Capacity In Schizophrenia Research Articles

Disrupted cognitive network revealed by task-induced brain entropy in schizophrenia.

Brain entropy (BEN), which measures the amount of information in brain activity, provides a novel perspective for evaluating brain function. Recent studies using resting-state functional magnetic resonance imaging (fMRI) have shown that BEN during rest can help characterize brain function alterations in schizophrenia (SCZ). However, there is a lack of research on BEN using task-evoked fMRI to explore task-dependent cognitive deficits in SCZ. In this study, we evaluate whether the reduced working memory (WM) capacity in SCZ is possibly associated with dynamic changes in task BEN during tasks with high cognitive demands. We analyzed data from 15 patients with SCZ and 15 healthy controls (HC), calculating task BEN from their N-back task fMRI scans. We then examined correlations between task BEN values, clinical symptoms, 2-back task performance, and neuropsychological test scores. Patients with SCZ exhibited significantly reduced task BEN in the cerebellum, hippocampus, parahippocampal gyrus, thalamus, and the middle and superior frontal gyrus (MFG and SFG) compared to HC. In HC, significant positive correlations were observed between task BEN and 2-back accuracy in several brain regions, including the MFG and SFG; such correlations were absent in patients with SCZ. Additionally, task BEN was negatively associated with scores for both positive and negative symptoms in areas including the parahippocampal gyrus among patients with SCZ. In conclusion, our findings indicate that a reduction in BEN within prefrontal and hippocampal regions during cognitively demanding tasks may serve as a neuroimaging marker for SCZ.

Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

Diverging effects of mentalization based treatment for patients with borderline personality disorder and schizophrenia: an explorative comparison.

There is robust evidence that both patients with schizophrenia (SCZ) and borderline personality disorder (BPD) display mentalizing difficulties. Less is known however about differences in the way mentalization based treatment (MBT) impacts mentalizing capacity in SCZ and BPD patients. This study compares the impact of MBT on mentalizing capacity in individuals with SCZ and BPD. The thematic apperception test was used to measure mentalizing capacity. It was administered at the beginning and end of treatment to 26 patients with SCZ and 28 patients with BPD who enrolled in an 18-month long MBT program. For comparison a sample of 28 SCZ patients who did not receive MBT was also included. Using the social cognition and object-relations system, these narratives were analyzed and scored. Missing data was imputed and analyzed using intention-to-treat ANCOVAs with post-treatment measures of mentalizing capacity as dependent variables, group type as independent variable and baseline mentalizing capacities as covariates. Results showed that patients with BPD showed significantly more improvement on several measures of mentalizing, including complexity of representation (ηp2 = 0.50, ppooled < 0.001), understanding of social causality (ηp2 = 0.41, ppooled < 0.001) and emotional investment in relationships (ηp2 = 0.41, ppooled < 0.001) compared to patients with SCZ who received MBT. No differences were found regarding affect-tone of relationships (ηp2 = 0.04, ppooled = 0.36). SCZ patients who received MBT showed greater performance on understanding of social causality (ηp2 = 0.12, ppooled = 0.01) compared to SCZ patients who did not receive MBT, but no differences were observed on complexity of representations, capacity for emotional investment or affect-tone of relationships. Patients with BPD performed better after receiving MBT on three dimensions of mentalizing capacity than SCZ patients who received MBT. Remarkably, SCZ patients who received MBT performed better on one dimension of mentalizing capacity compared to SCZ patients who did not receive MBT. Whereas MBT for BPD clearly involves improvement on most aspects of mentalizing, MBT for SCZ seems to thwart a further decline of other-oriented, cognitive mentalizing. Treatment goals should be adapted toward these disorder-specific characteristics.

The Impact of Poor Nonverbal Social Perception on Functional Capacity in Schizophrenia.

BackgroundNonverbal social perception is the ability to interpret the intentions and dispositions of others by evaluating cues such as facial expressions, body movements, and emotional prosody. Nonverbal social perception plays a key role in social cognition and is fundamental for successful social interactions. Patients with schizophrenia have severe impairments in nonverbal social perception leading to social isolation and withdrawal. Collectively, these aforementioned deficits affect patients’ quality of life. Here, we compare nonverbal social perception in patients with schizophrenia and controls and examine how nonverbal social perception relates to daily functioning.MethodsWe compared nonverbal social perception in 41 stable outpatients with schizophrenia and 30 healthy controls using the Mini Profile of Nonverbal Sensitivity (Mini-PONS). The participants evaluated 64 video clips showing a female actor demonstrating various nonverbal social cues. Participants were asked to choose one of two options that best described the observed scenario. We correlated clinical ratings (Positive and Negative Syndrome Scale, Brief Negative Syndrome Scale), Self-report of Negative Symptoms, and functional assessments (functional capacity and functional outcome) with Mini-PONS scores.ResultsPatients performed significantly poorer in the Mini-PONS compared to controls, suggesting deficits in nonverbal social perception. These deficits were not associated with either positive symptoms or negative symptoms (including self-report). However, impaired nonverbal social perception correlated with distinctive domains of BNSS (mainly avolition and blunted affect), as well as functional capacity and functional outcome in patients.ConclusionWe demonstrate that nonverbal social perception is impaired in stable outpatients with schizophrenia. Nonverbal social perception is directly related to specific negative symptom domains, functional capacity and functional outcome. These findings underline the importance of nonverbal social perception for patients’ everyday life and call for novel therapeutic approaches to alleviate nonverbal social perception deficits.

Lack of neural load modulation explains attention and working memory deficits in first-episode schizophrenia

ObjectiveAlthough working memory (WM) deficits are well-recognized core features of schizophrenia, the underlying pathophysiological substrates of impairment in early psychosis before medication remain unclear. One possibility is that deficits in selective attention contribute to WM impairment. MethodsEEG was acquired from 25 first-episode drug-naive schizophrenia patients and 26 matched controls while they performed a WM task. ResultsCompared with controls, schizophrenia patients showed a deficit in WM capacity in both behavioral and electrophysiological measures. Notably, the increased parieto-occipital pre-encoding stimulus alpha power in patients with schizophrenia predicted their subsequent reduced N2pc and symptom severity, whereas this relationship was absent in controls. Moreover, lacking load effect in neural activities predicted the serious impairment in behavior for schizophrenia. ConclusionsThis pilot study provides preliminary evidence that the lack of load effect in neural activities may serve as potential underlying mechanisms for the impaired selective attention and WM capacity in schizophrenia. Our results emphasize the importance of pre-encoding stimulus alpha power in first-episode drug-naive schizophrenia. SignificanceThese findings provide a neurophysiological correlate for the subjective reports of working memory deficits in schizophrenia and indicate the potential effective targets for clinical intervention.

Posterior Parietal Cortex Dysfunction is Central to Working Memory Storage and Broad Cognitive Deficits in Schizophrenia

Working memory (WM) deficiencies in patients with schizophrenia (PSZ) are thought to be caused by PFC dysfunction, but few research have looked at non-manipulated measures of WM storage. Storage capacity is more closely tied to the posterior parietal cortex (PPC) than the frontal cortex (PFC) in neurotypical people, suggesting that impairments in WM storage capacity in schizophrenia that are associated with widespread cognitive deficits may be related to neuronal activity in the PPC. While receiving fMRI, 37 PSZ and 37 matched healthy control volunteers of both sexes conducted a change detection test with varied set sizes. The assignment was created to emphasis WM storage while requiring minimal top-down management. BOLD activity correlated with the number of items kept in WM (K), as determined by task performance at a particular set size, according to whole-brain analyses. Independent of set size, K values predicted BOLD activity in the PPC, including the superior and inferior parietal lobules, intraparietal sulcus, and middle occipital gyrus, across groups. In the left PPC, whole-brain interaction analysis revealed that PSZ had much less K-dependent signal modulation than healthy control participants, a finding that could not be explained by a smaller K value range. The slope between K and PPC activation accounted for 43.4 percent of the variations in broad cognitive performance across groups. These findings suggest that PPC dysfunction is linked to WM storage abnormalities in PSZ and may play a role in schizophrenia's widespread cognitive deficiencies.

Cognitive function mediates the relationship between visual contrast sensitivity and functional outcome in schizophrenia

BackgroundIndividuals with schizophrenia exhibit deficits in visual contrast processing, though less is known about how these deficits impact neurocognition and functional outcomes. This study investigated effects of contrast sensitivity (CS) on cognition and capacity for independent living in schizophrenia. Methods: Participants were 58 patients with schizophrenia (n = 49) and schizoaffective disorder (n = 9). Patients completed a psychophysical paradigm to obtain CS with stimuli consisting of grating patterns of low (0.5 and 1 cycles/degree) and high spatial frequencies (4, 7, 21 cycles/degree). Patients completed the MATRICS Consensus Cognitive Battery and Wechsler Adult Intelligence Scales, Third Edition to assess cognition, and the problem-solving factor of the Independent Living Scales to assess functional capacity. We computed bivariate correlation coefficients for all pairs of variables and tested mediation models with CS to low (CS–LSF) and high spatial frequencies (CS–HSF) as predictors, cognitive measures as mediators, and capacity for independent living as an outcome. Results: Cognition mediated the relationship between CS and independent living with CS–LSF a stronger predictor than CS–HSF. Mediation effects were strongest for perceptual organization and memory-related domains. In an expanded moderated mediation model, CS–HSF was found to be a significant predictor of independent living through perceptual organization as a mediator and CS–LSF as a moderator of this relationship. Conclusion: CS relates to functional capacity in schizophrenia through neurocognition. These relationships may inform novel visual remediation interventions.

Factor structure of cognitive performance and functional capacity in schizophrenia: Evidence for differences across functional capacity measures

BackgroundCognition and functional capacity predict functional outcomes in mental illness. Traditional approaches conceptualize cognition as comprised of domains, but many studies support a unifactorial structure. Some functional capacity measures may share a single-factor structure with cognition. In this study, we examined the factor structure of two measures of functional capacity, a conventional assessment and a newer computerized assessment, testing for a shared factor structure with cognition. MethodsPatients with schizophrenia and healthy controls were examined with the MATRICS Consensus Cognitive Battery (MCCB), the UCSD Performance Based Skills Assessment (UPSA), and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT). Models of the factor structures of the MCCB, UPSA, and VRFCAT were calculated, as were correlations between MCCB scores and individual VRFCAT objectives. ResultsThe MCCB, VRFCAT, and UPSA all had unifactorial structures. The best fitting model of the correlations between MCCB and UPSA was a shared single factor, while the best fit for the relationship between MCCB and VRFCAT had two factors. Correlations between the MCCB domain and composite scores and the VRFCAT objectives suggested global rather than specific patterns of correlation. DiscussionThe relationship between cognitive performance and functional capacity was found to vary across functional capacity assessments. The UPSA and MCCB were not differentiated into separate factors, suggesting that the UPSA may overlap with neurocognitive performance. However, the VRFCAT appears to measure functional abilities that are separable from, yet correlated with, neurocognitive performance. It may provide a more distinctive assessment of the functional capacity construct.

M106. VIRTUAL-REALITY COGNITIVE TRAINING AND ASSESSMENT IN SCHIZOPHRENIA

BackgroundIt is widely accepted that neurocognitive performance is linked to functional outcomes in schizophrenia (Green, Kern, Braff, & Mintz, 2000). Research, however, shows that this relationship is likely to be mediated by other factors such as social competence (Brekke, Kay, Lee, & Green, 2005). Indeed, performance on cognitive tasks only explain 20% of the variance in work related skills (Bowie et al., 2008). Furthermore, the composite score generated by the gold standard neurocognitive measure, the MATRICS Consensus Cognitive Battery (MCCB), fails to predict work or education related functioning and independent living (August, Kiwanuka, McMahon, & Gold, 2012). To address these limitations, we developed a novel and ecologically valid virtual reality (VR) task with the aim to simultaneously measure cognition and functional capacity in schizophrenia. The assessment is set in a minimarket environment where participants are required to buy selected items from a shopping list. In this study, our objective was to establish the construct validity of the VR task in relation to the MCCB, and test whether it can predict functional outcomes. In addition, we tested whether app-based cognitive training can improve cognition and/or functional outcomes at follow-up as an exploratory objective.MethodsThirty patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited from South London. At baseline, participants completed the VR task and MCCB, the Positive and Negative Syndrome Scale (PANSS), and various functional capacity/outcome measures including the Global Assessment of Functioning (GAF), Social and Occupational Functioning Assessment Scale (SOFAS), UCSD Performance-Based Skills Assessment-Brief (UPSA-B), and World Health Organization Disability Assessment Schedule II (WHODAS-II). A subset of participants was randomly allocated to receive a 4-week long, app-based training; either playing with an immersive or a 2D spatial memory training game. Those who completed the training were invited back for a follow-up visit. Construct validity of the VR task will be assessed through a series of bivariate correlations. The predictive ability of the VR task for functional outcomes will be tested through linear regression models. Finally, the efficacy of spatial memory training will be assessed using repeated measures ANOVA.ResultsData analysis is currently ongoing, and results will be presented at the conference.DiscussionThis study will provide the first indication whether VR can be employed to test cognition and functional capacity simultaneously in patients with schizophrenia. Given the current lack of reliable and ecologically valid functional outcome measures, new assessments that are sensitive to clinically meaningful cognitive improvements are desperately needed.

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment.

Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly to the pathophysiology of schizophrenia. In this paper we assess research that has implicated both systems in the aetiology of this disorder. Weexamine evidence from post-mortem, preclinical, pharmacological and in vivo neuroimaging studies. Pharmacological and preclinical studies implicate both systems, and in vivo imaging of the dopamine system has consistently identified elevated striatal dopamine synthesis and release capacity in schizophrenia. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. Converging evidence indicates that genetic and environmental risk factors for schizophrenia underlie disruption of glutamatergic and dopaminergic function. However, while genetic influences may directly underlie glutamatergic dysfunction, few genetic risk variants directly implicate the dopamine system, indicating that aberrant dopamine signalling is likely to be predominantly due to other factors. We discuss the neural circuits through which the two systems interact, and how their disruption may cause psychotic symptoms. We also discuss mechanisms through which existing treatments operate, and how recent research has highlighted opportunities for the development of novel pharmacological therapies. Finally, we consider outstanding questions for the field, including what remains unknown regarding the nature of glutamate and dopamine function in schizophrenia, and what needs to be achieved to make progress in developing new treatments.

Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study.

Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine. Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans. No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups. The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.

Posterior Parietal Cortex Dysfunction Is Central to Working Memory Storage and Broad Cognitive Deficits in Schizophrenia.

PFC dysfunction is widely believed to underlie working memory (WM) deficits in people with schizophrenia (PSZ), but few studies have focused on measures of WM storage devoid of manipulation. Research in neurotypical individuals has shown that storage capacity is more closely related to posterior parietal cortex (PPC) than PFC, suggesting that reductions in WM storage capacity in schizophrenia that are associated with broad cognitive deficits may be related to neural activity in PPC. In the present human neuroimaging study, 37 PSZ and 37 matched healthy control subjects of either sex completed a change detection task with varying set sizes while undergoing fMRI. The task was designed to emphasize WM storage with minimal top-down control demands. Whole-brain analysis identified areas in which BOLD activity covaried with the number of items maintained in WM (K), as derived from task performance at a given set size. Across groups, K values independent of set size predicted BOLD activity in PPC, including superior and inferior parietal lobules and intraparietal sulcus, and middle occipital gyrus. Whole-brain interaction analysis found significantly less K-dependent signal modulation in PSZ than healthy control subjects in left PPC, a phenomenon that could not be explained by a narrower K value range. The slope between K and PPC activation statistically accounted for 43.4% of the between-group differences in broad cognitive function. These results indicate that PPC dysfunction is central to WM storage deficits in PSZ and may play a key role in the broad cognitive deficits associated with schizophrenia.SIGNIFICANCE STATEMENT People with schizophrenia exhibit cognitive deficits across a wide range of tasks. Explaining these impairments in terms of a small number of core deficits with clearly defined neural correlates would advance the understanding of the disorder and promote treatment development. We show that a substantial portion of broad cognitive deficits in schizophrenia can be explained by a failure to flexibly modulate posterior parietal cortex activity as a function of the amount of information currently stored in working memory. Working memory deficits have long been considered central to schizophrenia-related cognitive deficits, but the focus has been on paradigms involving some form of top-down control rather than pure storage of information, which may have unduly narrowed the focus on prefrontal dysfunction.

The impact of cognitive training on spontaneous gamma oscillations in schizophrenia.

Schizophrenia patients exhibit less gamma-frequency EEG/MEG activity (>30 Hz), a finding interpreted as evidence of poor temporal neural organization and functional network communication. Research has shown that neuroplasticity-oriented training can improve task-related oscillatory dynamics, indicating some reorganization capacity in schizophrenia. Demonstrating a generalization of such task training effects to spontaneous oscillations at rest would not only enrich understanding of this neuroplastic potential but inform the interpretation of spontaneous gamma oscillations in the service of normal cognitive function. In the present study, neuromagnetic resting-state oscillatory brain activity and cognitive performance were assessed before and after training in 61 schizophrenia patients, who were randomly assigned to 4 weeks of neuroplasticity-oriented targeted cognitive training or treatment as usual (TAU). Gamma power of 40-90 Hz increased after training, but not after TAU, in a frontoparietal network. Across two types of training, this increase was related to improved cognitive test performance. These results indicate that abnormal oscillatory dynamics in schizophrenia patients manifested in spontaneous gamma activity can be changed with neuroplasticity-oriented training parallel to cognitive performance.

O3.5. TESTING THE DOPAMINE HYPOTHESIS OF PSYCHOSIS USING POSITRON EMISSION TOMOGRAPHIC IMAGING IN FIRST EPISODE BIPOLAR AFFECTIVE DISORDER AND SCHIZOPHRENIA

BackgroundThe dopamine hypothesis of psychosis suggests that dopamine abnormalities are present in psychotic illness, irrespective of diagnostic class. Meta-analyses of Positron Emission Tomography (PET) studies of the dopamine system have shown elevated dopamine synthesis capacity in schizophrenia, though there is a dearth of studies examining this in other psychotic disorders.We therefore sought to answer the question of whether abnormalities of the presynaptic dopamine system are seen in bipolar psychosis, how this compared to schizophrenia, and whether positive psychotic symptoms were associated with dopamine synthesis capacity, irrespective of diagnostic class.MethodsCross-sectional, case-control 18F-DOPA Positron Emission Tomography (PET) study in people with first episode bipolar psychosis, schizophrenia and control subjects. Clinical measures included the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale and Global Assessment of Functioning (GAF).ResultsMean (SD) ages were 23.6 (3.6) years in 22 people with bipolar psychosis (13 male), 26.3 (4.4) years in 16 people with schizophrenia (14 male), and 24.5 (4.5) years in controls (14 male). There was a significant group difference in striatal dopamine synthesis capacity (Kicer) (F2,57=6.80, P=.002), post-hoc tests indicating Kicer was significantly elevated in both the bipolar group (mean [SD], 13.18 [1.08]×10–3 min-1; P=.002) and the schizophrenia group (mean [SD], 12.94 [0.79]×10–3 min-1; P=.04) compared with controls (mean [SD], 12.16 [0.92]×10–3 min-1). Kicer was positively correlated with positive psychotic symptom severity in the combined bipolar and schizophrenia sample currently experiencing psychosis, explaining 27% of the variance in symptom severity (n=32, r=0.52, P=.003).DiscussionThis is the first study to examine the presynaptic dopamine system in bipolar psychosis, finding an elevation compared to controls, equivalent to schizophrenia, from first onset of illness. A relationship was found between dopamine synthesis capacity and positive psychotic symptoms, across diagnostic classes, indicating a transdiagnostic role for dopamine synthesis capacity and positive psychotic symptoms.

Parameter-Based Evaluation of Attentional Impairments in Schizophrenia and Their Modulation by Prefrontal Transcranial Direct Current Stimulation.

Attentional dysfunctions constitute core cognitive symptoms in schizophrenia, but the precise underlying neurocognitive mechanisms remain to be elucidated. In this randomized, double-blind, sham-controlled study, we applied, for the first time, a theoretically grounded modeling approach based on Bundesen's Theory of Visual Attention (TVA) to (i) identify specific visual attentional parameters affected in schizophrenia and (ii) assess, as a proof of concept, the potential of single-dose anodal transcranial direct current stimulation (tDCS; 20 min, 2 mA) to the left dorsolateral prefrontal cortex to modulate these attentional parameters. To that end, attentional parameters were measured before (baseline), immediately after, and 24 h after the tDCS intervention in 20 schizophrenia patients and 20 healthy controls. At baseline, analyses revealed significantly reduced visual processing speed and visual short-term memory storage capacity in schizophrenia. A significant stimulation condition × time point interaction in the schizophrenia patient group indicated improved processing speed at the follow-up session only in the sham condition (a practice effect), whereas performance remained stable across the three time points in patients receiving verum stimulation. In healthy controls, anodal tDCS did not result in a significant change in attentional performance. With regard to question (i) above, these findings are indicative of a processing speed and short-term memory deficit as primary sources of attentional deficits in schizophrenia. With regard to question (ii), the efficacy of single-dose anodal tDCS for improving (speed aspects of visual) cognition, it appears that prefrontal tDCS (at the settings used in the present study), rather than ameliorating the processing speed deficit in schizophrenia, actually may interfere with practice-dependent improvements in the rate of visual information uptake. Such potentially unexpected effects of tDCS ought to be taken into consideration when discussing its applicability in psychiatric populations. The study was registered at http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00011665.

Effect of Transcranial Direct Current Stimulation on Functional Capacity in Schizophrenia: A Study Protocol for a Randomized Controlled Trial.

UMIN000028224; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000032305.

Presynaptic Dopamine Synthesis Capacity in Schizophrenia and Striatal Blood Flow Change During Antipsychotic Treatment and Medication-Free Conditions.

Standard-of-care biological treatment of schizophrenia remains dependent upon antipsychotic medications, which demonstrate D2 receptor affinity and elicit variable, partial clinical responses via neural mechanisms that are not entirely understood. In the striatum, where D2 receptors are abundant, antipsychotic medications may affect neural function in studies of animals, healthy volunteers, and patients, yet the relevance of this to pharmacotherapeutic actions remains unresolved. In this same brain region, some individuals with schizophrenia may demonstrate phenotypes consistent with exaggerated dopaminergic signaling, including alterations in dopamine synthesis capacity; however, the hypothesis that dopamine system characteristics underlie variance in medication-induced regional blood flow changes has not been directly tested. We therefore studied a cohort of 30 individuals with schizophrenia using longitudinal, multi-session [15O]-water and [18F]-FDOPA positron emission tomography to determine striatal blood flow during active atypical antipsychotic medication treatment and after at least 3 weeks of placebo treatment, along with presynaptic dopamine synthesis capacity (ie, DOPA decarboxylase activity). Regional striatal blood flow was significantly higher during active treatment than during the placebo condition. Furthermore, medication-related increases in ventral striatal blood flow were associated with more robust amelioration of excited factor symptoms during active medication and with higher dopamine synthesis capacity. These data indicate that atypical medications enact measureable physiological alterations in limbic striatal circuitry that vary as a function of dopaminergic tone and may have relevance to aspects of therapeutic responses.

176.3 Elevated Brain Lactate and Glutamine/glutamate in Schizophrenia: A 7T MRS Study

Background: Mitochondrial and bioenergetic alterations may play a role in the pathophysiology of schizophrenia, either directly or via alterations in underlying neurotransmitter systems. Postmortem, preclinical, cerebrospinal fluid, and 31P-magnetic resonance spectroscopy (MRS) studies provide some support. A recent 31P magnetization transfer MRS study found reduced creatine kinase reaction rate and pH in schizophrenia, consistent with dysfunctional glucose metabolism and the accumulation of lactate. This study tested the hypothesis that abnormal glycolysis leads to elevated lactate concentrations in subjects with schizophrenia. The high sensitivity of 7T MRS was used to measure brain lactate levels in vivo. The glutamatergic metabolites were also examined with the prediction that glutamine to glutamate (Gln/Glu) ratio would be higher in schizophrenia. Methods: Thirty-one controls and 29 participants with schizophrenia completed the study. MRS scanning was conducted on a Philips “Achieva” 7T scanner, and spectra were acquired from a voxel in the anterior cingulate cortex using STEAM (TE/TM/TR=14/33/3000 ms, 128 NEX, and 16 NEX water). Patients were assessed for psychiatric symptom severity, and all participants completed the MATRICS Consensus Cognitive Battery (MCCB) for general cognitive function and UCSD Performance-Based Skills Assessment (UPSA) for functional capacity. The relationship between lactate, psychiatric symptom severity, MCCB, and UPSA were examined. Results: Lactate was significantly higher in patients compared to controls (P = .045). Higher lactate was associated with lower general cognitive function (r = −.36, P = .01) and functional capacity (r = −.43, P = .001). The glutamine to glutamate ratio (Gln/Glu) was higher in patients compared to controls (P = .021). Similar to lactate, higher Gln/Glu was significantly related to lower general cognitive function (r = −.4, P = .004) and functional capacity (r = −.45, P = .001). Conclusion: This is the first study to report elevated in vivo anterior cingulate lactate levels in schizophrenia. Anterior cingulate Gln–Glu ratio was also higher in schizophrenia, which is consistent with previous reports. The results support the hypothesis that brain bioenergetics are altered in schizophrenia reflecting inefficient or diminished aerobic metabolism and a shift towards anaerobic metabolism. Elevated lactate may prove to be a useful biomarker of cognitive and functional capacity in schizophrenia. Interventions to promote more efficient mitochondrial energy metabolism may prove useful for enhancing cognition and alleviating functional impairments in schizophrenia.

61.2 The Functional Significance of Metacognitive Capacity in Schizophrenia: Associations With Negative Symptoms and Insight

61.2 The Functional Significance of Metacognitive Capacity in Schizophrenia: Associations With Negative Symptoms and Insight

The MacArthur Competence Assessment Tools for assessing decision-making capacity in schizophrenia: A meta-analysis

ObjectiveThis meta-analysis aimed to examine the decisional capacity measured by the MacArthur Competence Assessment Tools (MacCAT) in schizophrenia. MethodEnglish (PubMed, PsycINFO, Embase, Cochrane Library databases and the Cochrane Controlled Trials Register) and Chinese (Wan Fang Database and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from 1995 until August 1, 2016. Weighted and standardized mean differences were calculated. The random effects model was used in all cases. ResultsAltogether 10 studies were identified, with 7 studies using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and 3 studies using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). The meta-analysis showed that there was significant impairment in decision-making capacity in schizophrenia patients compared to the healthy control group in terms of Understanding (SMD=−0.81, 95% CI: −1.06 to −0.56, P<0.001), Reasoning (SMD=−0.57, 95% CI: −0.80 to −0.34, P<0.001), Appreciation (SMD=−0.87, 95% CI: −1.20 to −0.53, P<0.001), and Expression a choice (SMD=−0.24, 95% CI: −0.43 to −0.05, P=0.01). ConclusionCompared to the control group, schizophrenia patients are more likely to have impaired decision-making capacity in clinical research and treatment as measured by the MacCAT instruments. Researchers and clinicians need to consider the impaired decisional capacity in schizophrenia patients providing informed consent.