Investigation of anxiety and depressive disorders and psychiatric medication use before and after cancer diagnosis.

OBJECTIVE: Data regarding the prevalence of depression and anxiety among cancer patients, especially before cancer diagnosis, remains scarce. This study investigated the prevalence of these conditions and associated drug use among cancer patients pre- and post-diagnosis. METHODS: This population-based cohort study using data from Taiwan's National Health Insurance Research Database recruited patients with a registered cancer diagnosis and matched control between January 1, 2000, and December 31, 2011. We compared the prevalence of anxiety and depressive disorders between cancer patients and non-cancer participants during a 2-year period both pre- and post-diagnosis by Pearson's chi-square test. Psychiatric medication use was also examined for the associated mental condition. RESULTS: We examined participants diagnosed with liver (N = 17,154), colorectal (N = 30,391), breast (N = 40,036), gynecological (N = 23,218), and lung (N = 15,671) cancer. Before the cancer diagnosis, the prevalence of depression was higher in non-cancer participants than in gynecological cancer patients (p = 0.018) but anxiety is higher in liver, colorectal, and lung cancer patients when compared to non-cancer participants (p < 0.05). After the cancer diagnosis, the prevalence of anxiety and depression became significantly higher in all enrolled cancer patients than non-cancer participants (p < 0.05). Similar results were observed in psychiatric medication use trends. CONCLUSIONS: This study proposed that patients with liver, colorectal, and lung cancer had an increased risk of developing anxiety, which might be a sentinel diagnosis. The participants had a significantly higher level of anxiety and depressive disorder post-diagnosis, which highlights the importance of the care for both mental and physical conditions in cancer management.

Selective serotonin reuptake inhibitors use and hepatocellular carcinoma in patients with alcohol use disorder.

BACKGROUND: Research has proposed that selective serotonin reuptake inhibitors (SSRIs) were associated with a reduction of the risk of hepatocellular carcinoma (HCC). The objective of this study is to investigate whether SSRIs use is associated with decreased risk of HCC in patients with alcohol use disorder (AUD). PATIENTS AND METHODS: We conducted a retrospective population-based cohort study using Taiwan's National Health Insurance Research Database (NHIRD) from 1997 to 2013 and enrolled patients with newly diagnosed AUD. After propensity scores matching at a ratio 1:4, total of 4945 SSRI users and 19,785 non-SSRI users were included in the matched cohort. Patients were followed up from the 365th day after the date of first exposure to SSRIs to occurrence of HCC, the date of death, or the end of 2013. Cox proportional hazard regressions were performed to evaluate hazard ratio (HRs) for HCC in SSRI-exposed patients compared with unexposed patients. RESULTS: In the main study cohort, SSRI use was associated with significant lower risk of HCC compared to the non-SSRI users after adjusting for age, sex, income, urbanization, alcoholic fatty liver, alcoholic hepatitis and diabetes (adjusted hazard ratio [aHR] = 0.31, 95 % CI = 0.24-0.39). The negative association of SSRI use and HCC was replicated in the matched cohort (aHR = 0.58, 95 % CI = 0.44-0.77). The effect of SSRI use on HCC was dose-related in both cohorts (p for trend < 0.0001). CONCLUSIONS: This study showed that SSRIs use was associated with a reduction risk of HCC among AUD patients in a cumulative dose effect manner.

Potential disturbance of methylphenidate of gonadal hormones or pubescent development in patients with attention-deficit/hyperactivity disorder: A twelve-month follow-up study.

Several animal or case reports have demonstrated that methylphenidate (MPH) disrupts endogenous gonadal hormones and interferes with the pubescent development of children with attention-deficit/hyperactivity disorder (ADHD). Therefore, this prospective study examined the changes in gonadal hormones and pubescent development in children with ADHD undergoing 12-month MPH treatment. We recruited 146 patients with ADHD (mean age: 8.9 years, 76.7% males) and 70 healthy controls (mean age: 9.2 years, 65.7% males). Blood samples were obtained to measure the serum levels of sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, free testosterone, and prolactin in each child. The sex maturation of ADHD patients was evaluated using the Tanner Stage. Patients with ADHD (107 received MPH treatment and 39 were under natural observation) were followed up for 12 months, and we re-examined hormone levels and Tanner Stage at the endpoint. During a 12-month follow-up for all ADHD patients, the serum levels of SHBG and progesterone significantly decreased, while LH, FSH, and free-testosterone levels significantly increased. However, the duration, drug formulations, and doses of the MPH treatment did not significantly influence gonadal hormone trends or changes of Tanner Stage. This study provides evidence about gonadal hormone trends and pubescent development in children with ADHD who receive long-term MPH treatment in natural settings. We suggest that MPH treatment at usual doses does not significantly alter gonadal function trends in ADHD patients over the course of one year.

Association between selective serotonin reuptake inhibitors and kidney cancer risk: A nationwide population-based cohort study.

The association between selective serotonin reuptake inhibitor (SSRI) exposure and cancer incidence has been investigated; however, no epidemiological study has investigated the association between exposure to individual SSRIs and kidney cancer incidence. The aim of this study is to examine whether SSRI use affected the risk of kidney cancer. We conducted a population-based retrospective cohort study using data from Taiwan's National Health Insurance Research Database. After adjusting for sex, age, urbanization level, comorbidity and medication use through propensity score matching, we identified 222 024 SSRI users and 221 361 SSRI nonusers. A robust Cox proportional hazards model was used to examine the associations between use of individual SSRIs and the risk of kidney cancer with 1- and 2-year induction periods. The result showed that SSRI users tended to be associated with a lower risk of kidney cancer with a 2-year induction period than nonusers; however, the association was not statistically significant (adjusted hazards ratio [aHR] = 0.88, 95% confidence interval [CI] = 0.77-1.01). We further examined the effects of individual SSRIs and observed a significantly lower risk of kidney cancer associated with the use of citalopram (aHR = 0.67, 95% CI = 0.47-0.96) and paroxetine (aHR = 0.75, 95% CI = 0.58-0.97) with the 2-year induction period. These findings support that SSRIs are associated with decreased kidney cancer risk and indicate that citalopram and paroxetine have protective effects in depressed patients with kidney cancer.

Novel plasma metabolite markers of attention-deficit/hyperactivity disorder identified using high-performance chemical isotope labelling-based liquid chromatography-mass spectrometry.

OBJECTIVES: Metabolites are the intermediate and final products of biological processes and ultimately reflect the responses of these processes to genetic regulation and environmental perturbations, including those involved in attention deficit/hyperactivity disorder (ADHD). METHODS: We identified a quantitative profile of plasma metabolites in 58 ADHD patients (mean age 9.0 years, 77.6% males) and 38 healthy control subjects (mean age 10.2 years, 55.3% males) using the high-performance chemical isotope labelling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Using a volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we determined nine metabolites with differentially expressed levels in ADHD plasma samples. RESULTS: Compared to the control group, the plasma levels of guanosine, O-phosphoethanolamine, phenyl-leucine, hypoxanthine, 4-aminohippuric acid, 5-hydroxylysine, and L-cystine appeared increased in the ADHD patients, whilegentisic acid and tryptophyl-phenylalanine were down-regulated in the patients with ADHD. We found that the plasma levels of all nine metabolites were able to discriminate the ADHD group from the control group. Levels of O-phosphoethanolamine, 4-aminohippuric acid, 5-hydroxylysine, L-cystine, tryptophyl-phenylalanine, and gentisic acid were significantly correlated with clinical ADHD symptoms. CONCLUSIONS: This study is the first to use the CIL-based LC-MS to profile ADHD plasma metabolites, and we identified nine novel metabolite biomarkers of ADHD.

New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer.

Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. Methods: We used data from Taiwan's National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25-0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.

The Association between Selective Serotonin Reuptake Inhibitors (SSRIs) Use and the Risk of Bladder Cancer: A Nationwide Population-Based Cohort Study.

BACKGROUND: Past studies suggest mixed associations between selective serotonin reuptake inhibitor (SSRI) prescription and carcinogenic risk. There is no epidemiological study reporting on the association between SSRI use and the incidence of bladder cancer. The aim of this study is to determine whether SSRI use influences the risk of bladder cancer. METHODS: We conducted a nationwide retrospective cohort study by Taiwan's National Health Insurance Research Database from January 1, 1997 to December 31, 2013. 192,392 SSRI prescribed individuals were randomly matched 1 to 1 with 191,786 individuals who had never received any SSRIs by propensity scores match. The Cox Proportional Hazard models were conducted to examine the risk of bladder cancer between individuals prescribed SSRIs and individuals not prescribed SSRIs. RESULTS: SSRIs were associated with significant reduced risk of bladder cancer with 0.5, 1, and 2 year induction periods (adjusted hazard ratio (aHR) = 0.86, 95% CI (confidence interval) = 0.76-0.98, aHR = 0.85, 95% CI = 0.75-0.97, and aHR = 0.77, 95% CI = 0.66-0.89). When examining the effect of specific SSRI, there was significantly lower risk of bladder cancer in individuals prescribed fluoxetine (6 month induction period: aHR = 0.78, 95% CI = 0.65-0.93; 1 year induction period: aHR = 0.78, 95% CI = 0.65-0.94; 2 year induction period: aHR = 0.73, 95% CI = 0.60-0.89), paroxetine (6 month induction period: aHR = 0.78, 95% CI = 0.61-0.99; 1 year induction period: aHR = 0.79, 95% CI = 0.61-1.01; 2 year induction period: aHR = 0.72, 95% CI = 0.54-0.95), and citalopram (6 month induction period: aHR = 0.74, 95% CI = 0.53-1.03; 1 year induction period: aHR = 0.70, 95% CI = 0.50-0.99; 2 year induction period: aHR = 0.60, 95% CI = 0.41-0.88). CONCLUSIONS: Individuals prescribed fluoxetine, paroxetine, or citalopram had a reduced risk of bladder cancer in this large, cross-national database.

Dehydroepiandrosterone sulfate, free testosterone, and sex hormone-binding globulin on susceptibility to attention-deficit/hyperactivity disorder.

The neuroendocrine system may affect the pathophysiology of gender differences in attention deficit/hyperactivity disorder (ADHD). This study examines whether the relationships among dehydroepiandrosterone sulfate (DHEA-S), free testosterone, or sex hormone-binding globulin (SHBG) and ADHD presentations exhibit gender differences. A total of 113 boys and 35 girls with ADHD (all drug naïve) and 46 and 26 healthy control boys and girls, respectively, were recruited. Blood samples were obtained to measure the serum levels of DHEA-S, free testosterone, and SHBG in each child. The Swanson, Nolan, and Pelham Scale for ADHD Version IV (SNAP-IV) was used to evaluate behavioral symptoms and the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Conners' Continuous Performance Test (CPT) were utilized to assess neurocognitive functions. Patients with ADHD had lower DHEA-S levels than male and female healthy control subjects, and no significant differences were observed in free testosterone and SHBG levels between the patients and the controls. DHEA-S levels were negatively correlated with children's impulsivity performance in the CPT. SHBG levels were negatively correlated with ADHD behavior symptoms among boys. Free testosterone levels were not significantly correlated with either ADHD clinical symptoms or neuropsychological functions. We propose that DHEA-S serves as a potential biomarker of ADHD and is consistently involved in the pathogenesis of ADHD in both boys and girls. SHBG may be involved in behaviors associated with ADHD in boys. Additional studies with basic scientific measures are warranted to elucidate the relationship between androgen hormones and clinical presentations of ADHD.

Heavy Metals' Effect on Susceptibility to Attention-Deficit/Hyperactivity Disorder: Implication of Lead, Cadmium, and Antimony.

Background: Heavy metals are known to be harmful for neurodevelopment and they may correlate to attention deficit/hyperactivity disorder (ADHD). In this study, we aim to explore the relationships between multiple heavy metals (manganese, lead, cadmium, mercury, antimony, and bismuth), neurocognitive function, and ADHD symptoms. Methods: We recruited 29 patients with ADHD inattentive type (ADHD-I), 47 patients with ADHD hyperactivity/impulsivity type (ADHD-H/I), and 46 healthy control children. Urine samples were obtained to measure the levels of the aforementioned heavy metals in each child. Participants’ cognitive function and clinical symptoms were assessed, respectively. Results: We found ADHD-H/I patients demonstrated the highest antimony levels (p = 0.028), and ADHD-I patients demonstrated the highest cadmium levels (p = 0.034). Antimony levels were positively correlated with the severity of ADHD symptoms that were rated by teachers, and cadmium levels were negatively correlated with the Full Scale Intelligence Quotient. Lead levels were negatively correlated with most indices of the Wechsler Intelligence Scale for Children⁻Fourth Edition (WISC-IV), but positively correlated with inattention and hyperactivity/impulsivity symptoms (p < 0.05). Conclusion: Lead, cadmium and antimony were associated with susceptibility to ADHD and symptom severity in school-age children. Eliminating exposure to heavy metals may help to prevent neurodevelopmental disorders in children.