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Background Hoasca (also called ayahuasca ) is a N , N -dimethyltryptamine (DMT) – containing psychedelic brew originally used for magico-religious purposes by Amerindian populations of the Amazon Basin. Recently, Brazilian syncretic churches have helped spread the ritual use of hoasca to Western societies. The aim of this study was to evaluate substance use, and neuropsychological and psychological functioning of regular hoasca users within a religious setting. Methods Assessment of socio-economic status, mood, personality traits, impulsiveness, drug use, quality of life, extrinsic and intrinsic religiosity, and neuropsychological function was performed on 30 volunteers from a U.S. branch of Uniao do Vegetal (UDV), a Brazilian religion which uses hoasca ritually. We also assessed 27 non-hoasca-using control subjects matched by socio-demographic profile and church attendance. Mann–Whitney U , chi-squared and Fisher tests were used to analyze differences between groups. Spearman's association and simple logistic regression tests were used to analyze the impact of frequency of hoasca use on dependent variables. Results Relative to the control group, the UDV group demonstrated lower scores for depression ( p = 0.043, r = .27) and confusion ( p = 0.032, r = .29) as assessed by the Profile of Mood States (POMS); higher scores on the instrument Big Five Inventory (BFI) for the personality traits agreeableness ( p = 0.028, r = .29) and openness ( p = 0.037, r = .28); higher scores on the quality life domain role limitations due to physical health as determined by the instrument Medical Outcomes Study Short Form-36 – SF-36 ( p = 0.035, r = .28); less recent use of alcohol ( p φ c = .57), greater past use of alcohol to intoxication ( p = 0.007, φ c = .36) and past use of cannabis ( p = 0.001, φ c = .45) as measured by the Addiction Severity Index (ASI), 5th edition; better score on a measure of memory vulnerability to proactive interference as measured by the California Verbal Learning Test – CVLT ( p = 0.040, r = .27). Lifetime use of hoasca was positively correlated with role limitations due to physical health ( p = 0.032, r s = .39) and negatively associated with lifetime heavy alcohol use ( p = 0.034, OR = 0.979). Conclusions The findings indicate that religious use of hoasca does not adversely affect neuropsychological functioning and may have positive effects on substance abuse and mood.

Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH.

We explore how hallucinations might be studied within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which asks investigators to step back from diagnoses based on symptoms and focus on basic dimensions of functioning. We start with a description of the objectives of the RDoC project and its domains and constructs. Because the RDoC initiative asks investigators to study phenomena across the wellness spectrum and different diagnoses, we address whether hallucinations experienced in nonclinical populations are the same as those experienced by people with psychotic diagnoses, and whether hallucinations studied in one clinical group can inform our understanding of the same phenomenon in another. We then discuss the phenomenology of hallucinations and how different RDoC domains might be relevant to their study. We end with a discussion of various challenges and potential next steps to advance the application of the RDoC approach to this area of research.

Recent neuropsychological studies have distinguished deficits in verbal working memory, verbal memory, and confrontation naming from other neuropsychological domains as specifically related to the severity of auditory verbal hallucinations (AVH) in schizophrenia (Gisselgard et al., 2014; Siddi et al., 2017). To extend this research, it was hypothesized that AVH severity would be related only to measures within the language domain and the test battery was augmented with the [CTOPP2 and COWAT…define?] to more comprehensively define the language processing functions most predictive of AVH. A neuropsychological test battery was administered to a group of adult patients diagnosed with schizophrenia and schizoaffective disorder (N = 30), who continued to experience AVH despite clinical treatment. Multiple regression analyses demonstrated that poorer performance on measures of verbal working memory and verbal immediate memory significantly predicted greater AVH severity. Going beyond the prior studies, it was also shown that greater impairment of semantic fluency and lesser impairment in delayed general memory were also significant predictors of AVH. Intellectual ability and executive functioning, considered as covariates, were not significant predictors and their inclusion in regression analyses did not affect the pattern of results. Lastly, when cognitive predictors were accounted for, a trend toward an effect of medication (assessed as olanzapine equivalents) emerged such that higher dose predicted less severe AVH. Taken together, better performance on measures of linguistic processes associated with verbal working memory, semantic fluency and verbal learning predicts less severe AVH, perhaps most consistent with limited capacity language processing models. The finding that better delayed memory predicted more severe AVH is consistent with AVH memory models suggesting that AVH are dependent upon information recalled from memory storage.

Posttraumatic stress (PTSD) and alcohol use (AUD) disorders are associated with abnormal anterior cingulate cortex/ventromedial prefrontal cortex, thalamus, and amygdala function, yet microstructural white matter (WM) differences in executive-limbic tracts are likely also involved. Investigating WM in limbic-thalamo-cortical tracts, this study hypothesized (1) fractional anisotropy (FA) in dorsal cingulum, parahippocampal cingulum, and anterior corona radiata (ACR) would be lower in individuals with comorbid PTSD/AUD compared to in individuals with AUD-only and (2) that FA would be related to both AUD and PTSD severity. 22 combat veterans with comorbid PTSD/AUD or AUD-only completed DTI scans. ANCOVAs indicated lower FA in right (F(df= 1,19)=9.091, P=0.0071) and left (F(df= 1,19) = 10.375, P=0.0045) dorsal cingulum and right ACR (F(df= 1,19) = 18.914, P= 0.0003) for individuals with comorbid PTSD/AUD vs. individuals with AUD-only, even controlling for alcohol use. Multiple linear regressions revealed that FA in the right ACR was inversely related to PTSD severity (r= −0.683, P=0.004). FA was not significantly related to alcohol severity. Reduced WM integrity in limbic-thalamo-cortical tracts is implicated in PTSD, even in the presence of comorbid AUD. These findings suggest that diminished WM integrity in tracts important for top-down control may be an important anomaly in PTSD and/or comorbid PTSD/AUD.

Chronic, heavy alcohol consumption may affect the concentration of neurometabolites assessed with proton magnetic resonance spectroscopy (1H-MRS). We investigated the largest sample reported to date (N = 213) with the primary goal of determining how specific clinical features impact neurometabolite concentrations in an anterior cingulate gray matter voxel. This community dwelling sample included both treatment seeking and non-treatment seeking individuals. A healthy control group (N = 66) was matched for age and education. In multivariate analyses predicting neurometabolite concentrations, the heavy drinking group had greater concentrations overall. An age by group interaction was noted, as group difference across neurometabolites increased with age. More years drinking, but not more drinks per drinking day (DPDD) predicted greater concentrations of choline-containing compounds (Cho), creatine-phosphocreatine (Cre), glutamate-glutamine (Glx), and n-acetyl-aspartate (NAA). The effects of other clinical variables (depression, cigarette smoking, marijuana use) were negligible. After controlling for DPDD and years drinking, treatment-seeking status had no impact on neurometabolites. In the very oldest portion of the sample (mean age = 50), however, a negative relationship was seen between NAA and years drinking. These results suggest that the nature of neurometabolite abnormalities in chronic heavy drinkers may vary as a function of duration of abuse.

Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH). However, very little is known about how activated brain regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate onset and offset of AVH during fMRI scanning. When a general linear model was used to compare blood oxygenation level dependence signals during periods in which subjects indicated that they were versus were not experiencing AVH ("AVH-on" versus "AVH-off"), it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule, and extranuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICAs). Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated to the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial prefrontal), not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures.

Atrophy of brain white matter (WM) often is considered a signature injury of alcohol use disorders (AUDs). However, investigations into AUD-related changes in WM volume have yielded complex findings that are difficult to synthesize in a narrative review. The objective of this study was to obtain an averaged effect size (ES) for WM volume reduction associated with AUD diagnosis and to test potential moderators of ES. Study inclusion criteria were: (1) English language; (2) peer reviewed; (3) published before December 2011; (4) use of magnetic resonance imaging (MRI); (5) human participants; (6) inclusion of AUD group; (7) inclusion of non-AUD comparison group; and (8) reporting or testing of total or cerebral WM volume. Moderators included study design, MRI methodology and AUD characteristics. Nineteen studies with a total of 1302 participants (70% male) were included, and calculated ESs were confirmed by the corresponding author for 12 studies. The magnitude of the averaged ES adjusted for small sample bias (Hedges' g) for WM reduction in AUDs was 0.304 (standard error = 0.134, range = -0.57-1.21). Hierarchical linear modeling indicated that the overall ES differed significantly from 0, t(18) = 2.257, P = 0.037, and that the distribution of the 19 ESs showed significant heterogeneity beyond sampling error, χ(2) (18) = 52.400, P Language: en

Auditory sensory gating deficits have been reported in subjects with post-traumatic stress disorder (PTSD), but the hemispheric and neuronal origins of this deficit are not well understood. The objectives of this study were to: (1) investigate auditory sensory gating of the 50-ms response (M50) in patients diagnosed with PTSD by utilizing magnetoencephalography (MEG); (2) explore the relationship between M50 sensory gating and cortical thickness of the superior temporal gyrus (STG) measured with structural magnetic resonance imaging (MRI); and (3) examine the association between PTSD symptomatology and bilateral sensory gating. Seven participants with combat-related PTSD and eleven controls underwent the paired-click sensory gating paradigm. MEG localized M50 neuronal generators to the STG in both groups. The PTSD group displayed impaired M50 gating in the right hemisphere. Thinner right STG cortical thickness was associated with worse right sensory gating in the PTSD group. The right S1 M50 source strength and gating ratio were correlated with PTSD symptomatology. These findings suggest that the structural integrity of right hemisphere STG cortices play an important role in auditory sensory gating deficits in PTSD.

Background: Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. Methods: Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day (DPDD), percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. Results: More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. Conclusions: In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to visuospatial ability. Language: en

Abnormal 50- and 100-msec event-related brain activity derived from paired-click procedures are well established in schizophrenia. There is little agreement on whether group differences in the ratio score, i.e., the ratio of EEG amplitude after the second stimulus (S2) to the amplitude after the first stimulus (S1), reflect an encoding or gating abnormality. In addition, the functional implications remain unclear. In the present study, EEG and magnetoencephalography (MEG) were used to examine paired-click measures and cognitive correlates of paired-click activity.EEG and whole-cortex MEG data were acquired during the standard paired-click paradigm in 73 comparison subjects and 79 schizophrenia patients. Paired-click ratio scores were obtained at 50 msec (P50 evoked potential at Cz, M50 at left and right superior temporal gyrus [STG]) and 100 msec (N100 at Cz, M100 at left and right STG). A cognitive battery assessing attention, working memory, and long-delay memory was administered. IQ was also estimated.Groups differed on ratio score and amplitude of S1 response. Ratio scores at 50 msec and 100 msec and S1 amplitude predicted variance in attention (primarily S1 amplitude), working memory, and long-delay memory. The attention findings remained after removal of variance associated with IQ.Associations between paired-click measures and cognitive performance in patients support 50-msec and 100-msec ratio and amplitude scores as clinically significant biomarkers of schizophrenia. In general, cognitive performance was better predicted by the ability to encode auditory information than the ability to filter redundant information.

While the reliability of assessment instruments designed for use with adults is well established, much less is known about the adequacy of these instruments for adolescent substance abusers. As part of a comprehensive intake evaluation, the Inventory of Drug Use Consequences (InDUC) was administered both to forty adolescents assigned to a probationary substance abuse treatment program and to one of their parents. The correlation was statistically significant between Parent and Adolescent InDUC score(s), but the interrater reliability was relatively low. IQ scores and level of substance use were considered as moderator variables, but neither showed a significant effect. History of head injury, however, significantly moderated this relationship; those adolescents reporting no history of head injury showed little correspondence with Parent InDUC Score(s), whereas those adolescents with a history of head injury showed significant correlations with parent InDUC scores. This suggests that a history of head injury may affect the way in which adolescents perceive substance-related consequences.

The etiologic factors underlying schizophrenia have been conceptualized as reflecting two largely genetic components — those unique to schizophrenia and those representing vulnerability to neurodevelopmental deviation in general. The Developmental Instability (DI) approach suggests that the latter can be indexed by minor physical anomalies (MPAs), which assess early prenatal growth abnormalities, and fluctuating anatomic asymmetries (FA), which reflects later deviations. Individuals with schizophrenia ( N = 19) had elevated scores on both measures as compared to healthy controls ( N = 23). Further, MPAs and FA were very highly correlated in the sample of individuals with schizophrenia but not in controls. In order to identify neuroanatomic variation linked with the unique factor, we conducted gray matter Voxel Based Morphometry analyses of group membership, with and without treating a composite measure of DI (based on FA, and MPAs) as a covariate. When DI was treated as a covariate, many more gray matter regions were found to statistically differ as a function of diagnosis. These results support the DI approach and suggest that the unique etiologic factors associated with schizophrenia lead to widespread gray matter volume reductions.

Although many studies have compared the brains of normal controls and individuals with autism, especially older, higher-functioning individuals with autism, little is known of the neural correlates of the vast clinical heterogeneity characteristic of the disorder. In this study, we used voxel-based morphometry (VBM) to examine gray matter correlates of variation in communication skill and symptom severity within a heterogeneous group of 33 children with autism ranging in age from 3.4 to 11.4 years. Greater gray matter (GM) volume was associated with better communication skills in numerous frontal regions, especially in the left middle frontal gyrus. Further, greater GM volume in the right inferior frontal gyrus was associated with reduced severity of symptoms of autism. However, increased total GM volume was correlated with more severe symptoms of autism at a trend level, consistent with other studies, suggesting that while increased total GM volume is generally predictive of greater autistic severity, specific local increases in GM volume result in a reduction in symptoms. Our results suggest that communication and symptom severity have distinct neuroanatomic correlates and draw attention to the importance of studying the neuroanatomy of clinical heterogeneity within the autistic population.

Recent evidence suggests that changes in brain structure associated with alcohol abuse are compounded in individuals dually diagnosed with alcohol abuse and schizophrenia. To investigate the separate, and possibly interacting, effects of these diagnoses, an event-related brain potential (ERP) measure of auditory information processing (P50 sensory gating paradigm) and neuropsychological measures were administered to healthy control participants with either (1a) no history of alcohol abuse/dependence, or (1b) a remote history of alcohol abuse/dependence, and patients with schizophrenia with either (2a) no history of alcohol abuse/dependence, or (2b) a remote history of alcohol abuse/dependence. Schizophrenia was associated with impaired P50 sensory gating and poorer performance across neuropsychological scores compared to measurements in healthy control participants. Those with a positive alcohol history had impaired gating ratios in contrast to those with a negative alcohol history. There were additive effects of schizophrenia diagnosis and alcohol history for P50 sensory gating and for neuropsychological scores: attention, working memory, and behavioral inhibition. For executive attention and general memory there was an interaction, suggesting that the combination of schizophrenia and history of alcohol abuse results in greater impairment than that predicted by the presence of either diagnosis alone. (JINS, 2006, 12, 34–44.)

Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms.

Sensory gating assessed via EEG in a paired-click paradigm has often served as a neurophysiological metric of attentional function in schizophrenia. However, the standard EEG measure of sensory gating using the P50 component at electrode Cz does not foster differential assessment of left and right hemisphere contributions. Magnetoencephalography (MEG) is complementary to EEG, and its analogous M50 component may be better suited for localization and analysis of such lateralized cortical generators. The authors hypothesized that 1) auditory gating would be evident in M50 sources in superior temporal gyrus, demonstrating ratios similar to P50; 2) M50 would resemble P50 in distinguishing gating in comparison subjects and patients with schizophrenia, but M50 would show lateralization of the gating deficit; and 3) P50 and M50 sensory gating ratios would predict neuropsychological measures in patients and comparison subjects, with the MEG identification of left and right hemisphere sources allowing for the evaluation of lateralization in brain-behavior relationships.Event-related EEG and MEG recordings were simultaneously obtained from 20 patients with schizophrenia and 15 comparison subjects. P50 amplitudes, M50 dipole source strengths, and P50 and M50 gating ratios were compared and assessed with respect to scores on neuropsychological performance measures.M50 dipoles localizing to superior temporal gyrus demonstrated gating similar to that of P50. As expected, patients demonstrated less P50 gating than did comparison subjects. Left (but not right) hemisphere M50 gating 1) correlated with EEG gating, 2) differentiated patients and comparison subjects, and 3) correlated with neuropsychological measures of sustained attention and working memory.Converging evidence from EEG, MEG, and neuropsychological measures points to left hemisphere dysfunction as strongly related to the well-established sensory gating deficit in schizophrenia.

The purpose of this study was to explore the relationship between combat-related posttraumatic stress disorder (PTSD) and specific augmentation versus reduction patterns for the N100 and P200 components of auditory event-related potentials evoked by tones of increasing intensity.Event-related potentials of subjects with PTSD (N=36), subjects with no psychopathology (N=20), subjects with major depression but no PTSD (N=10), and subjects with a history of chronic alcohol abuse but no PTSD (N=8) were recorded. Brain responses were evoked by a 2000-Hz tone presented in intensity blocks of 65, 72.5, 80, 87.5, and 95 dB (SPL).Evoked data from five PTSD subjects were of poor quality and excluded from further analyses. For all but one subject with no psychopathology and for all subjects with a history of alcohol abuse or major depression (but no PTSD), the Cz amplitude of the P200 response component showed augmentation as a nearly linear function of tone intensity. As a group, subjects with PTSD showed no such increase in P200 response magnitude. Examination of the data from individual subjects with PTSD showed that 42% exhibited augmentation patterns similar to those seen for subjects in the comparison groups. However, 58% showed evidence of P200 reduction, with the response to the loudest tone being smaller than responses to tones of intermediate intensity.The data suggest that there is a significant subgroup of patients with combat-related PTSD who enter into a state of protective inhibition at relatively low stimulus intensities. It is hypothesized that this is an appropriate adaptive mechanism for these subjects rather than an indication of a core neurobiological abnormality.

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case-control investigation, we used independent component analysis (ICA) to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of five days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex. In a sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode and two other networks: the dorsal medial prefrontal cortex and left dorsal lateral prefrontal cortex. Relative to demographically healthy subjects (n = 12), the FNC between the posterior default mode areas and the dorsal medial prefrontal cortex normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the posterior default mode and left dorsal lateral prefrontal cortex networks following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between posterior default mode areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode.

As acute ethanol exposure inhibits N-methyl-D-aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu-Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy ((1)H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the (1)H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the (1)H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu-Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu-Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.

Individuals with alcohol use disorders show white matter abnormality relative to normal samples, yet differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least one year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared to HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness, whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use.

Previous studies of schizophrenia have suggested a linkage between neuropsychological (NP) deficits and hippocampus abnormality. The relationship between hippocampus volume and NP functioning was investigated in 24 patients with chronic schizophrenia and 24 matched healthy controls. Overall intracranial, white and gray matter, and anterior (AH) and posterior (PH) hippocampus volumes were assessed from magnetic resonance images (MRI). NP domains of IQ, attention, and executive function were also evaluated with respect to volumetric measures. It was hypothesized that AH and PH volumes and episodic memory scores would be positively associated in controls and that the schizophrenia group would depart from this normative pattern. NP functioning was impaired overall and AH volume was smaller in the schizophrenia group. In the controls, the hippocampus–memory relationships involved AH and PH, and correlations were significant for verbal memory measures. In the schizophrenia group, positive correlations were constrained to PH. Negative correlations emerged between AH and verbal and visual memory measures. For both groups, cortical volume negatively correlated with age, but a negative correlation between age and hippocampus volume was found only in the schizophrenia group. In this sample of adults with schizophrenia, atypical relationships between regional hippocampus volumes and episodic memory ability were found, as was an atypical negative association between hippocampus volume and age. (JINS, 2009, 15, 182–195.)

A large and growing literature has demonstrated a deficit in auditory gating in patients with schizophrenia. Although that deficit has been interpreted as a general gating problem, no deficit has been shown in other sensory modalities. Recent research in our laboratory has examined sensory gating effects in the somatosensory system showing no difference in gating of the primary somatosensory response between patients with schizophrenia and control subjects. This is consistent with recent structural studies showing no cortical structural abnormality in primary somatosensory area in schizophrenia. However, a significant decrease in cortical thickness and gray matter volume loss in secondary somatosensory cortex has recently been reported, suggesting this as a focus for impaired somatosensory gating. Thus, the current study was designed (1) to replicate previous work showing a lack of schizophrenia deficit in primary somatosensory cortex (SI) gating, and (2) to investigate a possible deficit in secondary somatosensory cortex (SII) gating. In a paired-pulse paradigm, dipolar sources were assessed in SI and SII contralateral to unilateral median nerve stimulation. Patients demonstrated no impairment in SI gating, but a robust gating deficit in SII, supporting the presence of cross modal gating deficits in schizophrenia.

Traditional neuropsychological tests of visual and verbal memory have been used to evaluate memory deficits in schizophrenia. However, these tests cannot be used in non-human animal research, which is important for the discovery of treatments that will improve cognition and for study of the etiology of schizophrenia. To help bridge the gap between human and non-human animal research on hippocampal function in schizophrenia, this study sought to characterize the behavioral performance exhibited by patients using the Morris water task (MWT). The MWT has been shown in human and non-human animal studies to be hippocampus-dependent. In the virtual MWT, human subjects navigate a computer-generated on-screen environment to escape from the “water” by locating a platform. Patients with schizophrenia and controls performed two versions of the virtual MWT: a hippocampal-dependent hidden-platform version, relying on allocentric navigational abilities, and a non-hippocampal-dependent visible-platform version, relying on cued-navigational abilities. Patients traveled further and took longer to find the hidden platform over training blocks and spent less time in the correct quadrant during a probe trial. There was no deficit in the visible-platform condition. These findings identify a behavioral impairment on a hippocampal-dependent task in schizophrenia and support using the MWT in testing animal models of schizophrenia.

The importance of genes in the etiology of schizophrenia is well known, but the manner in which the relevant genomic factors influence neural development and the nature of selection forces operating on these factors are poorly understood. In several prominent papers, Crow has provided a unique and comprehensive theory that attempts to deal with these issues. A central aspect of his theory is that a single gene leads to reduced cerebral lateralization, increased ventricular size, and risk for developing schizophrenia. He relies greatly on Annett's right shift theory of individual variation in handedness. An alternative approach, based on the construct of developmental instability, provides a different way to conceptualize genetic influences, selection forces, and atypical lateralization in schizophrenia. We suggest that the developmental instability model has stronger empirical support and is better grounded in contemporary evolutionary genetics.

Introduction: Previous investigations have assessed global cognitive scores or a single cognitive domain in the context of electroconvulsive therapy (ECT) in the elderly, but the specific cognitive domains that affected by electroconvulsive therapy are poorly understood. The present investigation used neuropsychological assessment to delineate the specific cognitive domains that are affected by treatment with ECT in late-life major depressive disorder (MDD). We hypothesized that ECT response would result in improvement in specific domains of cognitive functioning. Methods: Thirteen subjects (5 males and 8 females, average age 67.15 (+/8.93) years) with MDD met the following inclusion criteria: 1) DSM-IV TR diagnosis ofMDD; 2) the clinical indications for ECT including treatment resistance and a need for a rapid and definitive response; and 3) a Hamilton Depression Rating Scale-24 item (HDRS 24) > 21. The pre-ECT assessment was administered less than two days before the ECT series, and the post-ECT assessment was administered greater than five days after completing the ECT series. A Thymatron System IV delivered a right unilateral (n 1⁄4 11) or bitemporal ECT (n 1⁄4 2) stimulus delivery with a constant-current, brief pulse (0.50milliseconds (ms)). Seizure threshold obtained during the first sessionwith a dose titrationmethod guided subsequent stimulus dosage (6 threshold for right unilateral, 2 threshold for bitemporal). Treatments occurred thrice weekly until adequate clinical response or clinical decision to stop treatment in the context of non-response (11.17 +/3.33 sessions in the series). Depression was assessed with the Hamilton Depression Rating Scale 24-item (HDRS-24). The neuropsychological assessment included and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Randolf, 1998) and the Trails Making Test, Parts A and B (Trails A, B; Reitan, 1958). The RBANS measures several cognitive domains including immediatememory, visuospatial/construction, language, delayedmemory, and a total cognitive score. Trails A measures attention and processing speed, and Trails Bmeasures executive functioning.We used paired t-tests to test the hypothesis that longitudinal improvement in specific cognitive domains would occur with ECT response. Results: Subjects had a reduction in symptom severity as measured by the HDRS-24 (t121⁄4 8.52, p 0.05). Furthermore, subtracting the Trails B raw data (seconds) from Trails A did not show any change pre-/post-ECT. Pairwise correlations between changes in the pre-/post HDRS-24 and RBANS IM and the four learning trials of the RBANS verbal declarative memory task were not significant (p > 0.05). Conclusions: Subjects with MDD whose mood symptoms were reduced with ECT had a non-significant improvement in RBANS immediate memory. The pattern of larger differences in the first learning trial relative to the latter trials suggests an improvement in attention with ECT response. As depression episodes resolved, subjects did not experience global or specific cognitive impairments. We attribute this pattern of results to the following factors: 1) the reduction in depression symptomatology and 2) the time period between completion of the ECT series and the post-ECT neuropsychological assessment (> 5 days). The delay in the post-ECT assessment minimized the immediate effect of the seizure from sustained cognitive changes. Future work will include a larger sample size and a mixture of ECT responders and non-responders to test the hypothesis that resolution of a depressed episode is associated with cognitive improvement in the context of ECT response.

Background: Impairment in auditory sensory gating (ASG) has been documented in alcohol dependence [1]. Likewise, it has been shown that ASG becomes abnormal during alcohol administration in otherwise healthy individuals [2]. Patterns of gating abnormality associated with alcohol use are likely associated with an alcohol responsive neurochemical like glutamate (Glu), particularly since it is well-established that alcohol affects NMDA receptors and that glutamatergic functioning is abnormal in both acute alcohol use and in alcohol dependence [3]. Hence, a link between Glu metabolite levels and ASG was hypothesized. It was first hypothesized that Glu and ASG abnormality would be found in groups with alcohol dependence. A second hypothesis was that across groups, greater Glu would predict reduced ASG. Methods: Groups were comprised of healthy, non-drinking controls (Controls, N = 4), individuals with current alcohol dependence (AUD-current, N = 6), and with alcohol dependence in remission for at least 1 year (AUD-remission, N = 6). Participants underwent a diagnostic assessment for alcohol consumption, MRI, 1H-MRS for in vivo assessment of Glu and other metabolites, and MEG scanning during a paired click protocol. ASG was computed as the ratio of the source strength of the 50 ms component in the event related field (ERF) to the second click in the pair divided by the source strength of the 50 ms component to the first click in the pair. Results: Univariate MANOVAs controlling for age and gender revealed a significant effect for group on Glu and ASG, such that ASG ratios were significantly elevated, implying weakened gating. Glu concentration was reduced in AUD-current relative to the other two groups. Further analysis revealed that when additionally controlling for the group effect, reduced Glu predicted increasing impairment in ASG. Conclusions: The overall results were consistent with the hypothesis that differences in Glu metabolite levels associated with alcohol dependence result in impaired ASG.