Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia.

Pyk2 has been shown previously to be involved in several psychological and cognitive alterations related to stress, Huntington's disease, and Alzheimer's disease. All these disorders are accompanied by different types of impairments in sociability, which has recently been linked to improper mitochondrial function. We hypothesize that Pyk2, which regulates mitochondria, could be associated with the regulation of mitochondrial dynamics and social skills. In the present manuscript, we report that a reduction of Pyk2 levels in mouse pyramidal neurons of the hippocampus decreased social dominance and aggressivity. Furthermore, social interactions induced robust Pyk2-dependent hippocampal changes in several oxidative phosphorylation complexes. We also observed that Pyk2 levels were increased in the CA1 pyramidal neurons of schizophrenic subjects, occurring alongside changes in different direct and indirect regulators of mitochondrial function including DISC1 and Grp75. Accordingly, overexpressing Pyk2 in hippocampal CA1 pyramidal cells mimicked some specific schizophrenia-like social behaviors in mice. In summary, our results indicate that Pyk2 might play a role in regulating specific social skills likely via mitochondrial dynamics and that there might be a link between Pyk2 levels in hippocampal neurons and social disturbances in schizophrenia.

The Night and Day Challenge of Sleep Disorders and Insomnia: A Narrative Review.

This is a narrative review of sleep disorders, especially chronic insomnia, as a primary diagnosis or as a comorbid diagnosis associated with different psychiatric and organic diseases. The epidemiological evidence is reviewed, the diagnostic criteria most frequently used in clinical practice are examined, and a series of therapeutic recommendations for the correct treatment of this pathology is presented. Sleep disorders are very prevalent in the general population (one-third experiences difficulty with sleep initiation/maintenance at least once a week, and about 6-15% meet the criteria for insomnia disorders), but remain relatively poorly understood and frequently overlooked by healthcare professionals. Prevalence estimates of insomnia disorder vary between 5% and 20%. Sleep disorders co-exist with psychiatric and medical conditions with an interactive and bidirectional relationship. About 70-80% of psychiatric patients show some sleep disturbance and there is a correlation between the severity of the sleep disturbance and the severity of the psychopathology. Untreated sleep disorders increase the risk of cardiovascular events, cognitive impairment, motor vehicle accidents, obesity, diabetes, and efficiency and safety at work, leading to increased all-cause healthcare utilization and being a strong predictor of sick leave or disability pension and poor quality of life. Sleep disorders can cause drowsiness or excessive daytime sleepiness, which can lead to functional impairment in 15% of the general adult population. Sleep quality should be a routine target in the evaluation of patients with psychiatric and non-psychiatric diseases to ensure sleep health based on early diagnosis and adequate therapeutic approaches.

Clinical practice guideline on pharmacological and psychological management of adult patients with schizophrenia spectrum disorders and a comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno del espectro esquizofrénico y un diagnóstico comórbido de trastorno por uso de sustancias.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).

Aunque el correcto diagnóstico y manejo de los pacientes con esquizofrenia y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) determinaría una disminución de la morbilidad y mortalidad en estos pacientes, el desarrollo de estrategias terapéuticas eficientes es todavía una asignatura pendiente. Presentamos recomendaciones sobre el manejo farmacológico y psicológico de estos pacientes siguiendo la estructura PICO (Paciente-Intervención-Comparación-Outcome/resultados). Realizamos una evaluación de la calidad de los estudios y un resumen de la evidencia para cada pregunta siguiendo las recomendaciones del grupo de trabajo GRADE («Grading of Recommendations, Assessment, Development and Evaluation¼). Nuestros resultados sugieren: 1) En pacientes con esquizofrenia y trastorno por consumo de cannabis, no es posible recomendar un fármaco antipsicótico sobre otro (entre olanzapina, risperidona o haloperidol) para mejorar los síntomas psicóticos, reducir el consumo de cannabis o mejorar las variables pragmáticas (recomendación débil). No se puede recomendar la clozapina para reducir el consumo de cannabis (recomendación débil). 2) En pacientes con esquizofrenia y trastorno por consumo de cocaína, recomendamos haloperidol sobre olanzapina para reducir el craving (recomendación moderada) y olanzapina sobre haloperidol para mejorar los efectos secundarios motores en estos pacientes (recomendación moderada). 3) En pacientes con esquizofrenia y trastorno por consumo de alcohol, mientras que se recomienda naltrexona para reducir el consumo de alcohol (en términos de reducción del craving de alcohol) (recomendación débil), no hay evidencia suficiente para hacer ninguna recomendación sobre el uso de acamprosato como adyuvante (recomendación débil). 4) En pacientes con esquizofrenia y trastorno por consumo de nicotina, se recomiendan bupropión y vareniclina adyuvantes para reducir el consumo y la abstinencia de nicotina (recomendación fuerte/moderada). 5) En pacientes con esquizofrenia y trastorno por policonsumo, se recomiendan antipsicóticos de segunda generación sobre los de primera generación y olanzapina sobre otros antipsicóticos de segunda generación para mejorar los síntomas psicóticos (recomendación moderada/débil).

Clinical practice guideline on pharmacological and psychological management of adult patients with depression and a comorbid substance use disorder. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con depresión y un diagnóstico comórbido de trastorno por uso de sustancias.

Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.

La concurrencia de depresión y un trastorno por uso de sustancias (TUS) en pacientes que presentan patología dual ha sido reconocida desde hace mucho tiempo como una consideración importante en la práctica clínica. Esta revisión sintetiza la evidencia de intervenciones farmacológicas y psicosociales para trastornos comórbidos de depresión y uso de sustancias y además proporciona recomendaciones clínicas respecto de las mejores intervenciones para tratar a estos pacientes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Nuestros resultados sugieren que: 1) en pacientes con depresión y consumo de alcohol, se recomienda la administración de antidepresivos inhibidores de la recaptación de serotonina (ISRS) no selectivos en lugar de los ISRS para mejorar los síntomas depresivos (recomendación fuerte). No se recomiendan antidepresivos ISRS (recomendación fuerte) ni antidepresivos no ISRS (recomendación débil) para reducir el consumo de alcohol; 2) en pacientes con depresión y consumo de cannabis, no se recomienda el uso de venlafaxina (recomendación débil); 3) en pacientes con depresión y consumo de cocaína, no se recomienda el uso de antidepresivos ISRS para mejorar los síntomas depresivos (recomendación débil) o para reducir el consumo de cocaína (recomendación fuerte). El uso de antidepresivos no ISRS solo se recomienda para mejorar los síntomas depresivos (recomendación fuerte); 4) no se recomienda la administración de bupropión para reducir el consumo de nicotina (recomendación fuerte), y 5) en cuanto al tratamiento psicológico, en pacientes con depresión y trastorno de alcohol concurrente, tanto la farmacoterapia como la terapia cognitivo-conductual tienen efectos positivos en la internalización de los síntomas y en la reducción del consumo de alcohol (recomendación débil). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multisitio y más grandes para proporcionar más evidencia definitiva.

Clinical practice guideline on pharmacological and psychological management of adult patients with bipolar disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno bipolar y un diagnóstico comórbido de trastorno por uso de sustancias.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid bipolar disorder (BD) and substance use disorders (SUDs) while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Very few of the randomized trials performed so far have provided consistent evidence for the management of both mood symptoms and substance use in patients with a BD. No clinical trials are available for bipolar patients using cannabis. Some treatments have shown benefit for mood symptoms without benefits for alcohol or illicit substance use. Our results suggest that 1) we can (weakly) recommend the use of adjuvant valproate or naltrexone to improve symptoms of alcohol use disorder; 2) Lamotrigine add-on therapy seems to reduce cocaine-related symptoms and is therefore recommended (moderate strength); and 3) Varenicline is (weakly) recommended to improve nicotine abstinence. Integrated group therapy is the most-well validated and efficacious approach on substance use outcomes if substance use is targeted in an initial treatment phase.

Esta revisión resume las intervenciones farmacológicos y psicosociales que se han realizado en trastorno bipolar (TB) y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias versus los síntomas de estado de ánimo en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Muy pocos de los ensayos aleatorizados realizados hasta la fecha han proporcionado evidencia consistente para el manejo tanto de los síntomas de estado de ánimo como del uso de sustancias en pacientes con TB. No hay disponibilidad de ensayos clínicos para pacientes con TB que utilizan el cannabis. Algunos tratamientos han mostrado beneficios para los síntomas de estado de ánimo sin beneficios para el uso de alcohol o sustancias ilícitas. Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de ácido valproico o naltrexona adyuvante para aliviar los síntomas del trastorno por consumo de alcohol; 2) el tratamiento complementario con lamotrigina parece reducir los síntomas relacionados con la cocaína y, por tanto, es recomendable (fuerza moderada); y 3) la vareniclina es recomendable (débilmente) para mejorar la abstinencia de la nicotina. La terapia grupal integrada es el enfoque con más validación y eficacia sobre los resultados en el uso de sustancias cuando este uso es abordado durante la fase inicial de tratamiento.

Clinical practice guideline on pharmacological and psychological management of adult patients with an anxiety disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno de ansiedad y un diagnóstico comórbido de trastorno por uso de sustancias.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for posttraumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram). Our results suggest that 1) we can (weakly) recommend the use of desipramine over paroxetine to alleviate symptoms of anxiety in patients with a PTSD and alcohol use; 2) In these patients, the use of naltrexone to reduce symptoms of anxiety is also recommended (weak strength); and 3) SSRI antidepressants vs placebo can be recommended to reduce alcohol use (weak recommendation). Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.

Esta revisión resume las intervenciones farmacológicos y psicosociales que han sido llevadas a cabo en trastornos de ansiedad con un diagnóstico comórbido de trastorno por uso de sustancias y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias y los síntomas de ansiedad en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Hay ensayos clínicos disponibles únicamente para el trastorno por estrés postraumático (TEPT) y para el trastorno de ansiedad. En cuanto al diagnóstico comórbido de trastorno por uso de sustancias, todos los estudios han incluido pacientes con consumo de alcohol, ninguno de ellos ha abordado el consumo de cocaína, cannabis o nicotina. Aunque algunos tratamientos han mostrado beneficios para los síntomas de ansiedad sin beneficios para el consumo de alcohol u otras sustancias, solo se han ensayado enfoques farmacológicos limitados (sertralina, desipramina, paroxetina, buspirona, naltrexona y disulfiram). Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de desipramina sobre la paroxetina para aliviar los síntomas de ansiedad en pacientes con un TEPT y consumo de alcohol; 2) en estos pacientes, el uso de naltrexona para reducir los síntomas de ansiedad es también recomendable (fuerza débil); y 3) se pueden recomendar antidepresivos ISRS frente a placebo para reducir el consumo de alcohol (recomendación débil). Nuestra revisión pone de relieve la necesidad de realizar más investigaciones en esta área y de estudios más grandes, multisitio con muestras generalizables para proporcionar evidencia más definitiva para la práctica clínica.

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno por déficit de atención con hiperactividad y un diagnóstico comórbido de trastorno por uso de sustancias.

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.

La evidencia actual confirma la alta comorbilidad entre el trastorno por déficit de atención con hiperactividad (TDAH) y trastorno por uso de sustancias (TUS). Esta revisión resume las intervenciones farmacológicas y psicosociales que se han evaluado en pacientes con TDAH y TUS, y ofrece recomendaciones mediante el enfoque GRADE. Nuestros resultados sugieren: 1) En pacientes con TDAH y trastorno por uso de alcohol, la atomoxetina es recomendable para reducir los síntomas de TDAH (recomendación débil) y el craving de alcohol (recomendación débil). 2) En pacientes con TDAH y trastorno por uso de cannabis, la atomoxetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de cannabis (recomendación débil). 3) En pacientes con TDAH y trastorno por uso de cocaína, el metilfenidato no es recomendable para mejorar los síntomas de TDAH o para reducir el uso de cocaína (recomendación débil). 4) En pacientes con TDAH y trastorno por uso de nicotina, es recomendable el metilfenidato para mejorar los síntomas de TDAH (recomendación débil). Los psicoestimulantes, como metilfenidato o lisdexanfetamina, no son recomendables para reducir el uso de nicotina (recomendación débil). 5) Respecto de los pacientes con TDAH y cualquier TUS, el uso de los psicoestimulantes es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). En estos pacientes, el uso de atomexetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). La atomoxetina y los psicoestimulantes parecen ser seguros en pacientes con cualquier TUS (recomendación fuerte). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multicéntricos y de mayor tamaño muestral para proporcionar más evidencia definitiva y concluyente.

Detection of alcohol use disorders using the camouflaged CAGE questionnaire in three population groups. / Detección de trastornos por uso de alcohol mediante la aplicación del cuestionario CAGE camuflado en tres grupos poblacionales.

The objective was to evaluate the risk of presenting an alcohol use disorder (AUD) in outpatient psychiatric units and compare it with drug addiction outpatient units and with healthy controls in the same administrative health area. An observational, descriptive, multicenter study was carried out in which a total of 1054 participants were evaluated. Data were obtained by means of the camouflaged CAGE questionnaire, which consists of 4 basic questions camouflaged with 8 other questions about healthy lifestyle habits. Cut-off points 1 and 2 were considered.Of the total number of participants, 588 were psychiatric outpatients, 153 outpatients from addiction centers and 313 healthy individuals. The mean age of the total sample was 45.8 years and the percentage of men was 53.2%. Of the total sample, 38.3% scored ≥1, as did 34.2% of psychiatric patients, 72.5% of drug addicts and 29.4% of healthy people. The ≥2 cut-off was reached by 26.6% of the total sample, 22.6% of psychiatric patients, 64.7% of drug addicts and 15.3% of healthy subjects. The participants with the highest percentage of ≥1 scores were men (48.8%), those younger than 30 years (50%), those with a diagnosis of alcohol use disorder (95.9%) and ADHD (83.3%).Psychiatric patients are at a higher risk of having an AUD than the healthy subjects, although lower than those who are drug addicts, and the CAGE questionnaire is a simple and useful tool to detect the risk patients have to suffer the condition under study.

El objetivo fue evaluar el riesgo de presentar un trastorno por uso de alcohol (TUA) en las consultas psiquiátricas ambulatorias y compararlo con las consultas de drogodependencias y con individuos sanos de la misma zona de salud. Se realizó un estudio observacional, descriptivo, multicéntrico, en el que fueron incluidos un total de 1054 participantes. Se utilizó el cuestionario CAGE camuflado para la obtención de los datos, que consta de 4 preguntas básicas camufladas con otras 8 preguntas sobre hábitos de vida saludables. Se consideraron los puntos de corte de 1 y 2.Del total de participantes, 588 eran pacientes psiquiátricos ambulatorios, 153 de los centros de drogodependencias ambulatorios y 313 sanos. La edad media de la muestra fue de 45,8 años y el porcentaje de hombres fue del 53,2%. El 38,3% de los participantes presentaron una puntuación ≥1, el 34,2% en las consultas psiquiátricas, el 72,5% en las de drogodependencias y el 29,4% en sanos. El 26,6% presentaron una puntuación ≥2, el 22,6% en las consultas psiquiátricas, el 64,7% en las de drogodependencias y el 15,3% en sanos. Los que presentaron mayor porcentaje de puntuación ≥1 fueron los hombres (48,8%), los menores de 30 años (50%), y los que tenían un diagnóstico de trastorno por uso de alcohol (95,9%) y de TDAH (83,3%).Los pacientes psiquiátricos presentan un mayor riesgo de presentar un TUA que los individuos sanos, aunque menor que los drogodependientes, siendo el cuestionario CAGE una herramienta sencilla y útil para detectar el riesgo de presentarlos.

Sexual Dysfunction and Mood Stabilizers in Long-Term Stable Patients With Bipolar Disorder.

BACKGROUND: In addition to factors intrinsic to bipolar disorder (BD), sexual functioning (SF) can be affected by extrinsic causes, such as psychotropic drugs. However, the effect of mood stabilizers on SF and quality of life (QoL) is an underexplored research area. AIM: To analyze SF in BD outpatients in euthymia for at least 6 months treated only with mood stabilizers and the association between SF and QoL. METHODS: A multicenter cross-sectional study was conducted in 114 BD outpatients treated with (i) lithium alone (L group); (ii) anticonvulsants alone (valproate or lamotrigine; A group); (iii) lithium plus anticonvulsants (L+A group); or (iv) lithium plus benzodiazepines (L+B group). The Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14) was used. Statistical analyses were performed to compare CSFQ-14 scores among the pharmacological groups. An adaptive lasso was used to identify potential confounding variables, and linear regression models were used to study the association of the CSFQ-14 with QoL. MAIN OUTCOME MEASURES: Self-reports on phases of the sexual response cycle (ie, desire, arousal, and orgasm) and QoL were assessed. RESULTS: The A group had better total SF scores than the L group and the L+B group. Relative to the A group, the L and L+B groups had worse sexual desire; the L group had worse sexual arousal; and the L+A group and the L+B group had worse sexual orgasm. Regarding sociodemographic factors, being female and older age were associated with worse total SF and all subscale scores. Among all subscales scores, higher sexual arousal scores were associated with better QoL. CLINICAL IMPLICATIONS: Potential modified extrinsic factors such as psychotropic medication that can affect SF can be addressed and adjusted to lessen side effects on SF. STRENGTHS & LIMITATIONS: Sample of patients with euthymic BD in treatment with mood stabilizers and no antipsychotics or antidepressants, substance use as an exclusion criterion, and use of a validated, gender-specific scale to evaluate SF. Major limitations were cross-sectional design, sample size, and lack of information about stability of relationship with partner. CONCLUSIONS: Lithium in monotherapy or in combination with benzodiazepines is related to worse total SF and worse sexual desire than anticonvulsants in monotherapy. While the addition of benzodiazepines or anticonvulsants to lithium negatively affects sexual orgasm, sexual arousal (which plays a significant role in QoL) improves when benzodiazepines are added to lithium. Anticonvulsants in monotherapy have the least negative effects on SF in patients with BD. García-Blanco A, García-Portilla MP, Fuente-Tomás L de la, et al. Sexual Dysfunction and Mood Stabilizers in Long-Term Stable Patients With Bipolar Disorder. J Sex Med 2020;17:930-940.

Machine Learning to Understand the Immune-Inflammatory Pathways in Fibromyalgia.

Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, and physical and emotional symptoms. Although its pathophysiology is largely unknown, immune-inflammatory pathways may be involved. We examined serum interleukin (IL)-6, high sensitivity C-reactive protein (hs-CRP), CXCL-8, and IL-10 in 67 female FM patients and 35 healthy women while adjusting for age, body mass index (BMI), and comorbid disorders. We scored the Fibromyalgia Severity Score, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Hospital Anxiety (HADS-A), and Depression Scale and the Perceived Stress Scale (PSS-10). Clinical rating scales were significantly higher in FM patients than in controls. After adjusting for covariates, IL-6, IL-10, and CXCL-8 were lower in FM than in HC, whereas hs-CRP did not show any difference. Binary regression analyses showed that the diagnosis FM was associated with lowered IL-10, quality of sleep, aerobic activities, and increased HADS-A and comorbidities. Neural networks showed that WPI was best predicted by quality of sleep, PSS-10, HADS-A, and the cytokines, while SSS was best predicted by PSS-10, HADS-A, and IL-10. Lowered levels of cytokines are associated with FM independently from confounders. Lowered IL-6 and IL-10 signaling may play a role in the pathophysiology of FM.

Screening of alcohol use disorders in psychiatric outpatients: influence of gender, age, and psychiatric diagnosis. / Cribaje de trastornos por uso de alcohol en pacientes psiquiátricos ambulatorios: influencia de género, edad, y diagnóstico psiquiátrico.

Alcohol use disorders (AUD) are 2 times higher among psychiatric patients than in the general population. The under-recognition of this dual diagnosis can entail several negative outcomes. Early assessment with a screening tool like the CAGE questionnaire could be an opportunity to improve patients' prognoses. The objective of this study is to assess AUD risk in an outpatient psychiatric sample with a modified CAGE, considering the influence of age, gender and clinical psychiatric diagnosis. An observational, multicentric, descriptive study was carried out. The 4-item CAGE scale, camouflaged in a healthy lifestyle questionnaire, was implemented, using a cut-off point of one. 559 outpatients were assessed. 54% were female and the average age was 50.07 years. 182 patients presented a CAGE score ≥1 (45.1% of men and 21.9% of women). Gender was the strongest predictor of a positive result in CAGE, as men were 3.03 times more likely to score ≥1 on the CAGE questionnaire (p < .001, 95% CI: 0.22-0.49). Patients with bipolar and personality disorders had the highest rates of CAGE scores ≥1 (45.2 and 44.9%, respectively), with a significant association between diagnosis and a positive score (p = .002). Patients above 60 years were 2.5 times less likely to score ≥1 on the CAGE (p = .017, 95% CI: 0.19-0.85). Specific screening questionnaires, like the CAGE scale, can be an easy and useful tool in the assessment of AUD risk in psychiatric outpatients. Male patients with a bipolar or personality disorder present a higher risk of AUD.

Los trastornos por uso de alcohol (TUA) son 2 veces más frecuentes en pacientes psiquiátricos que en la población general. El infradiagnóstico de patología dual puede tener diversas consecuencias negativas; una valoración precoz con herramientas de cribaje como la escala CAGE podría mejorar el pronóstico de estos pacientes. El objetivo de este estudio es valorar el riesgo de TUA en pacientes psiquiátricos ambulatorios con una CAGE modificada, considerando la influencia de edad, género, y diagnóstico psiquiátrico. Se realizó un estudio descriptivo observacional, multicéntrico. La escala CAGE de 4 ítems, camuflada en un cuestionario de vida saludable, se aplicó utilizando el punto de corte de 1. Se valoraron 559 pacientes. El 54% eran mujeres, y la edad media fue de 50,07 años. 182 pacientes presentaron una puntuación ≥1 (45,1% de los hombres y 21,9% de las mujeres). El género fue el predictor principal de un resultado positivo en la escala CAGE, siendo 3,03 veces más probable que los hombres obtengan una puntuación ≥1 (p < ,001, 95% IC: 0,22-0,49). El trastorno bipolar y los trastornos de personalidad presentaron las tasas más altas de puntuaciones ≥1 (45,2 y 44,9%, respectivamente) con una asociación significativa entre diagnóstico y un resultado positivo (p = ,002). Los pacientes de más de 60 años mostraron 2,5 veces menos probabilidades de obtener una puntuación positiva (p = ,017, 95% IC: 0,19-0,85). Cuestionarios específicos, como CAGE, pueden ser herramientas sencillas y útiles para valorar el riesgo de TUA en pacientes psiquiátricos ambulatorios. Los pacientes hombres con trastorno bipolar o de personalidad presentan un riesgo más elevado de TUA.

How Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment.

OBJECTIVE: We aimed to study the relationship between hyperprolactinemia (HPRL) and sexual dysfunction (SED) in a sample of patients being prescribed a dose-stable antipsychotic medication, and to evaluate sex differences in the prevalence of HPRL and SED and their relationship. METHOD: A cross-sectional study was carried out including patients between 18 and 55 years of age with a psychotic spectrum diagnosis who were attending community mental health services or hospitalized in medium and long stay units. Positive and Negative Syndrome scale, Calgary depression scale for schizophrenia, Personal and Social Performance scale, and Changes in Sexual Functioning questionnaire-short form were administered. Not later than 3 months, a determination of prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen (only in women) and testosterone was performed. RESULTS: A final sample of 101 patients (30 women and 71 men) was recruited. Seventy-two patients (71.3%) showed HPRL. Sexual dysfunction was significantly higher in HPRL patients than in non-HPRL patients (79.17% vs 51.72%) (P = 0.006), and mean prolactin values were significantly higher in case of SED (P = 0.020). No sex differences were found in prevalence of HPRL or SED. Low Personal and Social Performance scale scores and HPRL were factors independently associated with SED, whereas alcohol use was an independent protector factor. CONCLUSIONS: In our study, SED was significantly related to HPRL without showing sex differences. Prevalence of HPRL and SED observed was higher than that in previous studies, which should be taken into consideration because these have been associated with higher morbimortality, and noncompliance and relapse, respectively.

Substance Use in Patients With First-Episode Psychosis: Is Gender Relevant?

OBJECTIVE: Only a few studies in patients with first-episode psychosis have included gender in the study hypothesis or considered this a primary study variable. The aim of this study was to explore the influence of gender in the pattern of substance use in patients with first-episode psychosis. METHODS: This is a sub-analysis of a randomized open clinical trial that compared 1-year treatment retention rates of patients with first-episode psychosis randomized to haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone. Our sub-analysis included 85 men and 29 women. RESULTS: Substance use was relatively high among these patients and differed significantly by gender. Men were more likely to use substances overall than women (89.4% for men vs. 55.2% for women), χ(2) = 16.2, df = 1, p <.001, and were also more likely to use alcohol (χ(2) = 13, df = 1, p <.001), cannabis (χ(2) = 9.9; df = 1, p <.002), and cocaine (χ(2) = 10.3; df = 1, p <.001), compared to women. While there were no gender differences in age at first consumption of alcohol or cocaine, men were significantly younger at first consumption of cannabis (M = 16.08 years, SD = 2.1) than women (M = 18.0 years, SD = 3.8), F(1, 59) = 5, p <.02. When analyzed separately by gender, women showed no significant differences in the influence of number of substances used on age at onset of psychosis, F(3, 29) = 1.2, p =.30. However, there was a significant difference among men, with earlier onset of psychosis noted in men consuming multiple substances; F(4, 85) = 5.8, p <.0001. Regarding prediction of age at onset of psychosis, both male gender and the use of a higher number of substances significantly predicted an earlier age at onset of psychosis. CONCLUSIONS: Our study provides some evidence of gender differences in the pattern of substance use in patients with first-episode psychosis, suggesting the possible need for gender-specific approaches in the interventions performed in these patients. This study is registered as #12610000954022 with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).

Methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphism is associated with antipsychotic-induced weight gain in first-episode schizophrenia.

Genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism may be important predictors of antipsychotic drug-induced weight gain (AIWG). We tested whether two functional MTHFR polymorphisms are related to AIWG. Weight gain was studied in two cohorts of first-episode, initially drug-naive schizophrenia patients; Chinese Han (n = 182) and Spanish Caucasians (n = 72) receiving antipsychotics for 10 wk and 3 months respectively. Blood DNA was genotyped for 677C/T and 1298A/C MTHFR polymorphisms. Patients with the 677 CC genotype had a significantly greater increase in BMI compared to T-allele carriers in both Chinese (p = 0.012) and Spanish (p = 0.017) samples. The 677C/T MTHFR polymorphism showed an additive effect, but no significant interaction, with the -759C/T HTR2C polymorphism previously associated with AIWG. These results suggest that the 677C/T MTHFR polymorphism might, along with the -759C/T HTR2C polymorphism and other genetic factors, provide a useful marker for the important and limiting side effect of AIWG.

Relationship Between Exposure to Emotional Neglect and the Inflammatory Biomarkers Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, and Platelet-to-Lymphocyte Ratios in Patients With First-Episode Psychosis.

Aim: To assess whether exposure to childhood traumatic experiences is linked to the inflammatory markers neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in people with a first-episode psychosis.Methods: A cross-sectional study was performed in 83 patients (21 females and 62 males) with a diagnosis of a first psychotic episode. All participants completed the self-reported Spanish version of the Childhood Trauma Questionnaire (CTQ). NLR, MLR, and PLR were calculated in each patient.Results: Highest CTQ scores were noted on the emotional neglect and abuse domains (mean ± SD = 10.92 ± 4.41; mean ± SD = 10.93 ± 4.78, respectively), being lowest for the sexual abuse domain (mean ± SD = 6.12 ± 2.41). Backward stepwise linear regressions showed that high emotional neglect significantly predicted increased PLR (ß = 0.452, P = .036), older age and high emotional neglect predicted increased NLR (ß = 0.483, P = .036; ß = 0.442, P = .06, respectively), and high emotional neglect, low physical neglect, high total Positive and Negative Syndrome Scale (PANSS) score, and cannabis and alcohol use predicted increased MLR (ß = 0.698, P = .003; ß = 0.672, P = .033; ß = 0.296, P = .027; ß = 0.390, P = .069; ß = 0.560, P = .078, respectively).Conclusions: Our results highlight the relationship between the exposure to emotional neglect and the inflammatory biomarkers NLR, MLR, and PLR in patients with a first-episode psychosis. This study has benefitted from controlling for confounders such as body mass index, smoking status, symptom severity, and alcohol and cannabis use.

From gut to brain: A network model of intestinal permeability, inflammation, and psychotic symptoms in schizophrenia.

Impaired intestinal permeability has recently been suggested as a possible source of chronic inflammation in schizophrenia, but its association with specific psychopathological features remains uncertain. This study aimed to explore the interaction between intestinal permeability, inflammation, and positive and negative symptoms in schizophrenia using a network analysis approach. The study sample comprised 281 adults with schizophrenia (age 40.29 ± 13.65 years, 63.0 % males), enrolled in a cross-sectional observational study assessing intestinal permeability. We estimated the network with a Gaussian graphical model, incorporating scores from 14 individual items of the Positive and Negative Syndrome Scale (PANSS), along with body mass index (BMI), and plasma C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) levels. We calculated strength centrality and expected influence and used bridge centrality statistics to identify the bridge nodes. Distinct but highly interconnected clusters emerged for positive and negative symptoms. The biological variables were closely associated with each other. LBP was positively linked with CRP and BMI, but only indirectly connected to psychopathology. CRP exhibited direct positive relationships with various PANSS items and bridged LBP and BMI with psychopathology. Bridge nodes included Conceptual Disorganisation (P2), Active Social Avoidance (G16), Suspiciousness/Persecution (P6), and CRP. These findings support the role of gut-derived inflammation as a mechanism underlying greater symptom severity in schizophrenia and emphasise the importance of addressing dietary habits not only to enhance physical health but also to contribute to improving psychotic symptoms.

Impact of cognitive reserve in clinical, neurocognitive and lifestyle factors in chronic schizophrenia and early stages of schizophrenia.

INTRODUCTION: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). MATERIAL AND METHODS: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. RESULTS: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2=0.091, p=0.001) and functioning (R2=0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003). CONCLUSIONS: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ.

The obesity risk gene FTO influences body mass in chronic schizophrenia but not initial antipsychotic drug-induced weight gain in first-episode patients.

Genetic factors contribute to the individual variability in weight gain caused by several antipsychotic drugs. The FTO gene is associated with obesity in the general population; we have investigated whether a common risk polymorphism (rs9939609) in this gene is associated with antipsychotic drug-induced weight gain and obesity. Two samples were studied: (1) 93 first-episode patients receiving antipsychotic drugs for the first time and having body weight monitored for up to 12 months; (2) 187 chronic patients with schizophrenia assessed for measures of obesity and metabolic dysfunction. No association of FTO genotype with weight gain was found in initially drug-naive patients. The chronically treated patients had a significant association of genotype with body mass index (BMI), reflected in associations with waist circumference, waist:hip ratio and the frequency of central obesity. These findings indicate that FTO genotype has a major effect on body weight determined by BMI in chronically treated patients with schizophrenia.

Factors predicting hostility in outpatients with schizophrenia: 36-month results from the SOHO study.

This analysis explored the prevalence, incidence, and predictors of hostility in the European Schizophrenia Outpatient Health Outcomes (EU-SOHO) study. Data were collected at baseline and up to 36 months on the presence of hostility, clinical course and severity, medication compliance, side effects, substance/alcohol abuse, and being a crime survivor. Regression models were fitted to test the association between predictors and the presence of hostility. Hostility prevalence in the 6 months before baseline was 27.9%, and the incidence at 3 years was 14.0%. Variables related to hostility during follow-up were age, male sex, alcohol/substance abuse, tardive dyskinesia, extrapyramidal symptoms, cognitive impairment, noncompliance, and hospitalization. Being a crime survivor, being married, not living independently, and not being in paid employment were associated with hostility at baseline. Clinical and social variables are related to hostility in schizophrenia. Extrapyramidal symptoms and tardive dyskinesia, alcohol/substance abuse, cognitive impairment, medication noncompliance, and hospitalizations are predictors of future hostility.