Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, 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 (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = -0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

Systemic inflammation and cortical neurochemistry in never-medicated first episode-psychosis individuals.

Studies of cellular and cytokine profiles have contributed to the inflammation hypothesis of schizophrenia; however, precise markers of inflammatory dysfunction remain elusive. A number of proton magnetic resonance spectroscopy (1H-MRS) studies in patients with first-episode psychosis (FEP) have shown higher brain levels of metabolites such as glutamate, myo-inositol (mI) and choline-containing compounds (tCho), suggesting neuroinflammation. Here, we present peripheral inflammatory profiles in antipsychotic-naive FEP patients and age-and-sex matched healthy controls, as well as cortical glutamate, mI and tCho levels using 1H-MRS. Inflammatory profiles were analyzed using cytokine production by peripheral blood mononuclear cells, that were either spontaneous or stimulated, in 48 FEP patients and 23 controls. 1H-MRS of the medial prefrontal cortex was obtained in 29 FEP patients and 18 controls. Finally, 16 FEP patients were rescanned after 4 weeks of treatment (open-label) with Risperidone. FEP patients showed a higher proportion of proinflammatory Th1/Th17 subset, and an increased spontaneous production of Interleukin (IL)-6, IL-2 and IL-4 compared with the control group. Results obtained from 1H-MRS showed no significant difference in either glutamate, mI or tCho between FEP and control groups. At baseline, CD8% showed a negative correlation with glutamate in FEP patients; after 4 weeks of risperidone treatment, the FEP group exhibited a decrease in glutamate levels which positively correlated with CD4 + T cells. Nevertheless, these correlations did not survive correction for multiple comparisons. FEP patients show evidence of immune dysregulation, affecting both the innate and adaptive immune response, with a predominantly Th2 signature. These findings, along with the changes produced by antipsychotic treatment, could be associated with both systemic and central inflammatory processes in schizophrenia.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

BACKGROUND: Social 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. AIMS: We 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. METHOD: This 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. RESULTS: A 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. CONCLUSIONS: Our 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.

Reconversion of neurosurgical practice in times of the SARS-CoV-2 pandemic: a narrative review of the literature and guideline implementation in a Mexican neurosurgical referral center.

OBJECTIVE: The 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. METHODS: The 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. RESULTS: According 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. CONCLUSIONS: The 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.

Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy.

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 naïve 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<.001) and Glx (P=.007) were found in the dorsal caudate of the subjects at ultra-high risk than in the healthy controls. In the medial prefrontal cortex, likewise, both γ-aminobutyric acid (P=.03) and Glx (P=.006) levels were higher in the ultra-high risk group than in the healthy controls. No group differences were found for any of the other metabolites (N-acetylaspartate, total choline, or total creatine) in the 2 regions of interest. CONCLUSIONS: This study presents the first evidence of abnormal elevations, in subjects at ultra-high risk, of γ-aminobutyric acid and Glx in 2 brain regions that have been implicated in the pathophysiology of psychosis, warranting longitudinal studies to assess whether these neurotransmitter abnormalities can serve as noninvasive biomarkers of conversion risk to psychosis as well as of illness progression and treatment response.

Proton Magnetic Resonance Spectroscopy Changes in Parkinson's Disease With and Without Psychosis.

BACKGROUND: Psychosis prevalence in Parkinson's disease is estimated at 8-30%. Proton magnetic resonance spectroscopy measures specific metabolites as markers of cell functioning. OBJECTIVE: To study N-acetyl-aspartate and glutamate levels in the caudate and putamen nuclei in subjects with Parkinson's disease with and without psychosis. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest that decreased metabolite levels in specific brain areas may be implicated in the development of psychosis in Parkinson's disease.

Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study.

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.

[Lifestyle and probabilty of dementia in the elderly]. / Estilo de vida en adultos mayores y su asociación con demencia.

INTRODUCTION: 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. OBJECTIVE: analyze the association between an increased participation in physical and cognitive activities and the probability of having dementia, using a Mexican open population sample. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: this study supports the hypothesis of a relationship between low cognitive and physical activity and the presentation of dementia.

Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis.

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.

Involuntary Emotional Expression Disorder in a Patient With Toluene Leukoencephalopathy.

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.

White matter alterations and the conversion to psychosis: A combined diffusion tensor imaging and glutamate 1H MRS study.

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 naïve 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.

Striatal glutamate, subcortical structure and clinical response to first-line treatment in first-episode psychosis patients.

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-naïve 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, <1%FDR), and group x time x glutamate interaction (t = 4.23, <15%FDR) were seen in several brain regions. Striatal volumes increased at trend level with treatment in both groups, and a positive association of striatal volumes with glutamate levels was seen in the non-responders. 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 Neurología y Neurocirugía 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.

Involuntary Emotional Expression Disorder in a Patient With Toluene Leukoencephalopathy.

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.

An imaging-based risk calculator for prediction of conversion to psychosis in clinical high-risk individuals using glutamate 1H MRS.

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.

[Glutamate increase in the associative striatum in schizophrenia: a longitudinal magnetic resonance spectroscopy preliminary study]. / Incremento del glutamato en el estriado de asociación en esquizofrenia. Resultados preliminares de un estudio longitudinal con espectroscopia con resonancia magnética.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Striatal Glutathione in First-episode Psychosis Patients Measured In Vivo with Proton Magnetic Resonance Spectroscopy.

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-naïve, 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 <0.001). These preliminary findings suggest a possible role of striatal oxidative stress in early-stage psychosis that warrants further scrutiny and confirmation in larger studies.

Imaging Social and Environmental Factors as Modulators of Brain Dysfunction: Time to Focus on Developing Non-Western Societies.

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.

Prefrontal γ-Aminobutyric Acid Levels in Never-Medicated Individuals With Chronic Schizophrenia.

This cross-sectional study analyzes spectroscopy data for long-term, never-medicated patients with schizophrenia to examine their levels of γ-aminobutyric acid (GABA) compared with those of healthy controls.

Prefrontal and Striatal Gamma-Aminobutyric Acid Levels and the Effect of Antipsychotic Treatment in First-Episode Psychosis Patients.

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-naïve 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-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment.