Comparing the performance of ChatGPT GPT-4, Bard, and Llama-2 in the Taiwan Psychiatric Licensing Examination and in differential diagnosis with multi-center psychiatrists.

AIM: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well-studied. METHOD: In the first step, we compared the performance of ChatGPT GPT-4, Bard, and Llama-2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis. RESULT: Only GPT-4 passed the 2022 Taiwan Psychiatric Licensing Examination (scoring 69 and ≥ 60 being considered a passing grade), while Bard scored 36 and Llama-2 scored 25. GPT-4 outperformed Bard and Llama-2, especially in the areas of 'Pathophysiology & Epidemiology' (χ2 = 22.4, P < 0.001) and 'Psychopharmacology & Other therapies' (χ2 = 15.8, P < 0.001). In the differential diagnosis, the mean score of the 24 experienced psychiatrists (mean 6.1, standard deviation 1.9) was higher than that of GPT-4 (5), Bard (3), and Llama-2 (1). CONCLUSION: Compared to Bard and Llama-2, GPT-4 demonstrated superior abilities in identifying psychiatric symptoms and making clinical judgments. Besides, GPT-4's ability for differential diagnosis closely approached that of the experienced psychiatrists. GPT-4 revealed a promising potential as a valuable tool in psychiatric practice among the three LLMs.

Association between parental bipolar disorder and increased risk of exposure to prescription opioids for their offspring.

PURPOSE: Individuals with bipolar disorder (BD) may have an increased risk of exposure to prescription opioids. However, it is still unknown whether such risk also occurs in their offspring. This study aimed to investigate the risk of exposure to prescription opioid use and related medical conditions in the offspring of parents with BD. METHODS: This study used the Taiwan National Health Research Database and included offspring who had any parent with a diagnosis of BD. The matched-control cohort was randomly identified from the offspring of parents without any major psychiatric disorders (MPD). We identified data pertaining to opioid prescription and related medical conditions, namely pain disorder, malignancy, autoimmune disease, and arthropathy. The Poisson regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: In total, 11,935 offspring of parents with BD and 119,350 offspring of parents without any MPD were included. After controlling for demographics and mental disorders, offspring of parents with BD demonstrated higher rates of prescription opioid use than those of parents without MPD, especially the intravenous/intramuscular form of opioids and prescription in hospital settings. In addition, offspring of parents with BD had a higher odds of pain disorders than those of parents without MPD. CONCLUSION: Our study identifies a higher odd for developing pain disorders and exposure to prescription opioids among children of parents with BD.

Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis.

AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.

Associations of parental mental disorders and age with childhood mental disorders: a population-based cohort study with four million offspring.

This Taiwan study examined the associations of parental age and mental disorders with the offspring risks of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), and bipolar disorder (BD). Children born between January 1991 and December 2004 in Taiwan were enrolled as the birth cohort (n = 4,138,151) and followed up until December 2011. A logistic regression analysis was performed to identify the odds ratio (OR). The advanced age effects were significant in ADHD (range of OR: 1.04 to 1.49) and ASD (range of OR: 1.35 to 2.27). Teenage mothers, teenage fathers, and fathers ≥ 50 years had higher offspring risks of MDD (range of OR: 1.24 to 1.46); and teenage mothers and fathers ≥ 50 years had increased offspring risks of BD (range of OR: 1.23 to 1.87). Both paternal and maternal mental disorders were associated with higher risks of within-disorder transmission for ADHD, ASD, MDD, and BD (range of OR: 2.64 to 30.41). Besides, parents with one of these four mental disorders (ADHD, ASD, MDD, and BD) might have higher risk of cross-disorder transmission to at least one of the other three mental disorders in the offspring (range of OR: 1.35 to 7.15). Parental age and mental disorders had complex and nuanced patterns in association with offspring mental disorders.

Resting-State EEG Connectivity at High-Frequency Bands and Attentional Performance Dysfunction in Stabilized Schizophrenia Patients.

Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Risk of pain disorders in offspring of parents with substance use disorders.

AIMS: Individuals with substance use disorders (SUD) have higher risk of developing pain disorders. This study aimed to investigate the risk of major psychiatric disorders (MPD), SUD, and pain disorders among their offspring. METHODS: This study used data from the Taiwan National Health Research Database. The case cohort included participants who had a parent diagnosed with SUD. The matched control cohort was offspring of parents without any SUD or major psychiatric disorder (MPD). Poisson regression was applied to estimate the risk of MPD, SUD, and pain disorder between case and control cohorts. RESULTS: We recruited 13,840 cases and 138,400 matched controls. After adjusting for demographic characteristics and family history of psychiatric disorder, the offspring of parents with SUD had higher risk for bipolar disorder (reported as risk ratio with 95% confidence interval: 2.48, 1.79-3.43), depressive disorder (2.22, 1.94-2.52), SUD (2.53, 2.18-2.92), and alcohol use disorder (1.43, 1.16-1.76) than controls. With adjustments of demographic characteristics, individual MPD, and family history of psychiatric disorder, they also presented higher risk than controls for several pain disorders, including migraine (1.43, 1.15-1.78), fibromyalgia (1.21, 1.03-1.42), dorsopathies (1.20, 1.06-1.37), dysmenorrhea (1.16, 1.04-1.29), irritable bowel syndrome (1.26, 1.11-1.43), and dyspepsia (1.14, 1.02-1.27). CONCLUSIONS: Clinicians should be aware of the influence of parental SUD on the elevated risk for MPD, SUD, and pain disorders in their offspring.

Protective Effects of Epigallocatechin Gallate for Male Sexual Dysfunction in Streptozotocin-Induced Diabetic Rats.

Sexual dysfunction is a common problem for men with diabetes. Epigallocatechin gallate (EGCG) is known to ameliorate erectile function in aging rats. However, there has not yet been a report to evaluate its effects on diabetic male rat sexual behavior in the literature. In this study, we investigated the effects of EGCG on male sexual behavior in diabetic rats. Diabetic rats were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin. After streptozotocin injection for one week, animals were then orally treated with 40 mg/kg of EGCG or vehicle. Copulatory behavior and fasting blood glucose levels were recorded before treatment, as well as 7 and 14 days after treatment. Serum LH, testosterone, and PDE5a levels were measured by EIA assay after the last behavioral test. Data showed that diabetic rats who had diminished sexual functions demonstrated significantly increased latencies in mount, intromission, and ejaculation, as well as significant decreases in frequencies of intromission and ejaculation, compared to non-diabetic controls, indicating sexual function recovery. Lower blood glucose levels were also found in diabetic rats after EGCG treatment. Additionally, the lower LH and higher PDE5a levels in diabetic rats than controls were also noted. The findings declared that EGCG had a protective effect on male sexual behavior in diabetic rats.

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis.

OBJECTIVES: To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits. METHODS: Electronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre-post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined. RESULTS: We included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%-11.1%). HFrTMS (1.08, 9, 0.35-1.80) and atDCS (0.56, 0.03-1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (-0.79, -2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77-2.54) and ctDCS (2.57, 0.20-4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated. CONCLUSIONS: HFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

Therapeutic benefits of pharmacologic and nonpharmacologic treatments for depressive symptoms after traumatic brain injury: a systematic review and network meta-analysis.

Background: Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods: We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results: Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations: Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion: The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.

Psychiatric Disorders After Traumatic Brain Injury: A Nationwide Population-Based Cohort Study and the Effects of Rehabilitation Therapies.

OBJECTIVE: 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. DESIGN: A register-based, retrospective cohort design. SETTING: 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. PARTICIPANTS: This study included 231,894 patients with TBI and 695,682 patients without TBI (N=927,576). INTERVENTIONS: Rehabilitation therapies in TBI patients. MAIN OUTCOME MEASURES: A multivariable Cox proportional hazards regression model was used to compare the risk of developing psychiatric disorders. RESULTS: 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. CONCLUSIONS: 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.

Mortality Risk of Atypical Antipsychotics for Behavioral and Psychological Symptoms of Dementia: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Evidence suggests that atypical antipsychotics (AAPs) exert a short-term mortality risk in people with dementia. We assessed whether additional randomized clinical trials influence the current evidence and the potential effect modifiers. METHODS: Electronic databases were systematically searched for randomized controlled trials from their inception through March 2018. A random-effects model was used for analysis. Potential effect modifiers were examined through meta-regression. Trial sequential analysis was performed to quantify the statistical reliability of data in the cumulative meta-analysis with adjustment of significance levels for sparse data and repetitive testing on accumulating data. Certainty of evidence and risk of bias were also evaluated. RESULTS: We found that compared with placebos, AAPs may increase the risk of mortality (odds ratio [OR], 1.536; 95% confidence intervals [CIs], 1.028-2.296; P = 0.036, high certainty). In the subgroup analysis, the estimated ORs were the highest for olanzapine (1.919; P = 0.232), followed by those for quetiapine (1.663; P = 0.506), aripiprazole (1.649; P = 0.297), and risperidone (1.354; P = 0.277); however, the mortality risk presented by individual AAPs did not exhibit between-group differences. The meta-regression did not identify any effect modifiers, including the chlorpromazine equivalent dose, trial duration, and cognitive status. The trial sequential analysis revealed that future similar trials are unlikely to alter our findings. CONCLUSIONS: Atypical antipsychotics are associated with increased short-term mortality risk, although a disease-drug interaction may contribute to such risk in people with dementia. Patients with dementia may still benefit by AAPs after appropriate assessment of the disease severity as well as the dosage of AAPs, treatment duration, and monitoring of AAPs.

Associations Between Depression/Anxiety and Headache Frequency in Migraineurs: A Cross-Sectional Study.

BACKGROUND: While migraines have been associated with emotional disturbances, it remains unknown whether the intensity of emotional expression is directly related to migraine frequency. OBJECTIVE: The present study investigated depression/anxiety among migraineurs. METHODS: This cross-sectional study included 588 clinical outpatients in Taiwan. Migraines were stratified by attack frequency, with and without auras, and with well-controlled confounding variables. Demographic and clinical data, including sleep characteristics, were collected. Multivariable linear regressions were employed to examine whether migraine frequency (1-4 headache days per month, 5-8 headache days per month, 9-14 headache days per month, or >14 headache days per month) was associated with depression/anxiety symptoms, as indicated by the Beck's Depression Inventory (BDI) and Hospital Anxiety and Depression Subscales (HADS). RESULTS: BDI total scores were highest in patients with chronic migraines (mean ± SD: 13.2 ± 8.5), followed by those with high frequency (12.1 ± 8.5), medium frequency (10.6 ± 8.0), low frequency (9.1 ± 7.1), and lowest in nonmigraine controls (6.6 ± 5.9), with a significant trend in frequency (P trend < .001); similar results were obtained for HADS scores. BDI and HADS scores were independently related to high-frequency episodic and chronic migraine frequency and to poor sleep quality. The relationship between BDI score and migraine frequency was present in both aura-present (P trend = .001) and aura-absent subgroups (P trend = .029). CONCLUSION: Higher migraine frequency, either with or without auras, correlated with higher symptom scores of anxiety and depression.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.