Cognitive biases in first-episode psychosis with and without attention-deficit/hyperactivity disorder.

Introduction: Psychotic disorders such schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with social cognitive deficits. Specifically, biased interpretation of social information can result in interpersonal difficulties. Cognitive biases are prevalent in psychosis, but no previous study has investigated whether the type and severity of cognitive biases differ between subjects experiencing first-episode psychosis (FEP) with (FEP-ADHD+) and without ADHD (FEP-ADHD-). Methods: A total of 121 FEP outpatients at the Early Intervention Service of Reus were screened for childhood ADHD through the Diagnostic Interview for ADHD (DIVA). Cognitive biases were assessed by the Cognitive Biases Questionnaire for Psychosis (CBQp). CBQp scores of FEPs groups were compared with those of healthy controls (HCs) with an analysis of covariance. Spearman correlation analysis explored associations between CBQp scores and psychopathology. Results: Thirty-one FEPs met the criteria for childhood ADHD and reported significantly more cognitive bias [median (interquartile range): 47 (38-56)] than FEP-ADHD- [42 (37-48)] and HCs [38 (35.5-43)]. CBQp scores did not differ between FEP-ADHD-and HCs when adjusted for age and sex. After controlling for clinical differences, Intentionalising (F = 20.97; p < 0.001) and Emotional Reasoning biases (F = 4.17; p = 0.04) were more strongly associated with FEP-ADHD+ than FEP-ADHD-. Cognitive biases were significantly correlated with positive psychotic symptoms in both groups but only with depressive symptoms in FEP-ADHD- (r = 0.258; p = 0.03) and with poor functioning in FEP-ADHD+ (r = -0.504; p = 0.003). Conclusion: Cognitive bias severity increased from HCs to FEP-ADHD-patients to FEP-ADHD+ patients. FEP-ADHD+ patients may be a particularly vulnerable group in which metacognitive targeted interventions are needed.

Comparación entre inmunomoduladores y crioterapia para el tratamiento de lesiones genitales en mujeres con VPH / Comparison between immunomodulators and cryotherapy for the treatment of genital lesions in women with HPV / Comparação entre imunomoduladores e crioterapia para o tratamento de lesões genitais em mulheres com HPV

El virus del papiloma humano es una infección prevalente, que puede infectar cualquier mucosa del cuerpo y causar verrugas genitales externas o condilomas genitales y cáncer de cuello uterino. El tratamiento es difícil con una alta recurrencia y persistencia de las mismas, lo que afecta mayormente a mujeres jóvenes. El objetivo del presente estudio fue realizar una comparación entre inmunomoduladores y crioterapia para el tratamiento de lesiones genitales en mujeres con VPH. Se realizó una revisión bibliográfica de la literatura científica, entre inmunomoduladores y crioterapia para el tratamiento de lesiones genitales en mujeres con VPH de los últimos 20 años, donde se identificaron publicaciones de revisiones sistemáticas y metaanálisis. Se concluyó que la elección de los inmunomoduladores al igual que la crioterapia es mejor utilizarlos cuando existe lesiones clínicas inducidas por el VPH en la región genital y perianal en mujeres, dependiendo de la cantidad, el tamaño, la gravedad, la ubicación de las verrugas y las preferencias del paciente.

Human papillomavirus is a prevalent infection, which can infect any mucosa of the body and cause external genital warts or genital warts and cervical cancer. Treatment is difficult with a high recurrence and persistence of the same, which mainly affects young women. The objective of the present study was to compare immunomodulators and cryotherapy for the treatment of genital lesions in women with HPV. A narrative bibliographic review of the scientific literature was carried out, between immunomodulators and cryotherapy for the treatment of genital lesions in women with HPV of the last 20 years, where publications of systematic reviews and meta-analyses were identified. It was concluded that the choice of immunomodulators, like cryotherapy, is better used when there are clinical lesions induced by HPV in the genital and perianal region in women, depending on the number, size, severity, location of the warts and patient preferences.

O papilomavírus humano é uma infecção prevalente, que pode infectar qualquer mucosa do corpo e causar verrugas genitais externas ou verrugas genitais e câncer cervical. O tratamento é difícil com alta recorrência e persistência da mesma, que acomete principalmente mulheres jovens. O objetivo do presente estudo foi comparar imunomoduladores e crioterapia para o tratamento de lesões genitais em mulheres com HPV. Foi realizada uma revisão bibliográfica narrativa da literatura científica, entre imunomoduladores e crioterapia para tratamento de lesões genitais em mulheres com HPV dos últimos 20 anos, onde foram identificadas publicações de revisões sistemáticas e metanálises. Concluiu-se que a escolha de imunomoduladores, como a crioterapia, é melhor utilizada quando há lesões clínicas induzidas pelo HPV na região genital e perianal em mulheres, dependendo do número, tamanho, gravidade, localização das verrugas e preferências da paciente.

The Role of Sleep Quality, Trait Anxiety and Hypothalamic-Pituitary-Adrenal Axis Measures in Cognitive Abilities of Healthy Individuals.

Sleep plays a crucial role in cognitive processes. Sleep and wake memory consolidation seem to be regulated by glucocorticoids, pointing out the potential role of the hypothalamic-pituitary-adrenal (HPA) axis in the relationship between sleep quality and cognitive abilities. Trait anxiety is another factor that is likely to moderate the relationship between sleep and cognition, because poorer sleep quality and subtle HPA axis abnormalities have been reported in people with high trait anxiety. The current study aimed to explore whether HPA axis activity or trait anxiety moderate the relationship between sleep quality and cognitive abilities in healthy individuals. We studied 203 healthy individuals. We measured verbal and visual memory, working memory, processing speed, attention and executive function. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Trait anxiety was assessed with the State-Trait Anxiety Inventory. HPA axis measures included the cortisol awakening response (CAR), diurnal cortisol slope and cortisol levels during the day. Multiple linear regression analyses explored the relationship between sleep quality and cognition and tested potential moderating effects by HPA axis measures and trait anxiety. Poor sleep quality was associated with poorer performance in memory, processing speed and executive function tasks. In people with poorer sleep quality, a blunted CAR was associated with poorer verbal and visual memory and executive functions, and higher cortisol levels during the day were associated with poorer processing speed. Trait anxiety was a moderator of visual memory and executive functioning. These results suggest that subtle abnormalities in the HPA axis and higher trait anxiety contribute to the relationship between lower sleep quality and poorer cognitive functioning in healthy individuals.

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

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.

Clinical and cognitive correlates of childhood attention-deficit/hyperactivity disorder in first-episode psychosis: A controlled study.

The relationship between childhood attention-deficit/hyperactivity disorder (c-ADHD) and psychosis has been understudied. Cognitive dysfunction is a core feature of both disorders, but no previous study has investigated whether first-episode psychosis (FEP) with c-ADHD (FEP-ADHD+) presents a different cognitive profile than FEP without c-ADHD (FEP-ADHD-). One hundred and thirty-three FEP outpatients were screened for c-ADHD through a diagnostic interview and underwent a comprehensive clinical and cognitive assessment with the MATRICS Consensus Cognitive Battery (MCCB). Cognitive differences among FEP groups, and a group of 65 healthy controls (HCs) were analysed by multivariate analysis of covariance. Nearly 25% of FEP fulfilled criteria for c-ADHD. Both FEP groups performed worse than HCs in speed processing, executive function and social cognition, but only the FEP-ADHD+group was significantly more impaired than the HC group in attention (F = 4.35; p = 0.04). Only the Trail Making Test A (TMT-A) (F = 6.99; p = 0.01) within the domain of processing speed and the Neuropsychological Assessment Battery (NAB) (F = 6.46; p = 0.01) within the domain of executive function reliably differentiated the two clinical groups. The FEP groups did not differ in the severity of psychopathology, but the FEP-ADHD+reported fewer years of education than the FEP-ADHD- and were more likely to use tobacco and cannabis and to require higher doses of antipsychotics to achieve a clinical response. In conclusion, we found a gradient of severity in cognitive performance between groups, with FEP-ADHD+ having the greatest cognitive impairment. Our results suggest that FEP-ADHD+ represents a subgroup with a worse prognosis than FEP-ADHD-.

The impact of sex and cannabis on clinical features in first-admitted patients with psychosis.

There is a scarcity of studies investigating the effect of sex on the clinical and treatment characteristics of first-admitted patients with first-episode psychosis (FEP). The reasons for using cannabis and the effect of cannabis on clinical features have not received enough attention either. We aim therefore, to investigate sex differences in the reasons for cannabis use and to determine the effects of sex, cannabis use and their interaction on clinical variables at admission and at discharge from the inpatient unit. 204 first-admitted FEPs in two inpatient units in Spain were included. The reasons for using cannabis were determined using the Dixon questionnaire. Clinical variables were compared between sexes and between cannabis users and non-users. Cannabis use was more frequent in males, but females were more likely to smoke cannabis to "feel relaxed". There was a main effect of sex on positive psychotic symptoms and antipsychotics dose and an interaction effect of cannabis and sex on global functioning at discharge .Our findings show sex differences in the reasons for cannabis use and in some clinical and treatment characteristics among FEP patients. More studies focusing on gender perspectives are needed to develop more individualized treatments.

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.

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.

Sex-specific association between the cortisol awakening response and obsessive-compulsive symptoms in healthy individuals.

BACKGROUND: Previous studies have shown associations between obsessive-compulsive disorder (OCD) and hypothalamic-pituitary-adrenal axis activity (HPA). We aimed to investigate the association between obsessive-compulsive (OC) symptoms and HPA axis functionality in a non-clinical sample and to explore whether there are sex differences in this relationship. METHODS: One hundred eighty-three healthy individuals without any psychiatric diagnosis (80 men, 103 women; mean age 41.3 ± 17.9 years) were recruited from the general population. The Obsessive-Compulsive Inventory Revised (OCI-R) was used to assess OC symptoms. State-trait anxiety, perceived stress, and stressful life events were also assessed. Saliva cortisol levels were determined at 6 time points (awakening, 30 and 60 min post-awakening, 10:00 a.m., 23:00 p.m. and 10:00 a.m. the following day of 0.25 mg dexamethasone intake [that occurred at 23:00 p.m.]). Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope, and cortisol suppression ratio after dexamethasone (DSTR). Multiple linear regression analyses were used to explore the association between OC symptoms and HPA axis measures while adjusting for covariates. Our main analyses were focused on OCI-R total score, but we also explored associations with specific OC symptom dimensions. RESULTS: No significant differences were observed between males and females in OC symptoms, anxiety measures, stress, or cortisol measures. In the multiple linear regression analyses between overall OC symptoms and HPA axis measures, a female sex by OC symptoms significant interaction (standardized beta = - 0.322; p = 0.023) for the CAR (but not cortisol diurnal slope nor DSTR) was found. Regarding specific symptom dimensions, two other sex interactions were found: a blunted CAR was associated with obsessing symptoms in women, whereas a more flattened diurnal cortisol slope was associated with ordering symptoms in men. CONCLUSIONS: There are sex differences in the association between OC symptoms and HPA axis measures in healthy individuals.

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.

The relationship between the level of exposure to stress factors and cannabis in recent onset psychosis.

BACKGROUND: There is a lack of studies investigating the dose-response effect of childhood trauma, recent events and cannabis use on recent psychosis. This study aims to determine the relationship between the level of exposure to stress factors and cannabis use with psychosis and to determine the combination effect among these factors in predicting a psychotic disorder. METHODS: 146 recent onset psychotic (ROP) patients and 61 healthy controls were included. Childhood trauma was evaluated using the childhood trauma questionnaire (CTQ) and recent events using the Holmes-Rahe social readjustment scale. The pattern of cannabis use was assessed by a detailed interview. A hierarchical multiple regression was run in order to determine both the cumulative and independent contribution of each factor in predicting a psychotic disorder. RESULTS: The highest levels of exposure to childhood trauma and cannabis were associated with psychosis while neither low nor high recent event exposure was associated. The combined effect of risk factors yielded a significant association with psychosis (×2 = 86.76, p < .001) explaining the 49% of its variation. ROP were more likely to be exposed to one, two or three environmental factors than HC. Exposed to two or all factors were 7.5-fold and 26.7-fold more likely to have a diagnosis of psychosis, respectively. CONCLUSIONS: Our study provides evidence for a cumulative and a dose-response effect of environmental factors on recent psychosis. Considering that cannabis use and stress are highly prevalent in the population with psychosis, investigations of their relationships are needed to implement targeted prevention and treatment strategies.

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.

Sex differences in the relationship between prolactin levels and impaired processing speed in early psychosis.

INTRODUCTION: Hyperprolactinaemia is commonly observed in people with psychotic disorders due to D2 receptor blockade by antipsychotic drugs, although it may also exist in drug-naïve patients with first-episode psychosis. Recent studies suggest that hyperprolactinaemia may have a negative impact on cognitive function in people with early psychosis. We aimed to explore whether there are sex differences in the association between prolactin levels and cognitive performance in early psychosis patients. METHODS: We studied 60 young patients with early psychosis (aged 18-35 years, 35% females) and a sex- and age-matched control group of 50 healthy subjects. Cognitive assessment was performed with the MATRICS Consensus Cognitive Battery. Prolactin, total cortisol, follicular-stimulating hormone, luteal hormone and sex steroids (testosterone in men, oestradiol and progesterone in women) were measured in plasma. Salivary cortisol was measured at different sampling times (awakening response, 10:00 and 23:00). Psychopathological status was assessed, and antipsychotic treatment was registered. Multiple linear regression analyses were used to explore the relationship between prolactin and cognitive tasks while adjusting for covariates. RESULTS: Prolactin levels were associated with impaired processing speed in men, and this association was independent of cortisol and testosterone. In women, prolactin levels were not associated with processing speed tasks, although we observed a negative effect of prolactin on verbal learning and spatial working memory in female healthy subjects. The male-dependent effect maintained its significance after adjusting for education status, antipsychotic treatment and negative symptoms. CONCLUSION: Our study demonstrates that the previously reported association between high prolactin levels and impaired cognitive processes in early psychosis is restricted to men.

Hypothalamic-pituitary-adrenal axis measures and cognitive abilities in early psychosis: Are there sex differences?

INTRODUCTION: Measures of hypothalamic-pituitary-adrenal (HPA) axis activity such as increased diurnal cortisol levels or a blunted cortisol awakening response (CAR) have been associated with cognitive impairments in people with psychotic disorders. We aimed to explore whether there are sex differences in the relationship between HPA axis measures and cognition in early psychosis (EP). METHODS: 60 EP outpatients and 50 healthy subjects (HS) were assessed with the MATRICS Consensus Cognitive Battery. Saliva cortisol levels were determined at the neuropsychological assessment and on another day at 6 sampling times: awakening; 30' and 60' post-awakening; and 10:00h, 23:00h and 10:00h the day after the administration of 0.25mg of dexamethasone, which occurred at 23:00h. Three HPA axis measures were calculated: CAR, cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). Multiple linear regression analyses were conducted to explore the relationship between HPA axis measures and cognitive tasks while adjusting for covariates (education level, smoking, cannabis use, and cortisol levels at the cognitive assessment). Interactions between female sex, EP diagnosis and HPA axis measures were examined. RESULTS: An increased CAR was associated with a poorer cognitive performance in EP women in processing speed and verbal memory. In contrast, a more flattened diurnal cortisol slope was associated with poorer functioning in the spatial working memory of EP women. DST suppression ratio was associated with better visual memory, without sex differences. CONCLUSIONS: Our study suggests that there are sex differences in the relationship between HPA axis measures and cognitive abilities in EP.

Sex differences in the effect of childhood trauma on the clinical expression of early psychosis.

Childhood trauma, a risk factor of psychosis, is associated the clinical expression of the illness (greater severity of psychotic symptoms; poorer cognitive performance). We aimed to explore whether there are sex differences in this relationship. We studied 79 individuals with a psychotic disorder (PD) with <3years of illness and 59 healthy subjects (HS). All participants were administered the MATRICS Cognitive Consensus Cognitive Battery (MCCB) to assess cognition. Depressive, positive and negative psychotic symptoms, and global functioning were also assessed. History of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Patients reported a greater history of childhood trauma on all CTQ domains (emotional, physical and sexual abuse, and physical and emotional neglect). A poorer cognitive performance was also observed in PD when compared to HS. No sex differences were found in the CTQ scores. In the relationship between childhood trauma and psychopathological symptoms, significant correlations were found between CTQ scores and positive and negative psychotic symptoms, depressive symptoms and poorer functionality, but only in women. Childhood trauma was associated with poorer social cognition in both men and women. Of all CTQ dimensions, emotional neglect and physical neglect were more clearly associated with a more severe psychopathological and cognitive profile. Our results suggest that childhood trauma, particularly emotional and physical neglect, is associated with the clinical expression of psychosis and that there are sex differences in this relationship.

Clinical correlates of obsessive-compulsive symptom dimensions in at-risk mental states and psychotic disorders at early stages.

We studied the clinical correlates of obsessive-compulsive symptom dimensions in 109 individuals with early psychosis (31 At-Risk Mental States [ARMS], 78 psychotic disorders with <3 years of illness) and 59 healthy subjects. Obsessive-compulsive symptoms were assessed by the Obsessive-Compulsive Inventory - Revised. We also assessed the severity of psychotic symptoms, depressive symptoms and functioning. ARMS and psychotic disorder patients reported more obsessive-compulsive symptoms than did healthy subjects. The ARMS individuals also reported more overall and checking obsessive-compulsive symptoms compared with the PD patients. Different types of obsessive-compulsive symptoms were related with depressive symptoms in both diagnostic groups. However, a different pattern was observed in the relationship between obsessive-compulsive dimensions and functioning by diagnosis (better functioning in ARMS; poorer functioning in psychotic disorders). Our study suggests that obsessive-compulsive symptoms are present in the early stages of psychotic illness, as well as in individuals at risk for psychosis. Future prospective studies are needed to elucidate how obsessive-compulsive symptoms in ARMS may influence the prognosis in terms of global functioning and the risk of psychosis transition.