Christian Núñez

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.

Cannabis use and cognitive function in first episode psychosis: differential effect of heavy use

RationaleFirst episode patients and patients with schizophrenia exhibit increased rates of cannabis use compared to the general population. Contrary to what has been reported in studies with healthy people, most of the published studies so far have reported no impairments or even beneficial effects on neurocognition associated with cannabis consumption in psychotic patients. However, these studies did not address the effects of very high cannabis consumption.ObjectivesOur aim in this study was to assess the effects on neurocognition of medium and heavy cannabis consumption in first psychotic episode patients.MethodsA total of 74 patients were included in the study and assigned to three different groups according to their mean cannabis consumption during the last year (non-users, medium users, and heavy users). Participants were administered verbal memory and other neurocognitive tasks.ResultsHeavy cannabis users were significantly impaired in all the verbal memory measures with respect to non-users, including immediate (p = .026), short-term (p = .005), and long-term (p = .002) memory. There were no significant differences between medium and non-users. Moreover, non-users performed better than all cannabis users in the arithmetic task (p = .020). Heavy cannabis consumption was associated with more commission errors in the continuous performance task (CPT) (p = .008) and more time to complete trail making test A (TMT-A) (p = .008), compared to the group of medium users.ConclusionsHeavy cannabis consumption seems to impair verbal memory in first psychotic episode patients. Heavy users also perform worse than medium users in other neurocognitive tasks. Based on the results and the available evidence, a dose-related effect of cannabis consumption is suggested.

Differential effects of sex on substance use between first episode psychosis patients and healthy people

BACKGROUND Substance use in psychosis is an important field of study given that it can be a risk factor for the development of psychosis and can give rise to psychotic symptoms. Studies of substance use in first episode psychosis patients do not frequently assess non-pathological substance consumption among patients, but rather the prevalence of substance abuse or dependence disorders. Moreover, most of these studies do not address the effects of sex in sufficient depth, and the consumption of caffeine or tobacco, which are two of the most frequently used substances, is often not assessed. OBJECTIVES The aim of this study was to compare patterns and quantities of substance use between first episode psychosis patients and healthy controls and between men and women, and explore the potential interactive effects between group (patients or controls) and sex. METHODS A total of 158 participants (82 first episode psychosis patients and 76 healthy controls) were included in the study. Both adults and adolescents were included in the study. Frequency and amount of use of caffeine, tobacco, alcohol, cannabis, cocaine, hallucinogens, stimulants, and opiates were gathered. RESULTS A significant main effect of sex was found for the frequency of use of tobacco (p=.050). Main effects of group were found for the quantity of tobacco (p<.001) and cannabis (p<.001) consumed, as well as main effects of sex for the quantity of alcohol (p=.003) and cannabis (p=.017) consumed. There were also interaction effects between group and sex for the frequency of use of tobacco (p=.005) and cannabis (p=.009), and for the amount of cannabis consumed (p=.049). Qualitative differences between males and females regarding combined substance use are also reported. CONCLUSIONS Among patients, men used tobacco more frequently than women, but this sex difference was not the same for the control group, in which women smoked more often than men. Regarding cannabis, men smoked cannabis more frequently and in larger amounts than women, but only in the patients group, whereas no sex differences for cannabis were found for the controls. Main effects of group and sex for tobacco and alcohol, as well as the lack of differences for the frequency and amount of use of caffeine, are also commented. This is the first study to assess the different effects of sex on substance use in first episode psychosis patients and healthy controls.

Effects of caffeine intake and smoking on neurocognition in schizophrenia.

Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.

Global brain asymmetry is increased in schizophrenia and related to avolition

Schizophrenia may be the result of a failure of the normal lateralization process of the brain. However, whole‐brain asymmetry has not been assessed up to date. Here, we propose a novel measure of global brain asymmetry based on the Dice coefficient to quantify similarity between brain hemispheres.

Three-Dimensional Map of Neonatal Arterial Ischemic Stroke Distribution From Early Multimodal Brain Imaging

Background and Purpose— Although neonatal arterial ischemic stroke (NAIS) location has considerable impact on long-term outcome, a map showing spatial distribution of NAIS is lacking. Our aim was to generate this distribution map, based on early magnetic resonance imaging data. Methods— Lesions from 34 consecutive neonates with NAIS from a single center were segmented using multimodal magnetic resonance imaging (median age at acquisition =5 days). Lesion masks for all subjects were registered onto a standard neonatal brain and then overlaid to generate a 3D map of NAIS distribution. Results— The region posterior to the central sulcus is the most frequently affected in neonates, with 24 of the 34 neonates (71%) showing lesions in this region in at least one hemisphere. Moreover, NAIS frequency is markedly higher in the left hemisphere. Conclusions— This is the first report of an NAIS distribution map. Regions posterior to the central sulcus present increased vulnerability. Our findings suggest that motor areas are not as frequently affected as has been previously reported. By contrast, we find high NAIS vulnerability in functional areas related to language. The distribution of ischemic strokes in neonates seems to be different from that seen in adults.

Neutrophil Count Is Associated With Reduced Gray Matter and Enlarged Ventricles in First-Episode Psychosis

Although there is recent evidence that cells from the peripheral immune system can gain access to the central nervous system in certain conditions such as multiple sclerosis, their role has not been assessed in psychosis. Here, we aimed to explore whether blood cell count was associated with brain volume and/or clinical symptomatology. A total of 218 participants (137 first-episode psychosis patients [FEP] and 81 healthy controls [HC]) were included in the study. For each participant, a T1 structural image was acquired, from which brain tissue volumes were calculated. We found that, in FEP, neutrophil count was associated with reduced gray matter (GM) volume (β = -0.117, P < .001) and increased cerebrospinal fluid volume (β = 0.191, P = .007). No associations were observed in HC. GM reduction was generalized but more prominent in certain regions, notably the thalamus, the anterior insula, and the left Heschls gyrus, among many others. Neutrophil count was also associated with the total PANSS score (β = 0.173, P = .038), including those items assessing hallucinations (β = 0.182, P = .028) and avolition (β = 0.197, P = .018). Several confounders, such as antipsychotic medication, body mass index, and smoking, were controlled for. Overall, the present study may represent the first indirect evidence of brain tissue loss associated with neutrophils in psychosis, and lends support to the hypothesis of a dysregulated immune system. Higher neutrophil count was also associated with more severe clinical symptomatology, which renders it a promising indicator of schizophrenia severity and could even give rise to new therapies.