Minji Bang

Neurocognitive impairments in individuals at ultra-high risk for psychosis: Who will really convert?

Objective: Impairments in neurocognitive function are considered as core features of schizophrenia. Individuals at ultra-high risk (UHR) for psychosis, the ‘putative’ prodrome of schizophrenia, generally show levels of impairments intermediate between schizophrenia patients and healthy controls. We investigated the neurocognitive performance of individuals at UHR for psychosis, comparing them with patients with first-episode schizophrenia (FES) and healthy controls (HC), and explored the predictivity of baseline neurocognitive function in the UHR group for transition to overt psychosis. Method: Individuals at UHR for psychosis (n = 60), patients with FES (n = 39), and HC subjects (n = 94) participated in the present study. All participants performed a comprehensive neurocognitive battery, consisting of tests for five separate neurocognitive domains (executive function, attention/working memory, processing speed, verbal memory, and spatial memory). UHR subjects were assessed for transition every month during 24 months of follow-up. Results: Neurocognitive performance in the UHR group was largely at intermediate levels. Attention/working memory and verbal memory were significantly different from both the FES and HC groups. In the UHR group, processing speed was decreased to the level of the FES group, while executive function and spatial memory were relatively preserved. In the Cox regression model, spatial memory significantly predicted the transition to overt psychosis in the UHR group. Conclusions: The present study showed that neurocognitive impairments were evident in UHR individuals prior to the onset of overt psychosis. Our findings generally support the neurodevelopmental model of schizophrenia and suggest that there could be different developmental trajectories between converters and non-converters.

Impaired facial emotion recognition in individuals at ultra-high risk for psychosis and with first-episode schizophrenia, and their associations with neurocognitive deficits and self-reported schizotypy.

OBJECTIVE This study aims to quantify facial emotion recognition abnormalities and their relation to neurocognitive dysfunction and schizotypy in individuals at ultra-high risk (UHR) for psychosis and patients with first-episode schizophrenia (FES). METHODS Forty individuals at UHR for psychosis, 24 patients with FES and 46 normal controls performed a facial emotion recognition task that presented facial photographs encompassing all basic emotions. The perceptual aberration scale and revised social anhedonia scale were employed for self-reported assessment of schizotypy. An intellectual functioning (IQ) test and a broad battery of neurocognitive tests were conducted. Emotional task performance indexed by accuracy rate of specific emotion was compared among three groups. The correlation of accuracy rate with neurocognitive tests and schizotypy scales were analyzed within each clinical group. RESULTS A recognition deficit of facial emotions was present in both clinical groups, even after adjusting for IQ and gender as covariates. This emotional deficit showed few significant relationships with broad range of individual neurocognitive measures. Meanwhile, this deficit demonstrated significant relationships with schizotypy, especially perceptual aberration in each clinical group. CONCLUSIONS Facial emotion recognition deficit may not only be present in FES patients, but may already have evolved prior to the onset of overt psychotic symptoms. This emotion recognition deficit may be linked to a perceptual aberration and largely independent of broad range of neurocognitive dysfunction.

Suicidal ideation in individuals at ultra-high risk for psychosis and its association with suspiciousness independent of depression

Psychotic experiences, including delusions and hallucinations, and their attenuated forms have been recently suggested as a significant but under‐recognized marker of suicide risk. However, the relationship between attenuated positive symptoms and suicide has not yet been clearly demonstrated in individuals at ultra‐high risk (UHR) for psychosis. Here, we investigated the effect of attenuated positive symptoms on suicidal ideation in UHR individuals.

Coping Styles in Individuals at Ultra-High Risk for Psychosis: Associations with Cognitive Appraisals

Maladaptive coping may play an important role in the manifestation of symptoms, functioning, and overt psychosis onset in individuals at ultra-high risk (UHR) for psychosis. To determine the factors associated with coping strategies, the relationships between cognitive appraisals and coping styles were investigated in UHR individuals. Sixty-five UHR individuals and 83 healthy controls were assessed for coping styles and cognitive appraisals of attribution bias as a primary appraisal and self-efficacy and perceived social support as a secondary appraisal. UHR participants relied more on a passive, tension-reduction coping style and less on an active, problem-focused coping style. These maladaptive coping styles in UHR individuals were significantly associated with their cognitive appraisals of stress. Aberrant attribution style of hostility perception and composite blaming bias were associated with problem-focused coping and tension-reduction, respectively. Perceived social support was related to problem-focused coping, seeking social support, and wishful thinking. General self-efficacy was associated with problem-focused coping. Our findings suggest that cognitive appraisals themselves may be the major determinants of coping styles in UHR individuals. The identified attribution styles, perceived social support, and self-efficacy may provide some clues regarding specialized interventions for the buildup of adaptive coping strategies in UHR individuals.

Fragile Self and Malevolent Others: Biased Attribution Styles in Individuals at Ultra-High Risk for Psychosis

Objective Biased attribution styles of assigning hostile intention to innocent others and placing the blame were found in schizophrenia. Attribution styles in individuals at ultra-high risk (UHR) for psychosis, however, have been less studied especially for its association with various psychological factors. We investigated whether UHR individuals show increased hostility perception and blaming bias and explored the associations of these biased styles of attribution with the factor structure of multifaceted self-related psychological variables and neurocognitive performances. Methods Fifty-four UHR individuals and 80 healthy controls were assessed by evaluating resilience, self-perception, self-esteem, and aberrant subjective experiences of schizotypy (physical anhedonia, social anhedonia, magical ideation, and perceptual aberration), basic symptoms, and carrying out a comprehensive neurocognitive test battery. Attribution styles were assessed using the Ambiguous Intentions Hostility Questionnaire. Results UHR individuals, compared with normal controls, showed increased hostility perception and blaming bias. Factor analysis of self-related psychological variables and neurocognitive performances in the entire subject population showed a three-factor solution, which was designated as reflective self, pre-reflective self, and neurocognition. Multiple regression analysis in UHR individuals revealed that hostility perception bias was associated with reflective self and composite blame bias was associated with reflective and pre-reflective self. Conclusion This study supports the emergence of attribution biases in the putative ‘prodromal’ phase of schizophrenia. The associations of biased attribution styles with multifaceted self-related psychological constructs suggest that psychosocial interventions for biased attribution styles in UHR individuals should focus not only on reflective self but also pre-reflective self-related psychological constructs.

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

Psychotic conversion of individuals at ultra-high risk for psychosis: The potential roles of schizotypy and basic symptoms

To improve strategies for the early identification of individuals at a heightened risk for the development of psychosis, we investigated the relationships and interactions between 3 psychosis‐proneness dimensions for the development of schizophrenia spectrum psychosis: schizotypy, basic symptoms and the ultra‐high risk (UHR) criteria.

T187. ALTERED DNA METHYLATION OF THE OXYTOCIN RECEPTOR GENE IS ASSOCIATED WITH SUSCEPTIBILITY TO PSYCHOSIS AND ANHEDONIA-ASOCIALITY IN FEMALES: EPIGENETIC EVIDENCE IN RECENT-ONSET SCHIZOPHRENIA AND ULTRA-HIGH RISK FOR PSYCHOSIS

Abstract Background Oxytocin is one of the key hormones involved in human social and emotional processing. In this regard, abnormal functioning of the oxytocin system has been suggested to influence on the clinical manifestation of schizophrenia, especially negative symptoms. The aim of the present study was to investigate epigenetic modification of the oxytocin receptor gene (OXTR) and its association with negative symptoms in individuals with recent-onset schizophrenia (SCZ) and at ultra-high risk (UHR) for psychosis. Methods Sixty-four SCZ patients (< 5 years of duration of illness; 25 men, 39 women), 46 UHR individuals (27 men, 19 women), and 98 healthy controls (HCs; 46 men, 52 women) participated in the present study. DNA methylation was quantified from peripheral blood using pyrosequencing at CpG sites in OXTR intron 1 (hg19, chr3: 8,810,729–8,810,845) and exon 3 (hg19, chr3: 8,809,281–8,809,534). The severity of negative symptoms in clinical groups was measured using the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS). Results A multivariate analysis of covariance revealed significant differences in OXTR methylation between groups (F = 16.00, p < 0.001) and gender (F = 2.84, p = 0.025). Compared to HCs, both UHR and SCZ participants showed lower levels of OXTR intron 1 methylation, particularly at CpG site -934 upstream of the OXTR start codon (HCs = 47.3 ± 4.1 [mean ± SD], UHR = 38.8 ± 4.8, SCZ = 40.2 ± 5.3; F = 73.74, p < 0.001). Besides, female participants showed higher OXTR intron 1 methylation at CpG site -934 than male participants (male = 42.3 ± 6.1, female = 44.1 ± 5.8, F = 9.08, p = 0.003). Multiple linear regression analysis with clinical symptoms demonstrated that the degree of DNA methylation at CpG site -934 was significantly associated with the SANS anhedonia-asociality subscale scores in the entire group of female UHR and SCZ participants (beta = -0.44, p = 0.001). Discussion The present study demonstrated decreased OXTR methylation in both UHR and SCZ individuals compared to HCs. Furthermore, the severity of anhedonia-asociality was significantly associated with the degree of OXTR methylation in female UHR and SCZ individuals. These findings suggest that epigenetic aberration of OXTR may confer susceptibility to schizophrenia spectrum psychosis and influence the early pathogenesis of schizophrenia prior to the onset of overt psychosis, particularly in females.

Aberrant Tendency of Noncurrent Emotional Experiences in Individuals at Ultra-High Risk for Psychosis

Objective This study aimed to investigate whether aberrant tendency of noncurrent emotion was present in individuals at ultra-high risk (UHR) for psychosis and to explore its associations with various clinical profiles. Methods Fifty-seven individuals at UHR and 49 normal controls were enrolled. The tendency of experiencing noncurrent emotion was assessed using various noncurrent emotional self-reported formats, including trait [Neuroticism and Extraversion of the Eysenck Personality Questionnaire], hypothetical (Chapman’s Revised Physical and Social Anhedonia Scales), and retrospective [Anhedonia-Asociality Subscale of the Scale for the Assessment of Negative Symptoms (SANS)] measures. Self-related beliefs (Self-Perception Scale), clinical positive and negative symptoms (SA Positive Symptoms and SANS), psychosocial function (Global Functioning Scale: Role Function and Global Functioning Scale: Social Function) were also examined. Results Subjects at UHR for psychosis reported more trait unpleasant and less trait pleasant emotions, more hypothetical physical and social anhedonia, and more retrospective anhedonia than normal controls. In UHR, self-perception was correlated to trait unpleasant emotion and hypothetical physical and social anhedonia. Negative symptoms in UHR were associated with hypothetical physical anhedonia and retrospective anhedonia. Global social functioning was related to trait pleasant emotion, hypothetical physical and social anhedonia, and retrospective anhedonia. Neurocognitive function, positive symptoms, and global role functioning were not related with any noncurrent emotional experience measures in UHR. Conclusion These findings suggest that the aberrant tendency of noncurrent emotional experience may be present at the ‘putative’ prodromal phase and are grossly associated with self-related beliefs and psychosocial functioning but not neurocognitive functioning.

PM462. Impaired self-referential processing in patients with first-episode schizophrenia: an event-related potential study

In previous studies, Self-referential tasks were set in a firstperson perspective, which did not allow an examination of the influence of perspectives on the evaluation of self and others. The objective of the present research is to examine the changes in the physiological correlates of self/other-evaluation based on perspectives, by adding a perspective variable to the previous self-referential tasks. The neuro-physiological correlates of the impaired concept of self and perspective conversion capacity in schizophrenic patients are also examined. Twelve first-episode schizophrenic patients and a control group of 18 subjects participated in the experiment. The task was to evaluate and determine the relevance of presented personality trait adjectives to the object of reference – either self or other, in each reference condition – under two different perspective conditions – self or other. The brainwaves of participants were measured while they were performing the tasks. N2 component, which reflects an inhibition reaction, exhibited greater amplitude when evaluating the object in the third-person perspective than in the first-person perspective, and in the control group compared to the patient group. There was a significant three-way interaction among perspective, reference, and subject groups on N2 amplitude and latency. The late positive component(LPC), which reflects the executive function, showed greater amplitude when the referential object and the perspective were incongruent, compared to congruent conditions. The results suggest that a greater inhibition is necessary in both groups when evaluating objects in the third-person perspective compared to the first-person perspective, and that decentering during self-perspective, self-referential condition only occurs in the control group but not in the schizophrenia patient group. This implies that schizophrenia patients have reduced capacity to objectively evaluate self. Greater LPC amplitude during the reference-perspective incongruent conditions compared to the congruent conditions suggests that more active processing of episodic memory occurs when the perspectives and references are incongruent. Acknowledgement: This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C2242. * correspondance: ansk@yuhs.ac PM463 Dysfunction of intrinsic and extrinsic motivation in schizophrenia: an fMRI study Byung-Hoon Kim1, Yu-Bin Shin2,3, Sunghyon Kyeong2, Seon-Koo Lee4, Seung-Koo Lee5, Jae-Jin Kim1,2,3 1 Department of Psychiatry, Yonsei University College of Medicine, Seoul, Korea 2 Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea 3 Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea 4 Department of Psychiatry, National Health Insurance Ilsan Hospital, Koyang Gyeonggi, Republic of Korea 5 Department of Radiology, Yonsei University College of Medicine, Seoul, Korea Abstract Motivational deficit is one of the central components of negative symptoms in schizophrenia. Although reward system of the brain including the striatum is known to account for this deficit, little is studied with the focus on intrinsic and extrinsic motivational deficits in the illness. In this study, we evaluated BOLD response in patients with schizophrenia during motivational processing to test the hypothesis of dysfunctional activation related to intrinsic and extrinsic motivation. Twenty patients meeting DSM-IV diagnostic criteria for schizophrenia and 20 control subjects participated in the study. The fMRI task required participants to accept or deny an avatar’s verbal suggestions or questions in the virtual environment. The task comprised 18 intrinsic motivation-related and 18 extrinsic motivation-related questions along with 18 neutral questions, which subjects were required to make true or false judgment to a fact-based thesis. Repeated measures ANOVA of participants’ acceptance rate showed a significant main effect of condition and interaction effect between group and condition. In post hoc analysis, acceptance rate responding to intrinsic motivation were significantly higher than to extrinsic motivation in healthy controls. Imaging analysis resulted in a significant main effect of group for the putamen, middle temporal gyrus and corpus callosum, while main effect of condition was observed for the dorsolateral prefrontal cortex, inferior frontal gyrus and precuneus. Post-hoc analysis resulted in greater activation in the precuneus for intrinsic motivation than for extrinsic motivation. The behavioral results were correspondent with activation pattern of the precuneus, which showed hyperactivation to intrinsic motivation relative to extrinsic motivation condition in the control group. Intrinsic motivation was known to be related to self-efficacy and retrieval of attitude-relevant memory, which are involved in function of the precuneus. Our findings support results of previous studies that reported the impairment of motivation being linked to self-related memory involving the precuneus in schizophrenia.Motivational deficit is one of the central components of negative symptoms in schizophrenia. Although reward system of the brain including the striatum is known to account for this deficit, little is studied with the focus on intrinsic and extrinsic motivational deficits in the illness. In this study, we evaluated BOLD response in patients with schizophrenia during motivational processing to test the hypothesis of dysfunctional activation related to intrinsic and extrinsic motivation. Twenty patients meeting DSM-IV diagnostic criteria for schizophrenia and 20 control subjects participated in the study. The fMRI task required participants to accept or deny an avatar’s verbal suggestions or questions in the virtual environment. The task comprised 18 intrinsic motivation-related and 18 extrinsic motivation-related questions along with 18 neutral questions, which subjects were required to make true or false judgment to a fact-based thesis. Repeated measures ANOVA of participants’ acceptance rate showed a significant main effect of condition and interaction effect between group and condition. In post hoc analysis, acceptance rate responding to intrinsic motivation were significantly higher than to extrinsic motivation in healthy controls. Imaging analysis resulted in a significant main effect of group for the putamen, middle temporal gyrus and corpus callosum, while main effect of condition was observed for the dorsolateral prefrontal cortex, inferior frontal gyrus and precuneus. Post-hoc analysis resulted in greater activation in the precuneus for intrinsic motivation than for extrinsic motivation. The behavioral results were correspondent with activation pattern of the precuneus, which showed hyperactivation to intrinsic motivation relative to extrinsic motivation condition in the control group. Intrinsic motivation was known to be related to self-efficacy and retrieval of attitude-relevant memory, which are involved in function of the precuneus. Our findings support results of previous studies that reported the impairment of motivation being linked to self-related memory involving the precuneus in schizophrenia. PM464 Effect of Anhedonia on Shopping Behavior in Schizophrenia Min-Kyeong Kim1,2, Yu-Bin Shin2, Seon-Koo Lee2,3, Jae-Jin Kim1,2,4 1 Department of Psychiatry, Yonsei University College of Medicine, Seoul, Korea 2 Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea 3 Department of Psychiatry, National Health Insurance Service Ilsan Hospital, Goyang, Korea 4 Department of Radiology, Yonsei University College of Medicine, Seoul, Korea