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Background and Hypothesis Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited. Study Design Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses. Study Results We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment. Conclusions We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.

Introduction Widespread white matter abnormalities and alterations in glutamate levels have been reported in patients with schizophrenia. We hypothesized that alterations in white matter integrity and glutamate levels in individuals at clinical high risk (CHR) for psychosis are associated with the subsequent development of psychosis. Methods Participants included 33 antipsychotic naive CHR (Female 7/Male 26, Age 19.55 (4.14) years) and 38 healthy controls (Female 10/Male 28, Age 20.92 (3.37) years). Whole brain diffusion tensor imaging for fractional anisotropy (FA) and right frontal white matter proton magnetic resonance spectroscopy for glutamate levels were acquired. CHR participants were clinically followed for 2 years to determine conversion to psychosis. Results CHR participants that transitioned to psychosis (N = 7, 21%) were characterized by significantly lower FA values in the posterior thalamic radiation compared to those who did not transition and healthy controls. In the CHR group that transitioned to psychosis only, positive exploratory correlations between glutamate levels and FA values of the posterior thalamic radiation and the retrolenticular part of the internal capsule and a negative correlation between glutamate levels and the cingulum FA values were found. Conclusion The results of the present study highlight that alterations in white matter structure and glutamate are related with the conversion to psychosis.

Objective Inhalant users may develop toluene leukoencephalopathy, a devastating neuropsychiatric disorder. We present a case of toluene-induced damage to the corticospinal and the corticonuclear tracts, which presented with involuntary emotional expression disorder. Methods Case study of a 20-year-old man with a 3-year history of frequent solvent abuse was admitted to the Neuropsychiatry Unit of the National Institute of Neurology and Neurosurgery because “he could not speak or walk” but would keep “laughing and crying without reason”. Results Neuropsychiatric examination revealed pathological laughter and crying, facial and speech apraxia, a bilateral pyramidal syndrome, and lack of control of urinary sphincter. Magnetic resonance imaging revealed a highly selective bilateral damage to the pyramidal system and the somatosensory pathway. SPECT imaging showed left fronto-parietal hypoperfusion. Conclusions This document provides support for the understanding of involuntary emotional expression disorders as a differential diagnosis in the clinical practice of psychiatrists, as well as the functional anatomy of these conditions.

Risk calculators for prediction of conversion of Clinical High-Risk (CHR) individuals to syndromal psychosis have recently been developed and have generated considerable clinical use and research interest. Predictor variables in these calculators have been clinical rather than biological, and our goal was to incorporate a neurochemical imaging measure into this framework and assess its impact on prediction. We combined striatal glutamate 1H MRS data with the SIPS symptoms identified by the Columbia Risk Calculator as having the greatest predictive value in order to develop an imaging-based risk calculator for conversion to psychosis. We evaluated the calculator in 19 CHR individuals, 7 (36.84%) of whom converted to syndromal psychosis during the 2-year follow up. The receiver operating characteristic (ROC) curve for the logistic model including only striatal glutamate and visual perceptual abnormalities showed an AUC = 0.869 (95% CI = [0.667, 1.000]) and AUCoa = 0.823, with sensitivity of 0.714, specificity of 0.917, positive predictive value of 0.833, and negative predictive value of 0.846. These results represent modest improvements over each of the individual ROC curves based on either striatal glutamate or visual perceptual abnormalities alone. The preliminary model building and evaluation presented here in a small CHR sample suggests that the approach of incorporating predictive imaging measures into risk classification is not only feasible but offers the potential of enhancing risk assessment.

SummaryBackgroundSocial and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.AimsWe studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.MethodThis is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.ResultsA total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = −0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.ConclusionsOur results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not.

Introduction Recent studies have observed that patients with treatment-resistant schizophrenia as well as patients with schizophrenia who do not respond within a medication trial exhibit excess activity of the glutamate system. In this study we sought to replicate the within-trial glutamate abnormality and to investigate the potential for structural differences and treatment-induced changes to improve identification of medication responders and non-responders. Methods We enrolled 48 medication-naive patients in a 4-week trial of risperidone and classified them retrospectively into responders and non-responders using clinical criteria. Proton magnetic resonance spectroscopy and T1-weighted structural MRI were acquired pre- and post-treatment to quantify striatal glutamate levels and several measures of subcortical brain structure. Results Patients were classified as 29 responders and 19 non-responders. Striatal glutamate was higher in the non-responders than responders both pre- and post-treatment (F1,39 = 7.15, p = .01). Volumetric measures showed a significant group x time interaction (t = 5.163, Conclusions Combining anatomic measures with glutamate levels offers the potential to enhance classification of responders and non-responders to antipsychotic medications as well as to provide mechanistic understanding of the interplay between neuroanatomical and neurochemical changes induced by these medications. Ethical statement The study was approved by the Ethics and Scientific committees of the Instituto Nacional de Neurologia y Neurocirugia in Mexico City. All participants over 18 years fully understood and signed the informed consent; in case the patient was under 18 years, informed consent was obtained from both parents. Participants did not receive a stipend.

Background Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. Methods Twenty-eight antipsychotic-naive patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. Results At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. Conclusions The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naive patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment.

Background Social and environmental factors such as poverty or violence, modulate the risk and course of schizophrenia, but how they affect the brain in patients with psychosis remains unclear. We here studied how they are related to brain structure in schizophrenia and healthy controls in Latin America, where these factors are large and unequally distributed. Methods This is an MRI multi-center study in patients with schizophrenia and healthy controls from six Latin American cities: Buenos Aires, Medellin, Mexico City, Santiago, Sao Paulo and Porto Alegre. Total and voxel-level gray matter volumes obtained from T1-weighted MRI images and their relationship with income and homicide rates were analyzed using a general linear model. Results 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total gray matter volume in the two groups (P=0.006). Controls showed a positive correlation between total gray matter volume and income (R=0.14, P=0.02). Surprisingly, this relationship was not present in schizophrenia (R=-0.076, P=0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. Discussion Our results highlight the interplay between the environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as those from low and middle-income countries: potentially less brain vulnerability (less gray matter loss) is sufficient to become unwell in adverse (poor) environments. The development of algorithms exploring clinically-useful information from structural brain images in psychosis should include representative samples from low and middle-income countries.

Deficits of brain glutathione (GSH), the most abundant and primary antioxidant in living tissue, and associated redox imbalance are postulated to be implicated in schizophrenia. This pilot clinical study compared the levels of striatal GSH, measured in vivo with proton magnetic resonance spectroscopy (1H MRS) at 3T, in 10 drug-naive, first-episode psychosis (FEP) patients with those in 9 matched healthy control subjects. The results revealed a significant GSH deficit in FEP patients (0.92 ± 0.24 × 10-3) compared to the healthy control group (1.10 ± 0.10 × 10-3) (U = 25.00, p = 0.02), as well as a positive correlation between GSH levels and the Positive Symptoms subscale of the PANSS in the FEP group (ρ = 0.96; p

Risk calculators for prediction of conversion of Clinical High-Risk (CHR) individuals to syndromal psychosis have recently been developed and have generated considerable clinical use and research interest. Predictor variables in these calculators have been clinical rather than biological, and our goal was to incorporate a neurochemical imaging measure into this framework and assess its impact on prediction. We combined striatal glutamate (1)H MRS data with the SIPS symptoms identified by the Columbia Risk Calculator as having the greatest predictive value in order to develop an imaging-based risk calculator for conversion to psychosis. We evaluated the calculator in 19 CHR individuals, 7 (36.84%) of whom converted to syndromal psychosis during the 2-year follow up. The receiver operating characteristic (ROC) curve for the logistic model including only striatal glutamate and visual perceptual abnormalities showed an AUC=0.869 (95% CI = [0.667, 1.000]) and AUC(oa)=0.823, with sensitivity of 0.714, specificity of 0.917, positive predictive value of 0.833, and negative predictive value of 0.846. These results represent modest improvements over each of the individual ROC curves based on either striatal glutamate or visual perceptual abnormalities alone. The preliminary model building and evaluation presented here in a small CHR sample suggests that the approach of incorporating predictive imaging measures into risk classification is not only feasible but offers the potential of enhancing risk assessment.

The concept of an attenuated psychosis syndromes has focused attention on early intervention to prevent or attenuate full-blown psychosis. This work is becoming increasingly internationalized, which warrants special consideration of cultural differences in conceptualization of mental illness and international differences in healthcare practices and rights regarding research participation. However, in Mexico, there is a scarcity of resources for mental healthcare, especially for psychosis spectrum disorders, and many clinicians are not very familiar with attenuated psychosis syndromes. Moreover, current studies have not allowed for an in-depth examination of the challenges and the strategies of working with youth from the range of specific cultures. The purpose of this chapter was to critically review in Mexico the health system, stigma, cultural values, and beliefs about mental illness (psychosis in particular) and how these may make adaptations to interventions necessary while highlighting specific challenges that Mexican populations encounter. We also present the implemented methodology in a local evaluation program and describe country-specific literature. Finally, we provide a clinical vignette to illustrate these challenges and the relevance of cultural aspects in clinical practice, highlighting the challenges of identifying and treating Mexican youth at risk for psychosis and their families.

Social and environmental factors are known risk factors and modulators of mental health disorders. We here conducted a nonsystematic review of the neuroimaging literature studying the effects of poverty, urbanicity, and community violence, highlighting the opportunities of studying non-Western developing societies such as those in Latin America. Social and environmental factors in these communities are widespread and have a large magnitude, as well as an unequal distribution, providing a good opportunity for their characterization. Studying the effect of poverty in these settings could help to explore the brain effect of economic improvements, disentangle the effect of absolute and relative poverty, and characterize the modulating impact of poverty on the underlying biology of mental health disorders. Exploring urbanicity effects in highly unequal cities could help identify the specific factors that modulate this effect as well as examine a possible dose–response effect by studying megacities. Studying brain changes in those living among violence, which is particularly high in places such as Latin America, could help to characterize the interplay between brain predisposition and exposure to violence. Furthermore, exploring the brain in an adverse environment should shed light on the mechanisms underlying resilience. We finally provide examples of two methodological approaches that could contribute to this field, namely a big cohort study in the developing world and a consortium-based meta-analytic approach, and argue about the potential translational value of this research on the development of effective social policies and successful personalized medicine in disadvantaged societies. Fil: Crossley, Nicolas A.. Pontificia Universidad Católica de Chile; Chile Fil: Alliende, Luz Maria. Pontificia Universidad Católica de Chile; Chile Fil: Ossandon, Tomas. Pontificia Universidad Católica de Chile; Chile Fil: Castañeda, Carmen Paz. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile Fil: González Valderrama, Alfonso. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile. Universidad Finis Terrae.; Chile Fil: Undurraga, Juan. Universidad del Desarrollo; Chile. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile Fil: Castro, Mariana Nair. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guinjoan, Salvador Martín. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Díaz Zuluaga, Ana M.. Universidad de Antioquia; Colombia Fil: Pineda-Zapata, Julián A.. Instituto de Alta Tecnología Médica; Colombia Fil: López-Jaramillo, Carlos. Hospital Universitario San Vicente Fundación; Colombia. Universidad de Antioquia; Colombia Fil: Reyes Madrigal, Francisco. Instituto Nacional de Neurología y Neurocirugía; México Fil: León-Ortíz, Pablo. Instituto Nacional de Neurología y Neurocirugía; México Fil: de la Fuente-Sandoval, Camilo. Instituto Nacional de Neurología y Neurocirugía; México Fil: Czepielewski, Leticia Sanguinetti. Hospital de Clinicas de Porto Alegre; Brasil Fil: Gama, Clarissa S.. Hospital de Clinicas de Porto Alegre; Brasil Fil: Zugman, Andre. Universidade Federal de Sao Paulo; Brasil Fil: Gadelha, Ary. Universidade Federal de Sao Paulo; Brasil Fil: Jackowski, Andrea. Universidade Federal de Sao Paulo; Brasil Fil: Bressan, Rodrigo. Universidade Federal de Sao Paulo; Brasil

OBJECTIVEThe coronavirus disease 2019 (COVID-19) pandemic has forced the modification of surgical practice worldwide. Medical centers have been adapted to provide an efficient arrangement of their economic and human resources. Although neurosurgeons are not in the first line of management and treatment of COVID-19 patients, they take care of patients with neurological pathology and potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, the authors describe their institutional actions against the pandemic and compare these actions with those in peer-reviewed publications.METHODSThe authors conducted a search using the MEDLINE, PubMed, and Google Scholar databases from the beginning of the pandemic until July 11, 2020, using the following terms: “Neurosurgery,” “COVID-19/SARS-CoV-2,” “reconversion/modification,” “practice,” “academy,” and “teaching.” Then, they created operational guidelines tailored for their institution to maximize resource efficiency and minimize risk for the healthcare personnel.RESULTSAccording to the reviewed literature, the authors defined the following three changes that have had the greatest impact in neurosurgical practice during the COVID-19 pandemic: 1) changes in clinical practices; 2) changes in the medical care setting, including modifications of perioperative care; and 3) changes in the academic teaching methodology.CONCLUSIONSThe Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez” is one of the major referral centers for treating highly complex neurosurgical pathologies in Mexico. Its clinical and neurosurgical practices have been modified with the implementation of specific interventions against the spread of COVID-19. These practical and simple actions are remarkably relevant in the context of the pandemic and can be adopted and suited by other healthcare centers according to their available resources to better prepare for the next event.

This cohort study examines cognition in never-medicated individuals at different stages of the illness.

Background Cognitive impairment is a key feature of schizophrenia. While one recent study suggested that individuals with psychosis experience a progressive decline in certain cognitive domains during the first 10 years of their illness, other clinical and functional MRI-based studies have proposed that most cognitive deficits are present during the first episode and remain stable over time, possibly as a result of medication response. To examine the temporal nature of cognitive deficits in the schizophrenia spectrum, we examined cognition in never-medicated individuals at different stages of the illness. Methods We recruited three groups of patients: 1) individuals at clinical high-risk (CHR) for psychosis (n=87), 2) individuals experiencing their first-episode of a non-affective psychosis (FEP) (n=64) (defined by a duration of untreated psychosis < 74 weeks), and 3) individuals with chronic schizophrenia (n=40) (CSz – duration of untreated psychosis > 74 weeks). All three groups were antipsychotic-naïve. Patients with any comorbid disorders or current substance abuse disorders were excluded from this study. We also recruited matched healthy control subjects (n=102). All subjects were recruited at the Instituto Nacional de Neurología y Neurocirugía in Mexico City. The study was approved by the institutional review board. Adults provided written informed consent and minors provided assent with written consent provided by both parents. Cognition was assessed with the MATRICS Consensus Cognitive Battery. Differences between groups were analyzed using a repeated measures analysis of variance (RM-ANOVA) with cognitive domain as inter-subject factor and Bonferroni correction for post hoc pairwise comparisons. Statistical significance was set at p ≤ .05. Results Since age, gender, and parental education were significantly different between the groups, they were included as covariates in the RM-ANOVA. In this revised model, there was no main effect of age (p = 0.69) nor any interaction between age and any cognitive domain. Therefore, age was removed from the final model. We observed a significant main effect of group (p .99). We also found a significant group by cognitive domain interaction (p Within the FEP and CSz groups, no significant correlations were observed between duration of untreated psychosis and any cognitive domain. Discussion We observed significant cognitive deficits since at-risk stages of the schizophrenia spectrum. Patients with FEP were as impaired as those with CSz, while cognitive functioning observed in CHR individuals was intermediate between controls and patients with syndromal psychosis. These results emphasize the importance of pre-syndromal detection and prediction of burgeoning psychotic illness. Future research on strategies to mitigate the decline in cognitive function between presyndromal and first-episode psychosis is warranted.

Glial disturbances are highly implicated in the pathophysiology of schizophrenia and may be linked with glutamatergic dysregulation. Myo-inositol (mI), a putative marker of glial cells, and choline (Cho), representative of membrane turnover, are both present in larger concentrations within glial cells than in neurons, and their elevation is often interpreted to reflect glial activation. Proton magnetic resonance spectroscopy ((1)H-MRS) allows for the evaluation of mI, Cho, glutamate, glutamate + glutamine (Glx), and N-acetylaspartate (NAA). A collective investigation of these measures in antipsychotic-naive patients experiencing their first nonaffective episode of psychosis (FEP) can improve the understanding of glial dysfunction and its implications in the early stages of schizophrenia. 3-Tesla (1)H-MRS (echo time = 35 ms) was performed in 60 antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls. mI, Cho, glutamate, Glx, and NAA were estimated using LCModel and corrected for cerebrospinal fluid composition within the voxel. mI, Cho, and glutamate were elevated in the FEP group. After correction for multiple comparisons, mI positively correlated with grandiosity. The relationships between mI and glutamate, and Cho and glutamate, were more positive in the FEP group. These findings are suggestive of glial activation in the absence of neuronal loss and may thereby provide support for the presence of a neuroinflammatory process within the early stages of schizophrenia. Dysregulation of glial function might result in the disruption of glutamatergic neurotransmission, which may influence positive symptomatology in patients with FEP.

Background: Glutamate level in the precommissural dorsal caudate (i.e., associative striatum) is increased in antipsychotic-naive patients with first-episode psychosis (FEP). This increase normalizes after effective clinical response to first-line antipsychotic treatment. However, it is unclear if glutamate level is different between FEP resistant and responsive to first-line treatment and if glutamate could assist as a biomarker to predict treatment response.

Event related potentials (ERP) associated with early sensory information processing have been proposed as possible vulnerability markers for psychosis. Compared to other ERPs reported in schizophrenia research, like Mismatch Negativity (MMN), little is known about P3a, an ERP related to novelty detection. The aim of this study was to analyze the MMN-P3a complex in 20 antipsychotic naive first-episode psychosis patients (FEP), 23 antipsychotic naive individuals at clinical high-risk for psychosis (CHR) and 24 healthy controls. The MMN-P3a amplitudes and latencies were obtained during a passive auditory mismatch frequency deviant ERP paradigm and analyzed in frontal and central scalp regions. There were no significant differences in MMN amplitude between groups. There was a significant group difference in P3a due to reduced amplitude (F[2,64] = 3.7, p = 0.03) in both CHR and FEP groups (Mean difference (MD) = 0.39, p = 0.04 and MD = 0.49, p = 0.02, respectively) compared to the control group and this effect was most prominent on the right side (Group × laterality effect: MD = 0.57, p < 0.01 and MD = 0.58, p < 0.01, respectively). No significant differences were observed for MMN or P3a latencies between groups. Although a P3a decrement in chronic schizophrenia and FEP has been previously reported, our results suggest that this novelty detection impairment is present even in pre-psychosis stages in antipsychotic naive subjects. This study supports the evidence that P3a could represent a neurophysiological vulnerability marker for the development of psychosis.

Neuroimaging studies investigating patients with schizophrenia often report appreciable volumetric reductions and cortical thinning, yet the cause of these deficits is unknown. The association between subcortical and cortical structural alterations, and glutamatergic neurometabolites is of particular interest due to glutamate's capacity for neurotoxicity; elevated levels may be related to neuroanatomical compromise through an excitotoxic process. To this end, we explored the relationships between glutamatergic neurometabolites and structural measures in antipsychotic-naive patients experiencing their first non-affective episode of psychosis (FEP). Sixty antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls underwent a magnetic resonance imaging session, which included a T1-weighted volumetric image and proton magnetic resonance spectroscopy in the precommissural dorsal caudate. Group differences in precommissural caudate volume (PCV) and cortical thickness (CT), and the relationships between glutamatergic neurometabolites (ie, glutamate+glutamine (Glx) and glutamate) and these structural measures, were examined. PCV was decreased in the FEP group (p

Diminished pain sensitivity in schizophrenia has been reported in clinical studies. While the role of antipsychotic medications as a cause of the decrease in pain perception has been questioned, little is known about neural pain processing in treated schizophrenia patients. The aim of this pilot study was to examine the blood oxygen level–dependent (BOLD) changes induced by an experimental pain tolerance (endure) hot stimuli vs. non-painful stimuli in clinically stable patients with schizophrenia and in healthy controls. Twelve patients with schizophrenia, treated with risperidone and considered clinically stable, and 13 gender- and age-matched healthy controls were studied using painful and non-painful thermal stimuli in a periodic block design. BOLD changes were assessed using high field, 3 T functional Magnetic Resonance Imaging (fMRI). Pain tolerance in stable patients was not statistically different than healthy controls. Interestingly, patients showed higher activation in the primary somatosensory cortex (S1) and superior prefrontal cortex, and less activation in the posterior cingulate cortex and brainstem than controls. Our pilot study indicates that pain tolerance is similar in clinically stable patients and controls, although the neural processing of pain is not normalized with antipsychotic treatment.

Psychosis prevalence in Parkinson's disease is estimated at 8-30%. Proton magnetic resonance spectroscopy measures specific metabolites as markers of cell functioning.To study N-acetyl-aspartate and glutamate levels in the caudate and putamen nuclei in subjects with Parkinson's disease with and without psychosis.We included 20 non-demented Parkinson's disease patients with psychosis and 20 Parkinson's disease patients without psychosis matched for age, sex, disease duration, and levodopa equivalent daily dose, all attended at an academic medical center. Proton magnetic resonance spectroscopy scans were performed in a 3T GE whole-body scanner.Decreased glutamate levels scaled to creatine were found in the dorsal caudate (p = 0.005) and putamen (p = 0.007) of the Parkinson's disease psychosis group compared with the without psychosis group. Glutamate plus glutamine levels scaled to creatine and N-acetyl-aspartate levels scaled to creatine were also significantly reduced in the dorsal caudate of the Parkinson's disease with psychosis group (p = 0.018 and p = 0.011, respectively). No group differences were found for any of the other metabolites in the two regions of interest.Our findings suggest that decreased metabolite levels in specific brain areas may be implicated in the development of psychosis in Parkinson's disease.

Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications.To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA).Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA.DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls.Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.

Several variables have been identified as risk factors for conversion to overt psychosis in ultra-high risk for psychosis (UHR) individuals. Although almost two-thirds of them do not experience a transition to psychosis, they still exhibit functional disabilities. Other subjective developmental features may be useful for a more precise identification of individuals at UHR. Avoidant behaviors are consistently reported in schizophrenia and in UHR individuals and may be the reflection of a pattern of personality. Thus, personality features in UHR individuals deserves further research. The objective of the present study was to compare temperament and character dimensions between UHR individuals, patients with schizophrenia and healthy controls. One hundred participants (25 UHR individuals, 25 schizophrenia patients and 50 control subjects) where evaluated with the Temperament and Character Inventory-Revised (TCI-R). Univariate ANOVAs followed by Bonferroni tests were used. UHR individuals and schizophrenia patients exhibited higher levels of Harm Avoidance (HA) when compared to control subjects. For HA1 Anticipatory worry vs Uninhibited optimism and HA4 Fatigability & asthenia, UHR and schizophrenia groups showed similar scores and both groups were higher compared to control subjects. With respect to Cooperativeness (CO), UHR and schizophrenia reported lower scores than control subjects, in particular CO2 Empathy vs Social disinterest and CO3 Helpfulness vs unhelpfulness. This study replicates and extends the consideration of HA as a psychopathological related endophenotype and gives us further information of the possible role of personality features in the expression of some of the social dysfunctions observed both in prodromal subjects and schizophrenia patients.

there is evidence of a relationship between physical and cognitive activity and the development of dementia, although this hypothesis has not been tested in Mexican population.analyze the association between an increased participation in physical and cognitive activities and the probability of having dementia, using a Mexican open population sample.we made a cross sectional survey in open Mexican population of residents in urban and rural areas of 65 of age and older; we performed cognitive assessments to identify subjects with dementia, as well as questionnaires to assess the level of participation in physical and cognitive activities. We performed a binary logistic regression analysis to establish the association between participation and the probability of having dementia.we included 2003 subjects, 180 with diagnosis of dementia. Subjects with dementia were older, had less education and higher prevalence of some chronic diseases. The low participation in cognitive activities was associated with a higher probability of developing dementia. Patients with dementia had significantly lower scores on physical activity scales.this study supports the hypothesis of a relationship between low cognitive and physical activity and the presentation of dementia.

Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.

The objective was to determine the psychometric properties of the Dimensions of Psychosis Instrument (DIPI) in Mexican patients with schizophrenia spectrum disorders. One-hundred patients were recruited. Convergent and divergent validity were determined with the positive and negative scores of the Positive and Negative Syndrome Scale; a forced five-factor exploratory principal-components analysis with varimax rotation was developed. Total DIPI score shows an adequate convergent validity. The rotated principal component matrix accounted for 82.1% of the variance. Our study gives further support of the adequacy of the DIPI for the assessment of the five most common subjective experiences related to psychosis.

The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy (1H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first- episode psychosis patients (FEP), and (3) 40 age- and sex- matched healthy controls. All subjects underwent a 1H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia., peer-reviewed

To compare glutamate levels (Glu) found in the dorsal-caudate nucleus (a dopamine rich region) and in the cerebellum (a low dopamine region) among: 1) schizophrenia patients undergoing an acute psychotic episode, 2) after receiving antidopaminergic treatment (Risperidone), and 3) healthy controls.Fourteen drug-free patients with schizophrenia and fourteen healthy controls were included. Patients underwent two proton magnetic resonance spectroscopy (1H-MRS) studies, one prior to treatment and the second after 6-weeks of daily Risperidone treatment. Controls underwent one 1H-MRS study. Glutamate levels were normalized according to the relative concentration of Creatine (Cr).The dorsal-caudate nucleus among schizophrenia patients showed higher levels of Glu/Cr during the drug-free condition (t = -2.16, p = 0.03) and after antipsychotic treatment (t = 2.12, p = 0.04) compared with controls. No difference was observed in the cerebellum between the drug-free, post-treatment and controls conditions.Our results suggest that the Glu increase observed in the dorsal-caudate in schizophrenia is illness-mediated and does not change after 6-weeks of antipsychotic treatment. Moreover, the lack of change detected in the cerebellum suggests that the Glu increase in schizophrenia is not ubiquitous within the brain and that may be associated with dopamine target regions.

Background: Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of γ-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis. Methods: Twenty-three antipsychotic naive subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of γ-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal. Results: Higher levels of γ-aminobutyric acid ( P

Importance Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. Objectives To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. Design, Setting, and Participants Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. Interventions Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. Main Outcomes and Measures Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. Results Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. Conclusions and Relevance Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.

Glutamatergic dysfunction is implicated in the pathoaetiology of schizophrenia, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls, using the log coefficient of variation ratio (CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data using Hartigan’s unimodality dip test. MEDLINE and EMBASE databases were searched from inception to October 2021 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia patients compared to controls. 116 studies reporting on 7,844 patients and 7,305 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p