS. Multivariate analyses found a significant negative association between HbA1c and cognitive functioning in five cognitive tasks dealing with executive functions, visual memory and attention/vigilance (a ROP diagnosis by HbA1c negative interaction was found in this latter cognitive domain, suggesting that HBA1c levels are associated with impaired attention only in ROP patients). CONCLUSIONS: Our study found that HbA1c was negatively associated with cognitive functioning in both ROP patients and HS in tasks dealing with executive functions and visual memory. In ROP patients, HbA1c was also associated with impaired attention. These results were independent of BMI and measures of HPA axis activity.

Pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia: A systematic review and meta-analysis.

Different therapeutic strategies are used for lowering prolactin concentrations in patients with psychotic disorders with antipsychotic-induced hyperprolactinaemia. We aimed to examine the evidence from open-label studies and randomized clinical trials (RCTs) that studied four prolactin-lowering therapeutic strategies in people with psychotic disorders and hyperprolactinaemia: 1) switching to prolactin-sparing antipsychotics; 2) adding aripiprazole; 3) adding dopamine agonists; and 4) adding metformin. RCTs were included in a meta-analysis. Effect sizes (Hedges' g) of prolactin reductions with each strategy were calculated. Withdrawal rates were also considered. We identified 26 studies. Nine studies explored switching antipsychotic treatment to aripiprazole (n = 4), olanzapine (n = 1), quetiapine (n = 2), paliperidone palmitate (n = 1) or blonanserin (n = 1). Twelve studies tested the addition of aripiprazole. Six studies explored the addition of cabergoline (n = 3), bromocriptine (n = 2) or terguride (n = 1). We also found one meta-analysis testing the addition of metformin to antipsychotic treatment but no other individual studies. A meta-analysis could only be performed for the addition of aripiprazole, the strategy with the best level of evidence. Five RCTs testing the addition of aripiprazole yielded a significant reduction in prolactin concentration compared to placebo (N = 3) or maintaining antipsychotic treatment (N = 2): Hedges' g was -1.35 (CI 95%: -1.93 to -0.76, p < 0.001). The three placebo-controlled RCTs for aripiprazole addition showed similar withdrawal rates for aripiprazole (10.1%) and placebo (11.5%), without significant differences in the meta-analysis. Our study suggests that, in terms of levels of evidence, adding aripiprazole is the first option to be considered for lowering prolactin concentrations in patients with schizophrenia and hyperprolactinaemia.

Association between anti-thyroid antibodies and negative symptoms in early psychosis.

AIM: In the current cross-sectional study, we aimed to explore whether thyroid function or thyroid autoimmunity are associated with psychopathological symptoms and social functioning in patients with early psychosis. We hypothesized that psychopathological severity is greater in those patients with positive thyroid autoimmunity. METHODS: We studied 70 outpatients with early psychosis (<3 years of illness) and 37 healthy subjects. Psychopathological symptoms (positive, negative, disorganized, excited and depressive) and social functioning were assessed. Thyroid autoimmunity (antibodies against thyroid peroxidase [TPO-Abs] and thyroglobulin [TG-Abs]) and thyroid function (thyroid-stimulating hormone [TSH] and free thyroxin [FT4]) were determined. Associations of thyroid variables and psychometric measures were assessed with Spearman's correlations. Logistic regression was performed to explore the association between psychopathological symptoms and positive anti-thyroidal antibodies while adjusting for covariates. RESULTS: When compared to patients without thyroid antibodies, those with positive thyroid antibodies had more negative symptoms and poorer function (P < .05). Titres of TPO-Abs were significantly correlated with negative and depressive PANSS domains and poorer functioning. TG-Abs were also associated with poorer functioning but not with psychopathological symptoms. TSH and FT4 concentrations were not associated with clinical symptoms. In the logistic regression analysis adjusted for age, gender, antipsychotic treatment, lithium, TSH and FT4 concentrations, negative symptoms were associated with thyroid autoimmunity (OR = 1.2, P = .019). CONCLUSIONS: Our study suggests that anti-thyroid antibodies are associated with a more severe phenotype with increased negative symptoms and poorer functioning in early psychotic patients. Since causality cannot be inferred with cross-sectional data, future longitudinal studies are needed to overcome this limitation.

Hypothalamic-pituitary-adrenal axis function and exposure to stress factors and cannabis use in recent-onset psychosis.

Objectives: Previous studies suggest that childhood trauma, stressful life events, and cannabis use are associated with psychosis. We aimed to explore whether these environmental factors have an effect on hypothalamic-pituitary-adrenal (HPA) axis indices in recent-onset psychosis.Methods: We studied 56 recent-onset psychosis outpatients and 47 healthy controls. Childhood trauma was assessed with the Childhood Trauma Questionnaire. Stressful life events were assessed with the Holmes-Rahe Social Readjustment Scale. Cannabis use was assessed by semistructured interviews. Several HPA axis measures were analysed in saliva: cortisol awakening response (CAR), diurnal cortisol slope, and dexamethasone suppression test ratio (DSTR) after 0.25 mg of dexamethasone. Multiple linear regression analyses were conducted to explore the contribution of environmental factors to each HPA axis measure while adjusting for covariates (diagnosis, age, gender, smoking, body mass index and treatments).Results: There were no significant differences in HPA axis measures between diagnostic groups. Cannabis use was associated with a more flattened diurnal cortisol slope (standardized ß = 0.21, p = 0.038), independent of recent-onset psychosis diagnosis. No associations were found between environmental factors and other HPA axis measures (CAR, DSTR).Conclusions: Our study provides evidence for the effect of cannabis exposure in cortisol secretion patterns in both healthy controls and recent-onset psychosis patients.

Perceived stress mediates the relationship between social adaptation and quality of life in individuals at ultra high risk of psychosis.

AIM: Quality of life (QoL) and social functioning have emerged as good predictors of the outcome of psychotic disorders. Poor QoL and social functioning are usually present before the onset of the first episode of psychosis. Our study aimed to explore the relationship between social adaptation and QoL in young people at risk of psychosis (ultra-high-risk, UHR) and healthy controls (HCs), and to investigate potential mediating effects of stress measures (perceived stress, stressful life events). METHODS: The study included 55 UHR subjects and 40 HC. Social functioning was assessed with the Social Adaptation Self-evaluation Scale (SASS). Stress measures included the assessment of stressful life events and perceived stress. We compared stress and QoL measures between UHR and HC, and also compared UHR with low or normal social adaptation. A mediation analysis was performed to explore whether stress measures mediated the relationship between social adaptation and QoL. RESULTS: UHR were less frequently employed and reported more stress, poorer QoL and lower social adaptation than HC. QoL and social adaptation were associated with stress measures. UHR with low social adaptation reported more perceived stress and less QoL than UHR with normal social adaptation and HC. Perceived stress mediated the relationship between social adaptation and QoL. CONCLUSIONS: Social adaptation is less developed in UHR subjects than in healthy subjects and has a negative impact on quality of life. This association is mediated by perceived stress.

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.

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.

Clinical correlates of hypothalamic-pituitary-adrenal axis measures in individuals at risk for psychosis and with first-episode psychosis.

Hypothalamic-pituitary-adrenal (HPA) axis alterations in at-risk mental states (ARMS) resemble those observed in established psychosis but are less consistent. We aimed to explore HPA axis abnormalities in both first-episode psychosis (FEP) and ARMS patients, while controlling for psychopathological symptoms. We studied 21 ARMS, 34 FEP patients and 34 healthy subjects. Clinical assessment included psychopathological symptoms (positive, negative, disorganized, excited and depressive symptoms) and stress measures. Saliva cortisol levels were determined at awakening, 30' and 60' post-awakening, 10:00 h, 23:00 h and 10:00 h on the day after the administration of 0.25 mg of dexamethasone, which occurred at 23:00 h. Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). There were no significant differences between groups in HPA axis measures. However, when exploring the relationship between HPA axis measures and psychopathological symptoms, in ARMS subjects (but not FEP patients), a flatter cortisol slope was associated with more prominent negative symptoms, whereas a blunted CAR was associated with excited symptoms. Although no significant differences in HPA axis measures were found between diagnostic groups, subtle abnormalities in the CAR or circadian cortisol rhythmicity might be important for the phenotype of ARMS individuals.

Gene-environment interaction between the brain-derived neurotrophic factor Val66Met polymorphism, psychosocial stress and dietary intake in early psychosis.

AIM: The brain-derived neurotrophic factor (BDNF) is a major participant in the regulation of food intake and may play a role in the regulation of the stress response. We aimed to investigate whether there is a gene-environment interaction in the relationship between stress and BDNF Val66Met polymorphism in relation to dietary patterns in a sample of subjects with early psychosis. METHODS: We studied 124 early psychotic disorder (PD) patients, 36 At-Risk Mental States (ARMS) and 62 healthy subjects (HS). Dietary patterns were examined by a dietician. Physical activity, life stress and perceived stress were assessed by validated questionnaires. BDNF Val66Met polymorphism (rs6265) was genotyped. A gene-environment interaction was tested with multiple linear regression analysis while adjusting for covariates. RESULTS: Perceived stress was not associated with calorie intake in HS. In ARMS subjects, Met-carriers who presented low-perceived stress were associated with increased caloric intake. Conversely, those who presented high-perceived stress were associated with reduced caloric intake. In PD, perceived stress was neither associated with increased calorie intake without an effect by BDNF genotype nor a gene-environment interaction. Perceived stress was associated with food craving in PD patients, independent of genotype, and in ARMS or HS who were Val homozygous. CONCLUSIONS: This study suggests that the common Val66Met polymorphism of the BDNF gene may modulate the relationship between life stress and calorie intake in subjects at risk for psychosis.