Jun Soo Kwon

Unravelling the intrinsic functional organization of the human striatum: a parcellation and connectivity study based on resting-state FMRI.

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders.

Patterns of changes in temperament and character inventory scales in subjects with obsessive–compulsive disorder following a 4-month treatment

Objective:  The purpose of this study was to assess changes in the temperament and character patterns in subjects with obsessive–compulsive disorder (OCD) following the treatment for obsessive/compulsive and accompanying depressive symptoms.

Association of seasonality and premenstrual symptoms in Bipolar I and Bipolar II disorders

BACKGROUND Although seasonal affective disorder and premenstrual syndrome (PMS) are frequently observed in mood disorders, little is known as to whether lifetime traits of seasonality and premenstrual distress are related to bipolar disorder independent of mood episodes. This study aimed at investigating these two cyclic traits with respect to bipolar I and II disorders as well as evaluating the association between them. METHODS Subjects included 61 female patients with bipolar I or II disorders and 122 healthy women. Seasonality and premenstrual symptoms were measured retrospectively on a lifetime basis using the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Premenstrual Symptoms Screening Tool (PSST). RESULTS Patients showed higher global seasonality scores on the SPAQ compared to the normal controls. Further, the patient-control difference was more prominent in cases of bipolar II disorder (p<0.0001) than in bipolar I disorder (p=0.001). The prevalence of moderate to severe PMS as indicated on the PSST was also significantly higher in bipolar II disorder patients (51.6%) as compared to controls (19.7%). A significant association between seasonality and PMS was observed in both patient and control groups. CONCLUSIONS The results suggested that female patients with bipolar disorder experience seasonal and premenstrual changes in mood and behavior regardless of their mood episodes, and traits of seasonality and PMS are associated with each other. A common biological mechanism of these two cyclic conditions may be involved in the development of the cyclicity of bipolar disorder.

Interaction between genetic variants of DLGAP3 and SLC1A1 affecting the risk of atypical antipsychotics-induced obsessive-compulsive symptoms.

Adverse effects of atypical antipsychotics (AAP) can include obsessive–compulsive (OC) symptoms. Based on biological evidence of the relationship between the glutamatergic system and both OC disorder and AAP, this study aimed to determine whether DLGAP3, coding a post‐synaptic scaffolding protein of glutamatergic synapses, is associated with AAP‐induced OC symptoms. Furthermore, we explored the interactions between DLGAP3 and a previously reported susceptibility gene, the glutamate transporter gene SLC1A1, regarding this phenotype. Subjects were clinically stable schizophrenia patients receiving AAP treatment (n = 94), and they comprised an OC group (n = 40) and a non‐OC group (n = 54) (patients with and without AAP‐induced OC symptoms, respectively). We performed allelic/genotypic/haplotype association analyses for seven tag single‐nucleotide polymorphisms of DLGAP3 and gene–gene interaction analyses with rs2228622 of SLC1A1, observing a nominally significant association between AAP‐induced OC symptoms and rs7525948 in both simple chi‐square tests and the regression analyses (nominal P < 0.05). In the logistic regression analysis of gene–gene interaction, we found a significant interaction effect of rs7525948 of DLGAP3 and rs2228622 of SLC1A1 (permutation P = 0.036) on AAP‐induced OC symptoms, with a 30.2 times higher odds for individuals carrying risk genotypes at both loci in comparison with the reference group, which had no risk genotypes. This study provides suggestive evidence that DLGAP3 and its interactive effect with SLC1A1 might be involved in susceptibility to developing OC symptoms in schizophrenia patients receiving AAP treatment.

Diagnostic stability of first-episode psychosis and predictors of diagnostic shift from non-affective psychosis to bipolar disorder: A retrospective evaluation after recurrence☆

Diagnostic changes during follow-up are not uncommon with a first-episode psychosis (FEP). This study aimed to evaluate the diagnostic stability of the FEP and to identify factors associated with a diagnostic shift from non-affective psychosis to bipolar disorder. Considering that the diagnosis of FEP is frequently more definite after recurrence in many clinical settings, a retrospective evaluation after recurrence was preformed. Subjects were 150 patients with psychotic disorders who had been admitted to a psychiatric ward both for first episode and recurrence of their psychosis. Consensus diagnosis was made for each episode through a review of hospital records. Patients diagnosed with non-affective psychoses at the first episode were included in the analysis of predictive factors of a diagnostic shift to bipolar disorder. First-episode diagnoses were revised upon recurrence in 20.7% of patients. The most common change was to bipolar disorder accounting for more than half of all diagnostic changes. Schizophrenia exhibited the highest prospective and retrospective diagnostic consistencies. Female gender, short duration of untreated psychosis, high level of premorbid functioning, and several symptoms including lability, mood elation, hyperactivity, and delusions with religious or grandiose nature were identified as predictive factors for a diagnostic shift from non-affective psychosis to bipolar disorder. Clinical features of psychoses seem to evolve during the disease course resulting in diagnostic changes upon recurrence in a significant portion of FEP. Special consideration on a diagnostic shift to bipolar disorder is required in patients exhibiting the predictive factors identified in the current study.

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.

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.

Do Organizational Strategies Mediate Nonverbal Memory Impairment in Drug-Naïve Patients With Obsessive-Compulsive Disorder?

OBJECTIVE The present study aimed to examine nonverbal memory and organizational skill functions in psychotropic-naïve patients with OCD. METHOD Forty-one drug-naïve, 41 medicated OCD patients and 41 healthy controls, all of whom were matched for gender, age, education and intelligence, were included in the study. The Rey-Osterrieth Complex Figure Test (RCFT) was administered to evaluate nonverbal memory ability and organizational skill. RESULTS OCD patients demonstrated impaired nonverbal memory irrespective of medication status (F = 6.54, p < .01, eta(2)p = .098 for immediate recall; F = 7.76, p < .01, eta(2)p = .114 for delayed recall). Medicated patients showed deficits in organizational strategies (eta(2)p = .079), which mediated nonverbal memory impairment (Z = -2.20, p = .027). The difference of organizational skill between drug-naïve and control groups did not reach statistical significance (eta(2)p = .054) and the association between organization and nonverbal memory was weak in the drug-naïve sample (Z = -1.74, = .081). There was no significant difference between the patient groups in RCFT indices. CONCLUSIONS Our findings suggest that the organizational strategies may not be an effective mediator of nonverbal memory impairment in OCD and indicate that the clinical characteristics may be important to be considered in future research. Further studies are needed to improve understanding of the nature of nonverbal memory dysfunction in OCD.

Association of genetic variations in DTNBP1 with cognitive function in schizophrenia patients and healthy subjects.

The dystrobrevin‐binding protein 1 gene (DTNBP1) has been regarded as a susceptibility gene for schizophrenia. Recent studies have investigated its role on cognitive function that is frequently impaired in schizophrenia patients, and generated inconsistent results. The present study was performed to elucidate effects of genetic variations in DTNBP1 on various cognitive domains in both schizophrenia patients and healthy subjects. Comprehensive neuropsychological tests were administered to 122 clinically stable schizophrenia patients and 119 healthy subjects. Based on positive findings reported in previous association studies, six SNPs were selected and genotyped. Compared to healthy subjects, schizophrenia patients showed expected lower performance for all of the cognitive domains. After adjusting for age, gender, and educational level, four SNPs showed a nominally significant association with cognitive domains. The association of rs760761 and rs1018381 with the attention and vigilance domain remained significant after applying the correction for multiple testing (P < 0.001). Similar association patterns were observed both, in patients and healthy subjects. The observed results suggest the involvement of DTNBP1 not only in the development of attention deficit of schizophrenia, but also in the inter‐individual variability of this cognitive domain within the normal functional range.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study.

Objective We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. Methods This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). Results The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. Conclusion The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.