Geumsook Shim

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.

Altered resting-state connectivity in subjects at ultra-high risk for psychosis: an fMRI study

BackgroundIndividuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex, are implicated in self-referential and social cognitive tasks. Thus, the neural substrates within the default mode network (DMN) have the potential to mediate self-referential and social cognitive information processing in UHR subjects.MethodsThis study utilized functional magnetic resonance imaging (fMRI) to investigate resting-state DMN and task-related network (TRN) functional connectivity in 19 UHR subjects and 20 matched healthy controls. The bilateral posterior cingulate cortex was selected as a seed region, and the intrinsic organization for all subjects was reconstructed on the basis of fMRI time series correlation.ResultsDefault mode areas included the posterior/anterior cingulate cortices, the medial prefrontal cortex, the lateral parietal cortex, and the inferior temporal region. Task-related network areas included the dorsolateral prefrontal cortex, supplementary motor area, the inferior parietal lobule, and middle temporal cortex. Compared to healthy controls, UHR subjects exhibit hyperconnectivity within the default network regions and reduced anti-correlations (or negative correlations nearer to zero) between the posterior cingulate cortex and task-related areas.ConclusionsThese findings suggest that abnormal resting-state network activity may be related with the clinical features of UHR subjects. Neurodevelopmental and anatomical alterations of cortical midline structure might underlie altered intrinsic networks in UHR subjects.

The Effects of Pharmacological Treatment on Functional Brain Connectome in Obsessive-Compulsive Disorder

BACKGROUND Previous neuroimaging studies of obsessive-compulsive disorder (OCD) have reported both baseline functional alterations and pharmacological changes in localized brain regions and connections; however, the effects of selective serotonin reuptake inhibitor (SSRI) treatment on the whole-brain functional network have not yet been elucidated. METHODS Twenty-five drug-free OCD patients underwent resting-state functional magnetic resonance imaging. After 16-weeks, seventeen patients who received SSRI treatment were rescanned. Twenty-three matched healthy control subjects were examined at baseline for comparison, and 21 of them were rescanned after 16 weeks. Topological properties of brain networks (including small-world, efficiency, modularity, and connectivity degree) were analyzed cross-sectionally and longitudinally with graph-theory approach. RESULTS At baseline, OCD patients relative to healthy control subjects showed decreased small-world efficiency (including local clustering coefficient, local efficiency, and small-worldness) and functional association between default-mode and frontoparietal modules as well as widespread altered connectivity degrees in many brain areas. We observed clinical improvement in OCD patients after 16 weeks of SSRI treatment, which was accompanied by significantly elevated small-world efficiency, modular organization, and connectivity degree. Improvement of obsessive-compulsive symptoms was significantly correlated with changes in connectivity degree in right ventral frontal cortex in OCD patients after treatment. CONCLUSIONS This is first study to use graph-theory approach for investigating valuable biomarkers for the effects of SSRI on neuronal circuitries of OCD patients. Our findings suggest that OCD phenomenology might be the outcome of disrupted optimal balance in the brain networks and that reinstating this balance after SSRI treatment accompanies significant symptom improvement.

Social functioning deficits in young people at risk for schizophrenia

Objective: Impairment in social functioning is a central feature of schizophrenia and is known to be evident before the onset of psychosis, acting as a potential vulnerability marker. The aim of the present study was to test the hypothesis that social impairment is simultaneously a state and trait marker of risk for schizophrenia and schizophrenia-related disorder. Method: Social functioning was examined in three groups: ultra-high-risk subjects (UHR, n =32), genetic high-risk subjects (GHR, n =32), and age- and IQ-matched healthy controls (HC, n =30). Social functioning was assessed using the Social Functioning Scale (SFS), and prodromal symptoms were assessed in high-risk subjects using the Comprehensive Assessment of At-Risk Mental States (CAARMS). Results: Both the UHR and GHR groups exhibited significantly impaired social functioning compared with the HC group, and the UHR group was more impaired than the GHR group. In the UHR group, duration of prodromal symptoms was related to impaired ‘interpersonal behaviour’. Positive and negative symptoms were not significantly associated with social functioning, whereas disorganized and general symptoms were significantly correlated with poor ‘independence–competence’ in UHR individuals. Conclusion: The findings support the hypothesis that impairment in social functioning is both a trait and state marker of risk for schizophrenia and other psychotic disorders, implying that social impairment constitutes a mediating vulnerability indicator of psychotic disorders including schizophrenia.

Disproportionate Alterations in the Anterior and Posterior Insular Cortices in Obsessive–Compulsive Disorder

Background Recent studies have reported that the insular cortex is involved in the pathophysiology of obsessive–compulsive disorder (OCD). However, specific morphometric abnormalities of the insular subregions remain unclear. In this study, we examined insular cortical volume to determine whether the volume of the anterior and posterior insular cortices of unmedicated OCD patients differed according to different symptom dimensions. Methods/Principal Findings Using magnetic resonance imaging, we measured the gray matter volumes of the insular cortex and its subregions (anterior and posterior divisions) in 41 patients with OCD (31 drug-naïve and 10 non-medicated) and 53 healthy controls. Volumetric measures of the insular cortex were compared according to different OC symptoms. Enlarged anterior and reduced posterior insular cortices were observed in OCD patients. The insular volumetric alterations were more significant in OCD patients with predominant checking rather than cleaning symptoms when compared with healthy controls. Conclusions/Significance Our results suggest the presence of unbalanced anterior and posterior insular volumetric abnormalities in unmedicated OCD patients and emphasize the distinct role of the insular cortex in different OC symptoms. We propose that the insular morphometric alterations may influence the modulation of interoceptive processing, the insular functional role, in OCD patients with different symptoms.

Pharmacotherapy and clinical characteristics of ultra-high-risk for psychosis according to conversion status: a naturalistic observational study

Aim: To explore the differences in pharmacotherapy and clinical characteristics of individuals at ultra‐high‐risk (UHR) for psychosis according to the conversion status, we analyzed the data for UHR patients seen at the Seoul Youth Clinic.

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.

Prospective outcome of early intervention for individuals at ultra-high-risk for psychosis

Aim: Based on previous reports of second‐generation antipsychotic agents having a beneficial effect on prodromal symptoms, we investigated the effectiveness and tolerability of atypical antipsychotic therapies in individuals at high risk for developing psychosis.

Clinical and neurocognitive profiles of subjects at high risk for psychosis with and without obsessive–compulsive symptoms

Objective: Obsessive–compulsive symptoms (OCS), which are common in psychotic-spectrum illnesses, are of clinical interest because of their association with poor prognosis or cognitive dysfunction. However, few studies on the clinical and neurocognitive implications of OCS in individuals at ultra-high risk for psychosis (UHR) have been conducted. Method: Sixty-five UHR subjects [24 with OCS (UHR+OCS), 41 without OCS (UHR−OCS)], and 40 healthy controls were assessed using clinical scales and neurocognitive tests. Results: Those with UHR+OCS showed more severe clinical symptoms and poorer global functioning as compared to both healthy controls and the UHR−OCS group, according to the results of the Global Assessment of Functioning, the Comprehensive Assessment of At-Risk Mental States, and the Positive and Negative Syndrome Scale (total, negative, and general scores). In the neurocognitive domain, those in the UHR−OCS group showed notably greater latency in the Stroop task and more confabulation errors in immediate recall in the Rey–Osterrieth Complex Figure Test compared with those in UHR+OCS group, whose performance levels were similar to those of the healthy control group. Conclusions: The OCS manifested in UHR individuals was associated with a more severe clinical symptomatic presentation, including lower global functioning and more psychotic symptoms. On the other hand, those with UHR−OCS performed more poorly on some cognitive tests. The features that distinguish the groups can be used for developing prognoses and intervention strategies for the heterogeneous UHR group.

Increased white matter integrity in the corpus callosum in subjects with high genetic loading for schizophrenia.

OBJECTIVE White matter abnormalities in the corpus callosum (CC) of schizophrenia have been reported to predate the illness onset. This study aimed to investigate the effect of genetic predisposition on the white matter integrity of the CC, in subjects at genetically high risk for schizophrenia (GHR) and schizophrenia patients. METHOD Fractional anisotropy (FA) of the mid-sagittal CC in 22 young GHR, 15 schizophrenia, and 26 control subjects were examined. GHR subjects were defined as non-prodromal individuals who had more than two relatives with schizophrenia within third-degree relatives, one of whom must be a first-degree relative. RESULTS ANCOVA with age and gender as covariates revealed overall difference of FA in the genu and splenium among the three groups. Post-hoc analysis found significantly increased FA in the genu of GHR subjects compared to controls (corrected p<0.01), whereas schizophrenia patients showed significantly decreased FA in the splenium. CONCLUSION The white matter change of the CC in young GHR subjects was the opposite of that in schizophrenia. To consider previous reports on FA decrease in the CC in schizophrenia and the impaired frontal functioning in GHR group, the increased FA may be an indicator of compensatory alteration in white matter integrity in young GHR people.