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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.

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.

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.

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.