Publications by authors named "Yen-Kuang Yang"

263 Publications

A Taiwanese study on real-world evidence with vortioxetine in patients with major depression in Asia (TREVIDA).

Curr Med Res Opin 2021 Sep 13. Epub 2021 Sep 13.

Lundbeck Singapore Pte Ltd, Singapore.

Objective: The TREVIDA study aimed to evaluate vortioxetine for the treatment of major depressive disorder (MDD) in Taiwanese adults.

Methods: Patients with active depressive episode were recruited in this non-interventional, prospective, multi-site study conducted between June 2019 and August 2020 in Taiwan. Patient eligibility was independent of the physician's decision to prescribe vortioxetine for an MDD episode. Vortioxetine was initiated on the first visit. Depression severity, cognitive function, work productivity, functioning and safety were evaluated over 3 months.

Results: Overall, 242 patients were analyzed. At baseline, 70.7% and 90.4% of patients had moderately severe-to-severe depression based on PHQ-9 (Patient Health Questionnaire-9) and TDQ (Taiwanese Depression Questionnaire), respectively. By Month 3, significant improvements from baseline in depression severity (mean [SD] changes in PHQ-9, TDQ and CGI-S [Clinical Global Impression-Severity]: -6.3 [7.3]; -13.2 [14.0]; -1.5 [1.3], respectively), cognitive function (mean [SD] change in PDQ-D: -8.0 [17.5]), functioning (mean [SD] change in SDS: -5.4 [7.6]), and presenteeism (38.9% from 56.3%), work productivity loss (40.9% from 58.7%) and activity impairment (43.2% from 61.0%) were observed (P < 0.001 for all). By Month 3, patient-reported (PHQ-9) response and remission rates were 43.4% and 52.9%, respectively; physician-reported (CGI-S) response and remission rates were 29.0% and 31.6%, respectively. Vortioxetine was well-tolerated and no unexpected side effects were reported.

Conclusions: Vortioxetine reduced depression severity and improved cognitive function, work productivity, and functioning in Taiwanese patients with MDD in the real-world setting. Vortioxetine was well-tolerated in this Taiwanese population.
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http://dx.doi.org/10.1080/03007995.2021.1980869DOI Listing
September 2021

Evidence-Based Expert Consensus Regarding Long-Acting Injectable Antipsychotics for Schizophrenia from the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN).

CNS Drugs 2021 Aug 27;35(8):893-905. Epub 2021 Jul 27.

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

Objective: Schizophrenia is a chronic, debilitating psychiatric disorder with a high risk of relapse. Nonadherence to medication is a significant contributor to poor outcomes. Although long-acting injectable (LAI) antipsychotics prevent the relapse of schizophrenia, several factors present obstacles to the use of LAI antipsychotics, and clinical guidelines for LAI antipsychotics remain limited. To provide clinical recommendations, the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) developed consensus statements for the effectiveness, target populations, initiation timing, and particular clinical situations for the use of LAI antipsychotics in patients with schizophrenia.

Methods: After a systematic literature review, a working group drafted consensus statements for the selected clinical topics and determined the levels of evidence-based recommendation based on the latest World Federation of Societies of Biological Psychiatry grading system. A scientific committee evaluated the draft statements and decided the final recommendations regarding the grades by anonymous voting after incorporating clinical experience and practice into the evidence from research.

Results: The TSBPN proposed ten consensus statements for the application of LAI antipsychotics. The current evidence supported that LAI antipsychotics could be a treatment option for all schizophrenia patients, including first-episode patients. LAI antipsychotics could be initiated both during an acute psychotic episode and when patients are stable. The consensus also gave recommendations for particular clinical situations with insufficient scientific data, such as for use in elderly or adolescent patients, patients with treatment-resistant schizophrenia, and breakthrough psychosis, and strategies to assist patients/caregivers with decision making.

Conclusions: The consensus statements developed by the TSBPN provide evidence-based clinical recommendations and could give clinicians more confidence when prescribing LAI antipsychotics to treat schizophrenia, thereby improving treatment outcomes.
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http://dx.doi.org/10.1007/s40263-021-00838-5DOI Listing
August 2021

Central Pontine Myelinolysis in a Normonatremic Patient with Depression.

Clin Psychopharmacol Neurosci 2021 Aug;19(3):564-567

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

A 76-year-old male presented with a recurrent depressive episode, an unsteady gait and cognitive impairment. Extensive blood tests, including hemogram, biochemical tests, folic acid, vitamin B12, and thyroid hormone, showed normal results. With the exception of the unsteady gait, neurological examination was negative. Brian magnetic resonance imaging (MRI) showed the typical feature of central pontine myelinolysis (CPM); however, there was no history of alcoholism, liver transplantation, malnutrition or rapid correction of hyponatremia. The patient had taken venlafaxine to treat major depressive disorder for more than 20 years. After discontinuation of venlafaxine, the unsteady gait gradually resolved, and subsequent MRI revealed reduction of the lesions over 6 months. We discuss herein the possible correlation between chronic use of venlafaxine and CPM.
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http://dx.doi.org/10.9758/cpn.2021.19.3.564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316663PMC
August 2021

Corrigendum to "More inflammation but less brain-derived neurotrophic factor in antisocial personality disorder" [Psychoneuroendocrinology (2017; 85, 42-48).

Psychoneuroendocrinology 2021 Sep 7;131:105233. Epub 2021 Jul 7.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan; Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.psyneuen.2021.105233DOI Listing
September 2021

Absence of negative associations of insular and medial frontal gray matter volume with dissociative symptoms in schizophrenia.

J Psychiatr Res 2021 06 20;138:485-491. Epub 2021 Apr 20.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. Electronic address:

Background: Dissociative symptoms have been constantly found in schizophrenia (SCZ). Traumatic experience seems to relate to dissociative symptoms and brain volume alterations in SCZ. The current study aimed to clarify the inter-relations of dissociative symptoms, traumatic experience, and brain volume in SCZ.

Methods: We employed voxel-based morphometry to compare the distributions of gray matter volumes (GMV) in 37 SCZ patients and 26 healthy volunteers (HV). All participants underwent T1-weighted images on a 1.5 T MRI system. Traumatic experience was examined by the Brief Betrayal Trauma Survey. Pathological and non-pathological dissociation were measured by the Dissociative Symptoms Scale and the Dissociative Experiences Scale, respectively.

Results: A GMV reduction was found in SCZ patients in the right thalamus. Importantly, a significant group by pathological dissociation interaction was observed in the medial frontal cortex (MFC), bilateral anterior insular area, and precuneus. A negative correlation between MFC/insular GMV and pathological dissociation was observed in HV; higher non-pathological dissociation and smaller volume in MFC/insula were associated with pathological dissociation. In contrast, higher traumatic experience, higher non-pathological dissociation, and larger volume in MFC/insula were associated with pathological dissociation in SCZ.

Conclusion: The negative association between MFC/insula GMV and pathological dissociation in HV was not observed in SCZ patients. The absent negative association in SCZ suggests a unique neural underpinning in SCZ with dissociative pathology, in which medial frontal and temporal regions play crucial roles.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.017DOI Listing
June 2021

Association of visual motor processing and social cognition in schizophrenia.

NPJ Schizophr 2021 Apr 13;7(1):21. Epub 2021 Apr 13.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Patients with schizophrenia have difficulties in social cognitive domains including emotion recognition and mentalization, and in sensorimotor processing and learning. The relationship between social cognitive deficits and sensorimotor function in patients with schizophrenia remains largely unexplored. With the hypothesis that impaired visual motor processing may decelerate information processing and subsequently affects various domains of social cognition, we examined the association of nonverbal emotion recognition, mentalization, and visual motor processing in schizophrenia. The study examined mentalization using the verbal subset of the Chinese version of Theory of Mind (CToM) Task, an equivalent task of the Faux Pas Test; emotion recognition using the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and visual motor processing using a joystick tracking task controlled for basic motor function in 34 individuals with chronic schizophrenia in the community and 42 healthy controls. Patients with schizophrenia had significantly worse performance than healthy controls in social cognition, including facial, prosodic emotion recognition, and mentalization. Visual motor processing was also significantly worse in patients with schizophrenia. Only in patients with schizophrenia, both emotion recognition (mainly in prosodic modality, happy, and sad emotions) and mentalization were positively associated with their learning capacity of visual motor processing. These findings suggest a prospective role of sensorimotor function in their social cognitive deficits. Despite that the underlying neural mechanism needs further research, our findings may provide a new direction for restoration of social cognitive function in schizophrenia by enhancing visual motor processing ability.
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http://dx.doi.org/10.1038/s41537-021-00150-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044174PMC
April 2021

Sex differences in the diagnosis of autism spectrum disorder and effects of comorbid mental retardation and attention-deficit hyperactivity disorder.

J Formos Med Assoc 2021 Apr 2. Epub 2021 Apr 2.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan.

Background/purpose: The association between sex and diagnostic behavior of autism spectrum disorder (ASD), and the effects of comorbid mental retardation (MR) and attention-deficit hyperactivity disorder (ADHD), were explored.

Methods: Based on the Taiwan Longitudinal Health Insurance Database (LHID)-2000 and data from 1996 through 2008, the cumulative incidence of ASD over time was compared between the sexes (both cohorts n = 38,117) using the log-rank test. The effects of comorbid MR and ADHD on the incidence of ASD were evaluated using Cox proportional hazard regression analysis. The age at first diagnosis of ASD in the two sexes was compared using the independent-sample t-test.

Results: The incidence was higher in males than in females (0.0007 vs. 0.0002) across ages. Comorbid MR or ADHD increased the incidence of ASD in both sexes; comorbid MR or ADHD also decreased the male to female hazard ratio of ASD, with no significant differences in the incidence density of ASD between sexes. ADHD delayed diagnosis in both sexes (males: 6.61 vs 5.10, p < 0.0001; females: 6.83 vs 4.69, p = 0.0037).

Conclusions: The general concept of a higher incidence of ASD among males was noted in this study of a Taiwanese population, but disappeared in those with comorbid MR or ADHD, indicating unique vulnerabilities to MR/ADHD or under-identification of high-functioning females with ASD in childhood. Increasing the diagnostic sensitivity of ASD in those with comorbid ADHD is important due to a delayed diagnostic age in this group.
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http://dx.doi.org/10.1016/j.jfma.2021.03.009DOI Listing
April 2021

Transcranial direct current stimulation (tDCS) may reduce the expired CO concentration among opioid users who smoke cigarettes: a randomized sham-controlled study.

Psychiatry Res 2021 05 15;299:113874. Epub 2021 Mar 15.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. Electronic address:

Transcranial direct current stimulation (tDCS) could be a potential treatment for nicotine dependency. Little is known with regards to the efficacy of this treatment in cigarette-smoking patients with heroin dependency. In this sham-controlled study, we probed the effect of 5-day, 20-min, 2-mA-intensity tDCS treatment on the outcomes of cigarette-smoking. Our objectives are to examine the effects of tDCS on two outcomes: objective expired CO concentration and subjective self-reported number of cigarettes smoked per day. A total of 30 patients were randomized into active or sham control groups. The stimulation site was randomized to anodal stimulation of the left dorsal lateral prefrontal cortex or the orbital frontal cortex. The expired CO concentration was recorded. The patients also reported their cigarette consumption and level of craving prior to each 5-day treatment period and after 5 days of follow-up. tDCS was found to be effective in terms of reducing the expired CO concentration, and both groups demonstrated reduced numbers of cigarettes smoked. However, no significant group difference was found with regards to craving tendency. tDCS may affect objective outcomes related to cigarette-smoking among patients with heroin dependence.
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http://dx.doi.org/10.1016/j.psychres.2021.113874DOI Listing
May 2021

Peripheral insulin sensitivity predicting cognitive function in euthymic bipolar disorder patients.

CNS Spectr 2021 Mar 11:1-6. Epub 2021 Mar 11.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Objective: High prevalence of insulin resistance (IR) has been reported in bipolar disorder (BD) patients. Importantly, impaired insulin sensitivity could modulate the course and treatment outcome in BD. Here, we hypothesized that insulin sensitivity could be potentially associated with the neurocognitive trajectory in euthymic BD. We aimed to examine differences in insulin sensitivity and executive function between BD patients and controls.

Methods: Sixty-two patients with BD receiving mood stabilizer treatment and 62 controls, matching age, sex, and body mass index, were recruited in this study. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The Wisconsin card-sorting test (WCST) was applied to test participants' ability to shift cognitive set. Group differences were measured and multivariate regression analysis was performed to examine relationships among factors.

Results: The results indicated that the HOMA-IR (P = .048) value in the patients with BD were significantly higher than those in controls. With regards to executive function, the BD patients performed significantly poorer than the control subjects (P < .05). Moreover, the interaction effect between BD diagnosis and HOMA-IR value on the WCST-preservation errors was significant (P = .01), and post-hoc analyses showed that the cognitive abilities were worse in the BD patients with a higher IR than in the others groups.

Conclusion: Insulin sensitivity is associated with the neurocognitive performance in euthymic BD patients. Although the underlying mechanisms remain unclear, interventions to improve insulin sensitivity could potentially improve the functional outcome of BD.
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http://dx.doi.org/10.1017/S1092852921000158DOI Listing
March 2021

Striatal dopamine D receptors in medication-naïve schizophrenia: an [I] IBZM SPECT study.

Psychol Med 2021 Mar 8:1-9. Epub 2021 Mar 8.

Mental Health Neurosciences Research Department, Division of Psychiatry, University College London, London, UK.

Background: The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.

Methods: We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.

Result: The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = -0.01(binding ratio); 95% CI -0.01 to -0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.

Conclusions: Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
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http://dx.doi.org/10.1017/S0033291720005413DOI Listing
March 2021

Impairment in Emotional Intelligence May Be Mood-Dependent in Bipolar I and Bipolar II Disorders.

Front Psychiatry 2021 18;12:597461. Epub 2021 Feb 18.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan.

An emotional intelligence (EI) deficit has been noticed in euthymic bipolar spectrum disorder (BD) patients. However, whether this deficit is affected by mood or subtype is unclear. The aim of this study was to investigate whether an EI deficit is mood-dependent, and which mood symptoms have more impact on EI in BD. Two hundred and thirty participants aged between 18 and 65 years old were recruited [130 BD patients (51 bipolar I disorder (BDI) and 79 bipolar II disorder (BDII): 39.2% males; 91 healthy controls (HCs): 48.4% males)]. The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), which contains experiential and strategic EI ratings, was used to assess social cognition. The Hamilton Depression Rating Scale (HDRS) and the Young's Mania Rating Scale (YMRS) were used for evaluating the severity [HAMD and YMRS scores ≦7 were euthymic (BD) and HAMD YMRS sores ≧8 were episodic (BD)]. Analyses of covariance (ANCOVA) were performed, with adjustment for background information between the BD patients and HCs. The results showed that, compared to the HCs, the BD patients showed no difference in any MSCEIT measures, while the BD patients showed lower scores in all MSCEIT measures, except for perceiving emotions. In addition, a main effect of mood state instead of BD subtype was found for the managing emotions branch ( < 0.0007). Regression analyses showed that the duration of illness and HDRS scores were correlated with the scores in the strategic area of the MSCEIT, while age and YMRS scores were more relevant to the scores in the experiential area of the MSCEIT. The results confirm that an EI deficit is mood-dependent in BD patients. In addition, a depressive mood is more related to the strategic EI area, while a manic mood is correlated with the experiential EI area. Understanding the different domains of EI deficits in BD patients may be helpful for developing interventions for BD.
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http://dx.doi.org/10.3389/fpsyt.2021.597461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931827PMC
February 2021

Collapsin response mediator protein 5 (CRMP5) modulates susceptibility to chronic social defeat stress in mice.

Mol Neurobiol 2021 Jul 26;58(7):3175-3186. Epub 2021 Feb 26.

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.

Collapsin response mediator protein 5 (CRMP5), a member of the CRMP family, is expressed in the brain, particularly in the hippocampus, an area of the brain that can modulate stress responses. Social stress has a well-known detrimental effect on health and can lead to depression, but not all individuals are equally sensitive to stress. To date, researchers have not conclusively determined how social stress increases the susceptibility of the brain to depression. Here, we used the chronic social defeat stress (CSDS) model and observed higher hippocampal CRMP5 expression in stress-susceptible (SS) mice than in control and stress-resilient (RES) mice. A negative correlation was observed between the expression levels of CRMP5 and the social interaction (SI) ratio. Reduced hippocampal CRMP5 expression increased the SI ratio in SS mice, whereas CRMP5 overexpression was sufficient to induce social avoidance behaviors in control mice following exposure to subthreshold social stress induced by lentivirus-based overexpression and inducible tetracycline-on strategies to upregulate CRMP5. Interestingly, increased CRMP5 expression in SS and lenti-CRMP5-treated mice also caused serum corticosterone concentrations to increase. These findings improve our understanding of the potential mechanism by which CRMP5 triggers susceptibility to social stress, and they support the further development of therapeutic agents for the treatment of stress disorders in humans.
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http://dx.doi.org/10.1007/s12035-021-02336-7DOI Listing
July 2021

Positive Symptoms in Antipsychotic-naïve Schizophrenia are Associated with Increased Body Mass Index after Treatment.

Clin Psychopharmacol Neurosci 2021 Feb;19(1):155-159

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Objective: Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain.

Methods: Twenty-two antipsychotic-naïve, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured.

Results: The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naïve patients with schizophrenia.

Conclusion: This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.
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http://dx.doi.org/10.9758/cpn.2021.19.1.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851461PMC
February 2021

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy.

Am J Drug Alcohol Abuse 2021 05 10;47(3):330-343. Epub 2021 Jan 10.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorder (OUD).: We conducted an add-on double-blinded, sham-controlled rTMS feasibility pilot trial to examine OUD participants undergoing methadone maintenance therapy (MMT). The current report focused on the effects of rTMS on (1) craving and heroin use behavior and (2) depression, impulsivity, and attention.: Active or sham rTMS treatment was applied to the left dorsolateral prefrontal cortex (DLPFC) over a total of 11 sessions in 4 weeks (15-Hz frequency, 4 seconds per train, intertrain interval of 26 seconds, 40 trains per session) in OUD participants (ClinicalTrials.gov registration number: NCT03229642). Craving, heroin use severity, urine morphine tests, the Hamilton Depression Rating Scale (HDRS), the Barratt Impulsiveness Scale-11 (BIS-11), and the Continuous Performance Tests (CPTs) were measured.: Twenty-two OUD participants were enrolled, of which eleven (8 males) were undergoing active rTMS and nine (8 males) were in the sham rTMS group. After 12 weeks of follow-up, the active rTMS group did not show significantly greater improvements than the sham group with respect to craving, heroin use, or urine morphine test results. However, HDRS scores, BIS-11 attentional subscales, and CPTs commission T-scores (C-TS) were significantly lower in the active rTMS group ( = .003, 0.04, and 0.02, respectively) than in the sham group.: Add-on rTMS did not appear to improve heroin use behavior but may have benefitted depressive symptoms, impulse control and attention in OUD participants undergoing MMT.
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http://dx.doi.org/10.1080/00952990.2020.1849247DOI Listing
May 2021

Changes in striatal dopamine transporters in bipolar disorder and valproate treatment.

Eur Psychiatry 2021 Jan 8;64(1):e9. Epub 2021 Jan 8.

Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: Previous studies suggested that a disturbance of the dopamine system underlies the pathophysiology of bipolar disorder (BD). In addition, the therapeutic action of medications for treating BD, such as valproate (VPA), might modulate dopamine system activity, but it remains unclear. Here, we aimed to investigate the role of the striatal dopamine transporter (DAT) in BD patients and in social defeat (SD) mice treated with VPA.

Methods: We enrolled community-dwelling controls (N = 18) and BD patients (N = 23) who were treated with VPA in a euthymic stage. The striatal DAT availabilities were approached by TRODAT-1 single photon emission computed tomography. We also established a chronic SD mouse model and treated mice with 350 mg/kg VPA for 3 weeks. Behavioral tests were administered, and striatal DAT expression levels were determined.

Results: In humans, the level of striatal DAT availability was significantly higher in euthymic BD patients (1.52 ± 0.17 and 1.37 ± 0.23, p = 0.015). Moreover, the level of striatal DAT availability was also negatively correlated with the VPA concentration in BD patients (r = -0.653, p = 0.003). In SD mice, the expression of striatal DAT significantly increased (p < 0.001), and the SD effect on DAT expression was rescued by VPA treatment.

Conclusions: The striatal DAT might play a role in the pathophysiology of BD and in the therapeutic mechanism of VPA. The homeostasis of DAT might represent a new therapeutic strategy for BD patients.
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http://dx.doi.org/10.1192/j.eurpsy.2021.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057387PMC
January 2021

Effects of adding a concurrent cognitive task on manual dexterity in people with schizophrenia: Implications for performance of daily life activities.

Asian J Psychiatr 2020 Dec 25;54:102456. Epub 2020 Oct 25.

School of Occupational Therapy, College of Medicine, National Taiwan University, No. 17, F4, Xuzhou Road, Taipei City, 100, Taiwan; Division of Occupational Therapy, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, No. 1, Changde Street, Taipei City, 100, Taiwan. Electronic address:

This study investigated the effect of dual task performance of hand dexterity tasks and the relationship to daily functioning in 40 people with chronic schizophrenia and 35 healthy participants. Participants performed the Purdue Pegboard Test, O'Connor Finger Dexterity Test, and the Serial Subtracting Seven Task as the secondary task under single- and dual-task conditions and completed the Activities of Daily Living Rating Scale-III (ADLRS-III). The hand dexterity of all participants declined from the single to the dual tasks, and the discrepancy between single- and dual-task performance was significantly greater in the schizophrenia group than in the control group. Significant condition and group effects were found for both hand dexterity tests. People with schizophrenia who took longer time in performing hand dexterity tasks had significantly worse daily life function. Negative correlations were noted between discrepancy of dual tasking and the ADLRS-III score in the schizophrenic group. Deficits in dual-task performance of hand dexterity is significant in people with schizophrenia and is related to daily life performance. Occupational therapy practitioners can consider using dual tasks as a therapeutic activity for people with schizophrenia to promote functional abilities in real-world environments.
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http://dx.doi.org/10.1016/j.ajp.2020.102456DOI Listing
December 2020

Childhood neglect is associated with corticostriatal circuit dysfunction in bipolar disorder adults.

Psychiatry Res 2021 01 4;295:113550. Epub 2020 Nov 4.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan. Electronic address:

Bipolar disorder (BD) is characterized with cognitive impairment, which may be mediated by corticostriatal dysfunction. Here we examined whether history of childhood trauma, a risk factor for BD, was linked to corticostriatal dysfunction in BD patients. Furthermore, the possible associations between childhood trauma and cognitive impairment were examined. Thirty-eight BD participants who met the DSM-IV diagnostic criteria were enrolled. Childhood trauma was identified via the Childhood Trauma Questionnaire (CTQ). Participants completed the Wisconsin Card-Sorting Test (WCST). Resting-state functional magnetic resonance imaging (rsfMRI) was performed in participants using a 3T scanner. Bilateral caudate to whole-brain functional connectivity (FC) were analyzed, and childhood trauma was entered as a regressor of interest when controlling for age. Results showed the level of physical neglect was negatively correlated with left-caudate-seed FC to the frontoparietal network, including the right supramarginal gyrus, left inferior parietal lobule, right middle frontal gyrus, and right superior parietal lobule. The level of physical neglect was also negatively correlated with WCST performance. And the left-caudate-seed FCs to the frontoparietal network were positively correlated with WCST performance. Unequivocally, the specific impacts of physical neglect on brain connectivity and executive function in the BD population merit further investigation.
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http://dx.doi.org/10.1016/j.psychres.2020.113550DOI Listing
January 2021

Editorial: Early Intervention in Psychotic Disorders.

Front Psychiatry 2020 18;11:574532. Epub 2020 Sep 18.

Department of Psychiatry, Chonbuk National University Medical School, Jeonju, South Korea.

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http://dx.doi.org/10.3389/fpsyt.2020.574532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531034PMC
September 2020

Add-on memantine may improve cognitive functions and attenuate inflammation in middle- to old-aged bipolar II disorder patients.

J Affect Disord 2021 01 6;279:229-238. Epub 2020 Oct 6.

Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC, USA.

Objectives: Chronic inflammation and neuroprogression underlie bipolar disorder (BP) and associated cognitive deficits. Memantine (MM) exerts neuroprotective effects by reducing neuroinflammation. Therefore, we investigated whether add-on low-dose MM (5 mg/day) in BP-II patients may improve cognition and inflammation.

Methods: We combined two 12-week randomized, double-blind, placebo-controlled studies (NCT01188148 and NCT03039842) for analysis. Each participant was allocated to the MM or placebo group. Symptom severity, neuropsychological tests, and the cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were evaluated at baseline and endpoint. A subgroup analysis of middle- to old-aged BP-II patients was also performed.

Results: We recruited 155 BP-II patients (23 of which were middle- to old-aged) for the MM group and 170 patients (20 of which were middle- to old-aged) for the placebo group. Add-on MM did not result in significant improvements in cognitive functions in all BP-II patients, but a group difference in TNF-α levels was found in the MM group (P=0.04). Specifically, in middle- to old-aged BP-II patients, there was a significant time and group interaction effect on omission T-scores, hit reaction time T-scores, and hit reaction time standard error T-scores on continuous performance tests (CPTs) in the MM group (P=0.007, 0.02, and 0.01, respectively), and a decrease in plasma TNF-α levels (P=0.04).

Limitations: The sample size of middle- to old-aged BP-II patients were limited.

Conclusion: Add-on MM may attenuate inflammation in BP-II and improve cognition in middle- to old-aged BP-II patients.
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http://dx.doi.org/10.1016/j.jad.2020.10.003DOI Listing
January 2021

Heart Rate Variability with Deep Breathing in Drug-Naïve Patients with Schizophrenia.

Appl Psychophysiol Biofeedback 2020 12 30;45(4):275-282. Epub 2020 Sep 30.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, North Dist., Tainan, 704, Taiwan.

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.
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http://dx.doi.org/10.1007/s10484-020-09489-6DOI Listing
December 2020

Peripheral inflammation is associated with dysfunctional corticostriatal circuitry and executive dysfunction in bipolar disorder patients.

Brain Behav Immun 2021 01 17;91:695-702. Epub 2020 Sep 17.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Bipolar disorder (BD) has been linked to abnormal frontal and striatal function, and elevated inflammatory responses. However, the impact of peripheral inflammation on the corticostriatal functional connectivity (FC) remains obscure in BD. The current study aimed to explore the association between peripheral inflammation and corticostriatal connectivity in euthymic BD. We recruited 25 euthymic BD patients and 43 healthy controls (HCs) from the community. Resting state functional images were obtained using 3T magnetic resonance imaging (fMRI), and striatal seed-based whole-brain functional connectivity analyses were performed, with the fasting plasma high-sensitivity C-reactive protein (hs-CRP) level entered as a regressor of interest. The participants also completed the Wisconsin Card-Sorting Test (WCST) and the Continuous Performance Test (CPT). The euthymic BD group had a similar hs-CRP level to the HC group, but a significantly poorer cognitive performance. Compared with the HC group, a higher connectivity between the right dorsal caudal putamen (dcP) and the ventral lateral prefrontal cortex (vlPFC) in the BD group was significantly correlated with a higher hs-CRP level. Stronger dcP-vlPFC connectivity was correlated with a lower CPT unmasked d' in the BD group. BD patients might be particularly sensitive to the effects of inflammation on corticostriatal connectivity. The potentially greater sensitivity of BD patients to peripheral inflammation may differentially modulate the cognitive and reward related corticostriatal circuitry, which may contribute to the pathophysiology of cognitive-affective dysregulation in the euthymic state. Anti-inflammatory or other circuit-specific treatment is warranted for individualized treatment in BD.
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http://dx.doi.org/10.1016/j.bbi.2020.09.010DOI Listing
January 2021

Effects of mood episodes and comorbid anxiety on neuropsychological impairment in patients with bipolar spectrum disorder.

Brain Behav 2020 11 30;10(11):e01813. Epub 2020 Aug 30.

Department of Psychiatry, National Cheng Kung University, Tainan City, Taiwan.

Objectives: Cases of patients with bipolar disorder (BD) having neuropsychological impairment have been reported, although inconsistently. The possibility of comorbidity with anxiety disorder (AD) has been suggested. The association between mood episodes and AD comorbidity on neuropsychological performance is unclear and thus was investigated in the current study.

Methods: All participants were informed about and agreed to participate in this study. Patients with BD were recruited from outpatient and inpatient settings, and healthy controls (HCs) were recruited as a comparison group. Six hundred and twenty-eight participants (175 HCs and 453 BD-56 BDI and 397 BDII) were studied based on their current mood episode, namely, depressive (BD ), manic/hypomanic (BDm), mixed (BDmix), and euthymic (BDeu), compared with/without AD comorbidity (164 with AD).

Results: Compared to HCs, all BD groups had significantly more impaired neuropsychological profiles, but the BDeu group was found to have less impairment in memory and executive function than the episodic BD groups. The percentage of AD comorbidity in BDd, BDm, BDmix, and BDeu was 33.9%, 40.3%, 33.0%, and 35.6%, respectively (χ  = 1.61, p > .05). The results show that AD plays a different role in neuropsychological impairment across various mood episodes in BD.

Conclusion: Memory impairment and executive dysfunction may be state-like cognitive phenotypes and are affected by AD comorbidity during mixed and depressive episodes in BD, while sustained attention deficiencies are more like trait markers, regardless of mood episodes, and persist beyond the course of the illness. The AD comorbidity effect on attentional deficit is greater when suffering from a manic episode.
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http://dx.doi.org/10.1002/brb3.1813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667309PMC
November 2020

The integrated model of glutamate and dopamine hypothesis for schizophrenia: Prediction and personalized medicine for prevent potential treatment-resistant patients.

Med Hypotheses 2020 Oct 3;143:110159. Epub 2020 Aug 3.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan; Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. Electronic address:

Treatment-resistant schizophrenia (TRS) is one of the subgroups of schizophrenia of which little is known with regard to its optimal mechanism. Treatment response, either as full remission of symptoms or prediction by biomarker, is important in psychiatry. We have proposed a model that integrates dopaminergic and glutamatergic systems with the biological interactions of TRS patients. We hypothesize that the subgroups of schizophrenia may be determined by glutamatergic and dopaminergic concentrations prior to medical treatment. This hypothesis implies that higher glutamatergic concentration in the brain with normalized or decreased dopamine synthesis capacity may explain aspects of TRS as observed in clinical medical practice, neuroimaging measurements, and brain stimulations. According to this hypothesis, the ability to prescribe a proper medication combination, to predict the outcome in first-episode psychosis, and personalized medicine for chronic schizophrenia patients can be applied into practice. This represents an initial step in explaining psychosis due to the valence of two neurotransmitters. Future studies are needed to examine the validity of this mechanism.
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http://dx.doi.org/10.1016/j.mehy.2020.110159DOI Listing
October 2020

Dysregulation of oxytocin and dopamine in the corticostriatal circuitry in bipolar II disorder.

Transl Psychiatry 2020 08 12;10(1):281. Epub 2020 Aug 12.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

The oxytocin (OXT) and dopamine systems synergistically facilitate striatal reactivity. Abnormal striatal activation has repeatedly been observed in patients with bipolar disorder (BD); however, such abnormality remains unclear in BD II. Here we aimed to investigate whether the corticostriatal connectivity was altered and the possible relationships among corticostriatal connectivity, OXT, and dopamine systems in BD II. Twenty-five BD II patients, as defined by the DSM-V, and 29 healthy controls (HC) were enrolled in this study. Plasma OXT was measured and striatal dopamine transporter (DAT) availability was assessed using [Tc]TRODAT-1 single-photon emission computed tomography (SPECT). Brain network functional connectivity (FC) was measured during the resting-state using functional magnetic resonance imaging, and the dorsal caudate (DC) was selected as the seed region. The results showed that the OXT level was significantly lower in the BD II patients, while the striatal DAT availability was not significantly different between the BD II and HC groups. The BD II patients exhibited significantly lower FC between the DC and the executive control network (dorsolateral prefrontal, anterior cingulate cortex, and posterior parietal cortex) as compared with the HC. Only observed in HC, the DC-posterior parietal cortex FC was negatively correlated with the OXT level and striatal DAT availability. Our findings in the HC support a model in which the OXT and dopamine systems act in tandem to regulate corticostriatal circuitry, while the synergistic interaction was perturbed in BD II. Taken together, these results implied a maladaptive neuroplasticity in BD II.
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http://dx.doi.org/10.1038/s41398-020-00972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423887PMC
August 2020

Comparative cardiometabolic risk of antipsychotics in children, adolescents and young adults.

Eur Child Adolesc Psychiatry 2021 May 29;30(5):769-783. Epub 2020 May 29.

School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, 701, Tainan, Taiwan.

Understanding different cardiometabolic safety profiles of antipsychotics helps avoid unintended outcomes among young patients. We conducted a population-based study to compare cardiometabolic risk among different antipsychotics in children, adolescents and young adults. From Taiwan's National Health Insurance Database, 2001-2013, we identified two patient cohorts aged 5-18 (children and adolescents) and 19-30 (young adults), diagnosed with psychiatric disorders and newly receiving antipsychotics, including haloperidol and sulpiride, and second generation antipsychotics (SGA, including olanzapine, quetiapine, risperidone, amisulpride, aripiprazole, paliperidone, and ziprasidone). Risperidone users were considered the reference group. We analyzed electronic medical records from seven hospitals in Taiwan and confirmed findings with validation analyses of identical design. Primary outcomes were composite cardiometabolic events, including type 2 diabetes mellitus, hypertension, dyslipidemia, and major adverse cardiovascular events. Multivariable Cox proportional hazards regression models compared cardiometabolic risk among antipsychotics. Among 29,030 patients aged 5-18 and 50,359 patients aged 19-30 years, we found 1200 cardiometabolic event cases during the total follow-up time of 37,420 person-years with an incidence of 32.1 per 1000 person-years. Compared to risperidone, olanzapine was associated with a significantly higher risk of cardiometabolic events in young adults (adjusted hazard ratio, 1.57; 95% CIs 1.13-2.18) but not in children and adolescents (1.85; 0.79-4.32). Specifically, we found young adult patients receiving haloperidol (1.52; 1.06-2.20) or olanzapine (1.75; 1.18-2.61) had higher risk of hypertension compared with risperidone users. Results from validation analyses concurred with main analyses. Antipsychotics' various risk profiles for cardiometabolic events merit consideration when selecting appropriate regimes. Due to cardiometabolic risk, we suggest clinicians may consider to select alternative antipsychotics to olanzapine in children, adolescents and young adults.
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http://dx.doi.org/10.1007/s00787-020-01560-1DOI Listing
May 2021

A pilot study on the association between the blood oxygen level-dependent signal in the reward system and dopamine transporter availability in adults with attention deficit hyperactivity disorder.

CNS Spectr 2021 06 20;26(3):299-306. Epub 2020 Apr 20.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.

Methods: Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.

Result: DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.

Conclusions: The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
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http://dx.doi.org/10.1017/S1092852920001133DOI Listing
June 2021

Bridging the associations between dopamine, brain volumetric variation and IQ in drug-naïve schizophrenia.

Schizophr Res 2020 06 20;220:248-253. Epub 2020 Mar 20.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. Electronic address:

Background: Although patients with schizophrenia are well-known to exhibit significant brain volume reduction and cognitive function impairment, it remains unclear as to whether the reduction/impairment is correlated with dopaminergic activity under drug-naïve conditions.

Methods: 51 drug-naïve patients with and 128 healthy subjects were recruited in this study. DAT by [Tc]TRODAT-1 single-photon emission computed tomography (SPECT), regional gray matter volume (GMV) by voxel-based morphometry (VBM) analysis, and cognitive function in terms of IQ were measured in both groups.

Result: A significantly lower DAT availability existed in the drug-naïve group as compared with the healthy subjects (1.67 ± 0.45 vs. 1.98 ± 0.37, P < 0.005). DAT availability was significantly positively correlated with GMV in the left middle frontal lobe (r = 0.58, P < 0.005), the GMV being significantly reduced in the patients with schizophrenia (0.45 ± 0.10 vs. 0.49 ± 0.07, P < 0.005). Furthermore, the GMV in the left middle frontal lobe was significantly and positively correlated with full IQ (r = 0.34, P = 0.02) in the patients with schizophrenia, but not in the controls.

Conclusions: Dysregulated dopaminergic activity may modulate volume variation in specific brain areas, and brain volume might alter IQ in drug-naïve patients with schizophrenia.
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http://dx.doi.org/10.1016/j.schres.2020.03.005DOI Listing
June 2020

Combination of dextromethorphan and memantine in treating bipolar spectrum disorder: a 12-week double-blind randomized clinical trial.

Int J Bipolar Disord 2020 Mar 2;8(1):11. Epub 2020 Mar 2.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan.

Background: The aim of this study is to determine whether adding combination of agents with anti-inflammatory and neurotrophic effects is more efficacious than mood stabilizer alone in improving clinical symptoms, plasma brain-derived neurotrophic factor (BDNF), cytokine levels, and metabolic profiles in patients with bipolar spectrum disorder.

Methods: In a randomized, double-blind, controlled 12-week clinical trial, patients with moderate mood symptoms (HDRS ≥ 18 or YMRS ≥ 14) were recruited. The patients were randomly assigned to a group while still undergoing regular valproate (VPA) treatments: VPA + dextromethorphan (DM) (30 mg/day) + memantine (MM) (5 mg/day) (DM30 + MM5) (n = 66), VPA + DM (30 mg/day) (DM30) (n = 69), VPA + MM (5 mg/day) (MM5) (n = 66), or VPA + Placebo (Placebo) (n = 69). Symptom severity, immunological parameters [plasma tumor necrosis factor (TNF)-α and C-reactive protein (CRP)] and plasma brain-derived neurotrophic factor (BDNF) were regularly examined. Metabolic profiles [cholesterol, triglycerides, glycosylated hemoglobin (HbA1C), fasting serum glucose, body mass index (BMI)] were measured at baseline and at 2, 8, and 12 weeks.

Results: Depression scores were significantly (P = 0.03) decreases and BDNF levels significantly (P = 0.04) increased in the DM30 + MM5 group than in the Placebo group. However, neither depressive scores nor BDNF levels were significantly different between the DM30, MM5, and Placebo groups. Changes in certain plasma cytokine and BDNF levels were significantly correlated with metabolic parameters.

Conclusion: We concluded that add-on DM30 + MM5 was significantly more effective than placebo for clinical symptoms and plasma BDNF levels. Additional studies with larger samples and mechanistic studies are necessary to confirm our findings. Trial registration NCT03039842 (https://register.clinicaltrials.gov/). Trial date was from 1 Jan 2013 to 31 December 2016 in National Cheng Kung University Hospital. Registered 28 February 1 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03039842?term=NCT03039842&rank=1.
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http://dx.doi.org/10.1186/s40345-019-0174-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049537PMC
March 2020

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder.

Clin Psychopharmacol Neurosci 2020 Feb;18(1):145-152

Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan, ROC.

Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets).

Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA+P, n = 57) or DM (30 mg/day, VPA+DM30, n = 56) or 60 mg/day (VPA+DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked.

Results: Paired test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA+P or VPA+DM30 treatment. VPA+DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment.

Conclusion: Hematological molecule levels were lower after long-term treatment with VPA. VPA+DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.
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http://dx.doi.org/10.9758/cpn.2020.18.1.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006988PMC
February 2020

Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment.

Clin Psychopharmacol Neurosci 2020 Feb;18(1):136-144

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan.

Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase () gene has been associated with OUD and gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT).

Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. gene polymorphisms were genotyped. Connors' Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the genotypes and performance on the CPTs and WMS-R.

Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the + ( inactive) genotypes had significantly higher commission error T-scores (= 0.03), significantly lower hit reaction time T-scores (= 0.04), and significantly lower WMS-R visual memory index scores (= 0.03) than did patients with the ( active) genotype.

Conclusion: OUD patients with the inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the active genotype. We conclude that the gene is important in OUD and is associated with neuropsychological performance after MMT.
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http://dx.doi.org/10.9758/cpn.2020.18.1.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006970PMC
February 2020
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