Publications by authors named "Ya-Mei Bai"

232 Publications

Interest-activity symptom severity predicts response to ketamine infusion in treatment-resistant depression.

Psychopharmacology (Berl) 2021 Mar 20;238(3):857-865. Epub 2021 Jan 20.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec.2, Shih-Pai Road, Beitou District, Taipei, 112, Taiwan.

Background: Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear.

Methods: Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2 mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40 min and up to 2 weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models.

Results: The interest-activity symptom domain as a continuous variable (β = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2 mg/kg ketamine infusion (β = 0.013) demonstrated the greatest antidepressant effect (p < .01) compared with 0.5 mg/kg ketamine (β = 0.739) and placebo infusions; however, in the high interest-activity, 0.5 mg/kg ketamine infusion (β = 0.001) demonstrated the best antidepressant effect (p < .01) compared with 0.2 mg/kg ketamine (β = 1.372) and placebo infusions.

Discussion: The symptom domain of interest-activity was an independent predictor for the treatment response to a single low-dose ketamine infusion.
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http://dx.doi.org/10.1007/s00213-020-05737-zDOI Listing
March 2021

Factors Affecting Delayed Initiation and Continuation of Medication Use for Attention-Deficit/Hyperactivity Disorder: A Nationwide Study.

J Child Adolesc Psychopharmacol 2021 04 18;31(3):197-204. Epub 2021 Jan 18.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

This study evaluated the predictors for delayed initiation and continuation of ADHD medication use in children and adolescents with ADHD in Taiwan. This longitudinal cohort study enrolled 188,061 children and adolescents with ADHD between 2001 and 2011. Delayed initiation of ADHD medications was defined as the interval >365 days between diagnosis and first prescription, and continuation of ADHD medications was defined as ≥365 defined daily doses of ADHD medications. Of the included patients, 39.2% were never treated with ADHD medications. Delayed initiation and continuation of ADHD medication use were found in 11.9% and 19.9% of the ever-treated patients, respectively. Younger age at ADHD diagnosis, male sex, older mother's age at child's ADHD diagnosis, and higher family income were associated with more delayed initiation but were also associated with more continuation of ADHD medication use. The initiation and continuation of ADHD medication use might be underlined by different mechanisms and warrant different strategies.
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http://dx.doi.org/10.1089/cap.2020.0136DOI Listing
April 2021

Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study.

Genomics 2021 Mar 25;113(2):507-514. Epub 2020 Dec 25.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address:

Backgrounds: Evidence suggested the crucial roles of brain-derived neurotrophic factor (BDNF) and glutamate system functioning in the antidepressant mechanisms of low-dose ketamine infusion in treatment-resistant depression (TRD).

Methods: 65 patients with TRD were genotyped for 684,616 single nucleotide polymorphisms (SNPs). Twelve ketamine-related genes were selected for the gene-based genome-wide association study on the antidepressant effect of ketamine infusion and the resulting serum ketamine and norketamine levels.

Results: Specific SNPs and whole genes involved in BDNF-TrkB signaling (i.e., rs2049048 in BDNF and rs10217777 in NTRK2) and the glutamatergic and GABAergic systems (i.e., rs16966731 in GRIN2A) were associated with the rapid (within 240 min) and persistent (up to 2 weeks) antidepressant effect of low-dose ketamine infusion and with serum ketamine and norketamine levels.

Discussion: Our findings confirmed the predictive roles of BDNF-TrkB signaling and glutamatergic and GABAergic systems in the underlying mechanisms of low-dose ketamine infusion for TRD treatment.
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http://dx.doi.org/10.1016/j.ygeno.2020.12.030DOI Listing
March 2021

Identification of common neural substrates with connectomic abnormalities in four major psychiatric disorders: A connectome-wide association study.

Eur Psychiatry 2020 12 3;64(1):e8. Epub 2020 Dec 3.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei112, Taiwan.

Background: Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).

Methods: This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.

Results: The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.

Conclusions: These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.
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http://dx.doi.org/10.1192/j.eurpsy.2020.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057470PMC
December 2020

Using classification and regression tree modelling to investigate treatment response to a single low-dose ketamine infusion: Post hoc pooled analyses of randomized placebo-controlled and open-label trials.

J Affect Disord 2021 02 11;281:865-871. Epub 2020 Nov 11.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address:

Background: Evidence suggests that clinical markers, such as comorbid anxiety, body weight, and others can assist in predicting response to low-dose ketamine infusion in treatment resistant depression patients. However, whether a composite of clinical markers may improve the predicted probability of response is uncertain.

Methods: The current study investigated the results of our previous randomized placebo-controlled and open-label trials in which 73 patients with treatment-resistant depression (TRD) received a single ketamine infusion of 0.5 mg/kg. Clinical characteristics at baseline, including depression severity, duration of the current episode, obesity, comorbidity of anxiety disorder, and current suicide risk, were assessed as potential predictors in a classification and regression tree model for treatment response to ketamine infusion.

Results: The predicted probability of a composite of age at disease onset, depression severity, duration of current episode, and obesity/overweight was significantly greater (area under curve = .736, p = .001) than that of any one marker (all p > .05). The most powerful predictors of treatment response to ketamine infusion were younger age at disease onset and obesity/overweight. The strongest predictors of treatment nonresponse were longer duration of the current episode and greater depression severity at baseline.

Discussion: Depression severity, duration of the current episode, obesity, and age at disease onset may predict treatment response versus nonresponse to low-dose ketamine infusion. However, whether our predicted probability for a single infusion may be applied to repeated infusions would require further investigation.

Clinical Trial Registration: UMIN Clinical Trials Registry (UMIN000023581 and UMIN000016985).
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http://dx.doi.org/10.1016/j.jad.2020.11.045DOI Listing
February 2021

Proinflammatory Cytokine Dysregulation and Cognitive Dysfunction Among Patients with Remitted Bipolar I and II Disorders.

J Affect Disord 2021 02 16;281:738-743. Epub 2020 Nov 16.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital. Electronic address:

Background: Euthymic patients with bipolar disorder reportedly demonstrated increased levels of proinflammatory cytokines and cognitive function deficits. Because uncertain differences exist in cognitive function and proinflammatory cytokines between remitted bipolar I (BD1) and bipolar II (BD2) disorders, we performed this study to further investigate these differences.

Method: We enrolled 58 patients with remitted BD1 and 27 with remitted BD2, and matched them for age and sex with 51 controls. Proinflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), C-reactive protein, and soluble tumor necrosis factor receptor 1 (sTNFR1) were measured, and performance in the Word List Memory Task (WLMT) and Wisconsin Card Sorting Task (WCST) was assessed.

Results: Significantly elevated levels of sTNFR1 were observed among patients with BD1 (p < .001) and BD2 (p = .038) compared with the controls; however, they did not differ between patients with BD1 and BD2 (p =.130). Working memory deficit measured by the WLMT was significantly greater in patients with BD1 (p < .001) and BD2 (p < .05) compared with controls, but did not differ between patients with BD1 and BD2 (p > 0.1). Furthermore, sTNFR1 levels were negatively correlated with cognitive function measured using the WLMT and WCST (all p < .05).

Discussion: Our results showed that euthymic patients with BD1 and BD2 showed similar levels of sTNFR1 and cognitive function (especially working memory) impairments. Further investigation is required to explore whether a common pathophysiology may contribute to the shared inflammatory and cognitive alterations between BD1 and BD2.
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http://dx.doi.org/10.1016/j.jad.2020.11.079DOI Listing
February 2021

Using Minimal-Redundant and Maximal-Relevant Whole-Brain Functional Connectivity to Classify Bipolar Disorder.

Front Neurosci 2020 20;14:563368. Epub 2020 Oct 20.

Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.

Background: A number of mental illness is often re-diagnosed to be bipolar disorder (BD). Furthermore, the prefronto-limbic-striatal regions seem to be associated with the main dysconnectivity of BD. Functional connectivity is potentially an appropriate objective neurobiological marker that can assist with BD diagnosis.

Methods: Health controls (HC; = 173) and patients with BD who had been diagnosed by experienced physicians ( = 192) were separated into 10-folds, namely, a ninefold training set and a onefold testing set. The classification involved feature selection of the training set using minimum redundancy/maximum relevance. Support vector machine was used for training. The classification was repeated 10 times until each fold had been used as the testing set.

Results: The mean accuracy of the 10 testing sets was 76.25%, and the area under the curve was 0.840. The selected functional within-network/between-network connectivity was mainly in the subcortical/cerebellar regions and the frontoparietal network. Furthermore, similarity within the BD patients, calculated by the cosine distance between two functional connectivity matrices, was smaller than between groups before feature selection and greater than between groups after the feature selection.

Limitations: The major limitations were that all the BD patients were receiving medication and that no independent dataset was included.

Conclusion: Our approach effectively separates a relatively large group of BD patients from HCs. This was done by selecting functional connectivity, which was more similar within BD patients, and also seems to be related to the neuropathological factors associated with BD.
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http://dx.doi.org/10.3389/fnins.2020.563368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641629PMC
October 2020

Bidirectional association between migraine and depression among probands and unaffected siblings: A nationwide population-based study.

J Affect Disord 2021 01 29;279:687-691. Epub 2020 Oct 29.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Evidence suggests a bidirectional association between migraine and depression in individuals and in twins. However, whether a bidirectional association between migraine and depression also occurs among siblings (probands and unaffected nontwin siblings) remains unknown.

Methods: Using the Taiwan National Health Insurance Research Database, we examined the data of 1504 probands with migraine, 1595 unaffected siblings, and 6380 nonmigrainous controls born before 2000 to identify new-onset depression for the period between 1996 and 2011. Conversely, 31824 probands with depression, 34325 unaffected siblings, and 137300 nondepressive controls were examined for the identification of new-onset migraine.

Results: Logistic regression analyses demonstrated that compared with the controls, patients with migraine (odds ratio [OR]: 4.09; 95% confidence interval [CI]: 3.75-4.46) and unaffected siblings (OR: 1.40; 95% CI: 1.24-1.58) were more likely to develop depression during the follow-up period. Moreover, patients with depression and unaffected siblings had a 4.13-fold (95% CI: 3.18-5.36) and 1.45-fold (95% CI: 1.03-2.05) increased risk of migraine.

Discussion: The bidirectional association between migraine and depression among probands and unaffected siblings suggests a familial coaggregation of these two conditions. Additional studies are required to investigate the genetic and environmental etiologies for this coaggregation.
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http://dx.doi.org/10.1016/j.jad.2020.10.056DOI Listing
January 2021

Happiness During Low-Dose Ketamine Infusion Predicts Treatment Response: Reexploring the Adjunctive Ketamine Study of Taiwanese Patients With Treatment-Resistant Depression.

J Clin Psychiatry 2020 11 10;81(6). Epub 2020 Nov 10.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec 2, Shih-Pai Rd, Beitou District, Taipei, 112, Taiwan.

Background: Studies have reported that ketamine potentially increases subjective happiness in healthy volunteers. However, whether ketamine-induced happiness can predict the treatment response of ketamine infusion among patients with treatment-resistant depression (TRD) remains unknown.

Methods: Between 2012 and 2015, 71 adult patients with TRD (based on DSM-IV-TR criteria) were enrolled and randomly assigned to receive a 40-minute ketamine (0.5 mg/kg or 0.2 mg/kg) or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale. Measurements were conducted prior to infusion, at 40 and 240 minutes postinfusion, and, sequentially, on days 2 to 7 and 14 postinfusion. The visual analog scale for happiness (VASH) was used to assess happiness during infusion. The positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS-P) was used to measure the potential psychotomimetic effects of ketamine.

Results: For both the 2-factor (ketamine vs placebo) and 3-factor (ketamine 0.5 mg/kg vs 0.2 mg/kg vs placebo) models, a generalized estimating equation model indicated that infusion response type (happiness vs nonhappiness) significantly (P = .008 vs P = .002) predicted the trajectory of depressive symptoms after infusion. Changes in VASH and BPRS-P measures were not associated with each other.

Conclusions: Subjective happiness during ketamine infusion predicted the antidepressant effect of both 0.5 mg/kg and 0.2 mg/kg ketamine infusion over time. Happiness during ketamine infusion, which was not related to the psychotomimetic effect of ketamine, may be associated with the reduction of depressive symptoms during the follow-up.

Trial Registration: UMIN Clinical Trials Registry registration number: UMIN000016985.
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http://dx.doi.org/10.4088/JCP.20m13232DOI Listing
November 2020

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis.

Prog Neuropsychopharmacol Biol Psychiatry 2021 03 7;106:110168. Epub 2020 Nov 7.

Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science and Brain Research Center, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Repetitive transcranial magnetic stimulation (rTMS) is the current treatment option for major depression (MD). Theta-burst stimulation (TBS), a variation of rTMS, affords a short stimulation duration, low stimulation pulse intensity, and possibility to improve rTMS efficiency. This systematic review and meta-analysis examined the studies on efficacy and tolerability of TBS in patients with MD.

Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature from 1990 until May 24, 2020, and performed a random-effects meta-analysis by including response and remission rates of depression and dropout rates as main outcome measures.

Results: In total, 10 studies including 6 randomized controlled trials (RCTs; n = 294) and 4 uncontrolled clinical trials (non-RCTs; n = 297) were included. The overall effect size of response rate and remission rates were 0.38 (95% confidence interval [CI]: 0.29-0.48) and 0.20 (95% CI: 0.13-0.29), respectively. Notably, the TBS group showed favorable efficacy without major adverse events.

Conclusions: TBS treatment was more efficient in terms of time and energy than the standard rTMS was. Our meta-analysis provided evidence that the application of TBS to the dorsolateral prefrontal cortex is associated with significant antidepressant effects along with favorable tolerability.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110168DOI Listing
March 2021

Network-Specific Corticothalamic Dysconnection in Attention-Deficit Hyperactivity Disorder.

J Dev Behav Pediatr 2021 Feb-Mar 01;42(2):122-127

Department of Psychiatry, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.

Background: Functional connectivity (FC) is believed to be abnormal in attention-deficit hyperactivity disorder (ADHD). Most studies have focused on frontostriatal systems, and the role of the thalamic network in ADHD remains unclear. The current study used FC magnetic resonance imaging (fcMRI) to explore corticothalamic network properties and correlated network dysconnection with ADHD symptom severity.

Methods: Eighteen adolescents with ADHD and 16 healthy controls aged 12 to 17 years underwent resting functional MRI scans, clinical evaluations, and 2 parent rating scales, namely the Swanson, Nolan, and Pelham IV scale and the Child Behavior Checklist. Six a priori cortical regions of interest were used to derive 6 networks: the dorsal default mode network, frontoparietal network, cingulo-opercular network (CON), primary sensorimotor network (SM1), primary auditory network, and primary visual network (V1). The corticothalamic connectivity for each network was calculated for each participant and then compared between the groups. We also compared the 2 scales with the network connectivity.

Results: The corticothalamic connectivity within the CON was significantly reduced (p < 0.05) among adolescents with ADHD compared with the controls. The corticothalamic dysconnection within the CON, SM1, and V1 networks negatively correlated with ADHD symptom severity.

Conclusion: This network analysis indicates that corticothalamic dysconnection in ADHD involves the CON, SM1, and V1 networks and relates to symptom severity. The findings provide evidence of dysfunctional thalamus-related networks in ADHD.
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http://dx.doi.org/10.1097/DBP.0000000000000875DOI Listing
February 2020

Cardiometabolic disease risk among siblings of patients with major depressive disorder.

J Dev Orig Health Dis 2021 06 14;12(3):530-535. Epub 2020 Sep 14.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.
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http://dx.doi.org/10.1017/S2040174420000860DOI Listing
June 2021

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study.

Psychol Med 2020 Sep 11:1-11. Epub 2020 Sep 11.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

Methods: This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

Results: FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50-19.67), ADHD 3.94 (CI 3.72-4.17), schizophrenia 3.05 (CI 2.74-3.40), BD 2.22 (CI 1.98-2.48) and MDD 1.88 (CI 1.76-2.00). Higher RRs of schizophrenia (4.47, CI 3.95-5.06) and ASD (18.54, CI 16.18-21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

Conclusions: The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.
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http://dx.doi.org/10.1017/S0033291720003207DOI Listing
September 2020

Role of appetite hormone dysregulation in the cognitive function among patients with bipolar disorder and major depressive disorder.

World J Biol Psychiatry 2021 07 23;22(6):428-434. Epub 2020 Sep 23.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Objectives: The association of appetite hormones with cognitive function in patients with affective disorders remains unknown.

Methods: All total, 58 adult patients with bipolar I disorder, 36 with bipolar II disorder, 40 with major depressive disorder were enrolled and age and sex-matched with 40 controls. The levels of appetite hormones leptin, ghrelin, insulin and adiponectin were assessed. Wisconsin Card Sorting Test was used to assess executive function.

Results: A general linear model, adjusted for demographic data and clinical symptoms, demonstrated the ghrelin levels were higher in patients with bipolar I or II disorder than in those with major depressive disorder and controls ( < 0.001). We also identified a positive correlation of ghrelin level and executive function among patients with bipolar I ( = 0.033) and II ( = 0.027) disorders, but not among those with major depressive disorder and controls.

Conclusions: Patients with bipolar I or II disorder were more likely to have high levels of ghrelin than patients with major depressive disorder and controls, which may have a positive correlation on the cognitive function of patients with bipolar I or II disorder.
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http://dx.doi.org/10.1080/15622975.2020.1819566DOI Listing
July 2021

Association of parental depression with offspring attention deficit hyperactivity disorder and autism spectrum disorder: A nationwide birth cohort study.

J Affect Disord 2020 12 19;277:109-114. Epub 2020 Jul 19.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217 Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address:

Background: Studies have indicated that parental depression was slightly related to the increased risk of offspring attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, the association between exposure to parental depression at different neurodevelopmental stages (i.e., perinatal or postnatal period) and subsequent ADHD and ASD development remained uncertain.

Method: 708,515 children born between 2001 and 2008 were screened for ADHD and ASD based on ICD-9-CM codes of 314 and 299 given by psychiatrists from their birth to the end of 2011. Paternal and maternal depression was separately assessed during five periods, namely those before pregnancy (pre-pregnancy), during pregnancy (perinatal), and <1, 1-3, and >3 years after childbirth (postnatal). Cox regression analyses were performed.

Results: Both paternal and maternal depression occurring in the pre-pregnancy, perinatal and postnatal periods were significantly associated with subsequent ADHD and ASD in the offspring, with hazard ratios between 1.42 (95% confidence interval [CI]: 1.35-1.49) and 2.25 (2.09-2.41). The chronicity and additive effect of paternal and maternal depression were related to increased risks of offspring ADHD and ASD. The effects of maternal depression were stronger than the effects of paternal depression for offspring ADHD (HR: 1.35, 95% CI: 1.27-1.45) and ASD (HR: 1.23, 95% CI: 1.05-1.46) risks.

Conclusion: Both paternal depression and maternal depression in the pre-pregnancy, perinatal and postnatal periods increases offspring ADHD and ASD risks, and these risks increase further with increases in the duration of parental depression and with the additive effect of parental and maternal depression.
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http://dx.doi.org/10.1016/j.jad.2020.07.059DOI Listing
December 2020

Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression.

Int J Neuropsychopharmacol 2020 12;23(12):791-798

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown.

Methods: In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls.

Results: Compared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion.

Conclusion: Reduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.
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http://dx.doi.org/10.1093/ijnp/pyaa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770518PMC
December 2020

Sexually transmitted infections among adolescents with conduct disorder: a nationwide longitudinal study.

Eur Child Adolesc Psychiatry 2021 Aug 28;30(8):1187-1193. Epub 2020 Jul 28.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, Taipei, 11217, Taiwan, ROC.

Studies have demonstrated that conduct disorder is related to risky sexual behaviors, the dominant risk factor for contracting a sexually transmitted infection (STI). However, the association between conduct disorder and STIs remains unclear. Using the Taiwan National Health Insurance Research Database, 5733 adolescents with conduct disorder and 22,932 age- and sex-matched controls without conduct disorder were enrolled from 2001 to 2009 and were subject to follow-up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was performed to examine the likelihood of subsequently contracting an STI for patients and controls. Patients with conduct disorder were more likely than controls to develop any STI (HR 3.95, 95% CI 2.97-5.26) after adjusting for demographic data, psychiatric comorbidities, and use of medications. Long-term use of second-generation antipsychotics (SGAs) was related to a reduced risk (HR 0.36, 95% CI 0.14-0.91) of developing an STI among patients with conduct disorder. Adolescents with conduct disorder had an increased risk of developing any STI later in life compared with those without conduct disorder. Long-term use of SGAs was associated with a lower risk of subsequent STI.
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http://dx.doi.org/10.1007/s00787-020-01605-5DOI Listing
August 2021

Increased Proinflammatory Cytokines, Executive Dysfunction, and Reduced Gray Matter Volumes In First-Episode Bipolar Disorder and Major Depressive Disorder.

J Affect Disord 2020 09 3;274:825-831. Epub 2020 Jun 3.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Backgrounds: The association between systemic inflammation, executive dysfunction, and gray matter (GM) volume difference in first-episode affective disorders, including bipolar and major depressive disorders, is unclear.

Methods: Twenty-two patients with first-episode bipolar disorder, 22 age- and sex-matched patients with first-episode major depressive disorder, and 22 matched controls were enrolled in our study; all patients underwent comprehensive assessments, including clinical assessment, executive function examination (Wisconsin card sorting test [WCST]), proinflammatory cytokine receptors (soluble interleukin-6 receptor and tumor necrosis factor-α receptor 1 [TNFR1]), and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze the GM volume difference between bipolar and major depressive disorders.

Results: Patients with bipolar disorder were more likely to exhibit higher levels of TNFR1 (P = .038), more number of deficits in WCST (P < .05), and smaller GM volume in the middle frontal cortex (uncorrected voxel level P < .001) compared with those with major depressive disorder and healthy controls. Positive associations were observed between the middle frontal cortex volume, executive function, and the TNFR1 level.

Discussion: GM volume reduction in the middle frontal cortex, a greater level of systemic inflammation, and executive dysfunction were observed in first-episode affective disorders, especially bipolar disorder. A positive correlation between middle frontal cortex volume, executive function, and the TNFR1 level may indicate a divergent effect of brain and systemic inflammation functioning in the early phase (first episode) of affective disorder.
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http://dx.doi.org/10.1016/j.jad.2020.05.158DOI Listing
September 2020

Treatment-Resistant depression enhances risks of dementia and alzheimer's disease: A nationwide longitudinal study.

J Affect Disord 2020 09 2;274:806-812. Epub 2020 Jun 2.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan. Electronic address:

Background: Previous evidence indicates late-onset depression or depression with greater severity are associated with subsequent risk of dementia or Alzheimer's disease (AD). However, whether treatment-resistant depression is associated with such risks remain elusive.

Methods: Using the Taiwan Nationwide Health Insurance Research Database, 3,345 patients with newly-diagnosed major depressive disorder (MDD) and 13,380 well-matched controls were enrolled between 2002 and 2004. MDD patients were stratified according to their treatment response to adequate antidepressant trials, and all participants were followed up until the end of 2013. Those who developed dementia and AD were identified.

Results: MDD patients were more likely to develop dementia and AD than controls. Difficult-to-treat patients (i.e., DTT; those who failed to respond to at least two adequate antidepressant trials) had the highest risk of developing dementia (hazard ratio [HR] = 5.19) and AD (HR 4.44), whereas easy-to-treat patients (i.e., ETT-1; those who had no prescription of antidepressants) had the lowest risk of developing dementia (HR 2.37) and AD (HR 2.59) compared with controls. Subsequent analysis demonstrated that only among patients with late-onset depression (age > 65 years), DTT patients consistently showed higher risks and faster development of dementia (HR 6.64, mean: 1.45 yr) and AD (HR 4.97, mean: 1.67 yr) than did ETT-1 patients and controls.

Limitations: Subjects who have not received medical examination were not included as diagnosis were determined by ICD codes. Also, longer follow-up period might be needed for the younger group.

Conclusions: Late-onset treatment-resistant depression is associated with an elevated risk of dementia and AD.
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http://dx.doi.org/10.1016/j.jad.2020.05.150DOI Listing
September 2020

Corrigendum to "Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion". J Affect Disord. 2018 Dec 1;241:1-7. doi: 10.1016/j.jad.2018.07.033. Epub 2018 Jul 27.

J Affect Disord 2020 Sep 24;274:1219. Epub 2020 Jun 24.

Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Me Tung-Ping Su dical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2020.05.137DOI Listing
September 2020

Corrigendum to "Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion". J Affect Disord. 2018 Dec 1;241:1-7. doi: 10.1016/j.jad.2018.07.033. Epub 2018 Jul 27.

J Affect Disord 2020 Sep 24;274:1219. Epub 2020 Jun 24.

Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Me Tung-Ping Su dical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2020.05.137DOI Listing
September 2020

Role of obesity in systemic low-grade inflammation and cognitive function in patients with bipolar I disorder or major depressive disorder.

CNS Spectr 2020 Jun 29:1-7. Epub 2020 Jun 29.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background.: Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.

Methods.: Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines-including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)-were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.

Results.: Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.

Conclusions.: Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.
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http://dx.doi.org/10.1017/S1092852920001534DOI Listing
June 2020

Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study.

Gut 2021 01 23;70(1):85-91. Epub 2020 Jun 23.

Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

Objective: Increasing evidence supports reciprocal communication between the enteric and the central nervous system in disease, termed the 'gut-brain axis'. Recent findings suggest a connection between IBD and development of Parkinson's disease. The role of IBD in dementia, another insidious neurodegenerative disorder, has not been explored.

Design: Using the Taiwanese National Health Insurance Research Database, we performed comparative analysis of 1742 patients with IBD ≥45 years old against 17 420 controls to assess dementia risk following IBD diagnosis. Controls were matched on bases of sex, access to healthcare, income and dementia-related comorbidities. All individuals were followed for dementia diagnosis for up to 16 years. Subanalyses included the relationship between sex, ulcerative colitis (UC) and Crohn's disease (CD), and dementia risk.

Results: Overall incidence of dementia among patients with IBD was significantly elevated (5.5% vs 1.4% among controls). Patients with IBD were diagnosed with dementia at 76.24 years old on average, compared with 83.45 among controls. The HR of developing dementia among patients with IBD was 2.54 (95% CI 1.91 to 3.37). Among dementia types, the risk of developing Alzheimer's dementia demonstrated the greatest increase. Dementia risk did not differ between sex differences nor UC versus CD.

Conclusion: This population-based cohort study demonstrates significant association between IBD and subsequent development of dementia. Dementia was diagnosed at an earlier age among patients with IBD, and disease risk appeared to increase with IBD chronicity. These findings highlight the need for future research to elucidate the relationship between IBD and dementia.
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http://dx.doi.org/10.1136/gutjnl-2020-320789DOI Listing
January 2021

Efficacy of low-dose ketamine infusion in anxious vs nonanxious depression: revisiting the Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression.

CNS Spectr 2021 08 18;26(4):362-367. Epub 2020 May 18.

Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.

Background: The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.

Methods: In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period.

Results: Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo.

Conclusions: Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.
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http://dx.doi.org/10.1017/S1092852920001194DOI Listing
August 2021

Proton pump inhibitors are associated with increased risk of alopecia areata: A nationwide nested case-control study.

J Am Acad Dermatol 2020 Nov 28;83(5):1460-1462. Epub 2020 Apr 28.

School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.02.076DOI Listing
November 2020

The Risk of Sexually Transmitted Infections Following First-Episode Schizophrenia Among Adolescents and Young Adults: A Cohort Study of 220 545 Subjects.

Schizophr Bull 2020 07;46(4):795-803

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Young people are disproportionately affected by sexually transmitted infections (STIs). The risk of STIs in young people following first-episode schizophrenia is unknown. This study using Taiwan's National Health Insurance Research Database enrolled 44 109 adolescents and young adults with first-episode schizophrenia and 176 436 age- and sex-matched controls without schizophrenia from 2001 through 2009 and followed to the end of 2011. New-onset STIs were identified. Survival analysis was performed. Cox regression analysis was used to examine the effects of comorbid substance use disorder (SUD), schizophrenia medications, and schizophrenia severity. The E value for causality of evidence was calculated. We found that young people had a higher risk of STIs following first-episode schizophrenia compared with controls without schizophrenia (hazard ratio [HR] = 2.35, 95% CI = 2.08-2.64); these STIs included human immunodeficiency virus (HIV) (3.70, 2.60-5.28) and syphilis (5.35, 3.96-7.23). They also showed a disproportionate distribution of STIs, with an increased proportion of syphilis (20.4% vs 8.2%) and HIV (9.1% vs 6.0%). When presenting with SUD, the risks of HIV (11.00, 7.02-17.25) and syphilis (9.11, 6.16-13.47) were further increased. The severe schizophrenia group had an extremely high risk of syphilis (41.26, 27.69-61.47) and HIV (7.50, 3.85-14.62). Schizophrenia medications may provide beneficial effects against contracting STIs (0.77, 0.68-0.89). We concluded that following first-episode schizophrenia, young patients are at higher risk of STIs, particularly HIV and syphilis. The risk further increased when subjects presented with SUD or severe schizophrenia. Importantly, antipsychotic treatment may lower the risk of STIs.
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http://dx.doi.org/10.1093/schbul/sbz126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344918PMC
July 2020

A comparison study of metabolic profiles, immunity, and brain gray matter volumes between patients with bipolar disorder and depressive disorder.

J Neuroinflammation 2020 Jan 30;17(1):42. Epub 2020 Jan 30.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.

Background: Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD.

Methods: In this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed.

Results: Compared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels.

Conclusions: Our results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.
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http://dx.doi.org/10.1186/s12974-020-1724-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990475PMC
January 2020

Functional connectivity of specific brain networks related to social and communication dysfunction in adolescents with attention-deficit hyperactivity disorder.

Psychiatry Res 2020 02 13;284:112785. Epub 2020 Jan 13.

Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan; Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Adolescents with attention-deficit hyperactivity disorder (ADHD) may have impaired social cognition and communication. However, the functioning of the brain networks involved in the social cognition and communication impairment in ADHD patients remains unclear.

Methods: In total, 18 adolescents with ADHD and 16 age- and sex-matched typically developing adolescents (controls)-all of whom underwent a brain magnetic resonance imaging examination-were enrolled. Their parents filled out Swanson, Nolan, and Pelham IV (SNAP-IV) and Social Responsiveness Scale (SRS) questionnaires. Functional connectivity analyses based on the default mode network, frontoparietal network, and cinguloopercular network were performed.

Results: Compared with controls, adolescents with ADHD exhibited higher total and subscale scores on SNAP-IV and SRS. Higher SNAP-IV and SRS scores were associated with higher functional connectivity between the default mode network (ventromedial prefrontal cortex) and cinguloopercular network (anterior insula) and between the FPN (dorsolateral and prefrontal cortex) and cinguloopercular network, but with lower functional connectivity between the default mode network (posterior cingulate cortex) and frontoparietal network (inferior parietal lobule) and between the default mode network (precuneus) and cinguloopercular network (temporoparietal junction).

Discussion: Social cognition and communication impairment and ADHD may commonly share the aberrant functional connectivity in the default mode network, frontoparietal network, and cinguloopercular network.
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http://dx.doi.org/10.1016/j.psychres.2020.112785DOI Listing
February 2020

Early Pregnancy Risk Among Adolescents With ADHD: A Nationwide Longitudinal Study.

J Atten Disord 2021 07 23;25(9):1199-1206. Epub 2020 Jan 23.

Taipei Veterans General Hospital, Taipei.

ADHD potentially leads to risky sexual behaviors, and is considered a major risk factor for early pregnancy (EP). However, the association between ADHD and subsequent EP remains unknown. Seven thousand five hundred five adolescents with ADHD and 30,020 age- and sex-matched individuals without ADHD were enrolled from 2001 to 2009 and were followed until the end of 2011. Adolescents who developed any pregnancy (at age ≤30 years) or EP (at age <20 years) during the follow-up period were identified. Adolescents with ADHD were found to be prone to pregnancy (hazard ratio [HR] = 1.27) and EP (HR = 2.30) compared with those without ADHD. Long-term ADHD medication use was related to a lower risk of subsequent any pregnancy (HR = 0.72) and EP (HR = 0.69). Adolescents with ADHD had an increased risk of any pregnancy and EP compared with their non-ADHD counterparts. Long-term ADHD medication use was associated with a lower subsequent EP risk.
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http://dx.doi.org/10.1177/1087054719900232DOI Listing
July 2021

Familial coaggregation of major psychiatric disorders among first-degree relatives of patients with obsessive-compulsive disorder: a nationwide study.

Psychol Med 2021 03 7;51(4):680-687. Epub 2020 Jan 7.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear.

Methods: Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD.

Results: FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68-8.57), bipolar disorder (RR 2.85, 95% CI 2.68-3.04), MDD (RR 2.67, 95% CI 2.58-2.76), ASD (RR 2.38, 95% CI 2.10-2.71), ADHD (RR 2.19, 95% CI 2.07-2.32), and schizophrenia (RR 1.97, 95% CI 1.86-2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder.

Conclusions: The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.
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http://dx.doi.org/10.1017/S0033291719003696DOI Listing
March 2021
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