Proyecto Piloto de Unidad Funcional para Mujeres con Esquizofrenia: Modelo Asistencial de Observatorio-Monitorización-Intervención / Pilot project of a functional unit for women with Schizophrenia: observatory-monitoring-intervention Care model

En los Centros de Salud Mental de Adultos (CSMAs) del Hospital Universitari Mutua Terrassa, en enero de 2023, iniciamos un proyecto piloto de innovación asistencial denominado Unidad Funcional para Mujeres con Esquizofrenia. El objetivo principal de esta comunicación es describir el proceso de designación de las mujeres diana en la unidad, y describir las funciones de los Observatorios de salud física, salud mental y de factores de riesgo psicosocial e inclusión de estas pacientes en los observatorios de salud. De forma complementaria, se describirá el diseño de las Estaciones de Monitorización /Equipos de Vigilancia y las actuaciones o intervenciones específicas centradas en la atención de las necesidades individuales. En la primera fase del proyecto (Enero-Marzo 2023) se revisan las historias clínicas de las mujeres con esquizofrenia para revisar vinculación a profesionales y programas comunitarios. Se describen necesidades de salud física y se revisan antecedentes de consumo de sustancias, uso de benzodiazepinas y opioides, así como aspectos de seguridad farmacológica. En la segunda fase del proyecto (Abril-Junio 2023) se han desarrollado 5 grupos de trabajo (Observatorios de Salud y de Riesgo Psicosocial): 1)Morbi-mortalidad somática, 2)hiperprolactinemia, 3)consumo de sustancias, 4)exclusión social y discriminación, y 5)prescripción y seguridad farmacológica. En la tercera fase del proyecto (Jumio-Septiembre 2023) se desarrollan los Equipos de Vigilancia/Monitorización en Morbi-Mortalidad Somática, hiperprolactinemia, consumo de sustancias, exclusión social/discriminación y seguridad farmacológica, así como intervenciones específicas: colaboración con otras especialidades médicas, consultoría con atención primaria, grupos de ejercicio físico y equipos de intervención en crisis.(AU)

In the context of the Adult Community Mental Health Units (CMHUs) of the Mutua Terrassa University Hospital, we initiated a pilot project of clinical innovation called the Functional Unit for Women with Schizophrenia in January 2023. The main objective of this report is to describe the process of designing a unit targeting women, to characterize the functions of the observatories of Physical Health, Mental Health, and Psychosocial Risk Factors, and to illustrate how these observatories provide surveillance of women’s health needs. The report also describes Monitoring Stations, Vigilance teams, and specific interventions.In the first phase of the project (January - March 2023), medical records from all women with schizophrenia were reviewed to ascertain compliance with clinical appointments and community programs. During this phase, we reviewed physical health records, history of substance use disorders including the use of benzodiazepines and opioid drugs, as well as related aspects of drug safety. In the second phase of the project (April - June 2023), five Observatories of health and social risk factors were developed: 1) somatic morbi-mortality, 2) hyperprolactinemia, 3) use of substances, 4) social exclusion and discrimination, and 5) prescription and drug safety. In the third phase of the project (June-September 2023), we are developing Monitoring Stations or Vigilance teams in these five areas as well as introducing specific interventions: collaboration with primary care and other medical specialties, consultation with primary care teams, physical exercise groups, and crisis intervention units.(AU)

Schizophrenia: A Review of Social Risk Factors That Affect Women.

Social risk factors are long-term or repeated environmental exposures in childhood and youth that change the brain and may, via epigenetic effects, change gene expression. They thus have the power to initiate or aggravate mental disorders. Because these effects can be mediated via hormonal or immune/inflammatory pathways that differ between men and women, their influence is often sex-specific. The goal of this narrative review is to explore the literature on social risk factors as they affect women with schizophrenia. We searched the PubMed and Scopus databases from 2000 to May 2023 using terms referring to the various social determinants of health in conjunction with "women" and with "schizophrenia". A total of 57 studies fulfilled the inclusion criteria. In the domains of childhood and adult abuse or trauma, victimization, stigma, housing, and socioeconomics, women with schizophrenia showed greater probability than their male peers of suffering negative consequences. Interventions targeting appropriate housing, income support, social and parenting support, protection from abuse, violence, and mothering-directed stigma have, to different degrees, yielded success in reducing stress levels and alleviating the many burdens of schizophrenia in women.

Sleep Disturbances in At-Risk Mental States and First Episode of Psychosis: A Narrative Review on Interventions.

Sleep disturbances are a common yet often overlooked symptom of psychosis that can drastically affect the quality of life and well-being of those living with the condition. Sleep disorders are common in people diagnosed with schizophrenia and have significant negative effects on the clinical course of the illness and the functional outcomes and quality of life of patients. There is a limited number of studies addressing this question in first-episode psychosis (FEP). In this narrative review, we aimed to provide an overview of sleep disorders in populations with FEP and at-risk mental states (ARMS). The review was focused on the various treatments currently used for sleep disorders, including both non-pharmacological and pharmacological treatments. A total of 48 studies were included. We found that sleep disturbances are associated with attenuated psychotic symptoms and other psychopathological symptoms in ARMSs. The association of sleep disturbances with the transition to psychosis has been poorly investigated. Sleep disturbances have an impact on the quality of life and the psychopathological symptoms of people suffering from FEP. The non-pharmacological treatments include cognitive behavioral therapy for insomnia, bright light therapy, cognitive restructuring techniques, sleep restriction therapy, basic sleep hygiene education, and the provision of portable sleep trackers. Other treatments include antipsychotics in acute phases and melatonin. The early intervention in sleep disturbances may improve overall prognosis in emerging psychosis populations.

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.

A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region.

We studied the prevalence of suicide attempts and cumulative incidence of completed suicide in schizophrenia (SZ), schizoaffective disorder (SZAF), delusional disorder (DD) and first-episode psychosis (FEP). A systematic review was performed using Scopus and PubMed databases (1990- July 2020). A random effects meta-analysis was conducted. Stratified analyses were conducted by diagnosis, clinical setting and geographical region. The prevalence of attempted suicide was 20.3% for SZ, 46.8% for SZAF, 11.1% for DD and 12.5% for FEP. Suicide attempts rates were higher for outpatient samples than for inpatient samples in SZ, SZAF and DD (but not FEP) studies. Analyses by geographical region in SZ showed greater prevalence of suicide attempts in North America and Northern Europe. The cumulative incidence of completed suicide was 2.0% for SZ, 2.4% for SZAF; 2.2% for DD and 1.9% for FEP. In schizophrenia and FEP studies, Northern European studies reported higher rates of completed suicide when compared to Western European countries. In conclusion, suicidal behaviour rates in psychoses differ by diagnoses, clinical setting and geographical region.

Ciclación Rápida en el Trastorno Bipolar: una Metarevisión / Rapid cycling in bipolar disorder: a meta-review

El descriptor evolutivo "Ciclación Rápida" (CR) en el Trastorno Bipolar constituye uno de los retos más importantes a la hora de realizar un plan terapéutico. Sin embargo, a pesar de su uso habitual en la clínica y los libros generalistas, existe poca bibliografía original y escasas publicaciones de investigación sobre el tema. La presente metarevisión analiza los datos más recientes al respecto, enfatizando especialmente los aspectos etiopatogénicos, evolutivos y de tratamiento. Para ello, hemos utilizado las revisiones y artículos recogidos en las bases de datos PubMed y Psychinfo en los últimos 10 años (entre abril del 2011 y abril del 2021), publicadas en inglés o castellano. Después de descartar duplicados, por consenso pudimos seleccionar 76 publicaciones que cumplían los criterios de inclusión. Como principales resultados, destacan los estudios que relacionan la futura aparición de CR con un inicio más precoz del trastorno bipolar, la comorbilidad con el trastorno límite de la personalidad y con el consumo de sustancias. Entre los factores biológicos favorecedores, estarían las alteraciones tiroideas, la obesidad, las alteraciones de los ritmos circadianos, la migraña y otros factores inflamatorios y (quizás) los tratamientos antidepresivos continuados. Entre los aspectos terapéuticos, destacan los bajos niveles de recomendación y de evidencia entre las pautas propuestas en las diferentes revisiones y guías terapéuticas, lo cual se corresponde también con las dificultades de tratamiento en la práctica clínica. Por otra parte, se evidencia la falta de ensayos clínicos y estudios randomizados adecuados y específicos para poder extraer mejores conclusiones al respecto.(AU)

The clinical descriptor “Rapid Cycling” (RC) in Bipolar Disorder is one of the most important challenges in designing a therapeutic plan. However, despite its usual use in medical practice and in general books, there is little original literature and few publications related to it. This umbrella review analyses most recent publications referred to Rapid Cycling, emphasizing specially in their etiology, outcomes and treatment aspects. Reviews from the databases PubMed and Psychinfo have been collected, including the ones from the last 10 years (between April 2011 and April 2021), published in English or Spanish. After discharging duplicates, we applied a consensus to finally recruit 76 publications that fulfilled the inclusion criteria.As main results it must be mentioned the studies that relate RC to early age of onset, the ones that relate it with Borderline Personality Disorder comorbidity and finally the ones with Substance Abuse. Biological factors considered for the etiology of RC would be thyroidal disorders, obesity, circadian rhythms disorders and other inflammatory factors, migraine and (maybe) the maintained antidepressant treatments. Among the therapeutic aspects, the low level of recommendation and evidence in the different therapeutic guidelines stands out. This corresponds with the treatment difficulties observed in the clinical practice. Finally, it is important to mention the lack of clinical trials and randomized studies that are necessary to obtain better conclusions in the area.(AU)

Collaboration between Psychiatrists and Other Allied Medical Specialists for the Treatment of Delusional Disorders.

BACKGROUND: There is increasing evidence that individuals with psychosis are at increased risk for cardiovascular disease, diabetes, metabolic syndrome, and several other medical comorbidities. In delusional disorder (DD), this is particularly so because of the relatively late onset age. AIMS: The aim of this narrative review is to synthesize the literature on the necessity for medical collaboration between psychiatrists and other specialists. METHODS: A non-systematic narrative review was carried out of papers addressing referrals and cooperation among specialists in the care of DD patients. RESULTS: Psychiatrists, the primary care providers for DD patients, depend on neurology to assess cognitive defects and rule out organic sources of delusions. Neurologists rely on psychiatry to help with patient adherence to treatment and the management of psychotropic drug side effects. Psychiatrists require ophthalmology/otolaryngology to treat sensory deficits that often precede delusions; reciprocally, psychiatric consults can help in instances of functional sensory impairment. Close collaboration with dermatologists is essential for treating delusional parasitosis and dysmorphophobia to ensure timely referrals to psychiatry. CONCLUSIONS: This review offers many other examples from the literature of the extent of overlap among medical specialties in the evaluation and effective treatment of DD. Optimal patient care requires close collaboration among specialties.

Biological and Clinical Aspects on the Treatment of Schizophrenia and Related Disorders: New Challenges.

For several decades, it has been postulated that dopaminergic pathways explain the neurobiology of schizophrenia, the biological underpinnings of treatment responses and the main mechanisms of action of antipsychotics [...].

The relationship between sex, personality traits, and the hypothalamic-pituitary-adrenocortical axis.

The aim of our study was to examine whether there are sex-based differences in the relationship between personality traits and hypothalamic-pituitary-adrenal (HPA) axis measures. A total of 106 healthy volunteers (56.6% women; age: 48.0 ± 15.8 years) were studied. The revised temperament and character inventory (TCI-R) and the Childhood Trauma Questionnaire (CTQ) were administered. HPA axis function was assessed using three dynamic measures: the cortisol awakening response (CAR), the diurnal cortisol slope, and the cortisol suppression ratio with 0.25 mg of dexamethasone (DSTR). Female sex was associated with an increased CAR and a more flattened diurnal cortisol slope, although a negative significant interaction between harm avoidance and female sex was found. Regarding the DSTR, perseverance was associated with increased cortisol suppression after dexamethasone; sex did not affect this association. Our study suggests that the relationship between specific personality traits (harm avoidance) and HPA axis measures (CAR, diurnal slope) differs according to sex.

Peri- and Post-Menopausal Women with Schizophrenia and Related Disorders Are a Population with Specific Needs: A Narrative Review of Current Theories.

BACKGROUND: While gender differences in antipsychotic response have been recognized, the potential role of menopause in changing drug efficacy and clinical outcome in schizophrenia related disorders has been understudied. We aimed to review the relevant literature to test whether optimizing menopausal and post-menopausal treatment and addressing specific health needs of this stage in life will improve outcome. METHODS: Non-systematic narrative review using the PubMed database (1900-July 2021) focusing on randomized controlled trial results addressing our question. Forty-nine studies met our criteria. RESULTS: Premenopausal women show significantly better antipsychotic response than postmenopausal women. Hormone replacement therapies (HRT) should be used in postmenopausal women with schizophrenia with caution. Raloxifene, combined with antipsychotics, is effective for psychotic and cognitive symptoms in postmenopausal women with schizophrenia and related disorders. Medical comorbidities increase after menopause, but the influence of comorbidities on clinical outcomes has been poorly investigated. Preventive strategies include weighing risks and benefits of treatment, preventing medical comorbidities, and enhancing psychosocial support. Ideal treatment settings for this population warrant investigation. CONCLUSIONS: Antipsychotic dose adjustment at menopause is recommended for schizophrenia. Raloxifene may play an important role in permitting dose reduction and lessening adverse effects. Prevention of comorbidities will help to reduce the mortality rate.

A conserved C-terminal peptide of sorghum phosphoenolpyruvate carboxylase promotes its proteolysis, which is prevented by Glc-6P or the phosphorylation state of the enzyme.

MAIN CONCLUSION: A synthetic peptide from the C-terminal end of C4-phosphoenolpyruvate carboxylase is implicated in the proteolysis of the enzyme, and Glc-6P or phosphorylation of the enzyme modulate this effect. Phosphoenolpyruvate carboxylase (PEPC) is a cytosolic, homotetrameric enzyme that performs a variety of functions in plants. Among them, it is primarily responsible for CO2 fixation in the C4 photosynthesis pathway (C4-PEPC). Here we show that proteolysis of C4-PEPC by cathepsin proteases present in a semi-purified PEPC fraction was enhanced by the presence of a synthetic peptide containing the last 19 amino acids from the C-terminal end of the PEPC subunit (pC19). Threonine (Thr)944 and Thr948 in the peptide are important requirements for the pC19 effect. C4-PEPC proteolysis in the presence of pC19 was prevented by the PEPC allosteric effector glucose 6-phosphate (Glc-6P) and by phosphorylation of the enzyme. The role of these elements in the regulation of PEPC proteolysis is discussed in relation to the physiological context.

The role of childhood trauma, HPA axis reactivity and FKBP5 genotype on cognition in healthy individuals.

Cognitive impairment has been associated with both childhood adversity and abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function. An interaction exists between the functional polymorphism rs1360780 in the FKBP5 gene and childhood maltreatment, influencing a variety of clinical outcomes. Our goal was to study the relationship between different types of childhood trauma, HPA axis functionality, rs1360780 genotype and cognitive function in 198 healthy individuals who participated in the study. We obtained clinical data, childhood maltreatment scores and neurocognitive performance by clinical assessment; HPA negative feedback was analysed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone; and the FKBP5 rs1360780 polymorphism was genotyped in DNA obtained from blood samples. The results showed a significant influence of physical neglect on measures of neurocognition as well as an interaction between the DSTR and physical and emotional neglect. Regarding social cognition, a significant association was found with sexual and physical abuse as well as with rs1360780 risk-allele carrier status. Moreover, an interaction between the rs1360780 genotype and the presence of physical abuse was significantly associated with social cognition results. Our results suggest a specific impact of different kinds of childhood maltreatment on measures of neurocognition and social cognition, which might be influenced by HPA axis reactivity and genetic variants in HPA axis-related genes such as FKBP5. Disentangling the relationship between these elements and their influence on cognitive performance might help identify susceptible individuals with higher stress vulnerability and develop preventive interventions.

Targeting the microbiome-gut-brain axis for improving cognition in schizophrenia and major mood disorders: A narrative review.

Cognitive impairment has been consistently found to be a core feature of serious mental illnesses such as schizophrenia and major mood disorders (major depression and bipolar disorder). In recent years, a great effort has been made in elucidating the biological causes of cognitive deficits and the search for new biomarkers of cognition. Microbiome and gut-brain axis (MGB) hormones have been postulated to be potential biomarkers of cognition in serious mental illnesses. The main aim of this review was to synthesize current evidence on the association of microbiome and gut-brain hormones on cognitive processes in schizophrenia and major mood disorders and the association of MGB hormones with stress and the immune system. Our review underscores the role of the MGB axis on cognitive aspects of serious mental illnesses with the potential use of agents targeting the gut microbiota as cognitive enhancers. However, the current evidence for clinical trials focused on the MGB axis as cognitive enhancers in these clinical populations is scarce. Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.

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.

The Effect of Child Sexual Abuse on Social Functioning in Schizophrenia Spectrum Disorders.

The objective of this study was to explore social functioning in schizophrenic patients who have suffered child sexual abuse (CSA) in comparison with those who have not suffered from it in a Spanish sample of 50 patients with schizophrenia or schizoaffective disorder. The Quality of Life (QOL) Scale, the Childhood Trauma Questionnaire (CTQ-SF), and the NEO Five Factor Inventory (NEO-FFI) were administered in this study. We found a CSA prevalence of 22% in our sample. Results showed that QOL global scores reduced by 9.34% at a statistically significant level (p = .037) in sexually abused patients in comparison with those who did not report experiencing sexual abuse. Regression analysis in the QOL scales showed no differences in intrapsychic foundation scores or in the social relations scale. Scores in the instrumental role scale were reduced by 4.42 points in patients with CSA (p = .009). Neither neuroticism nor extraversion results differ between the trauma group and those who did not suffer trauma. Clinical implications of these results are discussed.

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.

Women with Schizophrenia over the Life Span: Health Promotion, Treatment and Outcomes.

Women with schizophrenia show sex-specific health needs that differ according to stage of life. The aim of this narrative review is to resolve important questions concerning the treatment of women with schizophrenia at different periods of their life-paying special attention to reproductive and post-reproductive stages. Review results suggest that menstrual cycle-dependent treatments may be a useful option for many women and that recommendations re contraceptive options need always to be part of care provision. The pregnancy and the postpartum periods-while constituting vulnerable time periods for the mother-require special attention to antipsychotic effects on the fetus and neonate. Menopause and aging are further vulnerable times, with extra challenges posed by associated health risks. Pregnancy complications, neurodevelopmental difficulties of offspring, cancer risk and cognitive defects are indirect results of the interplay of hormones and antipsychotic treatment of women over the course of the lifespan. The literature recommends that health promotion strategies need to be directed at lifestyle modifications, prevention of medical comorbidities and increased psychosocial support. Careful monitoring of pharmacological treatment has been shown to be critical during periods of hormonal transition. Not only does treatment of women with schizophrenia often need to be different than that of their male peers, but it also needs to vary over the course of life.

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.