Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids.

Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that has emerged as a key regulator of neurotransmission in complex cognitive processes. Its expression is altered in treated schizophrenia patients, and cannabinoids modulate CDK5 levels in the brain of rodents. However, the role of this kinase, and its interaction with cannabis use in first-episode psychosis (FEP) patients is still not known. Hence, we studied the expression changes of CDK5 and its signaling partner, postsynaptic density protein 95 (PSD95) in olfactory neuroepithelial (ON) cells of FEP patients with (FEP/c) and without (FEP/nc) prior cannabis use, and in a dual-hit mouse model of psychosis. In this model, adolescent mice were exposed to the cannabinoid receptor 1 agonist (CB1R) WIN-55,212-2 (WIN: 1 mg/kg) during 21 days, and to the N-methyl-d-aspartate receptor (NMDAR) blocker phencyclidine (PCP: 10 mg/kg) during 10 days. FEP/c showed less social functioning deficits, lower CDK5 and higher PSD95 levels than FEP/nc. These changes correlated with social skills, but not cognitive deficits. Consistently, exposure of ON cells from FEP/nc patients to WIN in vitro reduced CDK5 levels. Convergent results were obtained in mice, where PCP by itself induced more sociability deficits, and PSD95/CDK5 alterations in the prefrontal cortex and hippocampus than exposure to PCP-WIN. In addition, central blockade of CDK5 activity with roscovitine in PCP-treated mice restored both sociability impairments and PSD95 levels. We provide translational evidence that increased CDK5 could be an early indicator of psychosis associated with social deficits, and that this biomarker is modulated by prior cannabis use.

Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis.

BACKGROUND: Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. STUDY DESIGN: 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these. RESULTS: Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case-control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. CONCLUSIONS: We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.

Improvement in prefrontal thalamic connectivity during the early course of the illness in recent-onset psychosis: a 12-month longitudinal follow-up resting-state fMRI study.

BACKGROUND: Previous research in resting-state functional magnetic resonance imaging (rs-fMRI) has shown a mixed pattern of disrupted thalamocortical connectivity in psychosis. The clinical meaning of these findings and their stability over time remains unclear. We aimed to study thalamocortical connectivity longitudinally over a 1-year period in participants with recent-onset psychosis. METHODS: To this purpose, 129 individuals with recent-onset psychosis and 87 controls were clinically evaluated and scanned using rs-fMRI. Among them, 43 patients and 40 controls were re-scanned and re-evaluated 12 months later. Functional connectivity between the thalamus and the rest of the brain was calculated using a seed to voxel approach, and then compared between groups and correlated with clinical features cross-sectionally and longitudinally. RESULTS: At baseline, participants with recent-onset psychosis showed increased connectivity (compared to controls) between the thalamus and somatosensory and temporal regions (k = 653, T = 5.712), as well as decreased connectivity between the thalamus and left cerebellum and right prefrontal cortex (PFC; k = 201, T = -4.700). Longitudinal analyses revealed increased connectivity over time in recent-onset psychosis (relative to controls) in the right middle frontal gyrus. CONCLUSIONS: Our results support the concept of abnormal thalamic connectivity as a core feature in psychosis. In agreement with a non-degenerative model of illness in which functional changes occur early in development and do not deteriorate over time, no evidence of progressive deterioration of connectivity during early psychosis was observed. Indeed, regionally increased connectivity between thalamus and PFC was observed.

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.

Brain activity and connectivity differences in reward value discrimination during effort computation in schizophrenia.

Negative symptoms in the motivational domain are strongly correlated with deficits in social and occupational functioning in schizophrenia. However, the neural substrates underlying these symptoms remain largely unknown. Twenty-eight adults with schizophrenia and twenty healthy volunteers underwent functional magnetic resonance while completing a lottery game designed to capture reward-related cognitive processes. Each trial demanded an initial investment of effort in form of key presses to increase the odds of winning. Brain activity in response to different reward cues (1 euro versus 1 cent) was compared between groups. Whereas controls invested more effort in improving their chances to win 1 euro compared to 1 cent in the lottery game, patients invested similarly high amounts of effort in both reward conditions. The neuroimaging analysis revealed lower neural activity in the bilateral caudate and cingulo-opercular circuits and decreased effective connectivity between reward-associated areas and neural nodes in the frontoparietal and salience network in response to high- versus low-reward conditions in schizophrenia patients compared to controls. Effective connectivity differences across conditions were associated with amotivation symptoms in patients. Overall, our data provide the evidence of alterations in neural activity in the caudate and cingulo-opercular "task maintenance" circuits and frontoparietal effective connectivity with reward-associated nodes as possible underlying mechanisms of reward value discrimination deficits affecting effort computation in schizophrenia.

Reduced willingness to invest effort in schizophrenia with high negative symptoms regardless of reward stimulus presentation and reward value.

BACKGROUND: Negative symptoms in schizophrenia, which are related to poor functioning, are thought to be grounded on aberrant functioning in the reward system. We aimed to disentangle how negative symptoms and two cognitive aspects of goal-directed behavior, mental representation of reward and reward value, affect willingness to invest effort to attain a reward in schizophrenia. AIMS AND PROCEDURES: To this purpose, 43 schizophrenia patients and 35 healthy controls were assessed for negative symptoms and general functioning, and completed an effort-based reward task. Patients were split in high and low negative symptoms scorers. A series of ANOVA tests were conducted in order to test the effects of group controlling for representation of reward (Task 1) and balance between reward value and effort (Task 2) on will to invest effort to attain a reward. MAIN FINDINGS: Schizophrenia patients with high negative symptoms chose to invest lower amounts of effort for a reward compared both to low negative symptoms patients and to controls in both tasks. Neither mental representation of reward (Task 1) nor reward value (Task 2) did differentially affect will to invest effort between-groups. CONCLUSIONS: These findings suggest that the lower willingness to invest effort observed in schizophrenia patients with high negative symptoms may not be related to cognitive aspects of goal-oriented behavior.

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.

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.

Limbic activity in antipsychotic naïve first-episode psychotic subjects during facial emotion discrimination.

The aim of this study was to determine brain activation during facial emotion discrimination in first-episode of psychosis. Eighteen patients underwent an fMRI while performing a facial emotion discrimination task during the acute episode, before starting antipsychotic drugs. A second fMRI and clinical evaluation were performed after evident clinical improvement. An equivalent control group underwent the same two fMRIs with a similar period of time between exams. The voxel-wise approach showed pre-treatment hypoactivation in ventro-limbic regions (cluster including right hippocampus and left amygdala; cluster size 528; p cluster <0.004) and facial perception involved in ventral-posterior regions (bilateral lingual gyrus, calcarine fissure and occipital superior gyrus, (k = 1,508, p < 0.001) and fronto-temporal regions. The region of interest approach also confirmed hypoactivation in right and left amygdala (cluster corrected p = 0.035 and 0.043, respectively). After treatment and clinical improvement, the voxel-wise approach showed a significant increase in activity in lingual gyrus and calcarine fissure in the group of patients. The regions of interest analysis showed an increase in amygdala activity during anger discrimination also in the group of patients. The results suggest a state-dependent model depicting a flattened and aberrant response of amygdala to emotion discrimination that could explain the seemingly contradictory previous findings of hypo- and hyper-amygdala activation.

Identification of distinct clinical profiles and trajectories in individuals at high risk of developing psychosis: A latent profile analysis of the north American prodrome longitudinal study consortium-3 dataset.

AIM: People at clinical high risk (CHR) for psychosis are a heterogeneous population in regard to clinical presentation and outcome. It is unclear, however, if their baseline clinical characteristics can be used to construct orthogonal subgroups that differ in their clinical trajectory to provide early identification of individuals in need of tailored interventions. METHODS: We used latent profile analysis (LPA) to determine the number of distinct clinical profiles within the CHR population using the NAPLS-3 dataset, focusing on the clinical features incorporated in the NAPLS psychosis risk calculator (including age, unusual thought content and suspiciousness, processing speed, verbal learning and memory function, social functioning decline, life events, childhood trauma, and family history of psychosis). We then conducted a between-profile comparisons of clinical trajectories based on psychotic and depressive symptoms as well as substance use disorder (SUD) related features over time. RESULTS: Two distinct profiles emerged. One profile, comprising approximately 25% of the sample, was significantly older, displayed better cognitive performance, experienced more types of traumatic and undesirable life events, exhibited a greater decline in functioning in the past year, and was more likely to have relatives with psychosis. This group showed worse positive symptoms and SUD-related features over time, although groups did not differ in the proportion of individuals who developed psychosis. CONCLUSIONS: LPA results suggest CHRs can be segregated into two profiles with different clinical trajectories. Characterizing individuals within these clinical profiles may help understand the divergent outcomes of this population and ultimately facilitate the development of specialized interventions.

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.

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.

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.

Structural covariance predictors of clinical improvement at 2-year follow-up in first-episode psychosis.

The relationship between structural brain alterations and prediction of clinical improvement in first-episode psychosis (FEP) has been scarcely studied. We investigated whether structural covariance, a well-established approach to identify abnormal patterns of volumetric correlation across distant brain regions, which allows incorporating network-level information to structural assessments, is associated with longitudinal clinical course. We assessed a sample of 74 individuals from a multicenter study. Magnetic resonance imaging scans were acquired at baseline, and clinical assessments at baseline and at a 2-year follow-up. Participants were split in two groups as a function of their clinical improvement after 2 years (i.e., ≥ < 40% reduction in psychotic symptom severity, (n = 29, n = 45)). We performed a seed-based approach and focused our analyses on 3 cortical and 4 subcortical regions of interest to identify alterations in cortical and cortico-subcortical networks. Improvers presented an increased correlation between the volumes of the right posterior cingulate cortex (PCC) and the left precentral gyrus, and between the left PCC and the left middle occipital gyrus. They also showed an increased correlation between right posterior hippocampus and left angular gyrus volumes. Our study provides a novel mean to identify structural correlates of clinical improvement in FEP, describing clinically-relevant anatomical differences in terms of large-scale brain networks, which is better aligned with prevailing neurobiological models of psychosis. The results involve brain regions considered to participate in the multisensory processing of bodily signals and the construction of bodily self-consciousness, which resonates with recent theoretical accounts in psychosis research.

Combining MRI and clinical data to detect high relapse risk after the first episode of psychosis.

Detecting patients at high relapse risk after the first episode of psychosis (HRR-FEP) could help the clinician adjust the preventive treatment. To develop a tool to detect patients at HRR using their baseline clinical and structural MRI, we followed 227 patients with FEP for 18-24 months and applied MRIPredict. We previously optimized the MRI-based machine-learning parameters (combining unmodulated and modulated gray and white matter and using voxel-based ensemble) in two independent datasets. Patients estimated to be at HRR-FEP showed a substantially increased risk of relapse (hazard ratio = 4.58, P < 0.05). Accuracy was poorer when we only used clinical or MRI data. We thus show the potential of combining clinical and MRI data to detect which individuals are more likely to relapse, who may benefit from increased frequency of visits, and which are unlikely, who may be currently receiving unnecessary prophylactic treatments. We also provide an updated version of the MRIPredict software.

Incidence rate and distinctive characteristics of first episode psychosis during the COVID-19 pandemic: a multicenter observational study.

The COVID-19 pandemic has affected the mental health of people around the world. However, its impact on first-episode psychosis (FEP) remains unclear. The aim of this study was to determine the incidence rate (IR) and the clinical and sociodemographic characteristics of patients who developed FEP during the nine-month period following the COVID-19 outbreak in Spain and to compare these data to the corresponding period in the previous year. We included all patients (n = 220) treated for the first time during these two time periods at three FEP programs in Spain. The IR was 0.42/100,000 person-years during the pandemic vs. 0.54/100,000 in the prior year (p = 0.057). Compared to prior year, women accounted for a significantly higher proportion of FEP patients (46.3% vs. 28%; p = 0.005) during the COVID-19 period. This association was significant on the logistic regression analysis (odds ratio, female: 2.12 [confidence interval 1.17-3.82]; p = 0.014). These data reveal a non-significant trend towards a lower incidence of FEP during the pandemic period. Female sex was associated with a greater risk of developing FEP during the pandemic period, perhaps due to differences between males and females in the susceptibility and expression of psychosis. The findings of this study contribute to a better understanding of stress-related disorders.

The network structure of cognitive deficits in first episode psychosis patients.

Network analysis is an important conceptual and analytical approach in mental health research. However, few studies have used network analysis to examine the structure of cognitive performance in psychotic disorders. We examined the network structure of the cognitive scores of a sample of 207 first-episode psychosis (FEP) patients and 188 healthy controls. Participants were assessed using a battery of 10 neuropsychological tests. Fourteen cognitive scores encompassing six cognitive domains and premorbid IQ were selected to perform the network analysis. Many similarities were found in the network structure of FEP patients and healthy controls. Verbal memory, attention, working memory and executive function nodes were the most central nodes in the network. Nodes in both groups corresponding to the same tests tended to be strongly connected. Verbal memory, attention, working memory and executive function were central dimensions in the cognitive network of FEP patients and controls. These results suggest that the interplay between these core dimensions is essential for demands to solve complex tasks, and these interactions may guide the aims of cognitive rehabilitation. Network analysis of cognitive dimensions might have therapeutic implications that deserve further research.

Neutrophil to Lymphocyte Ratio in Patients With a First Episode of Psychosis: A Two-Year Longitudinal Follow-up Study.

BACKGROUND AND HYPOTHESIS: A pro-inflammatory phenotype has been related to psychotic disorders. The neutrophil-lymphocyte ratio (NLR) is an accessible biomarker that could be helpful to characterize this systemic inflammation state. STUDY DESIGN: This study evaluated the NLR in a cohort of 310 subjects with a first episode of psychosis (FEP) and a matched group of 215 healthy controls, recruited in 16 Spanish centers participating in the PEPs Project. We investigated the NLR measures over 2 years in a prospective, naturalistic study. STUDY RESULTS: At baseline, the FEP group showed a significant higher mean NLR compared to the control group (1.96 ± 1.11 vs 1.72 ± 0.74, P = 0.03). These ratio differences between groups grew at the 24 months follow-up visit (2.04 ± 0.86 vs 1.65 ± 0.65, P < 0.001). Within the FEP group, there were no significant differences in NLR across the follow-up visits, between genders or diagnosis groups (affective vs nonaffective). NLR values did not correlate with the Positive and Negative Symptoms Scale scores. The group of patients who did not reach remission criteria at the end of the study showed a significant higher NLR than those who remitted (2.1896 ± 0.85 vs 1.95 ± 0.87, P = 0.042). A significant correlation between antipsychotic doses and NLR was found at the two-years follow-up visit (r=0.461, P < 0.001). CONCLUSIONS: Our results highlight the existence of an underlying predisposition of FEP patients to present an increased mean NLR. The use of NLR in clinical practice could be helpful to identify this inflammatory imbalance.

The influence of modifiable cardiovascular risk factors on cognition, functioning, and inflammatory markers in first-episode psychosis: Results from a 2-year follow-up study.

To explore the influence of cardiovascular risk factors (CVRFs) on cognitive symptoms, functional impairment, and systemic inflammatory markers in first-episode psychosis (FEP) patients at baseline and 2-year follow-up. Method: In a sample of 70 FEP patients and 85 age- and sex-matched healthy controls, we assessed nine modifiable CVRFs. All participants were classified into two subgroups according to their CVRF profile: lower (0-1 CVRFs) or higher (≥2 CVRFs). The following outcomes were measured at baseline and 2-year follow-up: cognition; functional outcomes; and white blood cell (WBC) subtype. Adjusted general linear models were conducted to study the effect of diagnosis and CVRF profile on cognition, functioning, WBC, and longitudinal changes in these variables. At baseline, FEP patients with a higher CVRF profile showed a significantly slower performance on the TMT-A test for psychomotor speed and higher lymphocyte levels than patients with a lower CVRF profile. No longitudinal changes were observed in primary outcomes at 2-year follow-up. Among FEP patients with a higher CVRF profile, slower psychomotor speed performance did not correlate with increased lymphocyte levels. Our findings suggest that the cognitive effects of CVRFs manifest early in the course of psychosis, thus highlighting the importance of targeting both CVRFs and cognitive deficits in FEP.