Predictors of Developmental Outcome in 4- to 6-Year-Olds With Developmental Disability.

OBJECTIVE: Studies on the early trajectories of developmental disability (DD) are limited. This study aimed to evaluate the diagnostic stability and developmental trajectories of autism spectrum disorder (ASD) and intellectual disability (ID), and to determine baseline clinical characteristics that affect future diagnosis. METHODS: We analyzed 192 children who were referred for possible DD through retrospective chart review. Clinical diagnosis was assessed once at baseline, aged 2-4, and at follow-up, aged 4-6. The participants' developmental profiles were measured by Psychoeducational Profile-Revised (PEP-R), Vineland Social Maturity Scale (VSMS), Beery-Buktenica Developmental Test of Visual Motor Integration (VMI), and Childhood Autism Rating Scale (CARS). RESULTS: On comparing the diagnostic change, 5% of children were no longer diagnosed as ASD, and 13% of children were no longer diagnosed as ID at follow-up. Trajectories of developmental profiles were compared between children with and without ID at follow-up, and significant time-by-group interaction were observed in PEP-R (p<0.001), VSMS (p<0.001), and VMI (p=0.003) scores, indicating that children without ID at follow-up showed significant improvement over time compared to children with ID. ASD diagnosis (p<0.001) and CARS score (p=0.007) at baseline were significantly associated with ASD at follow-up, while VSMS score (p=0.004) and VMI score (p=0.019) at baseline were significantly associated with ID at follow-up. CONCLUSION: A subset of children lost their diagnosis at follow-up, and such diagnostic change was significantly more common in ID compared to ASD. Baseline autism symptomatology was related to ASD at follow-up, and baseline adaptive and visuo-motor function was related to ID at follow-up.

Clinical Characteristics Associated with Suicidal Attempt and Non-Suicidal Self-Injury in Korean Adolescents.

OBJECTIVE: This study evaluated the association between mood and anxiety symptoms and suicidal attempt (SA) and/or non-suicidal self-injury (NSSI) in adolescents seeking mental health services. We also tested predictors of SA and NSSI. METHODS: We retrospectively reviewed the medical records of 220 adolescents who completed psychological assessment in clinical sample. Participants did the Adolescent General Behavior Inventory (A-GBI) and Children's Depression Inventory (CDI). SA and NSSI were assessed retrospectively by interview. The caregiver of participants completed the Beck Depression Inventory (BDI) for themselves. RESULTS: 17% of total participants had a history of SA, and 24% experienced NSSI. Both SA and NSSI were more common in girls. The score of depressive subscale on A-GBI was higher in adolescents with SA than those without. The participants with NSSI showed higher scores on CDI and depressive subscale on A-GBI than those without. SA was associated with maternal BDI and history of NSSI; female sex, depressive subscale on A-GBI, and history of SA with NSSI. CONCLUSION: Our study found that NSSI and SA are strongly associated in adolescents. Female sex and depressive symptoms of the adolescents were also significantly associated with NSSI in Korean adolescent. Findings are consistent with patterns in other countries.

Additive Burden of Abnormal Diffusivity in the Brain with Schizophrenia: A Diffusion Tensor Imaging Study with Public Neuroimaging Data.

OBJECTIVE: Diffusion tensor imaging has been extensively applied to schizophrenia research. In this study, we counted the number of abnormal brain regions with altered diffusion measures in patients with schizophrenia to enumerate the burden of abnormal diffusivity in the brain. METHODS: The public neuroimaging data of the COBRE project from SchizConnect were used for the study. The studied dataset consisted of data from 57 patients with schizophrenia and 71 healthy participants. FreeSurfer and FSL were applied for image processing and analysis. After verifying 161 regions of interest (ROIs), mean diffusion measures in every single ROI in all study participants were measured and normalized into Z-scores. Each ROI was then defined as normal or abnormal on the basis of a cutoff absolute Z-score of 1.96. The number of abnormal ROIs was obtained by each diffusion measure. RESULTS: The numbers of ROIs with increased radial diffusivity and increased trace were significantly larger in the patient group than in healthy participants. CONCLUSION: Thus, the patient group showed a significant increase in abnormal ROIs, strongly indicating that schizophrenia is not caused by the pathology of a single brain region, but is instead attributable to the additive burden of structural alterations within multiple brain regions.

Diagnosing schizophrenia with network analysis and a machine learning method.

OBJECTIVE: Schizophrenia is a chronic and debilitating neuropsychiatric disorder. It has been suggested that impaired brain connectivity underlies the pathophysiology of schizophrenia. Network analysis has thus recently emerged in the field of schizophrenia research. METHODS: We investigated 48 schizophrenia patients and 24 healthy controls using network analysis and a machine learning method. A number of global and nodal network properties were estimated from graphs that were reconstructed using probabilistic brain tractography. These network properties were then compared between groups and used for machine learning to classify schizophrenia patients and healthy controls. RESULTS: In classifying schizophrenia patients and healthy controls via network properties, the support vector machine, random forest, naïve Bayes, and gradient boosting machine learning models showed an encouraging level of performance. The overall connectivity was revealed as the most significant contributing feature to this classification among the global network properties. Among the nodal network properties, although the relative importance of each region of interest was not identical, there were still some patterns. CONCLUSION: In conclusion, the possibility exists to classify schizophrenia patients and healthy controls using network properties, and we have found that there is a provisional pattern of involved brain regions among patients with schizophrenia.

Continuation of schizophrenia treatment with three long-acting injectable antipsychotics in South Korea: A nationwide population-based study.

Long-acting injectable (LAI) antipsychotics have been developed to prevent symptom relapse in patients with schizophrenia; relapse has a detrimental clinical impact and high social burden. However, data on treatment continuation rates of LAI antipsychotics are inconsistent, primarily because of study design; limited data exist for patients taking oral psychotropic medications taken along with LAI antipsychotics, and factors related to LAI antipsychotics treatment discontinuation. Patients with schizophrenia in the South Korea Health Insurance Review Agency database from 2007 to 2016 who had received LAI haloperidol, LAI paliperidone, or LAI risperidone were included. Treatment continuation rates and proportions of patients using concurrent oral psychotropic medications were calculated. Cox proportional hazard ratios were used for analysis related to discontinuation. There was a significant difference in treatment continuation rates at 6 months after initiation (36.8% LAI haloperidol, 57.5% LAI paliperidone, and 34.5% LAI risperidone). A substantial proportion of patients in all three groups were prescribed oral antipsychotics during LAI antipsychotics treatment. In the LAI paliperidone group, type of hospital was significantly associated with a higher risk of treatment discontinuation, with a hazard ratio of 1.195-1.598. Early discontinuation of LAI antipsychotic treatment occurs in a large number of patients with schizophrenia. Intervention strategies for improving the LAI antipsychotics treatment adherence are needed.

Gray Matter Microstructural Abnormalities and Working Memory Deficits in Individuals with Schizophrenia.

OBJECTIVE: Working memory impairments serve as prognostic factors for patients with schizophrenia. Working memory deficits are mainly associated with gray matter (GM) thickness and volume. We investigated the association between GM diffusivity and working memory in controls and individuals with schizophrenia. METHODS: T1 and diffusion tensor images of the brain, working memory task (letter number sequencing) scores, and the demographic data of 90 individuals with schizophrenia and 97 controls were collected from the SchizConnect database. T1 images were parcellated into the 68 GM Regions of Interest (ROI). Axial Diffusivity (AD), Fractional Anisotropy (FA), Radial Diffusivity (RD), and Trace (TR) were calculated for each of the ROIs. RESULTS: Compared to the controls, schizophrenia group showed significantly increased AD, RD, and TR in specific regions on the frontal, temporal, and anterior cingulate area. Moreover, working memory was negatively correlated with AD, RD, and TR in the lateral orbitofrontal, superior temporal, inferior temporal, and rostral anterior cingulate area on left hemisphere in the individuals with schizophrenia. CONCLUSION: These results demonstrated GM microstructural abnormalities in the frontal, temporal, and anterior cingulate regions of individuals with schizophrenia. Furthermore, these regional GM microstructural abnormalities suggest a neuropathological basis for the working memory deficits observed clinically in individuals with schizophrenia.

Exploratory Factor Analysis of the Adolescent Version of the General Behavior Inventory in Korean Youth.

OBJECTIVES: We examined the factor structure of the Adolescent version of the General Behavior Inventory (A-GBI) for Koreans. METHODS: We retrospectively reviewed the medical records of 220 adolescents (age, 12-18 years) who completed the A-GBI through the Department of Psychiatry at Asan Medical Center, Seoul, Korea, from October 2011 to December 2018. Caregivers of the study participants completed the Parent version of the GBI (P-GBI) 10-item Mania Scale. The adolescents were evaluated based on the A-GBI, Children's Depression Inventory (CDI), and Revised-Children's Manifest Anxiety Scale (RCMAS). Subsequently, an exploratory factor analysis (EFA) using the maximum likelihood method with direct oblimin rotation and correlation analyses with other scales were performed. RESULTS: The EFA identified a two-factor structure as having the best fit: factor I included depressive symptoms and factor II included hypomanic/biphasic symptoms. Factor I was very strongly correlated with the A-GBI depressive subscale (r=0.990, p<0.001) and strongly correlated with CDI (r=0.764, p<0.001) and RCMAS (r=0.666, p<0.001). Factor II was also very strongly correlated with the A-GBI hypomanic/biphasic subscale (r=0.877, p<0.001) and weakly correlated with CDI (r=0.274, p<0.001) and RCMAS (r=0.332, p<0.001). CONCLUSION: The above findings support a two-dimensional model of mood symptoms in Korean youth.

Antidepressant Prescription Patterns in Bipolar Disorder: a Nationwide, Register-based Study in Korea.

BACKGROUND: The role of antidepressants (ADs) in bipolar disorder is long-standing controversial issue in psychiatry. Many clinicians have used ADs as a treatment for bipolar depression, and the selection of therapeutic agents is very diverse and inconsistent. This study aimed to examine recent AD prescription patterns for patients with bipolar disorder in Korea, using the nationwide, population-based data. METHODS: This study utilized the Korean nationwide, whole population-based registry data of the year 2010, 2011, and 2013. All prescription data of the ADs, antipsychotics, and mood stabilizers of the sampled patients diagnosed with bipolar disorder (n = 2,022 [in 2010]; 2,038 [in 2011]; 2,626 [in 2013]) were analyzed for each year. RESULTS: Annual prescription rate of ADs was 27.3%-33.6% in bipolar disorder, which was gradually increasing over the 3-year period. The combination pattern of ADs and antipsychotic drugs tended to increase over 3 years. The proportion of females and the prevalence of comorbid anxiety disorder were significantly higher in AD user group in all three years. Among individual ADs, escitalopram was prescribed most frequently, and fluoxetine and bupropion were prescribed to the next many patients. The mean duration of bipolar depressive episodes was 135.90-152.53 days, of which ADs were prescribed for 115.60-121.98 days. CONCLUSION: Our results show prescription rate of ADs in bipolar disorder was maintained at substantial level and increased in recent 3 years. More empirical data and evidence are needed to establish practical treatment consensuses.

Altered white matter connectivity in patients with schizophrenia: An investigation using public neuroimaging data from SchizConnect.

Several studies have produced extensive evidence on white matter abnormalities in schizophrenia (SZ). However, optimum consistency and reproducibility have not been achieved, and reported low white matter tract integrity in patients with SZ varies between studies. A whole-brain imaging study with a large sample size is needed. This study aimed to investigate white matter integrity in the corpus callosum and connections between regions of interests (ROIs) in the same hemisphere in 122 patients with SZ and 129 healthy controls with public neuroimaging data from SchizConnect. For each diffusion-weighted image (DWI), two-tensor full-brain tractography was performed; DWIs were parcellated by processing and registering T1 images with FreeSurfer and Advanced Normalization Tools. White matter query language was used to extract white matter fiber tracts. We evaluated group differences in means of diffusion measures between the patients and controls, and correlations of diffusion measures with the severity of clinical symptoms and cognitive impairment in the patients using the Positive and Negative Syndrome Scale (PANSS), a letter-number sequencing (LNS) test, vocabulary test, letter fluency test, category fluency test, and trail-making test, part A. To correct for multiple comparisons, a false discovery rate of q < 0.05 was applied. In patients with SZ, we observed significant radial diffusivity (RD) and trace (TR) increases in left thalamo-occipital tracts and the right uncinate fascicle, and a significant RD increase in the right middle longitudinal fascicle (MDLF) and the right superior longitudinal fascicle ii. Correlations were present between TR of left thalamo-occipital tracts, and the letter fluency test and the LNS test, and RD in the right MDLF and PANSS positive subscale score. However, these correlations were not significant after correction for multiple comparisons. These results indicated widespread white matter fiber tract abnormalities in patients with SZ, contributing to SZ pathophysiology.

Relationship Between Aggravation of Seizures and Methylphenidate Treatment in Subjects with Attention-Deficit/Hyperactivity Disorder and Epilepsy.

OBJECTIVES: We aimed to investigate the effectiveness and safety of methylphenidate (MPH), and especially its influence on seizures, in subjects with attention-deficit/hyperactivity disorder (ADHD) and epilepsy through a retrospective chart review of subjects treated with MPH in a clinical setting. We also evaluated factors that could affect seizure aggravation during MPH treatment. METHODS: From April 2004 to July 2011, MPH was prescribed to 105 subjects with ADHD and epilepsy. The demographic characteristics, psychiatric and medical history, and electroencephalography (EEG) results were reviewed. Two pediatric neurologists reviewed seizure type, epilepsy diagnosis, changes in seizure frequency, and EEG parameters during MPH treatment. Pediatric neurologists and psychiatrists determined the temporal relationship between seizure aggravation and MPH treatment. RESULTS: The mean age of the subjects was 14.8 ± 3.4 years (range: 7-24 years). Sixty-five (61.9%) of the subjects were male. The mean duration of MPH treatment was 22 months (range: 2 weeks to 89 months) and the mean dose of MPH was 0.84 mg/kg/day. MPH was effective in controlling ADHD symptoms in both the seizure aggravation and nonaggravation groups. However, 21 (20%) subjects had aggravated seizures and 32 (32.3%) subjects had worsened EEG findings. Subjects with uncontrolled seizure or anxiety disorders at baseline were more likely to show aggravated seizures. Subjects who had epileptiform discharges, anxiety disorders, or were free of antiepileptic drug use at baseline experienced EEG worsening more frequently. The median duration of MPH treatment was significantly longer in subjects who did not show seizure aggravation than in those who did (p < 0.001). CONCLUSIONS: MPH treatment may be related to aggravation of seizures or significant worsening of EEG findings in subjects with ADHD and epilepsy. Thus, clinicians should closely monitor seizure aggravation after MPH administration, especially for high-risk subjects with uncontrolled seizures or anxiety disorders at baseline.

Deterioration in Global Organization of Structural Brain Networks in Schizophrenia: A Diffusion MRI Tractography Study.

Schizophrenia is a heterogenous neuropsychiatric disorder with varying degrees of altered connectivity in a wide range of brain areas. Network analysis using graph theory allows researchers to integrate and quantify relationships between widespread changes in a network system. This study examined the organization of brain structural networks by applying diffusion MRI, probabilistic tractography, and network analysis to 48 schizophrenia patients and 24 healthy controls. T1-weighted MR images obtained from all participants were parcellated into 87 regions of interests (ROIs) according to a prior anatomical template and registered to diffusion-weighted images (DWI) of the same subjects. Probabilistic tractography was performed to obtain sets of white matter tracts between any two ROIs and determine the connection probabilities between them. Connectivity matrices were constructed using these estimated connectivity probabilities, and several network properties related to network effectiveness were calculated. Global efficiency, local efficiency, clustering coefficient, and mean connectivity strength were significantly lower in schizophrenia patients (p = 0.042, p = 0.011, p = 0.013, p = 0.046). Mean betweenness centrality was significantly higher in schizophrenia (p = 0.041). Comparisons of node wise properties showed trends toward differences in several brain regions. Nodal local efficiency was consistently lower in the basal ganglia, frontal, temporal, cingulate, diencephalon, and precuneus regions in the schizophrenia group. Inter-group differences in nodal degree and nodal betweenness centrality varied by region and showed inconsistent results. Robustness was not significantly different between the study groups. Significant positive correlations were found between t-score of color trails test part-1 and local efficiency and mean connectivity strength in the patient group. The findings of this study suggest that schizophrenia results in deterioration of the global network organization of the brain and reduced ability for information processing.

Lamotrigine treatment of adolescents with unipolar and bipolar depression: a retrospective chart review.

OBJECTIVE: The purpose of this study was to investigate the preliminary effectiveness and safety of lamotrigine for the treatment of depressive episodes in adolescents. METHODS: This was a 12 week retrospective chart review of lamotrigine treatment among 37 adolescents (mean age 16.3±1.3 years) with depressive episodes (15 with bipolar disorder and 22 with major depressive disorder). Illness severity at the 4th, 8th, and 12th weeks were retrospectively scored using Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I). RESULTS: The mean dose of lamotrigine was 65.4±37.5 mg/day (range 12.5-181.7 mg/day) for a mean duration of 199.9±217.4 days (range 14-879 days). The CGI-S scores were significantly decreased over 12 weeks (F=39.611, p<0.001, partial η2=0.531). Seventeen subjects (45.9%) showed a treatment response at 12 week follow up (defined by a CGI-I score ≤2). There were no differences in treatment effectiveness between the bipolar and unipolar groups. Overall, lamotrigine was well tolerated. The most common adverse event was skin rash (n=5, 13.5%), which resolved spontaneously after drug discontinuation. CONCLUSION: Our results provide preliminary evidence of the effectiveness and safety of lamotrigine in adolescents with bipolar and depressive disorders. Large, prospective, placebo-controlled studies are needed to confirm these findings.

Comparison of clinical characteristics of bipolar and depressive disorders in Korean clinical sample of youth: a retrospective chart review.

The purpose of this study was to compare the clinical characteristics of bipolar disorder I, II (BD I and II) and not otherwise specified (BD NOS) to those of major depressive disorder (MDD) in a clinical sample of Korean children and adolescents. This study was a cross-sectional review of longitudinal observational data. Two psychiatrists retrospectively reviewed the medical records of 198 children and adolescents (age 6-18) that were diagnosed as having bipolar or depressive disorders from March 2010 to February 2012 at Department of Psychiatry of Asan Medical Center, Seoul, Korea. Every subject's diagnoses were reviewed and confirmed. BD I, II and MDD were assessed according to the Diagnostic and Statistical Manual-IV criteria. BD NOS was defined based on the criteria for the Course and Outcome of Bipolar Youth study. Comparisons were made in demographic information, clinical characteristics, family history, and psychiatric comorbidities at baseline and during observation. Among 198 subjects, 20 (10.1 %) subjects were diagnosed as having BD I, 10 (5.1 %) as BD II, 25 (12.6 %) as BD NOS and 143 (73.7 %) as MDD. BD depression was associated with mood change while taking an antidepressant, familial bipolarity, aggressive behaviors, and atypical features. Comorbid obsessive-compulsive disorder tended to be higher in BD NOS than in MDD. Presence of psychosocial stressors was more common in MDD than in BD depression. In children and adolescents, bipolar depression is distinct from unipolar depression in family history, comorbidity, and clinical characteristics.