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.

Comparison of male and female non-refugee immigrants with psychosis: clinical, sociodemographic, and migration-related differences and impact on stress.

PURPOSE: To compare social, clinical, and migration-related factors between male and female immigrants with psychotic disorders and to determine the association between these variables and stress in the last year. METHODS: We administered the Holmes and Rahe Social Readjustment Scale to evaluate psychological stress in 99 non-refugee immigrants (26 women, 73 men) who presented ≥ one psychotic episode (ICD-10 criteria). We compared the two groups in terms of sociodemographic, clinical, cultural, and migration-related variables. A multivariable analysis using a linear regression model (stepwise method) was performed to evaluate potential associations between these variables and stress. RESULTS: Women were more likely to be married and divorced, had less access to welfare payments, and lower unemployment and homeless rates than men. The most common psychiatric diagnosis was psychosis not otherwise specified with more women being affected (61.5% in women vs. 45.2% in men), but the diagnosis of schizophrenia was more common in men (38.4% vs 15.4%). Both groups exhibited very high levels of stress in the past year (mean total distress score > 300). In women, stress was significantly associated with age at first migration and be a racialized person. By contrast, among men stress was significantly associated with language barrier and comorbidity with a physical disorder. CONCLUSIONS: The results of this study reveal important differences between men and women immigrants. These findings underscore the importance of understanding how gender-specific roles and social expectations intersect with the timing and nature of migration to influence stress levels differently in immigrant women and men with psychotic disorders.

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.

Hoarding behaviour: special features and complications in real-world clinical practice.

OBJECTIVE: Hoarding behaviour is a common but poorly characterised problem in real-world clinical practice. Although hoarding behaviour is the key component of Hoarding Disorder (HD), there are people who exhibit hoarding behaviour but do not suffer from HD. The aim of the present study was to characterise a clinical sample of patients with clinically relevant hoarding behaviour and evaluate the differential characteristics between patients with and without HD. METHODS: This study included patients who received treatment at the home visitation program in Barcelona (Spain) from January 2013 through December 2020, and scored ≥ 4 on the Clutter Image Rating scale. Sociodemographic, DSM-5 diagnosis, clinical data and differences between patients with and without an HD diagnosis were assessed. RESULTS: A total of 243 subjects were included. Hoarding behaviour had been unnoticed in its early stages and the median length in the sample was 10 years (IQR 15). 100% of the cases had hoarding-related complications. HD was the most common diagnosis in 117 patients (48.1%). CONCLUSIONS: The study found several differential characteristics between patients with and without HD diagnosis. Alcohol use disorder could play an important role among those without HD diagnosis. Home visitation programs could improve earlier detection, preventing hoarding-related complications.

Multidimensional predictors of negative symptoms in antipsychotic-naive first-episode psychosis.

BACKGROUND: Despite a large body of schizophrenia research, we still have no reliable predictors to guide treatment from illness onset. The present study aimed to identify baseline clinical or neurobiological factors - including peripheral brain-derived neurotrophic factor (BDNF) levels and amygdala or hippocampal relative volumes - that could predict negative symptomatology and persistent negative symptoms in first-episode psychosis after 1 year of follow-up. METHODS: We recruited 50 drug-naive patients with first-episode psychosis and 50 age- and sex-matched healthy controls to study brain volumes. We performed univariate and multiple and logistic regression analyses to determine the association between baseline clinical and neurobiological variables, score on the PANSS negative subscale and persistent negative symptoms after 1 year of follow-up. RESULTS: Low baseline serum BDNF levels (p = 0.011), decreased left amygdala relative volume (p = 0.001) and more severe negative symptomatology (p = 0.021) predicted the severity of negative symptoms at 1 year, as measured by the PANSS negative subscale. Low baseline serum BDNF levels (p = 0.012) and decreased left amygdala relative volume (p = 0.010) predicted persistent negative symptoms at 1 year. LIMITATIONS: We were unable to assess negative symptoms and their dimensions with next-generation scales, which were not available when the study was initiated. CONCLUSION: This study shows that a set of variables at baseline, including low BDNF levels, smaller left amygdala relative volume and score on the PANSS negative subscale are significant predictors of outcomes in first-episode psychosis. These findings might offer an initial step for tailoring treatments in first-episode psychosis.

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.

Obstetric Phenotypes in the Heterogeneity of Schizophrenia.

Schizophrenia is a complex mental disorder with genetic and environmental components. Obstetric complications (OCs) are one of the most common environmental risk factors described. However, despite being different in timing and outcome, OCs are usually described as a homogeneous entity. In the present study, we evaluate the presence of different patterns of OCs evaluated with the Lewis-Murray Scale in chronic schizophrenia patients (n = 101) and their association with a crude marker of the intrauterine environment such as weight at birth.OCs related with abnormal fetal growth (p < 0.001) and OCs during gestation (p = 0.003) were associated with lower birth weight. However, difficulties in delivery, complications in pregnancy, and OCs all together (as a set) were not associated with weight at birth.Our results infer that OCs cannot be taken as a homogeneous group. Different patterns of OCs result in different birth weights, which is associated with specific metabolic, cognitive, and brain structure outcomes.

A prospective study contrasting the psychiatric outcome in drug-resistant epilepsy between patients who underwent surgery and a control group.

OBJECTIVE: Psychiatric morbidity in drug-resistant epilepsy is frequent and has a negative influence on quality of life. Surgery is proven to be the best therapeutic alternative for treating seizures. However, it is inconclusive with the current evidence whether surgery, per se, is a risk factor or promotes amelioration of psychiatric disorders. Until now, most studies have been cross-sectional with small or heterogeneous groups. In addition, the few prospective studies did not have an identical control group. The present study aims to clarify the role of surgery in psychopathologic alterations. METHODS: We analyzed, through a prospective case-control study, the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery and those who continued with pharmacologic treatment due to not being suitable for surgery. The assessments were performed during presurgical evaluation and 6 months after surgery. We studied psychiatric changes for each group, compared differences between groups, and also analyzed de novo and remission cases. Finally, we determined associated factors for postsurgical psychiatric disturbances. RESULTS: The surgical group experienced a significant decrease in psychopathologic alterations in comparison with the control group. In addition, distress perception of surgical patients also improved, whereas it did not decrease in the control group. Patients who underwent surgery presented a decrease in depressive and anxiety symptoms, whereas the nonsurgical group increased its anxiety levels. De novo disturbances that appeared after surgery were less frequent than in nonsurgical patients. We observed significant favorable outcomes considering de novo versus remission cases for anxiety, depression, and total symptoms only in the surgical group. The two main predictors for psychiatric disorders after surgery were presurgical psychiatric functioning and surgery. SIGNIFICANCE: Provides evidence that surgery improves psychiatric functioning in drug-resistant epilepsy through a prospective controlled study.

Patient Management and Psychopharmacological Treatment Associated to Smoking Ban in an Acute Psychiatric Unit.

This study investigates differences in terms of clinical and treatment management in psychiatric hospitalization associated to smoking ban. We collected data regarding medication, socio-demographic and admission characteristics from all patients admitted to an acute psychiatric hospital before and after a smoking ban was in force. We also assessed a limited sample of patients before and after the ban regarding nicotine dependence, motivation to quit smoking and attitudes towards the ban. More number of leaves of absence and movement restrictions during the ban period occurred in comparison to the pre-ban period. On the contrary a lack of significant differences in terms of hospital stay (duration, rate of voluntary admissions and voluntary discharges), use of sedatives and doses of antipsychotics was found. A period of adjustment regarding the deal with leave of access and facilitate nicotine replacement treatment may help future psychiatric facilities planning smoking free policies.

Clinical decision-making before discharge in hospitalized persons with schizophrenia: a Spanish Delphi expert consensus.

Introduction: The care of people with schizophrenia (PWS) is usually provided in an outpatient setting by community mental health teams. However, PWS frequently require inpatient treatment because of a wide array of clinical, personal and/or social situations. Unfortunately, to our knowledge, there are no guidelines available to help psychiatrists in the decision-making process on hospital discharge for PWS. The aim of this project was to develop an expert consensus on discharge criteria for PWS after their stay in an acute inpatient psychiatric unit. Methods: Using a modified Delphi method a group of 42 psychiatrists throughout Spain evaluated four areas of interest regarding this issue: clinical symptomatology, treatment-related factors, follow-up health care units after discharge, and physical health and monitoring. Results: After two rounds, among the 64 statements, a consensus was reached for 59 (92.2%) statements. In three (17.7%) of the 17 statements on 'clinical symptomatology' and 2 (13.3%) of the 15 statements on 'follow-up health care units after discharge', a consensus was not reached; in contrast, a consensus was reached for all statements concerning 'treatment-related factors' and those concerning 'physical health and monitoring'. The consensus results highlight the importance for discharge of the control of symptoms rather than their suppression during admission and of tolerability in the selection of anantipsychotic. Discussion: Although there is a lack of relevant data for guiding the discharge of PWS after hospitalization in an acute inpatient psychiatric unit, we expect that this consensus based on expert opinion may help clinicians to take appropriate decisions.

Clozapine use in the first two years after first-episode psychosis in a real-world clinical sample.

BACKGROUND: Approximately 20-30% of patients with schizophrenia fail to respond to antipsychotic treatment and are considered treatment resistant (TR). Although clozapine is the treatment of choice in these patients, in real-world clinical settings, clinicians often delay clozapine initiation, especially in first-episode psychosis (FEP). AIM: The main aim of this study was to describe prescription patterns for clozapine in a sample of patients diagnosed with FEP and receiving specialized treatment at a university hospital. More specifically, we aimed to determine the following: (1) the proportion of patients who received clozapine within two years of disease onset, (2) baseline predictors of clozapine use, (3) time from starting the first antipsychotic to clozapine initiation, (4) concomitant medications, and (5) clozapine-related adverse effects. METHODS: All patients admitted to a specialized FEP treatment unit at our hospital between April 2013 and July 2020 were included and followed for two years. The following variables were assessed: baseline sociodemographic characteristics; medications prescribed during follow-up; clozapine-related adverse effects; and baseline predictors of clozapine use. We classified the sample into three groups: clozapine users, clozapine-eligible, and non-treatment resistant (TR). RESULTS: A total of 255 patients were consecutively included. Of these, 20 (7.8%) received clozapine, 57 (22.4%) were clozapine-eligible, and 178 (69.8%) were non-TR. The only significant variable associated with clozapine use at baseline was the Global Assessment of Functioning (GAF) score (R2=0.09, B=-0.07; OR=0.94; 95% CI: 0.88-0.99; p=0.019). The median time to clozapine initiation was 55.0 (93.3) days. The most common side effect was sedation. CONCLUSIONS: A significant proportion (30.2%) of patients in this cohort were treatment resistant and eligible for clozapine. However, only 7.8% of the sample received clozapine, indicating that this medication was underprescribed. A lower baseline GAF score was associated with clozapine use within two years, suggesting that it could be used to facilitate the early identification of patients who will need treatment with clozapine, which could in turn improve treatment outcomes.

Substance use Specificities in Women with Psychosis: A Critical Review.

BACKGROUND: Women with schizophrenia or other psychotic disorders differ from male patients in many respects, including psychopathology, prognosis, disease course, and substance use comorbidities. Most studies performed to date to investigate the association between drug use and psychosis have not evaluated gender differences, although this has started to change in recent years. METHODS: We briefly summarize the available evidence on gender differences in drug use and substance use disorders (SUD) in psychotic patients during the early phases of the psychotic illness and during the course of schizophrenia. RESULTS: Substance use and SUD are both less prevalent in women, both in the general population and at all phases of the psychotic spectrum. Some studies suggest that SUD may be under diagnosed in female patients, in part due to their more vulnerable profile. Substance use, especially cannabis, may more negatively impact females, especially on the disease course and prognosis. The available data suggest that it may be more difficult to treat SUD in female patients with schizophrenia, which could negatively impact prognosis. CONCLUSION: Women with concomitant psychotic illness and SUD comprise a highly vulnerable subgroup. This should be considered when selecting the treatment approach, especially in the early phases of the illness, to ensure better outcomes.

Higher lymphocyte count associated with larger hippocampal volume and fewer depressive symptoms in drug-na ïve first-episode psychosis.

Circulating white blood cells (leucocytes), which form the peripheral immune system, are crucial in inflammatory processes but their role in brain structural change in schizophrenia has been scarcely studied. With this study we want to determine how and which type of white blood cells are associated with hippocampal volume (as a key structure in schi- zophrenia etiopathology) in first episode psychosis (FEP) patients. Moreover, to determine the association between white blood cells and clinical symptomatology, including positive and negative symptoms, cognition and depression. For this purpose fifty drug-naïve FEP were included in this study. All patients underwent an assessment at baseline and at 1 year follow-up, including sociodemographic and clinical variables (substance use, DUP, PANSS, GAF and CDSS). Fasting blood samples were obtained before administering any medication at baseline. Structural T1 MRI was performed at baseline and brain volumes were quantified. In the present study, higher lymphocyte count was associated with larger right hippocampal volume at baseline in FEP drug-naive patients. Higher lymphocyte count was associated with lower depressive symptomatology measured with CDSS and Marder depressive factor from PANSS at baseline and 1-year follow -up. These results suggest that lymphocytes may have a protective effect in hippocampal volume at baseli- ne in antipsychotic naïve FEP and also, are associated with a better depressive course over follow up. These results open the door to identify new biomarkers and therapeutic targets for patients with schizophrenia.

Factors associated with suicide attempts in first-episode psychosis during the first two years after onset.

The risk of suicide in first-episode psychosis (FEP) is high. However, there are many unknowns about this phenomenon and the risk factors associated with higher risk are not well-understood. Therefore, we aimed to determine the baseline sociodemographic and clinical factors associated with suicide attempts in FEP patients over two-years after psychosis onset. Univariate and logistic regression analyses were performed. Between April 2013 and July 2020, 279 patients treated at the FEP Intervention Program at our hospital (Hospital del Mar, Spain) were enrolled and 267 completed the follow-up. Of these, 30 patients (11.2%) made at least one suicide attempt, mostly during the untreated psychosis period (17 patients, 48.6%). Several variables-prior history of suicide attempts and low functionality, depression, and feelings of guilt at baseline-were all significantly associated with suicide attempts. These findings suggest that targeted interventions, especially in prodromal stages, could play a key role in identifying and treating FEP patients with a high suicide risk.

Mapping alterations in the local synchrony of the cerebral cortex in schizophrenia.

BACKGROUND: Observations from different fields of research coincide in indicating that a defective gamma-aminobutyric acid (GABA) interneuron system may be among the primary factors accounting for the varied clinical expression of schizophrenia. GABA interneuron deficiency is locally expressed in the form of neural activity desynchronization. We mapped the functional anatomy of local synchrony in the cerebral cortex in schizophrenia using functional connectivity MRI. METHODS: Data from 86 patients with schizophrenia and 137 control subjects were obtained from publicly available repositories. Resting-state functional connectivity maps based on Iso-Distant Average Correlation measures across three distances were estimated detailing the local functional structure of the cerebral cortex. RESULTS: Patients with schizophrenia showed weaker local functional connectivity (i.e., lower MRI signal synchrony) in (i) prefrontal lobe areas, (ii) somatosensory, auditory, visual, and motor cortices, (iii) paralimbic system at the anterior insula and anterior cingulate cortex, and (iv) hippocampus. The distribution of the defect in cortical area synchrony largely coincided with the synchronization effect of the GABA agonist alprazolam previously observed using identical functional connectivity measures. There was also a notable resemblance between the anatomy of our findings and cortical areas showing higher density of parvalbumin (prefrontal lobe and sensory cortices) and somatostatin (anterior insula and anterior cingulate cortex) GABA interneurons in humans. CONCLUSIONS: Our results thus provide detail of the functional anatomy of synchrony changes in the cerebral cortex in schizophrenia and suggest which elements of the interneuron system are affected. Such information could ultimately be relevant in the search for specific treatments.

Relationship between thyroid-stimulating hormone, BDNF levels, and hippocampal volume in antipsychotic-naïve first-episode psychosis patients.

Introduction: Thyroid hormones play an essential role in hippocampal development, a key structure in psychosis. However, the role of these hormones in first-episode psychosis (FEP) has received limited attention. It has been hypothesized that thyroid hormones could cause morphological modifications in the hippocampal structure through the upregulation of brain-derived neurotrophic factor (BDNF). In this study, we primarily aimed to determine the relationship between thyroid-stimulating hormone (TSH) levels, peripheral BDNF levels, and hippocampal volume in antipsychotic-naïve FEP patients. We also aimed to determine whether TSH levels were associated with clinical symptomatology. Materials and methods: A total of 50 antipsychotic-naïve FEP patients were included in the study. At baseline, we collected fasting blood samples and registered sociodemographic and clinical variables (substance use, DUP, PANSS, GAF, and CDSS). Structural T1 MRI was performed at baseline to quantify brain volumes. No control group was used for this study. Results: Of the 50 patients, more than one-third (36%) presented alterations in TSH levels, mainly elevated levels (32% of patients). The TSH levels were inversely correlated with both peripheral BDNF and hippocampal volume. On the multivariate analysis, the model that best predicted the relative hippocampal volume was a single variable model (TSH levels). No significant association was observed between TSH levels and clinical symptomatology. Discussion: These results suggest that thyroid hormones could have a neuroprotective effect on the hippocampus in FEP patients, possibly through their effect by increasing BDNF concentrations, which could attenuate brain injury and neuroinflammation. Nevertheless, thyroid hormones could also affect hippocampal volume through other pathways.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP. A cohort of 249 FEP individuals were evaluated during 12 months. Symptom severity was measured with the Positive and Negative Severity Scale and cannabis use with the EuropASI scale. Individual PRS for lifetime cannabis initiation (PRSCI) and cannabis use disorder (PRSCUD) were constructed. Current cannabis use was associated with increased positive symptoms. Cannabis initiation at younger ages conditioned the 12-month symptom progression. FEP patients with higher cannabis PRSCUD reported increased baseline cannabis use. PRSCI was associated with the course of negative and general symptomatology over follow-up. Cannabis use and symptom progression after a FEP were modulated by cannabis PRS, suggesting that lifetime initiation and use disorders may have partially independent genetic factors. These exploratory results may be the first step to identify those FEP patients more vulnerable to cannabis use and worse outcomes to ultimately develop tailored treatments.

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.

Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations.

BACKGROUND: Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. METHODS: A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. RESULTS: At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. CONCLUSIONS: Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.

The polygenic basis of relapse after a first episode of schizophrenia.

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.