Minah Kim

Auditory P300 as a predictor of short-term prognosis in subjects at clinical high risk for psychosis

BACKGROUND The aim of this study was to investigate whether P300 could predict the short-term prognosis of subjects at clinical high risk (CHR) for psychosis who do not convert to psychotic disorder (non-converters). METHOD CHR subjects were examined with auditory P300 at baseline, and their clinical state was regularly assessed up to 2 years. 45 CHR non-converters were divided into remitter and non-remitter groups. Repeated-measures analysis of variance (ANOVA) was performed to compare baseline P300 between the two groups. Multiple regression analysis was used to identify factors predicting symptomatic or functional improvement in CHR subjects during the follow-up period. RESULTS There were no group differences in P300 amplitude or latency between CHR remitters and non-remitters. In the multiple regression analysis, P300 amplitude at Pz (β=0.206, 95% confidence interval [95CI]=0.035 to 0.567, p=0.028) significantly predicted later amelioration of the Scale of Prodromal Symptoms (SOPS) negative symptoms. Improvement in SOPS general symptoms was significantly predicted by P300 amplitude at Pz (β=0.255, 95CI=0.065 to 0.455, p=0.010) and mood stabilizer use (β=0.199, 95CI=0.081 to 4.154, p=0.042). CONCLUSIONS These results indicate that P300 may be a possible predictor of improvement in negative and general symptoms in CHR non-converters. Our findings support the recommendation that a broader concept of assessment guidelines is needed to forecast clinical outcome and provide appropriate interventions for CHR non-converters.

Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive-compulsive disorder: Perspectives from impulsivity and compulsivity

Although internet gaming disorder (IGD) and obsessive-compulsive disorder (OCD) represent opposite ends of the impulsivity and compulsivity dimensions, the two disorders share common neurocognitive deficits in response inhibition. However, the similarities and differences in neurophysiological features of altered response inhibition between IGD and OCD have not been investigated sufficiently. In total, 27 patients with IGD, 24 patients with OCD, and 26 healthy control (HC) subjects participated in a Go/NoGo task with electroencephalographic recordings. N2-P3 complexes elicited during Go and NoGo condition were analyzed separately and compared among conditions and groups. NoGo-N2 latency at the central electrode site was delayed in IGD group versus the HC group and correlated positively with the severity of internet game addiction and impulsivity. NoGo-N2 amplitude at the frontal electrode site was smaller in OCD patients than in IGD patients. These findings suggest that prolonged NoGo-N2 latency may serve as a marker of trait impulsivity in IGD and reduced NoGo-N2 amplitude may be a differential neurophysiological feature between OCD from IGD with regard to compulsivity. We report the first differential neurophysiological correlate of the altered response inhibition in IGD and OCD, which may be a candidate biomarker for impulsivity and compulsivity.

Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis

OBJECTIVE Although disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis. METHODS MMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups. RESULTS Schizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups. CONCLUSIONS Impairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis. SIGNIFICANCE These findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia.

Predicting Remission in Subjects at Clinical High Risk for Psychosis Using Mismatch Negativity

Background The declining transition rate to psychotic disorder and the increasing rate of nonpsychotic poor outcomes among subjects at clinical high risk (CHR) for psychosis have increased the need for biomarkers to predict remission regardless of transition. This study investigated whether mismatch negativity (MMN) predicts the prognosis of CHR individuals during a 6-year follow-up period. Methods A total of 47 healthy control (HC) subjects and 48 subjects at CHR for psychosis participated in the MMN assessment. The clinical statuses of the CHR subjects were examined at baseline and regularly for up to 6 years. The CHR subjects were divided into remitter and nonremitter groups, and the baseline MMN amplitudes and latencies were compared across the remitter, nonremitter, and HC groups. Regression analyses were performed to identify the predictive factors of remission, the improvement of attenuated positive symptoms, and functional recovery. Results CHR nonremitters showed reduced MMN amplitudes at baseline compared to CHR remitters and HC subjects. A logistic regression analysis revealed that the baseline MMN amplitude at the frontal electrode site was the only significant predictor of remission. In a multiple regression analysis, the MMN amplitude, antipsychotic use, and years of education predicted an improvement in attenuated positive symptoms. The MMN amplitude at baseline predicted functional recovery. Conclusions These results suggest that MMN is a putative predictor of prognosis regardless of the transition to psychotic disorder in subjects at CHR. Early prognosis prediction and the provision of appropriate interventions based on the initial CHR status might be aided using MMN.

Early referral and comorbidity as possible causes of the declining transition rate in subjects at clinical high risk for psychosis.

A clinical high risk (CHR) for psychosis is regarded as the state of being at risk of developing psychosis. However, the rate of transition to psychosis among CHR subjects has been declining over time. We aimed to investigate the effects of the possible causes of the declining transition rate.

Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders

Abstract Recent evidence has suggested that psychosis could develop not only in people at clinical high risk for psychosis (CHR-P) but also in those with clinical risk syndromes for emergent nonpsychotic mental disorders. The proportion of people with these clinical risk syndromes who will develop psychosis rather than to other nonpsychotic mental disorders is undetermined. Electronic databases were searched for studies reporting on clinical risk syndromes for the development of emergent nonpsychotic mental disorders. Incidence of emerging psychotic and nonpsychotic mental disorders defined on the ICD or DSM. Of a total of 9 studies relating to 3006 nonpsychotic at-risk individuals were included. Within prospective studies (n = 4, sample = 1051), the pooled incidence of new psychotic disorders across these clinical risk syndromes was of 12.9 per 1000 person-years (95% CI: 4.3 to 38.6) and that of nonpsychotic disorders (n = 3, sample = 538) was of 43.5 per 1000 person-years (95% CI: 30.9 to 61.3). Psychotic disorders may emerge outside the CHR-P paradigm, from clinical risk syndromes for incident nonpsychotic disorders, albeit at lower rates than in the CHR-P group. The clinical risk syndromes for emerging nonpsychotic disorders may exhibit a pluripotential risk of developing several types of mental disorders compared with CHR-P. If substantiated by future research, the current findings suggest that it may be useful to move beyond the current strategy of identifying individuals meeting CHR-P criteria only.

Genetic variation in cytokine genes and risk for transition to psychosis among individuals at ultra-high risk

Cytokines play important neurodevelopmental roles in the brain and the levels at which they are expressed are, in part, dependent on an individuals genetic background (Kronfol and Remick, 2000). A number of genetic studies have demonstrated associations between common variation in genes encoding inflammatory cytokines and schizophrenia in ethnically diverse populations (Butler et al., 2016). However, analogous genetic studies have not been conducted within an ultra-high risk (UHR) for psychosis population. Herein, we report on our investigation of the effect genetic and haplotype variationwithin six inflammatory cytokine genes have on transition to psychosis in a prospective cohort of 134 Korean UHR individuals (An et al., 2010; Kim et al., 2011; Lee et al., 2014). Participants underwent a clinical assessment at baseline and every six months after baseline for up to 7.7 years, as previously described (Lee et al., 2014). Transition to psychosis was defined as at least one fully positive psychotic symptom several times a week for over one week as measured by the SIPS (Miller et al., 2002). Written informed consent was obtained from all participants and the Institutional Review Board of Seoul National University Hospital and Yonsei University Severance Hospital approved the study. Twenty-three single nucleotide polymorphisms (SNPs) spanning six cytokine genes (IL-1A, IL-1B, IL-1RN, IL-2, IL-18, TNFA) were genotyped (Supplementary Table S1). Logistic regression analysis was used to estimate the odds ratios and corresponding 95% confidence intervals for each SNP and haplotype on transition to psychosis. For significant SNPs and haplotypes, transition prediction accuracy, sensitivity, and specificity were calculated based on the 2 × 2 tables of allelic/haplotype counts by transition status as previously described (Baratloo et al., 2015). Post-hoc power analyses were conducted using the Genetic Power Calculator (Purcell et al., 2003) with type I error rate = 0.05 and type II error rate = 0.80. Fifteen percent (n=20) of participants in this study transitioned to psychosis. The mean number of days to transition was 528 (s.d. = 389; median = 447, range = 11–1356) and the mean age of those who transitioned was 21.6 (s.d. = 4.6, median = 20.4, range = 16.3–36.0). Those who transitioned did not differ demographically or clinically from thosewhodid not transition at baseline (Supplementary Table S2). Three SNPs (rs1143633, rs16944, rs12621220) and one haplotype (rs16944|rs4848306|rs12621220) within the interleukin-1 beta (IL1B) gene were associated with psychosis transition after correction for covariates andmultiple testing (Table 1). Transition prediction accuracy for the three SNPs ranged from 61% (95% CI = 53%–74%; sensitivity = 55%; specificity = 61%) for rs1143633 to 65% (95% CI = 53%–75%; sensitivity = 68%; specificity = 62%) for rs12621220. The IL-1B SNPs rs16944 and rs12621220, in part, formed a three-marker haplotype, whereas the rs1143633 had membership in a two-marker haplotype

Is There an Association Between Mismatch Negativity and Cortical Thickness in Schizophrenia Patients

Introduction. Mismatch negativity (MMN) is thought to reflect preattentive, automatic auditory processing. Reduced MMN amplitude is among the most robust findings in schizophrenia research. MMN generators have been shown to be located in the temporal and frontal cortices, which are key areas in the pathophysiology of schizophrenia. This study investigated whether frontotemporal cortical thickness was associated with reduced MMN current source density (CSD) strength in patients with schizophrenia. Methods. Sixteen schizophrenia patients and 18 healthy controls (HCs) were examined using magnetoencephalography while they performed a passive auditory oddball paradigm. All participants underwent a T1 structural magnetic resonance imaging scan in a separate session. We evaluated MMN CSD and cortical thickness, and their associations, in the superior and transverse temporal gyri, as well as in the inferior and middle frontal gyri. Results. Patients exhibited significantly reduced CSD strength in all temporal and frontal areas of interest relative to HCs. There was a positive correlation between CSD strength and cortical thickness in both temporal and frontal areas in HCs. However, schizophrenia patients showed negative correlations between CSD strength and cortical thickness in the bilateral inferior frontal gyri. Additionally, we found positive correlations between frontal cortical thickness and negative and total scores on the Positive and Negative Syndrome Scale (PANSS). Conclusions. Our findings provide evidence for deficient temporal and frontal MMN generators and a disruption of normal structure-function relationship in patients with schizophrenia.

Aberrant within- and between-network connectivity of the mirror neuron system network and the mentalizing network in first episode psychosis

INTRODUCTION It has been suggested that the mentalizing network and the mirror neuron system network support important social cognitive processes that are impaired in schizophrenia. However, the integrity and interaction of these two networks have not been sufficiently studied, and their effects on social cognition in schizophrenia remain unclear. METHODS Our study included 26 first-episode psychosis (FEP) patients and 26 healthy controls. We utilized resting-state functional connectivity to examine the a priori-defined mirror neuron system network and the mentalizing network and to assess the within- and between-network connectivities of the networks in FEP patients. We also assessed the correlation between resting-state functional connectivity measures and theory of mind performance. RESULTS FEP patients showed altered within-network connectivity of the mirror neuron system network, and aberrant between-network connectivity between the mirror neuron system network and the mentalizing network. The within-network connectivity of the mirror neuron system network was noticeably correlated with theory of mind task performance in FEP patients. CONCLUSION The integrity and interaction of the mirror neuron system network and the mentalizing network may be altered during the early stages of psychosis. Additionally, this study suggests that alterations in the integrity of the mirror neuron system network are highly related to deficient theory of mind in schizophrenia, and this problem would be present from the early stage of psychosis.

T180. LOWER GLUTAMATE LEVEL IN TEMPORO-PARIETAL AREA MAY PREDICT A BETTER RESPONSE TO TDCS IN SCHIZOPHRENIA: A PILOT STUDY

Abstract Background Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique which uses a weak electric current from electrodes across the scalp to modulate targeted brain areas. It has been suggested that tDCS may be useful in reducing psychotic symptoms such as auditory hallucination. The aim of this study was to find alteration of key neurotransmitters in schizophrenia in temporo-parietal area (TPA) after tDCS intervention, using magnetic resonance spectroscopy (MRS) technique. Methods Ten schizophrenia patients with auditory hallucination were recruited from the outpatient clinic of Seoul National University Hospital (SNUH). The anode was placed over the left dorsolateral prefrontal cortex (DLPFC), and the cathode was placed over the left TPA. Patients underwent MRS scan with the very short echo time phase rotation STEAM sequence before and after the tDCS sessions, respectively. Results Seven of the participants completed MRS scans before and after the tDCS sessions. Positive and Negative Symptom Scale (PANSS) total and general psychophathology scale showed a significant improvement after tDCS. There was no significant difference between glutamate/creatinine (Cr) level before and after tDCS sessions. However, a significant positive correlation between the pre-tDCS glutamate/Cr value in left TPA and the improvement in auditory hallucination measured by Auditory Hallucination Rating Scale (AHRS) after tDCS was found. Discussion The results of this investigation show that the schizophrenia patients whose auditory hallucination benefits the most from tDCS treatment had lower glutamate/Cr level in left TPA. Previous studies regarding the relationship between glutamatergic system and treatment response mostly have only focused on the frontal area and striatum. However, this study suggests a potential role of glutamatergic system in TPA in predicting treatment response of auditory hallucination.