Na Young Shin

Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder

OBJECTIVE Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables. METHOD A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects. RESULTS Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age). CONCLUSIONS These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction.

Social cognition and neurocognition as predictors of conversion to psychosis in individuals at ultra-high risk

BACKGROUND While deficits in cognitive functions are frequently reported in psychotic disorders, further longitudinal research is needed to confirm the specific risk factors for the development of psychosis. We examined longitudinally the social-cognitive and neurocognitive function of individuals at ultra-high risk for schizophrenia who developed psychosis later as predictive markers. METHOD The investigators studied 49 subjects at ultra-high risk (UHR) for psychosis and 45 healthy controls. The UHR subjects were followed for up 5.2 years (mean: 2.8 years) and 13 of these subjects developed psychosis. Theory of mind (ToM) tasks and neuropsychological tests were administered at baseline. Analyses compared the UHR patients who later developed psychosis, those who did not develop, and healthy controls. To examine the cognitive variables to predict transition to psychosis, Cox regression analyses were conducted. RESULTS At baseline, we found significant differences among the three groups in social cognition according to the False Belief and cartoon tasks and in neurocognition according to tasks measuring executive function, working memory, verbal memory, and visual memory. Our study showed that a model combining working memory, visual memory, executive function, and ToM tasks was significantly predictive of time to conversion to psychosis. CONCLUSION This study indicated that UHR patients who later converted to psychosis performed more poorly on tasks involving social cognition and neurocognition than did those who did not convert. We suggest that these deficits can serve as specific markers to predict the development of psychosis.

Reduced prefrontal functional connectivity in the default mode network is related to greater psychopathology in subjects with high genetic loading for schizophrenia

OBJECTIVE Neuroimaging studies in subjects at genetic high risk (GHR) of schizophrenia can provide clues to the causes for the development of schizophrenia. Little is known about genetic influence on functional connectivity status, although studies on schizophrenia have reported an abnormal default mode network (DMN). We sought to identify putative genetic vulnerability markers by examining whether aberrant DMN connectivity was present in GHR subjects with high genetic loading. METHOD Sixteen GHR subjects who had at least two relatives with schizophrenia and 16 age- and sex-matched controls were included and scanned using resting-state functional magnetic resonance imaging. A posterior cingulate cortex (PCC) seed region connectivity analysis was used to identify the DMN. Correlations between severity of psychopathology, level of genetic loading and DMN connectivity were calculated. RESULTS The DMN network in GHR subjects showed reduced functional connectivity in the prefrontal areas, PCC, and precuneus. In addition, this reduced connectivity in the prefrontal cortices correlated with total and general scores on the Positive and Negative Syndrome Scale. GHR subjects having two first-degree relatives with schizophrenia showed a trend toward greater reduction in DMN connectivity in the precuneus and anterior cingulate cortex. CONCLUSION This study suggests significant abnormalities in the DMN of subjects at GHR of schizophrenia. Alterations of DMN connectivity in the prefrontal cortex may reflect psychopathologies such as an inability to allocate resources properly between internal thoughts and external stimuli. Dysfunction of the anterior cingulate cortex and precuneus might be related to genetic risk for schizophrenia.

Multi-level comparison of empathy in schizophrenia: an fMRI study of a cartoon task.

Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal pole to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize.

The Reliability and Validity of the Korean Version of the Structured Interview for Prodromal Syndrome

Objective The Structured Interview for Prodromal Syndrome (SIPS) from Yale University is intended to diagnose prodromal syndrome of psychosis and to measure the severity of prodromal symptoms. Here, a Korean version of SIPS is presented, and its reliability, validity, and factor structures are examined using a representative Korean sample. Methods The Korean version of SIPS was administered to 40 participants over a period of 1 year. The inter-rater reliability and internal consistency of the SIPS were then evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was explored using Pearson correlation coefficients with the Positive and Negative Syndrome Scale (PANSS). Results Of the 40 subjects, 12.5% developed psychotic disorders during the 1-year follow-up period. Inter-rater reliability was good (intra-class correlations=0.96), and internal consistency was acceptable (Cronbachs alpha=0.83). A three-factor resolution displayed the best simple structure and accounted for 52.6% of all item variance. Factors 1 and 2 showed strong correlations with negative symptoms and cognitive dysfunction, respectively, on the PANSS. Factor 3 was not correlated with any factor on the PANSS. Conclusion The Korean version of SIPS is a reliable instrument for the assessment of prodromal symptoms in subjects and may be used to evaluate prodromal psychosis.

Processing of facial configuration in individuals at ultra-high risk for schizophrenia

BACKGROUND Discrepancies in the ability to recognize faces constitute an important aspect of the impaired social cognitive abilities of patients with schizophrenia. Previous studies have suggested that specific problems with the processing of facial configuration affect the face-recognition deficit in patients with schizophrenia. However, little is known about whether these deficits in face recognition are present before the onset of schizophrenia. METHOD This study compared performances on a face processing task among three groups: individuals at ultra-high risk for schizophrenia (n=20), patients with schizophrenia (n=18), and normal controls (n=20) using a face-discrimination task involving pairs of photographs depicting upright and inverted images with changing features and configurations. Chair stimuli were used as the control task. RESULTS The individuals at ultra-high risk for schizophrenia performed more poorly than did normal controls with regard to the processing of facial configuration but not the facial feature and did not differ significantly from the patients with schizophrenia with regard to the processing of facial configuration and upright facial features. CONCLUSION This study suggests that a specific dysfunction in the processing of facial configuration, which has an impact on face recognition, might be present before and deteriorate in patients with schizophrenia. Deficits in face recognition among individuals at risk for psychosis might contribute significantly to the social dysfunction associated with schizophrenia.

Nonverbal memory and organizational dysfunctions are related with distinct symptom dimensions in obsessive-compulsive disorder

Recent acceptance that obsessive-compulsive disorder (OCD) represents a heterogeneous phenomenon has underscored the need for dimensional approaches to this disorder. However little is known about the relation between neuropsychological functions and symptom dimensions. The purpose of this study was to identify the cognitive deficits correlated with specific symptom dimensions. Thirteen categories in the Yale-Brown Obsessive Compulsive Scale symptom checklist from 144 patients with OCD were analyzed by principal component analysis. Correlations between identified symptom dimensions and neuropsychological functioning, measured by the Boston Qualitative Scoring System, were analyzed. Five factors or dimensions were identified: contamination/cleaning, hoarding, symmetry/ordering, obsessions/checking, and repeating/counting. Dysfunctions in nonverbal memory and organizational strategies were related to the symmetry/ordering dimension and the obsessions/checking dimension, respectively. The results of the present study support a transculturally stable symptom structure for OCD. They also suggest the possibility that nonverbal memory dysfunction and organizational impairment are mediated by distinct obsessive-compulsive dimensions.

Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia

Na Young Shin, Hye Yoon Park, Wi Hoon Jung, Jin Woo Park, Je-Yeon Yun, Joon Hwan Jang, Sung Nyun Kim, Hyun Jung Han, So-Yeon Kim, Do-Hyung Kang and Jun Soo Kwon Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea

Longitudinal patterns of social functioning and conversion to psychosis in subjects at ultra-high risk

Objective: Impaired social functioning is one of the defining features of patients with schizophrenia and subjects at ultra-high risk (UHR) for psychosis. This prospective study aimed to investigate the course of social dysfunction in UHR subjects and to examine its relationship with later conversion to psychosis. The effect of pharmacotherapy on the course of social dysfunction was also examined. Method: A total of 57 UHR subjects and 58 healthy controls participated in this study. The Social Functioning Scale (SFS) was used to assess social functioning of UHR subjects at baseline and at the 1 year follow up. The changes in social functioning of UHR subjects have been examined to compare the social functioning of those who later converted to psychosis (‘converters’) with those who did not (‘non-converters’). The effect of pharmacotherapy on longitudinal change in social functioning was also evaluated. Results: Subjects at UHR for psychosis showed more impaired social functioning at baseline than did healthy controls. Moreover, the course of social dysfunction of the converter and non-converter groups differed during the 1 year follow up period. The converters showed decreases in SFS average (F (1,32) = 7.85, p = 0.009) and interpersonal behaviour (F (1,32) = 10.43, p = 0.003) scores over time, whereas the non-converters showed increased scores. Additionally, we found that pharmacological treatment was associated with increased prosocial activities score (F (1,32) = 4.66, p = 0.038). Conclusions: We found that the social functioning of converters was impaired before the onset of the psychosis and further declined during the at-risk phase. A series of social functioning indices in the longitudinal course may be helpful in predicting conversion to psychosis in subjects at UHR. Appropriate pharmacotherapy can offer clinical benefits by improving social functioning in UHR individuals.

General intellectual functioning as a buffer against theory-of-mind deficits in individuals at ultra-high risk for psychosis

The influence of neurocognition, including general intelligence, on theory of mind (ToM) among patients with schizophrenia spectrum disorder is controversial. The purpose of the present study was to identify the influences of the non-ToM cognition and general intelligence on ToM performance in individuals at ultra-high risk (UHR) for psychosis. Fifty-five UHR subjects and 58 healthy controls (HCs) completed neurocognitive, verbal, and nonverbal ToM tasks. UHR individuals showed poorer performance in the two verbal ToM tasks, the false-belief task and the strange-story tasks. Moreover, the UHR subjects displayed poorer recall on the interference list of the verbal learning test. Linear regression analysis revealed that neurocognitive functioning, including executive functioning, working memory, and general intelligence, accounted for significant amounts of the variance in the results for UHR individuals: 20.4% in the false-belief task, 44.0% in the strange-story task, and 49.0% in the nonverbal cartoon task. Neurocognition, including general intelligence, was not a significant contributor to performance on ToM tasks in HCs. ToM deficits were not noted in UHR individuals with above-average IQ scores (≥ 110) compared with UHR subjects with IQ scores less than 110, who displayed significant differences on all ToM tasks compared with HCs. The present results suggest that ToM deficits in UHR individuals are complex and may be influenced by non-ToM cognition. Our findings are discussed in relation to the role of neurocognitive abilities in ToM-related impairments in UHR individuals.