Investigating genetic variants for treatment response to selective serotonin reuptake inhibitors in syndromal factors and side effects among patients with depression in Taiwanese Han population.

Major depressive disorder (MDD) is associated with high heterogeneity in clinical presentation. In addition, response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably among patients. Therefore, identifying genetic variants that may contribute to SSRI treatment responses in MDD is essential. In this study, we analyzed the syndromal factor structures of the Hamilton Depression Rating Scale in 479 patients with MDD by using exploratory factor analysis. All patients were followed up biweekly for 8 weeks. Treatment response was defined for all syndromal factors and total scores. In addition, a genome-wide association study was performed to investigate the treatment outcomes at week 4 and repeatedly assess all visits during follow-up by using mixed models adjusted for age, gender, and population substructure. Moreover, the role of genetic variants in suicidal and sexual side effects was explored, and five syndromal factors for depression were derived: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. Subsequently, several known genes were mapped to suggestive signals for treatment outcomes, including single-nucleotide polymorphisms (SNPs) in PRF1, UTP20, MGAM, and ENSG00000286536 for psychomotor-insight and in C4orf51 for anorexia. In total, 33 independent SNPs for treatment responses were tested in a mixed model, 12 of which demonstrated a p value <0.05. The most significant SNP was rs2182717 in the ENSR00000803469 gene located on chromosome 6 for the core syndromal factor (ß = -0.638, p = 1.8 × 10-4) in terms of symptom improvement over time. Patients with a GG or GA genotype with the rs2182717 SNP also exhibited a treatment response (ß = 0.089, p = 2.0 × 10-6) at week 4. Moreover, rs1836075352 was associated with sexual side effects (p = 3.2 × 10-8). Pathway and network analyses using the identified SNPs revealed potential biological functions involved in treatment response, such as neurodevelopment-related functions and immune processes. In conclusion, we identified loci that may affect the clinical response to treatment with antidepressants in the context of empirically defined depressive syndromal factors and side effects among the Taiwanese Han population, thus providing novel biological targets for further investigation.

Illicit Drug Use and Smell and Taste Dysfunction: A National Health and Nutrition Examination Survey 2013-2014.

Taste and smell dysfunction are suspected to be associated with substance use. However, representative epidemiological studies remain insufficient. This cross-sectional study explored the relationship between drug use (including cannabis or hashish, cocaine, heroin, and methamphetamine) and olfactory/gustatory dysfunction using data from the 2013-2014 National Health and Nutrition Examination Survey. In this study, participants who completed the smell examination with mean age of 59 were classified into four groups: cannabis users (n = 845), participants without cannabis use (n = 794), illicit drug users (n = 450), and participants without illicit drug use (n = 2000). Participants who completed the taste examination with mean age of 58 were also categorised into four groups: cannabis users (n = 810), participants without cannabis use (n = 714), illicit drug users (n = 428), and participants without illicit drug use (n = 1815). Logistic regression models investigated the association between cannabis or illicit drug use and smell or taste dysfunctions among study participants. Odds ratios and 95% confidence intervals were calculated. Finally, we did not find correlations between illicit drug use and dysfunction of taste or smell senses; our findings were consistent in many subgroup analyses. We recommend that further studies explore the mechanism and dose of illicit drug use that could have chemosensory impacts.

The association between depression and chronic lower back pain from disc degeneration and herniation of the lumbar spine.

OBJECTIVE: Chronic lower back pain induced by lumbar disc degeneration or herniation exerts a great impact on patients' daily lives. Depression and anxiety often exist among patients with lower back pain. Some studies mentioned about mechanisms, such as inflammatory biomarkers, which are commonly seen in herniated intervertebral disc (HIVD) and major depressive disorder (MDD). Method: Our study used a large database from the National Health Insurance to explore the incidence rate of MDD in patients with HIVD and correlated risk factors. A total of 41,874 patients with HIVD were included in this work. The control group was matched by using propensity scores. Results: The results showed a temporal association between prior HIVD and subsequent MDD after adjusting for potential confounding factors. Patients with HIVD were at high risk of developing MDD (hazard ratio, HR: 9.00, 95% confidence interval, CI: 7.196-11.257) even after adjusting for demographic characteristics and comorbidities (HR: 8.47, 95% CI: 6.84-10.49, p < 0.0001). Conclusions: The combination of HIVD and MDD represents an important health problem that is associated with higher disability rates, socioeconomic disadvantage, and greater utilization of health care resources. Early detection and combined treatment of depressive symptoms may benefit patients with HIVD.

Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistant depression in a 13-year nationwide cohort study.

BACKGROUND: To investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities. METHODS: In total, 31,422 depressive inpatients were followed-up from diagnostic onset for more than 10-years. Patients were diagnosed with TRD if their antidepressant treatment regimen was altered ≥two times or if they were admitted after at least two different antidepressant treatments. Multiple Cox regression model were used to determine whether physical and psychiatric comorbidities, psychosis, and prescription patterns increased the risk of TRD by controlling for relevant demographic covariates. Survival analyses were performed for important TRD-associated clinical variables. RESULTS: Females with depression (21.24%) were more likely to suffer from TRD than males (14.02%). Early anxiety disorders were more commonly observed in the TRD group than in the non-TRD group (81.48 vs. 58.96%, p < 0.0001). Lifetime anxiety disorders had the highest population attributable fraction (42.87%). Seventy percent of patients with multiple psychiatric comorbidities developed TRD during follow-up. Cox regression analysis further identified that functional gastrointestinal disorders significantly increased TRD risk (aHR = 1.19). Higher doses of antidepressants and benzodiazepines and Z drugs in the early course of major depressive disorder increased TRD risk (p < 0.0001). CONCLUSION: Our findings indicate the need to monitor early comorbidities and polypharmacy patterns in patients with depression associated with elevated TRD risk.

Panic Disorder Correlates With the Risk for Sexual Dysfunction.

BACKGROUND: Reports have suggested that sexual dysfunction is an underestimated complication of panic disorder, but little research has focused on sexual dysfunction associated specifically with panic disorder. The purpose of this systematic review was to investigate whether patients with panic disorder who are not currently receiving treatment had a higher risk of sexual dysfunction than healthy people, as well as to clarify the appropriate treatment for this patient group. METHODS: Articles that reported panic disorder complicated with sexual dysfunction were identified by a systematic literature search of electronic databases, including PubMed, the Cochrane databases, EMBASE, and PsycINFO. RESULTS: Six articles were included in the review. Patients with panic disorder showed a high prevalence of sexual aversion (35.7% to 64%) and sexual infrequency (36% to 44%). One cohort study indicated that untreated patients with panic disorders had a higher risk of erectile dysfunction than controls. Another article that focused specifically on female patients reported that the patients with panic disorder exhibited decreased frequency of sexual behavior and decreased sexual desire compared with the controls. However, 2 studies found conflicting results after adjustment for confounding factors. CONCLUSIONS: Although the results were mixed, it appears that patients with panic disorder tended to be more susceptible to sexual dysfunction than the general population. Further trials with larger sample sizes and rigorous research designs are needed to establish the relationship between sexual dysfunction and panic disorder.

Newly diagnosed panic disorder and the risk of erectile dysfunction: A population-based cohort study in Taiwan.

Previous studies indicated that panic disorder is correlated with erectile dysfunction (ED). The primary aim of this study was to explore the incidence rate of ED among panic disorder patients in an Asian country. The secondary aim was to compare the risk of ED in panic disorder patients that were treated with different kinds of antidepressants, and to explore the possible mechanism between these two disorders. We identified 1393 male patients with newly diagnosed panic disorder from the Taiwan's National Health Insurance Database. Four matched controls per case were selected for the study group by propensity score. After adjusting for age, obesity and comorbidities, the panic disorder patients had a higher hazard ratio of ED diagnosis than the controls, especially among the untreated panic disorder patients. This retrospective dynamic cohort study supports the link between ED and prior panic disorder in a large sample of panic disorder patients. This study points out the need of early antidepressant treatment for panic disorder to prevent further ED.

Association of lower hemoglobin levels with depression, though not with cognitive performance, in healthy elderly men.

Lower hemoglobin (Hb) levels are a common feature in the elderly. The present study recruited 180 healthy elderly men. Participants were assessed using the Geriatric Depression Scale, the Cognitive Abilities Screening Instrument Chinese version, and the Wechsler Digit Span Task test. The mean age of the participants was 85.8 years (SD = 10.5). Pearson's correlation tests demonstrated that Hb concentrations negatively correlated with Geriatric Depression Scale (r = -0.245, P = 0.001), but did not correlate with Cognitive Abilities Screening Instrument, Forward or Backward Digit Span tests. Lower Hb levels, therefore, were associated with depression in the elderly men.