Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Prodromal symptoms and the duration of untreated psychosis in first episode of psychosis patients: what differences are there between early vs. adult onset and between schizophrenia vs. bipolar disorder?

To assess the role of age (early onset psychosis-EOP < 18 years vs. adult onset psychosis-AOP) and diagnosis (schizophrenia spectrum disorders-SSD vs. bipolar disorders-BD) on the duration of untreated psychosis (DUP) and prodromal symptoms in a sample of patients with a first episode of psychosis. 331 patients with a first episode of psychosis (7-35 years old) were recruited and 174 (52.6%) diagnosed with SSD or BD at one-year follow-up through a multicenter longitudinal study. The Symptom Onset in Schizophrenia (SOS) inventory, the Positive and Negative Syndrome Scale and the structured clinical interviews for DSM-IV diagnoses were administered. Generalized linear models compared the main effects and group interaction. 273 AOP (25.2 ± 5.1 years; 66.5% male) and 58 EOP patients (15.5 ± 1.8 years; 70.7% male) were included. EOP patients had significantly more prodromal symptoms with a higher frequency of trouble with thinking, avolition and hallucinations than AOP patients, and significantly different median DUP (91 [33-177] vs. 58 [21-140] days; Z = - 2.006, p = 0.045). This was also significantly longer in SSD vs. BD patients (90 [31-155] vs. 30 [7-66] days; Z = - 2.916, p = 0.004) who, moreover had different profiles of prodromal symptoms. When assessing the interaction between age at onset (EOP/AOP) and type of diagnosis (SSD/BD), avolition was significantly higher (Wald statistic = 3.945; p = 0.047), in AOP patients with SSD compared to AOP BD patients (p = 0.004). Awareness of differences in length of DUP and prodromal symptoms in EOP vs. AOP and SSD vs. BD patients could help improve the early detection of psychosis among minors.

Obstetric complications and clinical presentation in first episode of psychosis.

OBJECTIVE: Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs. METHODS: Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis-Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia. RESULTS: Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use. CONCLUSIONS: Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.

The impact of cognitive reserve, cognition and clinical symptoms on psychosocial functioning in first-episode psychoses.

BACKGROUND: Functional impairment is a defining feature of psychotic disorders. A range of factors has been shown to influence functioning, including negative symptoms, cognitive performance and cognitive reserve (CR). However, it is not clear how these variables may affect functioning in first-episode psychosis (FEP) patients. This 2-year follow-up study aimed to explore the possible mediating effects of CR on the relationship between cognitive performance or specific clinical symptoms and functional outcome. METHODS: A prospective study of non-affective FEP patients was performed (211 at baseline and 139 at follow-up). CR was entered in a path analysis model as potential mediators between cognitive domains or clinical symptoms and functioning. RESULTS: At baseline, the relationship between clinical variables or cognitive performance and functioning was not mediated by CR. At follow-up, the effect of attention (p = 0.003) and negative symptoms (p = 0.012) assessed at baseline on functioning was partially mediated by CR (p = 0.032 and 0.016), whereas the relationship between verbal memory (p = 0.057) and functioning was mediated by CR (p = 0.014). Verbal memory and positive and total subscales of PANSS assessed at follow-up were partially mediated by CR and the effect of working memory on functioning was totally mediated by CR. CONCLUSIONS: Our results showed the influence of CR in mediating the relationship between cognitive domains or clinical symptoms and functioning in FEP. In particular, CR partially mediated the relationship between some cognitive domains or clinical symptoms and functioning at follow-up. Therefore, CR could improve our understanding of the long-term functioning of patients with a non-affective FEP.

The longitudinal effect of antipsychotic burden on psychosocial functioning in first-episode psychosis patients: the role of verbal memory.

BACKGROUND: Previous literature supports antipsychotics' (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning. METHODS: A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables. RESULTS: Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011-0.0091) and (b = 0.0026, 95% CI 0.0001-0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033-0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden. CONCLUSION: CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant.

Trajectories of suicidal ideation after first-episode psychosis: a growth mixture modeling approach.

OBJECTIVE: The period immediately after the onset of first-episode psychosis (FEP) may present with high risk for suicidal ideation (SI) and attempts, although this risk may differ among patients. Thus, we aimed to identify trajectories of SI in a 2-years follow-up FEP cohort and to assess baseline predictors and clinical/functional evolution for each trajectory of SI. METHODS: We included 334 FEP participants with data on SI. Growth mixture modeling was used to identify trajectories of SI. Putative sociodemographic, clinical, and cognitive predictors of the distinct trajectories were examined using multinomial logistic regression. RESULTS: We identified three distinct trajectories: Non-SI trajectory (85.53% sample), Improving SI trajectory (9.58%), and Worsening SI trajectory (6.89%). Multinomial logistic regression model revealed that greater baseline pessimistic thoughts, anhedonia, and worse perceived family environment were associated with higher baseline SI followed by an Improving trajectory. Older age, longer duration of untreated psychosis, and reduced sleep predicted Worsening SI trajectory. Regarding clinical/functional evolution, individuals within the Improving SI trajectory displayed moderate depression at baseline which ameliorated during the study period, while the Worsening SI subgroup exhibited persistent mild depressive symptoms and greater functional impairment at follow-up assessments. CONCLUSION: Our findings delineated three distinct trajectories of SI among participants with FEP, one experiencing no SI, another in which SI might depend on acute depressive symptomatology, and a last subset where SI might be associated with mild but persistent clinical and functional impairments. These data provide insights for the early identification and tailored treatment of suicide in this at-risk population.

Positive and Useful Voices in Patients With Schizophrenia: Prevalence, Course, Characteristics, and Correlates.

Auditory verbal hallucinations (AVHs) in schizophrenia have been characterized by their negative emotional valence. However, positive hallucinations have also been described. The objective of the current study is to explore the prevalence, course, characteristics, and associations of positive and useful voices. The Positive and Useful Voices Inquiry and some clinical and functioning instruments were administered to a sample of 68 patients with schizophrenia or schizoaffective disorder presenting with AVHs. Both the lifetime and current prevalences of positive and useful voices were high. Although AVHs tended to remain stable, there was a trend to decrease over time. The strongest positive attributions of such voices were that they help patients to feel important, amuse them, and help them to conduct their studies and carry out their profession. They seem to be mainly related to more grandiosity and to worse general functioning. Interference with biological and psychological treatments and the need for personalized formulations in patients with auditory hallucinations are discussed.

Is cognitive impairment associated with antipsychotic dose and anticholinergic equivalent loads in first-episode psychosis?

BACKGROUND: Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups. METHODS: Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively]. RESULTS: Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup. CONCLUSIONS: Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.

Validation of a Spanish version of the Schizotypal Personality Questionnaire (SPQ): Psychometric characteristics and underlying factor structure derived from a healthy university student sample.

OBJECTIVE: The need for early detection, prevention and intervention in psychosis has prompted the study of prodromal and threshold syndromes. One strategy involves the assessment of schizotypy, a personality construct involving unusual perceptual experiences, magical thinking or bizarre behavior. Sensitive measurement instruments could potentially allow detection of signs heralding transition to psychosis in high-risk individuals, or risk of relapse in patients after a first psychotic episode. The Schizotypal Personality Questionnaire (SPQ) is a self-report scale, originally developed for English speakers, that covers the nine DSM-IV criteria for schizotypal personality disorder (SPD). Our aim was to validate a Spanish version of the SPQ and assess its psychometric properties. METHODS: The original SPQ was back-translated and administered to university students (n=250). We assessed the internal consistency, the convergent, discriminant and criterion validity of the instrument, and analyzed its factor structure. RESULTS: Our version of the SPQ showed good internal consistency, and convergent (O-LIFE), discriminant (P-scale of EPQ) and criterion validity (SCID-II). Factor analyses supported a four-factor structure in fitting SPQ data. CONCLUSIONS: Our Spanish version of the SPQ questionnaire preserved the psychometric properties of the original questionnaire. This adaptation will provide a useful tool for the early detection of prodromal schizophrenia symptoms and clinical relapse in Spanish-speaking populations.

m-RESIST, a complete m-Health solution for patients with treatmentresistant schizophrenia: a qualitative study of user needs and acceptability in the Barcelona metropolitan area.

BACKGROUND: Despite the theoretical potential of m-health solutions in the treatment of patients with schizophrenia, there remains a lack of technological solutions in daily practice. The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to an integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment Resistant Schizophrenia (m-RESIST). METHODS: A qualitative study of the needs and acceptability of outpatients with treatment-resistant schizophrenia was carried out in Parc Sanitari Sant Joan de Déu (Barcelona). We analyzed the opinions of patients, informal carers, and clinicians concerning the services initially thought to be part of the solution. Five focus groups and eight interviews were carried out, using discourse analysis as the analytical approach. RESULTS: A webpage and a virtual forum were perceived as suitable to get reliable information on both the disease and support. Data transmission service, online visits, and instant messages were evaluated as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and medical appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions for improving the effectiveness of the solution. CONCLUSIONS: Positive acceptance of m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact.

A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project.

BACKGROUND: The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. METHODS: Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. RESULTS: The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, P<.001). CONCLUSIONS: These data indicate that the overall pharmacologic prescription for treating a first episode of psychosis in Spain follows the clinical practice guideline recommendations, and, together with security issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines.

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).

Alterations in the volume and shape of the basal ganglia and thalamus in schizophrenia with auditory hallucinations.

Different lines of evidence indicate that the structure and physiology of the basal ganglia and the thalamus is disturbed in schizophrenia. However, it is unknown whether the volume and shape of these subcortical structures are affected in schizophrenia with auditory hallucinations (AH), a core positive symptom of the disorder. We took structural MRI from 63 patients with schizophrenia, including 36 patients with AH and 27 patients who had never experienced AH (NAH), and 51 matched healthy controls. We extracted volumes for the left and right thalamus, globus pallidus, putamen, caudate and nucleus accumbens. Shape analysis was also carried out. When comparing to controls, the volume of the right globus pallidus, thalamus, and putamen, was only affected in AH patients. The volume of the left putamen was also increased in individuals with AH, whereas the left globus pallidus was affected in both groups of patients. The shapes of right and left putamen and thalamus were also affected in both groups. The shape of the left globus pallidus was only altered in patients lacking AH, both in comparison to controls and to cases with AH. Lastly, the general PANSS subscale was correlated with the volume of the right thalamus, and the right and left putamen, in patients with AH. We have found volume and shape alterations of many basal ganglia and thalamus in patients with and without AH, suggesting in some cases a possible relationship between this positive symptom and these morphometric alterations.

Impact of traumatic life events on clinical variables of individuals with first-episode psychosis and healthy controls.

BACKGROUND: Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP). AIMS: To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age. METHODS: Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered. RESULTS: We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes. CONCLUSIONS: The number and cumulative TLEs should be taken into account in the detection, epidemiology and process of recovery in FEP.

Volume alterations of the hippocampus and amygdala in patients with schizophrenia and persistent auditory hallucinations.

INTRODUCTION: Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. MATERIAL AND METHODS: We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. RESULTS: In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. CONCLUSIONS: We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.

m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study.

BACKGROUND: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. OBJECTIVE: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. METHODS: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. RESULTS: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. CONCLUSIONS: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03064776; https://clinicaltrials.gov/ct2/show/record/NCT03064776. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2017-021346.

Identifying risk factors for predominant negative symptoms from early stages in schizophrenia: A longitudinal and sex-specific study in first-episode schizophrenia patients.

BACKGROUND: People with schizophrenia and predominant negative symptoms (PNS) present a different clinical and functional profile from those without such symptomatology. Few studies have examined the risk factors and the incidence of PNS in first-episode schizophrenia patients (FES) and differentiating by sex. This study aims to assess prevalence, demographic and clinical characteristics related to PNS from early stages and to study if there are sex-specific features in terms of developing PNS. METHODS: In a sample of 121 FES patients derived from a multicentre and naturalistic study, those who developed PNS at 12-months were identified. Environmental, clinical, functional, and cognitive ratings were examined longitudinally. Binary logistic regressions were applied to detect baseline risk factors for developing PNS at one-year follow-up. RESULTS: In the present FES cohort, 24.8% of the patients (n=30) developed PNS (20% of the women, 27.6% of the men). Compared to non-PNS (75.2%, n=91), at baseline, PNS group had more negative (t=-6.347; p<0.001) and depressive symptoms (t=-5.026; p<0.001), poorer premorbid adjustment (t=-2.791; p=0.006) and functional outcome (t=-2.649; p<0.001), more amotivation (t=-7.333; p<0.001), more expressivity alterations (t=-4.417; p<0.001), worse cognitive reserve (t=2.581; p<0.011), a lower estimated intelligent quotient (t=2.417; p=0.017), worse verbal memory (t=2.608; p=0.011), and worse fluency (t=2.614; p=0.010). Regressions showed that the premorbid adjustment was the main predictor of PNS in females (p=0.007; Exp(B)=1.106) while in males were a worse verbal memory performance (p=0.031; Exp(B)=0.989) and more alterations in the motivation domain (p=0.001; Exp(B)=1.607). CONCLUSIONS: A different baseline clinical profile and notable risk factors differences in the development of PNS between males and females were found. Results suggest that sex may be an important confounder in studies comparing schizophrenia patients with predominant and non-predominant negative symptomatology.

Negative symptoms and sex differences in first episode schizophrenia: What's their role in the functional outcome? A longitudinal study.

INTRODUCTION: Negative symptoms (NS) include asociality, avolition, anhedonia, alogia, and blunted affect and are linked to poor prognosis. It has been suggested that they reflect two different factors: diminished expression (EXP) (blunted affect and alogia) and amotivation/pleasure (MAP) (anhedonia, avolition, asociality). The aim of this article was to examine potential sex differences among first-episode schizophrenia (FES) patients and analyze sex-related predictors of two NS symptoms factors (EXP and MAP) and functional outcome. MATERIAL AND METHODS: Two hundred and twenty-three FES (71 females and 152 males) were included and evaluated at baseline, six-months and one-year. Repeated measures ANOVA was used to examine the effects of time and sex on NS and a multiple linear regression backward elimination was performed to predict NS factors (MAP-EXP) and functioning. RESULTS: Females showed fewer NS (p=0.031; Cohen's d=-0.312), especially those related to EXP (p=0.024; Cohen's d=-0.326) rather than MAP (p=0.086), than males. In both male and female group, worse premorbid adjustment and higher depressive symptoms made a significant contribution to the presence of higher deficits in EXP at one-year follow-up, while positive and depressive symptoms predicted alterations in MAP. Finally, in females, lower deficits in MAP and better premorbid adjustment predicted better functioning at one-year follow-up (R2=0.494; p<0.001), while only higher deficits in MAP predicted worse functioning in males (R2=0.088; p=0.012). CONCLUSIONS: Slightly sex differences have been found in this study. Our results lead us to consider that early interventions of NS, especially those focusing on motivation and pleasure symptoms, could improve functional outcomes.

The role of striatal dopamine D2 receptors in the occurrence of extrapyramidal side effects: iodine-123-iodobenzamide single photon emission computed tomography study.

Levels above 75% of striatal dopamine 2 receptor occupancy (D2RO) have been associated with extrapyramidal symptoms (EPS). The aim of the present study is to investigate the relationship between D2RO and EPS in a sample of psychotic patients in current treatment with both typical and atypical antipsychotics. Brain iodine-123-iodobenzamide single photon emission computed tomography ((123)I-IBZM SPECT) was performed in 81 patients taking stable doses of haloperidol, risperidone, olanzapine, quetiapine, clozapine or ziprasidone. First, the degree of D2RO and Positive and Negative Syndrome Scale (PANSS) scores was compared between the group of patients who presented EPS and the group free of EPS. Afterwards, these variables were compared among the different antipsychotic medications. The group with EPS presented means of D2RO significantly higher than the group free of EPS. Significant differences in D2RO were found in clozapine, quetiapine and ziprasidone groups compared with the haloperidol group. No differences were observed between either olanzapine or risperidone and haloperidol. No quetiapine- or clozapine-treated patients developed EPS. Haloperidol and risperidone demonstrated a relationship between striatal D2RO and EPS. The findings suggest that higher D2RO is related to appearance of EPS. Occupancy in the group with EPS was in agreement with previous studies that suggested a high degree of D2RO is necessary for the occurrence of EPS.

Target selection for deep brain stimulation in treatment resistant schizophrenia.

The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.