Child behavior checklist profiles in adolescents with bipolar and depressive disorders.

OBJECTIVE: We aimed to evaluate the Child Behavior Checklist (CBCL) profiles in youths with bipolar and depressive disorders. METHODS: Seventy-four subjects with a mean age of 14.9±1.6years (36 boys) with mood disorders and their parents were recruited from September 2011 to June 2013 in the Department of Psychiatry, Asan Medical Center, Seoul, Korea. Diagnosis of mood disorder and comorbid psychiatric disorder was confirmed by child psychiatrists using the Schedule for Affective Disorders and Schizophrenia for School Age Children - Present and Lifetime version (K-SADS-PL). The parents of the subjects completed the Parent General Behavior Inventory-10-item Mania Scale (P-GBI-10M), Parent-version of Mood Disorder Questionnaire (P-MDQ), ADHD rating scale (ARS) and CBCL. The adolescents completed the 76-item Adolescent General Behavior Inventory (A-GBI), Beck Depression Inventory (BDI), and Adolescent-version of Mood Disorder Questionnaire (A-MDQ). RESULTS: When adjusted for gender and the comorbidity with ADHD, the Withdrawn and Anxious/Depressed subscale scores of the CBCL were higher in subjects with bipolar disorder than in those with depressive disorder. Higher scores of A-GBI Depressive subscale, A-MDQ and BDI were shown in subjects with bipolar disorder than in those with depressive disorder. There was no significant difference on CBCL-DP, P-GBI-10M, P-MDQ, A-GBI Hypomanic/Biphasic subscale and ARS between two groups. All eight subscales of the CBCL positively correlated with the P-GBI-10M and P-MDQ scores, and seven of all eight subscales of the CBCL positively correlated with A-GBI Depressive and Hypomanic/Biphasic subscales. The BDI score was positively associated with the Withdrawn, Somatic Complaints, Anxious/Depressed, and Social Problems subscale scores. CBCL-DP score was strongly correlated with manic/hypomanic symptoms measured by P-GBI-10M and P-MDQ (r=0.771 and 0.826). CONCLUSIONS: This study suggests that the CBCL could be used for measuring mood symptoms and combined psychopathology, especially internalizing symptoms, in youth with mood disorder. However, CBCL-DP had limited ability to differentiate bipolar from depressive disorder, at least in adolescents.

Diagnostic validity and reliability of a Korean version of the Parent and Adolescent General Behavior Inventories.

OBJECTIVES: The purpose of this study was to evaluate the validity and reliability of a Korean version of the Parent General Behavior Inventory-10-item Mania Scale (P-GBI-10M) and the Adolescent General Behavior Inventory (A-GBI) for bipolar and depressive disorder in youths. METHODS: Ninety-two subjects with mood disorder and their parents were recruited from September 2011 to June 2013 through the Department of Psychiatry at the Asan Medical Center, Seoul, Korea. In addition, 125 community participants were recruited through two middle schools and one high school in Seoul. The parents of subjects completed the Parent-version Mood Disorder Questionnaire (P-MDQ), P-GBI-10M and Attention-deficit/hyperactivity disorder Rating Scale (ARS). Adolescents complete the 76-item A-GBI, Beck Depression Inventory (BDI), and Adolescent version of the Mood Disorder Questionnaire (A-MDQ). RESULTS: Different profiles were evident between the clinic-referred group and the community control, including different P-GBI-10M (t=3.07, p=0.003), A-GBI Depressive (t=4.99, p<0.001), Hypomanic/Biphasic subscales (t=3.17, p=0.002), and BDI (t=4.76, p<0.001) scores. The A-GBI Depressive subscale score (t=3.02, p=0.003), BDI score (t=2.12, p=0.037) and A-GBI Hypomanic/Biphasic subscale score (t=2.71, p=0.008) were significantly different between patients with bipolar disorder and those with depressive disorder. Of the 73 items of the Depressive and Hypomanic/Biphasic subscales of the A-GBI, eight discriminated between bipolar and depressive disorder. Furthermore, A-GBI Depressive subscale scores were significantly correlated with BDI (r=0.81, p<0.001), A-GBI Hypomanic/Biphasic subscale (r=0.88, p<0.001), A-MDQ (r=0.58, p<0.001), P-MDQ (r=0.22, p=0.005), and ARS (r=0.26, p<0.001) scores. Cronbach's α of the A-GBI was 0.98. CONCLUSION: The Korean version of the Parent and Adolescent General Behavior Inventories showed excellent internal consistency, fair-to-good construct, and discriminant validity.

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.

Correlates of Psychological Distress in Patients With Cancer at a Psycho-oncology Clinic.

BACKGROUND: Patients with cancer experience significant psychological distress. Most studies investigated individual risk factors for distress in their respective treatment setting, which limit generalizability of results or comparison of relative importance. OBJECTIVE: To investigate the relation between psychological distress in patients referred to a psycho-oncology clinic and its correlates in a comprehensive manner. METHOD: Medical charts of patients who visited the psycho-oncology clinic at a tertiary hospital from May 2019 to May 2020 were reviewed. Demographic, cancer-related, and psychiatric factors; health-related quality of life; and somatic pain were investigated. The Hospital Anxiety and Depression Scale, item 9 on the Patient Health Questionnaire-9, Functional Assessment of Cancer Therapy-General, Present Pain Intensity, and Distress Thermometer were measured at the index visit. Simple and multiple linear regression analyses were performed with the Distress Thermometer score as a dependent variable. RESULTS: A total of 454 patients were included. The univariate analyses showed age and physical, emotional, and functional well-being scores on the Functional Assessment of Cancer Therapy-General were negatively associated with the Distress Thermometer scores, while female genital cancer, advanced disease, recent radiotherapy, the Hospital Anxiety and Depression Scale score, and the Present Pain Intensity score showed a positive relation. After adjusting for all other variables, female genital cancer (P = 0.027), anxiety subscale of the Hospital Anxiety and Depression Scale (P < 0.001), the Present Pain Intensity (P = 0.002), and physical (P < 0.001) and functional (P = 0.019) well-being subscales of the Functional Assessment of Cancer Therapy-General remained significant. CONCLUSIONS: Patients with cancer who visited a psycho-oncology clinic experienced more distress if they had female genital cancer, low health-related quality of life score, severe anxiety, or somatic pain.

Clinical Use of Continuous Performance Tests to Diagnose Children With ADHD.

OBJECTIVE: This study evaluated the diagnostic application of continuous performance tests in children with ADHD. METHOD: We recruited 114 children (aged 6-12) from August 2012 to May 2014. Seventy-nine children were diagnosed with ADHD and 35 were enrolled as controls. The Advanced Test of Attention (ATA) was administered to all participants. RESULTS: There were significant between-group differences for the frequency distribution of four ATA variables. The ATA criteria yielded a diagnostic sensitivity and specificity of 84.8% and 45.7%, respectively. Discriminant analysis revealed that auditory reaction time variability and visual commission errors helped distinguish between the groups. Discriminate functions indicated correct classification of 64.9% children. ADHD children tended to have lower intra-class correlation coefficients. CONCLUSION: Our results suggest that the ATA distributions of ADHD individuals may differ from the general population; in addition, the ATA results could not independently diagnose ADHD. Therefore, they should be considered carefully before diagnosis.

Genome-Wide Analysis Reveals Four Novel Loci for Attention-Deficit Hyperactivity Disorder in Korean Youths.

OBJECTIVES: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. METHODS: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. RESULTS: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. CONCLUSION: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

Region-specific phosphorylation of ATF-2, Elk-1 and c-Jun in rat hippocampus and cerebellum after electroconvulsive shock.

There have been reports of regional differences in the activation of mitogen activated protein kinases (MAPKs) and in the induction of immediate early genes after electroconvulsive shock (ECS) in the rat brain. This study was performed to determine whether ECS induce the region-specific phosphorylation of MAPK-downstream transcription factors, ATF-2, Elk-1, c-Jun, in rat hippocampus and cerebellum. Following ECS, the phosphorylation of ATF-2 was highly increased in the hippocampus but slightly in the cerebellum. The phosphorylation of Elk-1 was increased in the cerebellum but not in the hippocampus. In contrast, the phosphorylation of c-Jun was increased only in the hippocampus. These results indicate that ECS can induce the region-specific phosphorylation of MAPK-downstream transcription factors in rat hippocampus and cerebellum.

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.

Antidepressant-emergent mood switch in Korean adolescents with mood disorder.

OBJECTIVES: The objectives of this study were to compare clinical characteristics of children and adolescents who experienced antidepressant-emergent mood switch (AEMS) and those who did not, and to investigate the predictors of AEMS in a clinical sample of Korean children and adolescents. METHODS: Two psychiatrists retrospectively reviewed the medical records of 115 children and adolescents (age, 15.0 [2.0] years; 45 boys) that were prescribed antidepressants or lamotrigine for the treatment of a depressive episode of bipolar or depressive disorders from March 2010 to February 2012 at the Department of Psychiatry of Asan Medical Center. The diagnosis was reviewed and confirmed for each subject. Demographic information, clinical characteristics, family history, and psychiatric comorbidities were compared across subjects with and without AEMS. RESULTS: Twelve subjects (10.4%) experienced AEMS. The latency to AEMS was 25.9 (20.9) days (range, 2-56 days; median, 18 days). Antidepressant-emergent mood switch was more frequent in subjects with bipolar disorder (BD) than in subjects with depressive disorder (P < 0.001) and in subjects with high socioeconomic status (P < 0.001). Previous suicidal attempt (P = 0.001), previous antidepressant exposure (P = 0.001), number of previous antidepressant exposures (P < 0.001), family history of other psychiatric disorder (P = 0.001), and concomitant antipsychotics (P = 0.006) were more common in subjects with AEMS than in subjects without AEMS. In multivariate logistic regression, diagnosis of BD (odds ratio [95% confidence interval], 15.94 [1.83-139.16]), concomitant antipsychotics (26.90 [2.43-297.38]), and family history of other psychiatric disorder (39.55 [3.05-512.22]) were significant predictors of AEMS. CONCLUSIONS: Children and adolescents who experienced AEMS had distinct profiles of clinical characteristics. Antidepressant-emergent mood switch may be more associated with BD than with depressive disorder.

Age structure at diagnosis affects aggression in a psychiatric inpatient population: age structure affecting inpatient aggression.

Study of inpatient aggression in psychiatric inpatient units (PIUs), where vulnerable patients interact intensely in small groups, is hampered by a lack of systematic monitoring of aggressive events in the context of group dynamics. Our current study examines the relationship between aggression and group structure in the PIU of a general tertiary-care hospital over a 9-month period. The severity of aggression was monitored daily using the Overt Aggression Scale (OAS). Clinical data including the daily number and mean age of subpopulations with different diagnoses were acquired. Cross-correlation function and autoregressive integrated moving average modeling were used to assess the effects of various group structure parameters on the incidence of aggressive events in the PIU. The daily total OAS score correlated positively with the daily mean age of patients with schizophrenia and bipolar disorder. By contrast, the OAS total score demonstrated a negative correlation with the daily mean age of patients with major depression. The age of the patients at diagnosis is an important group structure that affects the incidence of aggression in a PIU.

Experience of subjective symptoms in euthymic patients with bipolar disorder.

Bipolar patients often experience subjective symptoms even if they do not have active psychotic symptoms in their euthymic state. Most studies about subjective symptoms are conducted in schizophrenia, and there are few studies involving bipolar patients. We examined the nature of the subjective symptoms of bipolar patients in their euthymic state, and we also compared it to that of schizophrenia and normal control. Thirty bipolar patients, 25 patients with schizophrenia, and 21 normal control subjects were included. Subjective symptoms were assessed using the Korean version of the Frankfurter Beschwerde Fragebogen (K-FBF) and the Symptom Check List 90-R (SCL90-R). Euthymic state was confirmed by assessing objective psychopathology with the Positive and Negative Syndrome scale of Schizophrenia (PANSS), the Young Mania Rating Scale (YMRS), and the Montgomery Asberg Depression Rating Scale (MADRS). K-FBF score was significantly higher in bipolar patients than in normal controls, but similar to that in schizophrenia patients (F=5.86, p=0.004, R2=2033.6). In contrast, SCL90-R scores did not differ significantly among the three groups. Euthymic bipolar patients experience subjective symptoms that are more confined to cognitive domain. This finding supports the hypothesis that subtle cognitive impairments persists in euthymic bipolar patients.

Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans.

Catechol-O-methyltransferase (COMT) inactivates circulating catechol hormones, catechol neurotransmitters, and xenobiotic catecholamines by methylating their catechol moieties. The COMT gene has been suggested as a candidate gene for schizophrenia through linkage analyses and molecular studies of velo-cardio-facial syndrome. A coding polymorphism of the COMT gene at codon 108/158 (soluble/membrane-bound form) causing a valine to methionine substitution has been shown to influence enzyme activity, but its association with schizophrenia is inconclusive. We have screened 17 known polymorphisms of the COMT gene in 320 Korean schizophrenic patients and 379 controls to determine whether there is a positive association with a nonsynonymous single-nucleotide polymorphism (rs6267) at codon 22/72 (soluble/membrane-bound form) causing an alanine-to-serine (Ala/Ser) substitution. With the Ala/Ala genotype as a reference group, the combined genotype (Ala/Ser and Ser/Ser)-specific adjusted odds ratio was 1.82 (95% CI = 1.19-2.76; P = 0.005), suggesting the Ser allele as a risk allele for schizophrenia. However, the Val/Met polymorphism was not associated with an increased risk of schizophrenia in Koreans (OR = 0.88, 95% CI = 0.64-1.21; P = 0.43). The Ala72Ser substitution was correlated with reduced COMT enzyme activity. Our results support previous reports that the COMT haplotype implicated in schizophrenia is associated with low COMT expression.

Korean version of the diagnostic interview for genetic studies: Validity and reliability.

The Diagnostic Interview for Genetic Studies (DIGS), developed in 1994 by the National Institute of Mental Health (NIMH), was translated into Korean and tested for reliability and diagnostic validity. Concurrent validity was tested using the Structured Clinical Interview for DSM-IV (SCID) and clinical diagnoses in 53 patients, most of whom had either schizophrenia or bipolar disorder. Inter-rater reliability was tested in 24 patients. Test-retest reliability was also tested in 17 patients. Overall and specific diagnostic validity for the Korean version of DIGS (DIGS-K) was excellent for most diagnoses. Inter-rater and test-retest reliability for overall and specific diagnoses also ranged from fair to excellent. For schizoaffective disorder, the test-retest reliability of DIGS-K was in a fair range, although the level was lower than that of other diagnoses. However, its diagnostic validity and inter-rater reliability was below fair range. In conclusion, DIGS-K appears to be a reliable interview for major psychiatric disorders.