Jesús Cobo

Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review

Recent studies have begun to look at gender differences in schizophrenia and first-episode psychosis in an attempt to explain the heterogeneity of the illness. However, a number of uncertainties remain. This paper tries to summarize the most important findings in gender differences in schizophrenia and first-psychosis episodes. Several studies indicate that the incidence of schizophrenia is higher in men. Most of the studies found the age of onset to be earlier in men than in women. Findings on symptoms are less conclusive, with some authors suggesting that men suffer more negative symptoms while women have more affective symptoms. Premorbid functioning and social functioning seem to be better in females than males. However, cognitive functioning remains an issue, with lack of consensus on differences in neuropsychological profile between women and men. Substance abuse is more common in men than women with schizophrenia and first-episode psychosis. In terms of the disease course, women have better remission and lower relapse rates. Lastly, there is no evidence of specific gender differences in familial risk and obstetric complications. Overall, gender differences have been found in a number of variables, and further study in this area could help provide useful information with a view to improving our care of these patients.

Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. In this study, we assess the utility of raloxifene as an adjunctive treatment for negative symptoms and other psychotic symptoms in postmenopausal women with schizophrenia. METHOD This was a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Barcelona, Spain, and Corporació Sanitària Parc Taulí, Sabadell, Spain. Thirty-three postmenopausal women with schizophrenia (DSM-IV criteria) who exhibited prominent negative symptoms were randomized to either adjunctive raloxifene (16 women; mean age = 60.14 years, SD = 6.41 years) or adjunctive placebo (17 women; mean age = 62.66 years, SD = 4.54 years) for 12 weeks. The period of recruitment lasted from January 2005 through June 2009. Psychopathological symptoms were assessed at baseline and weeks 4, 8, and 12 by means of the Positive and Negative Syndrome Scale. RESULTS The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .044), positive (P = .031), and general psychopathological (P = .045) symptoms during the 12-week trial as compared with women receiving placebo. CONCLUSIONS Raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia who exhibit prominent negative symptoms appears to be useful in improving negative, positive, and general psychopathological symptoms. If more extensive and longer-term studies confirm and expand upon these positive results, the use of raloxifene could be recommended in postmenopausal patients with schizophrenia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01041092.

Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial

Studies of estrogen therapy in postmenopausal women provide evidence of an effect of sex hormones on cognitive function. Estrogen has demonstrated some utility in the prevention of normal, age-related decline in cognitive functions, especially in memory. The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator (SERM), appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems, and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. We assessed the utility of raloxifene as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments. Thirty-three postmenopausal women with schizophrenia (DSM-IV) were randomized to receive either adjuvant raloxifene (16 women) or adjuvant placebo (17 women) for three months. The main outcome measures were: Memory, attention and executive functions. Assessment was conducted at baseline and week 12. The total sample is homogenous with respect to: age, years of schooling, illness duration, baseline symptomatology and pharmacological treatment. The addition of raloxifene (60 mg) to regular antipsychotic treatment showed: we found significant differences in some aspects of memory and executive function in patients treated with raloxifene. This improvement does not correlate with clinical improvement. The use of raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia seems to be useful in improving cognitive symptoms.

Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial

UNLABELLED The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a larger sample and a longer follow-up. TRIAL REGISTRATION NCT01573637.

Cognitive executive performance influences functional outcome in euthymic type I bipolar disorder outpatients

BACKGROUND There is a debate about the influence of executive functioning impairment in the functionality of Bipolar Disorder Type I, even when euthymic (EutBDI). The aim of this study was to explore this relationship, taking functional outcome from a multidimensional point of view. METHODS An extended neuropsychological battery of executive tests and measures of social functioning were administered to 31 EutBDI and 25 non-psychiatric patients. Percentage of patients scoring lower than -1.64 SD was calculated for each executive measure. This was compared in terms of clinical features to those with normal performance. Partial correlations and ANCOVA were applied between psychosocial and executive variables within the EutBDI-group. RESULTS Patients reached poorer scores in mental flexibility, plan implementing, set-shifting, and fluency (p<0.05). 76% of patients performed poorly on some of the executive tests, although only around 1/3 reached a clinical deficit (<-1.64SD). Executive functioning was related to some clinical, evolution, and treatment variables. A better use of leisure time, higher competence for independent living and holding a skilled type of profession were significantly associated with a better performance on planning, set-shifting, and fluency tasks. CONCLUSIONS Persistent executive deficits in EutBDI may be related to their frequently reported difficulties in personaland occupational adjustment.

Insight, symptomatic dimensions, and cognition in patients with acute-phase psychosis

AIMS This study was designed to evaluate the relationship between insight and the severity of psychotic symptomatology in a sample of patients in an acute phase of psychosis, as well as to analyze the relationship between insight and the symptomatic profile of the patient. In addition, the role of general cognitive abilities in this relationship was explored. METHOD Cross-sectional observational study of 96 acute psychotic adults. To evaluate psychopathology we used the Positive and Negative Syndrome Scale; for insight, the Scale of Unawareness of Mental Disorder; and for general cognitive abilities, the Screen for Cognitive Impairment in Psychiatry. RESULTS Insight showed significant and moderate positive correlations with positive and general symptoms but not with negative symptoms. In the subgroup with positive symptomatic profile, awareness of the disorder and of the effects of medication were positively associated with severity of positive and general psychotic symptoms. Awareness of social consequences of the disease was positively associated with positive symptoms. In the subgroup with a negative symptomatic profile, awareness of the disorder and of the effects of medication were positively associated with severity of positive and general psychotic symptoms. In this subgroup, these relationships were significantly affected by general cognitive abilities. CONCLUSIONS Insight was not related with the severity of negative psychotic symptoms. The symptomatic profile of subjects played an important role in determining the relationship between insight and its dimensions and the severity of psychotic symptoms. Cognitive function moderated these relationships only in the negative symptomatic profile.

A deeper view of insight in schizophrenia: Insight dimensions, unawareness and misattribution of particular symptoms and its relation with psychopathological factors

OBJECTIVE 1. To describe insight in a large sample of schizophrenia subjects from a multidimensional point of view, including unawareness of general insight dimensions as well as unawareness and misattribution of particular symptoms. 2. To explore the relationship between unawareness and clinical and socio-demographic variables. METHODS 248 schizophrenia patients were assessed with the Positive and Negative Syndrome Scale (PANSS, five factor model of Lindenmayer) and the full Scale of Unawareness of Mental Disorder (SUMD). Bivariate associations and multiple linear regression analyses were used to investigate the relationship between unawareness, symptoms and socio-demographic variables. RESULTS Around 40% of the sample showed unawareness of mental disorder, of the need for medication and of the social consequences. Levels of unawareness and misattribution of particular symptoms varied considerably. General unawareness dimensions showed small significant correlations with positive, cognitive and excitement factors of psychopathology, whereas these symptom factors showed higher correlations with unawareness of particular symptoms. Similarly, regression models showed a small significant predictive value of positive symptoms in the three general unawareness dimensions while a moderate one in the prediction of particular symptoms. Misattribution showed no significant correlations with any symptom factors. CONCLUSIONS Results confirm that insight in schizophrenia is a multi-phased phenomenon and that unawareness into particular symptoms varies widely. The overlap between unawareness dimensions and psychopathology is small and seems to be restricted to positive and cognitive symptoms, supporting the accounts from cognitive neurosciences that suggest that besides basic cognition poor insight may be in part a failure of self-reflection or strategic metacognition.

Lack of confirmation of thyroid endophenotype in Bipolar Disorder Type I and their first-degree relatives

BACKGROUND Among the biological factors associated with the development and outcomes in Bipolar Disorder Type I (BD-I), previous studies have highlighted the involvement of both thyroid function and/or auto-immunity, proposing a thyroid endophenotype. The objective of this study was to determine the presence of thyroid alterations in BD-I and their first-degree relatives (FDR). METHODOLOGY Unselected, cross-sectional case-control study with parallel analysis of individuals affected by BD-I (239), their FD-R (131), and 108 healthy controls. Thyroidal functional abnormalities (TSH and free T4) and thyroidal antibodies (thyroglobulin and thyroperoxidase antibodies) were studied. Assessments were carried out in parallel. The sample was described using arithmetic means, standard deviations, percentages and ranges. Chi-square, Student-t tests, ANOVA and Pearson correlation coefficients were used when indicated. RESULTS BD-I on actual and/or ever treated with lithium showed significant thyroidal functional abnormalities as compared to their FD-R and healthy controls. This BD-I subgroup showed a significant greater proportion of subjects suffering from subclinical hypothyroidism (22%). The role of gender/lithium interactions was relevant. The groups did not show differences in terms of positivization of thyroidal antibodies. LIMITATIONS The crosssectional design and the lack of determination of dietary iodine deficiencies and/or thyroidal ecographical controls may be a drawback. CONCLUSIONS The present study supports previous findings on the effect of lithium treatment on thyroidal functional, but did not support previous findings related to a familial association or endophenotype. In addition, the present study did not support a familial aggregation of thyroidal antibodies positivization in pedegrees of BD-I.

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

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

Psychosis and gender.

Psychosis, mainly schizophrenia, is a heterogeneous disorder with a great variability in its clinical presentation. This heterogeneity may be explained by the role of gender; thus a gender-based approach could help us to better define the disease. Gender differences in social functioning, age of onset, course of the illness, and other domains have been described by several authors, showing better functioning and improved outcome in women with schizophrenia. Moreover, several treatments are gender sensitive, with differences in treatment response depending upon gender. The estrogen hypothesis is one of the most interesting explanations for this gender difference. Estrogens could be useful for understanding the pathophysiology of the illness or tailoring specific gender-related treatments.