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To investigate the risk of psychiatric disorders after traumatic brain injury (TBI), and to clarify whether the post-TBI rehabilitation was associated with a lower risk of developing psychiatric disorders. A register-based, retrospective cohort design. Using data from the National Health Insurance Research Database of Taiwan, we established an exposed cohort with TBI and a nonexposed group without TBI matched by age and year of diagnosis between 2000 and 2015. This study included 231,894 patients with TBI and 695,682 patients without TBI (N=927,576). Rehabilitation therapies in TBI patients. A multivariable Cox proportional hazards regression model was used to compare the risk of developing psychiatric disorders. The incidence rate of psychiatric disorders was higher in the TBI group than the control group. Compared with the control group, the risk of psychiatric disorders in the TBI group was twofold (hazard ratio [HR]=2.072; 95% confidence interval [95% CI], 1.955-2.189; P <.001). Among the participants with TBI, 49,270 (21.25%) had received rehabilitation therapy and had a lower risk of psychiatric disorders (HR=0.691; 95% CI, 0.679-0.703; P <.001). In the subgroup analysis, the medium- to high-level intensity rehabilitation therapy was associated with lower risks of psychiatric disorder (HR=0.712 and 0.568, respectively), but there was no significant finding in the low-intensity group. We found that TBI was associated with a high risk for developing psychiatric disorders, and that the post-TBI rehabilitation significantly reduced the risk of psychiatric disorders in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between males with pinworm infections and the risk of developing psychiatric disorders. A total of 2044 enrolled patients, with 511 pinworm subjects and 1533 unexposed subjects (1:3) matched for sex, age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, the Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up. Of all the enrollees, 24 in the pinworm cohort and 18 in the unexposed cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214–9.480, p <.001, p <.001). Pinworm infections were associated with the increased risk in anxiety disorders, depressive disorders, and sleep disorders, respectively. Patients who suffered from pinworm infections have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues. • Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD) was used in this study. • During the 15 years of follow-up, 24 in the pinworm cohort and 18 in the non-PSD cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. • The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214–9.480, p <.001, p <.001). • Pinworm infections were associated with the increased risk in anxiety disorders, depressive disorders, and sleep disorders, respectively. [ABSTRACT FROM AUTHOR]

Recent commentary in Neurotherapeutics by Nath critically addresses the earlier report by Tzeng et al. that aggressive antiviral treatment (AVT) against herpes simplex virus (HSV) was associated with a later decrease in the incidence of Alzheimer's disease (AD). Nath raises issues that we respond to: we point out that (i) the treated group (probably with severe infection) is likely to harbor genetic risk alleles that predispose to both AD and HSV infection-the potential treatment bias cited by Nath would support (rather than challenge) the preventive effect of AVT; (ii) HSV is well known to establish persistent infection in the brain; and (iii) current AVT compounds used to combat herpes viruses are highly specific for this class of viruses. Instead of "alternative fact," the findings of Tzeng et al. argue in favor of clinical trials of AVT in AD. [ABSTRACT FROM AUTHOR]

This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795, P < 0.001) for the development of dementia in the HSV-infected cohort relative to the non-HSV cohort. Thus, patients with HSV infections may have a 2.56-fold increased risk of developing dementia. A risk reduction of dementia development in patients affected by HSV infections was found upon treatment with anti-herpetic medications (adjusted HR = 0.092 [95% CI 0.079-0.108], P < 0.001). The usage of anti-herpetic medications in the treatment of HSV infections was associated with a decreased risk of dementia. These findings could be a signal to clinicians caring for patients with HSV infections. Further research is, therefore, necessary to explore the underlying mechanism(s) of these associations. [ABSTRACT FROM AUTHOR]

Background A substantial amount of evidence suggests that dysfunction of the dopamine transporter may be involved in the pathophysiology of amphetamine dependence (AD). The aim of this study was to examine whether the dopamine transporter gene ( DAT1 , SLC6A3 ) is associated with development of AD and whether this gene influences personality traits in patients with AD. Methods Eighteen polymorphisms of the DAT1 gene were analyzed in a case-control study that included 909 Han Chinese men (568 patients with AD and 341 control subjects). The patients fulfilled the DSM-IV-TR criteria for AD. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits and to examine the association between these traits and DAT1 gene variants. Results A weak association was found between the rs27072 polymorphism and development of AD, but these borderline associations were unconfirmed by logistic regression and haplotype analysis. Although harm avoidance and novelty seeking scores were significantly higher in patients than in controls, DAT1 polymorphisms did not influence these scores. Conclusions This study suggests that high harm avoidance and novelty seeking personality traits may be a risk factor for the development of AD. However, the DAT1 gene may not contribute to AD susceptibility and specific personality traits observed in AD among Han Chinese men. [ABSTRACT FROM AUTHOR]

Abstract: Bipolar disorder, characterized by a dysregulation of mood, impulsivity, risky behavior and interpersonal problems, is a recurrent and often becomes chronic psychiatric illness. However, bipolar subtypes are not often recognized in psychiatric settings, especially bipolar II subtype, until Akiskal and Angst made clear definition to bipolar I (BP-I) and bipolar II (BP-II) disorder in 1999. More and more studies, not only on family inheritance, diagnosis, but also on disease process have been reported that BP-I and BP-II are two different disorders with distinct pathological mechanisms. In general, patients with BP-II express less symptoms and have shorter hypomania stages than BP-I. According to a longitudinal research, patients with BP-II have poor recovery than do BP-I patients. Memantine used to be recognized as a noncompetitive N-methyl-d-aspartate receptor antagonist. However, it was found to have neuroprotective and neurogenesis effect in several neurodegenerative diseases in the past years. We found that memantine could inhibit brain inflammatory response through its action on neuroglial cells and provide neurotrophic effect. The above evidences of benefit on auto-immune system with memantine would support that memantine as add-on therapy to valproate might be more effective than valproate alone on improvement of the neuron degeneration in bipolar disorders. Review articles indicate that not only the mood stabilizers provide with good neuroprotection, but the memantine also have conspicuous anti-autoimmune and neurogenesis effect. Therefore, we propose that drugs with neuroprotective effect and neurotrophic effect may treat neurodegenerative diseases including BP-II. The combination treatment of mood stabilizers memantine may not only augment and improve the remedy for bipolar disorders, but also repair the damaged neurons and neurogenesis through activation of astroglial cell and release of neurotrophic factors. [Copyright &y& Elsevier]

The objective of this study was to investigate disordered eating among female college students. The study sought to establish a predictive model for the risk of eating disorders in young female university students in Taiwan. A group of 336 student participants were recruited with the results showing that more than one third (43.2%) of the college women surveyed were identified to be at risk for developing an eating disorder. The results of multiple logistic regression showed that bulimia score, elevated depression index, eating binges, the use of laxatives and medicine to control weight, and having lost 20 lb, or more, in the past 6 months were all considered to be risk factors for developing an eating disorder (the corresponding area under receiver operating characteristic curve = 0.905). The results demonstrate that unhealthy dietary behaviors are rapidly spreading among young Taiwanese female students. For the sample described in this article, 67.6% of the female college students had lost weight: 51% had dieted at least once to lose weight, 43% used exercise to lose weight, 24% used low-calorie diets to lose weight, 11% used healthy food to lose weight, 9.2% used rubber clothing and a diet patch to lose weight, 17.9% of the students used weight-loss drugs, and a few students sought medical assistance from weight-loss clinics or actually underwent liposuction (1.5%). [Copyright &y& Elsevier]

The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study. [ABSTRACT FROM AUTHOR]

Abstract: We coined a new word, “dromosagnosia”, from the Greek words, dromos (“way, road”) + agnosia, to describe the loss of direction while driving, an orientation disorder similar to but different from pure topographic disorientation. Historically, human beings have moved more quickly, from using domesticated animals to high speed vehicles, and this may be beyond the brain’s ability to react. Without the benefit of an automatic navigation system, automobiles are associated with more problems of dromosagnosia than are fast-moving aircraft or ships. Previous studies have noted that some areas of the brain are associated with spatial orientation, spatial memory, and even emotion, and abnormalities there could exacerbate the loss of sense of direction. We hypothesize that some people are especially disadvantaged from these brain differences and emotional disturbances when driving their cars. Functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) studies combined with a virtual reality driving simulation might be used to find the areas of the brain related to dromosagnosia. Future applications: some people with dromosagnosia might benefit from special remedial training and a driving safety support system to avoid potential problems. [Copyright &y& Elsevier]

Abstract: Up to 60% of depressed patients do not respond to two months of pharmacotherapy, and late treatment responses are often correlated with poor outcomes and may be characterized as treatment-resistant depression (TRD). Previous studies have noted that the addition of a psychostimulant such as methylphenidate to the therapeutic regimen of patients with TRD or those depressed patients with comorbid fatigue, advanced age, or a major medical illness showed significant improvement within two weeks. One explanation for the benefit of methylphenidate in treating TRD is that it enhances the level of dopamine in the brain. Adjunctive low dose aripiprazole in patients with TRD has also become a common intervention. Several studies have focused on aripiprazole’s pharmacodynamic and pharmacokinetic profiles, but no definitive comments on its antidepressant effects. We hypothesize that a low dose of aripiprazole might play a role as a dopamine agonist similar to that of methylphenidate due to its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. In addition to its use in patients with TRD, adjunctive aripiprazole might work like methylphenidate in those depressed patients with fatigue, advanced age, or major illnesses. A new drug invention which combined an antidepressant with an adequate dose of aripiprazole should be considered. The neurobiological basis for this combination in treating TRD awaits further study. [Copyright &y& Elsevier]

Dementia is a cluster of brain dysfunctions with a characteristic of progressively debilitating in individuals' ability of operating cognitive functions and that affects seriously to patients' daily life. We presented a hypothesis in this article that earlier exposure of a common used cognitive enhancer amphetamine may lead to individuals to be more liable to develop dementia in their later life based on the opponent process theory. The theory proposes that following a positive response, homeostatic changes in brain circuits may function to go opposite to the positive response, thus a cognitive deterioration may incur in later life in the individuals who exposed to amphetamine earlier. Along with the hypothesis, amphetamine is also highly associated with the working hypothesis updated for dementia in terms of beta-amyloid cascade, tau protein, oxidative stress and neural inflammation. Finally, we presented two practical methods to evaluate the hypothesis. In non-human approach, rat model of amphetamine dependence would be employed together with evaluations of behavioral performance of memory test and neurochemical markers associated with oxidative stress. In human approach, a matched-cohort design observational study would be highly recommended. [ABSTRACT FROM AUTHOR]

Febrile seizures occur commonly in children aged between six months and six years. A previous Danish study found a positive correlation between febrile seizures and the overall incidence of psychiatric disorders. This population-based nationwide observational study was conducted to investigate the association between febrile seizures and different psychiatric disorders in Taiwan and the associated risk factors. This cohort study used data from the National Health Insurance Research Database in Taiwan—a nationwide claims database covering >99% of the Taiwanese population. The study period was from January 2000 to December 2015; the overall median follow-up time was 11.04 ± 10.95 years. Overall, 2464 children with febrile seizures diagnosed between 2000 and 2015 met the inclusion criteria, and 7392 children without febrile seizures matched by index year, age, and sex were included in the control cohorts. Febrile seizures and psychiatric disorders were measured as the exposure and main outcomes, respectively. Children with febrile seizures (n = 2463) were at a high risk of psychiatric disorders (adjusted hazard ratio, 4.70; 95% confidence interval [CI], 2.44 to 7.30; P < 0.001). The risk for anxiety was the highest (adjusted hazard ratio, 21.92; 95% CI, 11.40 to 34.05; P < 0.001). When treating children with febrile seizures, particular attention should be paid to the symptoms of psychiatric disorders, as early referral may be beneficial for these children. [ABSTRACT FROM AUTHOR]

High-frequency transcranial random noise stimulation (hf-tRNS) is a non-invasive neuromodulatory technique capable of increasing human cortex excitability. There were only published case reports on the use of hf-tRNS targeting the lateral prefrontal cortex in treating negative symptoms of schizophrenia, thus necessitating systematic investigation. We designed a randomized, double-blind, sham-controlled trial in a cohort of stabilized schizophrenia patients to examine the efficacy of add-on hf-tRNS (100–640 Hz; 2 mA; 20 min) using a high definition 4 × 1 electrode montage (anode AF3, cathodes AF4, F2, F6, and FC4) in treating negative symptoms (ClinicalTrials.gov ID: NCT04038788). Participants received either active hf-tRNS or sham twice daily for 5 consecutive weekdays. Primary outcome measure was the change over time in the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), which was measured at baseline, after 10-session stimulation, and at one-week and one-month follow-ups. Among 36 randomized patients, 35 (97.2%) completed the trial. Intention-to-treat analysis showed a significantly greater decrease in PANSS-FSNS score after active (−17.11%) than after sham stimulation (−1.68%), with a large effect size (Cohen's d = 2.16, p < 0.001). The beneficial effect lasted for up to one month. In secondary-outcome analyses, the authors observed improvements with hf-tRNS of disorganization symptoms, unawareness of negative symptoms, subjective response to taking antipsychotics, and antipsychotic-induced extrapyramidal symptoms. No effects were observed on the neurocognitive performance and other outcome measures. Overall, hf-tRNS was safe and efficacious in improving negative symptoms. Our promising findings should be confirmed in a larger sample of patients with predominant negative symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Duloxetine is a serotonin and norepinephrine re-uptake inhibitor with both anti-depressant and pain-relieving properties. Its pain-relieving properties are due to its action on the descending inhibitory pain pathways. However, the fast onset of analgesia may be mediated by mechanisms other than the descending inhibitory pain pathways. This study posits the hypothesis that duloxetine may have pain-relieving property by peripheral analgesic effects. Ways of testing this hypothesis and its potential topical use are discussed. [Copyright &y& Elsevier]

Abstract: Growing evidence suggests that proinflammatory responses will be a crucial issue for developing neuropsychiatric disorders. Recent clinical trials demonstrated that adjunctive therapy of cyclo-oxygenase (COX)-2 inhibitor was effective for major depression. Here, we present the case of an elderly depressed woman with acute cognitive deficit who was refractory to multiple antidepressants but only responsive to celecoxib, a COX-2 inhibitor, in acute treatment and sustaining remission for a 5-year treatment course. Our finding suggests that a therapeutic effect of celecoxib exists for major depressive disorder comorbid with neurocognitive dysfunction. [Copyright &y& Elsevier]

Background: Obstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD.Methods: This study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD.Results: The OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301-1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs.Conclusions: Our study demonstrates that the OSA patients are at a higher risk of developing ARDs. [ABSTRACT FROM AUTHOR]

Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20–65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n = 29 for agomelatine, n = 27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone. [ABSTRACT FROM AUTHOR]

• Age moderated the association of COMT Val158Met polymorphism with resting vagal control. • In the younger age groups, Met allele carriers exhibited lower resting vagal control. • However, an opposite pattern was found in the older age groups. • Using path analysis, this was, in turn, associated with increased risk for GAD. • We provided an age-specific neural mechanism for the complex role of COMT in GAD. The functional Val158Met polymorphism (rs 4680) of the Catechol-O-Methyltransferase (COMT) gene has been implicated in generalized anxiety disorder (GAD); however, the underlying neural mechanisms remain unexamined. Recent evidence reveals that low resting parasympathetic (vagal) control is an endophenotypic predictor of anxiety, while the effect of COMT rs 4680 differs at different ages. Thus, we examined whether the COMT Val158Met variant could increase the risk of GAD through decreased resting parasympathetic nervous control in an age-specific manner. COMT rs 4680 polymorphism was genotyped in 1,655 Han Chinese adults (1,142 healthy subjects and 513 patients with GAD; age: 20–65). High-frequency power (HF) of heart rate variability (HRV) was used to measure resting state parasympathetic nervous regulation. Non-genetic factors, such as gender, smoking status, medication use and comorbidity conditions, were treated as covariates. After adjusting for relevant covariates, there was a significant age x COMT genotype interaction on resting HF of HRV. In younger adults, Met allele carriers had a significantly lower HF index; however, older adults exhibited the opposite pattern, with Val/Val homozygotes exhibiting decreased HF values. Moreover, reduced HF-HRV is associated with increased risk of GAD. Finally, pathway analysis revealed a significant indirect effect of COMT on the risk of GAD via reduced resting HF-HRV, in the aforementioned age-dependent manner. Our findings are the first to demonstrate that COMT Val158Met polymorphism is associated with risk of GAD via reduced resting parasympathetic nervous control, an age-specific risk pathway. [ABSTRACT FROM AUTHOR]

Background: Patients with opioid use disorder (OUD) show memory deficiencies and impaired treatment outcomes. Emerging evidence suggests that opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neuroprotection, which damages the memory function in OUD patients. Therefore, we investigated whether plasma-based inflammatory and neurotrophic markers correlate with memory function in OUD patients.Method: OUD patients undergoing methadone maintenance therapy (MMT) were investigated and followed up for 12 weeks. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF) levels, and Wechsler Memory Scale-Revised (WMS-R) scores were assessed at baseline and after 12 weeks of MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between cytokines and memory performance.Results: We enrolled 89 patients at baseline; 47 patients completed the end-of-study assessments. Although Pearson correlations showed that CRP and TGF-β1 levels were significantly, negatively associated with some memory indices, the results were not significant after correction. The GEE results, controlled for several confounding factors and multiple testing, showed that changes in TNF-α levels were negatively correlated with changes in the visual memory index (P = 0.01), and that changes in IL-6 levels were negatively correlated with changes in the verbal memory index (P = 0.009).Conclusion: Memory performance, TNF-α, and IL-6 levels in OUD patients were negative correlated. Additional studies on regulating TNF-α and IL-6 expression to improve memory function in OUD patients might be warranted. [ABSTRACT FROM AUTHOR]