Publications by authors named "Tung-Ping Su"

246 Publications

Risks of Coaggregation of Major Psychiatric Disorders Among First-Degree Relatives of Patients With Bipolar I and Bipolar II Disorder: Evidence From a Nationwide Population-Based Study.

J Clin Psychiatry 2021 Sep 7;82(5). Epub 2021 Sep 7.

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

Etiologic differences between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) have been challenged recently, and family epidemiologic studies may elucidate the matter. Nevertheless, it remains unclear whether BD-I and BD-II display different familial aggregation patterns within each bipolar disorder subtype and coaggregation with other psychiatric disorders.

Per the Taiwan National Health Insurance Research Database (N = 23,258,175), patients with bipolar disorder were classified as having BD-I or BD-II based on the history of psychiatric hospitalization for a manic episode. During the study period (2001-2011), 184,958 first-degree relatives (FDRs) of patients with BD-I and BD-II were identified. By comparing patients with 1:4 age-, sex-, and kinship-matched samples without BD-I/BD-II probands, the relative risks (RRs) of major psychiatric disorders were estimated.

FDRs of BD-I probands had a significantly higher risk of BD-I than those of BD-II probands (BD-I proband: RR = 15.80 vs BD-II proband: RR = 5.68,  < .001). The risk of BD-II was similar between FDRs of BD-I and BD-II probands (BD-I proband: RR = 6.48 vs BD-II proband: RR = 5.89,  = .1161). Familial aggregation was greater within each BD subtype than among cross-subtypes. Furthermore, FDRs of BD-I probands had an increased risk of schizophrenia (BD-I probands: RR = 5.83 vs BD-II probands: RR = 2.72,  < .001); FDRs of BD-II probands had a higher likelihood of attention-deficit/hyperactivity disorder (BD-II probands: 2.36 vs BD-I probands: 1.93,  = .0009).

The risk of psychiatric disorders is higher among the FDRs of patients with either BD-I or BD-II. Furthermore, the familial specificity of BD-I and BD-II assessed in this study may further the current understanding of etiologic boundaries between bipolar disorder subtypes.
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http://dx.doi.org/10.4088/JCP.20m13810DOI Listing
September 2021

Dengue and dementia risk: A nationwide longitudinal study.

J Infect 2021 Aug 27. Epub 2021 Aug 27.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address:

Background: Accumulating evidence suggests neurological manifestations after dengue infection. However, the relationship between dengue and long-term neurocognitive sequel remains unclear.

Methods: We recruited 816 patients with dengue and 8,160 controls between 1997 and 2012 using data from Taiwan National Health Insurance Research Database and followed them up until the end of 2013. Individuals who exhibited any type of dementia were identified during the follow-up period. Cox regression analyses were performed with adjustments for demographic data and medical and mental comorbidities (cerebrovascular diseases, traumatic brain injury, hypertension, dyslipidemia, diabetes mellitus, depression, alcohol use disorder, and substance use disorder). The E-value for the causality of the evidence was calculated. Sensitivity analysis was conducted to exclude patients with prodromal dementia.

Results: Patients with dengue were more likely to develop dementia (hazard ratio [HR]: 2.23, 95% confidence interval [CI]: 1.51-3.28), Alzheimer's disease (HR: 3.03, 95% CI: 1.08-8.45), and unspecified dementia (HR: 2.25, 95% CI: 1.43-3.53), but not vascular dementia compared to controls during the follow-up period. Sensitivity analyses after exclusion of the observation period over the first three years or first five years and after exclusion of patients' enrollment before 2010 or 2008 showed consistent findings. The E-values for the HR (range 3.62-5.51) supported the association between dengue and subsequent dementia among the whole population, men, and women.

Conclusion: The risk of dementia was 2.23-fold higher in patients diagnosed with dengue during the follow-up period than in the controls. Further studies are necessary to investigate the underlying pathophysiology of dengue and dementia.
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http://dx.doi.org/10.1016/j.jinf.2021.08.037DOI Listing
August 2021

Identifying subtypes of bipolar disorder based on clinical and neurobiological characteristics.

Sci Rep 2021 Aug 24;11(1):17082. Epub 2021 Aug 24.

Institute of Biophotonics, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Taipei, 112, Taiwan.

The ability to classify patients with bipolar disorder (BD) is restricted by their heterogeneity, which limits the understanding of their neuropathology. Therefore, we aimed to investigate clinically discernible and neurobiologically distinguishable BD subtypes. T1-weighted and resting-state functional magnetic resonance images of 112 patients with BD were obtained, and patients were segregated according to diagnostic subtype (i.e., types I and II) and clinical patterns, including the number of episodes and hospitalizations and history of suicide and psychosis. For each clinical pattern, fewer and more occurrences subgroups and types I and II were classified through nested cross-validation for robust performance, with minimum redundancy and maximum relevance, in feature selection. To assess the proportion of variance in cognitive performance explained by the neurobiological markers, multiple linear regression between verbal memory and the selected features was conducted. Satisfactory performance (mean accuracy, 73.60%) in classifying patients with a high or low number of episodes was attained through functional connectivity, mostly from default-mode and motor networks. Moreover, these neurobiological markers explained 62% of the variance in verbal memory. The number of episodes is a potentially critical aspect of the neuropathology of BD. Neurobiological markers can help identify BD neuroprogression.
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http://dx.doi.org/10.1038/s41598-021-96645-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385023PMC
August 2021

Identifying subtypes of bipolar disorder based on clinical and neurobiological characteristics.

Sci Rep 2021 Aug 24;11(1):17082. Epub 2021 Aug 24.

Institute of Biophotonics, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Taipei, 112, Taiwan.

The ability to classify patients with bipolar disorder (BD) is restricted by their heterogeneity, which limits the understanding of their neuropathology. Therefore, we aimed to investigate clinically discernible and neurobiologically distinguishable BD subtypes. T1-weighted and resting-state functional magnetic resonance images of 112 patients with BD were obtained, and patients were segregated according to diagnostic subtype (i.e., types I and II) and clinical patterns, including the number of episodes and hospitalizations and history of suicide and psychosis. For each clinical pattern, fewer and more occurrences subgroups and types I and II were classified through nested cross-validation for robust performance, with minimum redundancy and maximum relevance, in feature selection. To assess the proportion of variance in cognitive performance explained by the neurobiological markers, multiple linear regression between verbal memory and the selected features was conducted. Satisfactory performance (mean accuracy, 73.60%) in classifying patients with a high or low number of episodes was attained through functional connectivity, mostly from default-mode and motor networks. Moreover, these neurobiological markers explained 62% of the variance in verbal memory. The number of episodes is a potentially critical aspect of the neuropathology of BD. Neurobiological markers can help identify BD neuroprogression.
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http://dx.doi.org/10.1038/s41598-021-96645-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385023PMC
August 2021

Risk of attention deficit hyperactivity and autism spectrum disorders among the children of parents with autoimmune diseases: a nationwide birth cohort study.

Eur Child Adolesc Psychiatry 2021 Aug 13. Epub 2021 Aug 13.

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

Studies have suggested that maternal autoimmune diseases are associated with an increased risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, research on the association of paternal autoimmune diseases with ADHD and ASD risk has remained inconclusive. Using the Taiwan National Health Insurance Research Database, we selected 708,517 family triads (father-mother-child) between 2001 and 2008 and followed them until the end of 2011. Parental autoimmune diseases as well as ADHD and ASD in children were identified during the study period. Increased ADHD risk in children in terms of hazard ratios (HRs) and 95% confidence intervals (CIs) was associated with prenatal exposure to paternal autoimmune diseases, including Sjögren's syndrome (HR: 8.41, 95% CI: 2.72-26.05), psoriasis (HR: 1.95, 95% CI: 1.05-3.63), and ankylosing spondylitis (HR: 2.02, 95% CI: 1.29-2.15), as well as maternal autoimmune diseases, such as systemic lupus erythematosus (HR: 1.53, 95% CI: 1.09-2.15), type 1 diabetes mellitus (HR: 1.55, 95% CI: 1.02-2.36), inflammatory bowel disease (HR: 2.37, 95% CI: 1.59-3.52), psoriasis (HR: 1.70, 95% CI: 1.00-2.87), and ankylosing spondylitis (HR: 2.07, 95% CI: 1.11-3.86). However, ASD was only associated with paternal inflammatory bowel disease (HR: 3.08, 95% CI: 1.15-8.28) and ankylosing spondylitis (HR: 2.65, 95% CI: 1.10-6.39). Both paternal and maternal autoimmune diseases were associated with increased likelihood of ADHD in children. However, only paternal autoimmune diseases were related to offspring ASD risk. The precise pathomechanism underlying the correlation between parental autoimmunity and child neurodevelopment requires further investigation.
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http://dx.doi.org/10.1007/s00787-021-01860-0DOI Listing
August 2021

Postpartum Depression and Psychosis and Subsequent Severe Mental Illnesses in Mothers and Neurodevelopmental Disorders in Children: A Nationwide Study.

J Clin Psychiatry 2021 Jul 27;82(4). Epub 2021 Jul 27.

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

The association between postpartum depression and postpartum psychosis and subsequent maternal and offspring mental disorders in Western countries has been established; however, whether the relationship can be generalized to the Asian population is unknown.

Using the Taiwan National Health Insurance Research Database, this study enrolled 933,745 mother-infant pairs who delivered their first child and had no history of severe mental illness before childbirth from 2001 to 2010. Postpartum depression and postpartum psychosis were assessed in 3 periods between childbirth and 3, 6, or 12 months after childbirth. Subsequent maternal schizophrenia ( code: 295), bipolar disorder ( code: 296 except 296.2x, 296.3x, 296.9x, and 296.82), and depressive disorder ( codes: 296.2x, 296.3x, 300.4, and 311) and offspring autism spectrum disorder (ASD; code: 299) and attention-deficit/hyperactivity disorder (ADHD; code: 314) were identified during the follow-up period to the end of 2011.

Both postpartum depression and postpartum psychosis were found to be related to increased risks of schizophrenia, bipolar disorder, and depressive disorder in mothers, with hazard ratios (HRs) ranging between 8.80 (95% CI, 7.95-9.74) and 63.96 (95% CI, 50.39-81.18). Children exposed to maternal postpartum depression and psychosis were more likely to develop ADHD. Only postpartum depression was related to the likelihood of offspring ASD.

Per these findings, we clinicians and health care providers should closely monitor the mental health condition of postpartum women and their children.
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http://dx.doi.org/10.4088/JCP.20m13735DOI Listing
July 2021

Increased Risk of Stroke in Patients With Obsessive-Compulsive Disorder: A Nationwide Longitudinal Study.

Stroke 2021 Aug 27;52(8):2601-2608. Epub 2021 May 27.

Department of Psychiatry (M.-H.C., S.-J.T., T.-P.S., C.-T.L., W.-C.L., Y.-M.B.), Taipei Veterans General Hospital, Taiwan.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032995DOI Listing
August 2021

Obsessive-Compulsive Disorder and Dementia Risk: A Nationwide Longitudinal Study.

J Clin Psychiatry 2021 May 11;82(3). Epub 2021 May 11.

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

Background: Several case reports have suggested an association between obsessive-compulsive disorder (OCD) and dementia. However, the exact relationship remains unclear.

Methods: Using the Taiwan National Health Insurance Research Database, 1,347 patients with OCD (ICD-9-CM code 300.3) aged ≥ 45 years and 13,470 controls matched for age, sex, residence, income, and dementia-related comorbidities were included between 1996 and 2013 for investigation of subsequent dementia from enrollment to the end of 2013. Stratified Cox regression analysis on each matched pair was applied to assess the dementia risk between the OCD and control groups. The analysis for the current study was performed in 2018.

Results: Patients with OCD had increased risk of developing any dementia (hazard ratio [HR] = 4.28; 95% confidence interval [CI], 2.96-6.21), Alzheimer's disease (HR = 4.04; 95% CI, 1.55-10.54), and vascular dementia (HR = 3.95; 95% CI, 1.70-9.18) compared with controls.

Discussion: Future research on the pathogenic mechanisms and molecular underpinnings of the relationship between OCD and dementia may lead to the development of novel therapeutics.
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http://dx.doi.org/10.4088/JCP.20m13644DOI Listing
May 2021

Effect of relative age on childhood mental health: A cohort of 9,548,393 children and adolescents.

Acta Psychiatr Scand 2021 08 1;144(2):168-177. Epub 2021 Jun 1.

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

Background: The effect of relative age on the diagnoses of attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DD), anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications remains unclear.

Aim: To clarify the impact of relative age in a school year with the diagnoses of ADHD, DD, anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications.

Methods: The annual cutoff birthdate for entry to school in Taiwan is August 31. The Taiwan National Health Insurance Research Database was used to enroll 9,548,393 children and adolescents aged 3-17 years during the study period (September 1, 2001, to August 31, 2011). The Poisson regression model was performed to examine the likelihood of receiving diagnoses of ADHD, DD, anxiety disorder, and depressive disorder, as well as the prescription of ADHD and antidepressant medications among children born in August (the youngest) and September (the oldest).

Results: Both boys and girls born in August had a higher risk of being diagnosed as having ADHD (odds ratio [OR] = boys: 1.65, girls: 1.80), DD (1.29, 1.45), anxiety disorder (1.49, 1.33), and depressive disorder (1.10, 1.10). Furthermore, children born in August were more likely to be prescribed ADHD medication (1.71, 1.72) and antidepressants (1.18, 1.09) compared with those born in September.

Discussion: Relative age, as an indicator of neurocognitive maturity, is a critical factor for the likelihood of being diagnosed as having ADHD, DD, anxiety disorder, and depressive disorder among children and adolescents.
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http://dx.doi.org/10.1111/acps.13327DOI Listing
August 2021

Effect of relative age on diagnosis of autism spectrum disorder in children: a nationwide study in Taiwan.

Eur Child Adolesc Psychiatry 2021 May 8. Epub 2021 May 8.

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

Background: The annual cut-off birthdate for entry into school in Taiwan is August 31. Thus, children and adolescents born in August are typically the youngest in their grades. The potential effect of relative age on the diagnosis of autism spectrum disorder (ASD) remains uncertain.

Methods: A total of 9,548,393 individuals aged 3-17 years during the study period (from September 1, 2001, to August 31, 2011) identified from the Taiwan National Health Insurance Research Database were enrolled into our study. Logistic regression analysis was used to examine the likelihood of receiving ASD diagnosis for those who were born in August (the youngest) compared with those who were born in September (the oldest).

Results: Both boys and girls born in August had a higher likelihood of being diagnosed with ASD (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.16-1.32; OR: 1.23, 95% CI 1.06-1.42) than did those born in September. Sensitivity analysis conducted over different periods revealed consistent findings.

Discussion: Relative age, as an indicator of neurocognitive maturity, is a crucial contributor to the risk of being diagnosed with ASD among children and adolescents. Our findings highlight the importance of considering the age of a child within a grade when diagnosing ASD.
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http://dx.doi.org/10.1007/s00787-021-01791-wDOI Listing
May 2021

Effects of treatment refractoriness and brain-derived neurotrophic factor Val66Met polymorphism on antidepressant response to low-dose ketamine infusion.

Eur Arch Psychiatry Clin Neurosci 2021 Oct 7;271(7):1267-1274. Epub 2021 May 7.

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

Evidence suggests that levels of treatment refractoriness and brain-derived neurotrophic factor (BDNF) rs6265 polymorphism are related to the antidepressant effects of conventional antidepressants and repetitive transcranial magnetic stimulation. However, whether these factors are associated with the antidepressant effects of low-dose ketamine remains unclear. In total, 71 patients with treatment-resistant depression (TRD) were randomized to 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline control infusion groups. They were further divided into three treatment refractoriness groups according to the Maudsley staging method and were genotyped for Val66Met BDNF polymorphism. Participants' Hamilton Depression Rating Scale (HDRS) scores were assessed preinfusion, at 40, 80, 120, and 240 min postinfusion, and sequentially on days 2-7 and 14 after infusion. Patients with any Val allele exhibited an antidepressant response (p = 0.029) to 0.5 mg/kg ketamine vs. 0.2 mg/kg ketamine vs. saline control infusions. However, the trajectory of HDRS scores did not differ (p = 0.236) between the treatment groups among Met/Met carriers. In the low treatment refractoriness group, the 0.2 mg/kg ketamine infusion exhibited the optimal antidepressant effect (p = 0.002); in the moderate treatment refractoriness group, the 0.5 mg/kg ketamine infusion achieved the strongest antidepressant effect (p = 0.006); however, in the high treatment refractoriness group, the trajectory of depressive symptoms did not differ between treatments (p = 0.325). In future clinical practice, ketamine dose may be adjusted according to the level of treatment refractoriness and BDNF rs6265 polymorphism to achieve the optimal antidepressant effect for patients with TRD.
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http://dx.doi.org/10.1007/s00406-021-01264-wDOI Listing
October 2021

Task-Modulated Brain Activity Predicts Antidepressant Responses of Prefrontal Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Control Study.

Chronic Stress (Thousand Oaks) 2021 Jan-Dec;5:24705470211006855. Epub 2021 Apr 8.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei.

Background: Prolonged intermittent theta-burst stimulation (piTBS) and repetitive transcranial magnetic stimulation (rTMS) are effective antidepressant interventions for major depressive disorder (MDD). Cognition-modulated frontal theta (frontalθ) activity had been identified to predict the antidepressant response to 10-Hz left prefrontal rTMS. However, whether this marker also predicts that of piTBS needs further investigation.

Methods: The present double-blind randomized trial recruited 105 patients with MDD who showed no response to at least one adequate antidepressant treatment in the current episode. The recruited patients were randomly assigned to one of three groups: group A received piTBS monotherapy; group B received rTMS monotherapy; and group C received sham stimulation. Before a 2-week acute treatment period, electroencephalopgraphy (EEG) and cognition-modulated frontal theta changes (Δfrontalθ) were measured. Depression scores were evaluated at baseline, 1 week, and 2 weeks after the initiation of treatment.

Results: The Δfrontalθ at baseline was significantly correlated with depression score changes at week 1 (r = -0.383, p = 0.025) and at week 2 for rTMS group (r = -0.419, p = 0.014), but not for the piTBS and sham groups. The area under the receiver operating characteristic curve for Δfrontalθ was 0.800 for the rTMS group (p = 0.003) and was 0.549 for the piTBS group (p = 0.619).

Conclusion: The predictive value of higher baseline Δfrontalθ for antidepressant efficacy for rTMS not only replicates previous results but also implies that the antidepressant responses to rTMS could be predicted reliably at baseline and both piTBS and rTMS could be effective through different neurobiological mechanisms.
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http://dx.doi.org/10.1177/24705470211006855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040384PMC
April 2021

Atopic dermatitis and dementia risk: A nationwide longitudinal study.

Ann Allergy Asthma Immunol 2021 08 11;127(2):200-205. Epub 2021 Mar 11.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address:

Background: Retrospective studies have suggested that patients with dementia have higher prevalence of atopic dermatitis (AD) than those without dementia. However, the temporal association of AD with subsequent dementia remains unknown.

Objective: To assess the temporal association of AD with subsequent dementia.

Methods: We included data of patients with AD aged 45 years and older (n = 1059) and 1:10 age, sex, residence, income, and dementia-related comorbidity-matched controls (n = 10,590) from the Taiwan National Health Insurance Research Database and reviewed their subsequent dementia development from the enrollment date to the end of 2013.

Results: After adjustments for dementia-related comorbidities, patients with AD were found to be more likely to develop any dementia (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.24-3.29), particularly Alzheimer's disease (HR, 3.74; 95% CI, 1.17-11.97), during the follow-up period than those in the control group. Moderate-to-severe AD was associated with a high subsequent dementia risk (HR, 4.64; 95% CI, 2.58-8.33). Sensitivity analyses with the exclusion of the first 3 (HR, 2.20; 95% CI, 1.28-3.80) or 5 (HR, 2.05; 95% CI, 1.08-3.89) years of observation revealed consistent findings.

Conclusion: AD may be an independent risk factor for new-onset dementia. Clinicians may monitor the trajectory of neurocognitive function among elderly patients with AD. Additional studies elucidating the pathomechanisms between AD and subsequent dementia are warranted.
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http://dx.doi.org/10.1016/j.anai.2021.03.001DOI Listing
August 2021

Proton Pump Inhibitor Exposure and Acute Myocardial Infarction Risk: A Nested Cohort Study.

Cardiovasc Toxicol 2021 Jun 24;21(6):444-450. Epub 2021 Feb 24.

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

Background: Association of proton pump inhibitor (PPI) exposure with acute myocardial infarction (AMI) risk in the Caucasian population remains under debate. Here, we clarified whether PPI exposure might be related to an increased new-onset AMI risk in an Asian population.

Method: Data of 27,624 patients with PPI exposure followed by new-onset AMI development were extracted from Taiwan National Health Insurance Research Database and age- and sex-matched with 27,624 controls with PPIs exposure, but without subsequent AMI and ischemic heart disease development. The amount of PPI exposure was calculated based on the cumulative defined daily dose (cDDD) during the follow-up period. Subsequent AMI risk was measured after adjustments of demographic data and indication of PPI use.

Results: AMI risk increased with an increase in PPI exposure: with cDDD ≤ 30 as the reference, the odds ratios (95% confidence intervals) for cDDDs of > 365 was 1.56 (1.45-1.69). All five PPI categories, including pantoprazole, lansoprazole, omeprazole, esomeprazole, and rabeprazole, increased AMI risk.

Conclusions: Our study demonstrated long-term or high-dose PPI exposure associated with increased new-onset AMI risk in patients without a history of any ischemic heart disease. The underlying mechanisms of PPI-related cardiovascular effects deserve more investigation.
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http://dx.doi.org/10.1007/s12012-021-09637-2DOI Listing
June 2021

Treatment response and age of onset as risk indicators for parkinson disease in patients with major depressive disorder: A nationwide longitudinal study.

J Affect Disord 2021 03 5;283:329-334. Epub 2021 Feb 5.

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

Background: Individuals with major depressive disorder (MDD) have a higher risk of developing Parkinson disease (PD). This study investigated whether response to treatment with antidepressants for MDD can determine patients at risk of developing PD later in life.

Methods: We enrolled 3303 patients with newly-diagnosed MDD and 13,212 controls between 2002 and 2004 using Taiwan's Nationwide Health Insurance Research Database. We stratified patients with MDD according to the number of antidepressant regimens prescribed to them and the age at MDD onset and followed all participants until the end of 2013. During follow-up, we evaluated patients for the possibility of developing PD.

Results: Patients with MDD had a greater likelihood of developing PD than controls. Patients with difficult-to-treat (DTT) MDD had a higher risk of developing PD than the other MDD subgroups (hazard ratio [HR] = 3.44, 95% confidence interval [95% CI]: = 1.99-5.95). When stratified by age (<50, 50-65, >65 years), DTT patients with middle-age or late-onset MDD exhibited elevated risks of developing PD (50-65 years: HR: 7.03, 95% CI: 2.95-16.76; >65 years: HR: 2.89, 95% CI: 1.26-6.65).

Discussion: Patients with MDD and an onset age of >50 years who responded poorly to antidepressant treatment have an associated higher risk of subsequently developing PD. Therefore, when treating patients with MDD, clinicians should provide intensive antidepressant treatment and evaluations for PD so that risk-prevention measures can be implemented upon MDD diagnosis.
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http://dx.doi.org/10.1016/j.jad.2021.01.056DOI Listing
March 2021

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

A pilot study on essential oil aroma stimulation for enhancing slow-wave EEG in sleeping brain.

Sci Rep 2021 01 13;11(1):1078. Epub 2021 Jan 13.

Department of Psychiatry, Cheng Hsin General Hospital, Taipei City, Taiwan.

Sleep quality is important to health and life quality. Lack of sleep can lead to a variety of health issues and reduce in daytime function. Recent study by Fultz et al. also indicated that sleep is crucial to brain metabolism. Delta power in sleep EEG often indicates good sleep quality while alpha power usually indicates sleep interruptions and poor sleep quality. Essential oil has been speculated to improve sleep quality. Previous studies also suggest essential oil aroma may affect human brain activity when applied awake. However, those studies were often not blinded, which makes the effectiveness and mechanism of aroma a heavily debated topic. In this study, we aim to explore the effect of essential oil aroma on human sleep quality and sleep EEG in a single-blinded setup. The aroma was released when the participants are asleep, which kept the influence of psychological expectation to the minimum. We recruited nine young, healthy participants with regular lifestyle and no sleep problem. All participants reported better sleep quality and more daytime vigorous after exposing to lavender aroma in sleep. We also observed that upon lavender aroma releases, alpha wave in wake stage was reduced while delta wave in slow-wave sleep (SWS) was increased. Lastly, we found that lavender oil promote occurrence of SWS. Overall, our study results show that essential oil aroma can be used to promote both subjective and objective sleep quality in healthy human subjects. This makes aroma intervention a potential solution for poor sleep quality and insomnia.
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http://dx.doi.org/10.1038/s41598-020-80171-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806966PMC
January 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

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

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

J Dev Orig Health Dis 2021 Jun 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
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