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.

Intermittent theta burst stimulation for the treatment of autonomic dysfunction and depressive symptoms in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is one of the most prevalent forms of neurodegenerative dementia, second to Alzheimer's disease, and autonomic abnormalities and depressive symptoms are common. There are currently no cures or treatments with evidence of disease-modifying effects for DLB, and the treatment for the amelioration of targeted symptoms is challenging due to the risk of side effects and drug-drug interactions. In the present case, we report a female elder with DLB suffering from poor tolerance to the adverse events of numerous approaches. Following intermittent theta burst stimulation (iTBS), the autonomic abnormalities and depressive symptoms remarkably improved without significant side effects.

Early Antidepressant Resistance in Late-Onset Major Depressive Disorder: A Nationwide Population-Based Cohort Study.

Background: The association of treatment resistance with physical and psychiatric comorbidities remains unclear in elderly patients with late-onset major depressive disorder (MDD).Methods: Participants were selected from the Taiwan National Health Insurance Research Database. We included patients aged ≥ 65 years with first-episode MDD (ICD-9-CM codes: 296.2X and 296.3X) between January 1, 2001, and December 31, 2010. All participants were followed for 1 year to investigate the incidence of treatment resistance. Treatment-resistant depression (TRD) was defined as unresponsiveness to at least 2 antidepressants, and treatment-resistant tendency (TRT) was defined as unresponsiveness to the first antidepressant. Physical comorbidities were assessed with the Charlson Comorbidity Index (CCI).Results: 27,189 patients with late-onset MDD were included, among whom 16.6% had the diagnosis of anxiety disorders, 1.5% had alcohol use disorders, and 1.6% had substance use disorder. For physical comorbidities, only 16.6% of patients had a CCI score of 0. During the first year of treatment, 22.1% of patients met TRT criteria, and 1.6% developed TRD. Anxiety disorders (odds ratio: 2.06; 95% confidence interval [CI], 1.67-2.53), substance use disorders (2.11; 95% CI, 1.26-3.53), and higher CCI scores (1.06; 95% CI, 1.01-1.10) were significantly associated with TRD, while anxiety disorders (1.44; 95% CI, 1.34-1.55) and higher CCI scores (1.06; 95% CI, 1.05-1.08) were significantly associated with TRT.Conclusions: Approximately one-fourth of elderly patients responded poorly to the first antidepressant treatment during the first year of late-onset MDD. Psychiatric comorbidities were more associated with the risk of early TRT than were physical comorbidities.

Bipolar women's antepartum psychotropic exposure and offspring risk of attention-deficit/hyperactivity disorder and autism spectrum disorder.

BACKGROUND: Women with bipolar disorder (BD) may continue psychotropics during pregnancy. The association of exposure to antidepressant, antipsychotics, and mood stabilizers with offspring risks of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) remains unexplored in mothers with BD. METHODS: A total of 5669 pregnant women with BD and 5669 psychiatrically healthy controls were identified between 2002 and 2011 from the Taiwan Longitudinal Health Insurance Database. We analyzed the odds ratios (ORs) of psychotropic types and exposure periods (3 months before pregnancy [3MbPreg] and first, second, and third trimesters [T1, T2, T3, respectively]) on the risk of ADHD and ASD by using adjusted logistic regression analyses. RESULTS: Antidepressant exposure during 3MbPreg (OR=2.15, 95% CI=1.45-3.20), T1 (OR=2.62, 95% CI=1.68-4.09), T2 (OR=2.33, 95% CI=1.18-4.63), and T3 (OR=2.33, 95% CI=1.67-6.61) was associated with increased offspring risk of ADHD, particularly for selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor. Mood stabilizer exposure during 3MbPreg increased the risks of ADHD (OR=2.39, 95% CI=1.45-3.95) and ASD (OR=3.89, 95% CI=1.30-11.65); a higher ADHD risk was associated with valproic acid (OR=2.43, 95% CI=1.32-4.47) and lamotrigine exposure (OR=8.24, 95% CI = 1.49-45.67); ASD risk was higher for lithium exposure (OR=6.75, 95% CI=1.41-32.28). LIMITATION: In claims-data analyses, several clinical parameters or potential confounders may be incompletely captured. CONCLUSIONS: Antidepressants were associated with higher offspring risk of ADHD over all gestation periods among mothers with BD than psychiatrically healthy controls, while mood stabilizers were associated with higher risk of ADHD and ASD during 3MbPreg.

Better Identification of Cognitive Decline With Interleukin-2 Than With Amyloid and Tau Protein Biomarkers in Amnestic Mild Cognitive Impairment.

The rate of cognitive decline among patients with amnestic mild cognitive impairment (aMCI) varies, and it is thus crucial to accurately predict the probability of cognitive deterioration in patients with MCI. We compared the potential of cytokines with amyloid beta (Aß) and tau biomarkers for predicting cognitive decline in patients with aMCI or Alzheimer's disease (AD). All participants (controls, aMCI, and AD patients) underwent plasma biomarker examinations for Aß1-40, Aß1-42, total tau (t-tau), tau phosphorylated at threonine 181 [p-Tau181]), and 29 cytokines and baseline cognitive tests, including Mini-Mental State Examination (MMSE). The correlation between biomarker levels and annual MMSE change during the follow-up was examined. Receiver operating characteristic (ROC) curve analysis was performed to determine whether the statistically significant plasma biomarkers could identify cognitive decline. Higher baseline levels of IL-2, sCD40L, IL-8, and VEGF were associated with a lower annual cognitive decline in the aMCI group, and higher baseline levels of Aß1-40, IFNγ, IL-5, IL-17A, IL-25, and FGF were associated with a rapid annual cognitive decline in the AD group. IL-2 had a high discriminatory capacity for identifying cognitive decline, with an area under curve (AUC) of 85.7% in the aMCI group, and the AUC was slightly increased when combining IL-2 with Aß or tau biomarkers. However, none of the biomarkers had a satisfactory discriminatory capacity in the AD group. IL-2 may have a better discriminatory capacity for identifying cognitive decline than Aß and tau biomarkers in patients with aMCI.

The Risk of Epilepsy after Long-term Proton Pump Inhibitor Therapy.

BACKGROUND: Prescription-event monitoring studies have reported incident epilepsy or seizures in proton pump inhibitor (PPI) recipients. We examined the risk of epilepsy after prolonged PPI exposure and determine what age group was at higher risk of epilepsy. METHODS: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000). PPI users with subsequent epilepsy were selected as the case cohort. Controls were PPI users without subsequent epilepsy, matched for age, sex, PPI use indication, enrollment time, end point time, follow-up period, overall systemic health, and comorbidities. The total dose of PPI was defined as the cumulative defined daily dose (cDDD). Prolonged PPI use was defined as a cDDD > 365. A logistic regression analysis was performed. Population attributable risk was calculated. RESULTS: Epilepsy occurred 4.13 years after the initiation of PPI use. PPI users with the highest risk of incident epilepsy received a cDDD > 365 [odds ratio = 1.63, 95% confidence interval = 1.37-1.95], followed by 121-365 cDDD (1.33, 1.18-1.51) and 31-120 cDDD (1.15, 1.02-1.29), compared to those receiving a cDDD ≤ 30, after adjusting for potential confounders. Prolonged PPI use increased the risk of epilepsy in all age groups, and the risk was highest for those older than 80 years (3.11, 1.67-5.79). The population attributable risk was 12.2% (> 365 cDDD vs ≤ 30 cDDD). DISCUSSION: Prolonged PPI therapy was associated with an increased risk of epilepsy, particularly in the elderly population.

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is the current treatment option for major depression (MD). Theta-burst stimulation (TBS), a variation of rTMS, affords a short stimulation duration, low stimulation pulse intensity, and possibility to improve rTMS efficiency. This systematic review and meta-analysis examined the studies on efficacy and tolerability of TBS in patients with MD. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature from 1990 until May 24, 2020, and performed a random-effects meta-analysis by including response and remission rates of depression and dropout rates as main outcome measures. RESULTS: In total, 10 studies including 6 randomized controlled trials (RCTs; n = 294) and 4 uncontrolled clinical trials (non-RCTs; n = 297) were included. The overall effect size of response rate and remission rates were 0.38 (95% confidence interval [CI]: 0.29-0.48) and 0.20 (95% CI: 0.13-0.29), respectively. Notably, the TBS group showed favorable efficacy without major adverse events. CONCLUSIONS: TBS treatment was more efficient in terms of time and energy than the standard rTMS was. Our meta-analysis provided evidence that the application of TBS to the dorsolateral prefrontal cortex is associated with significant antidepressant effects along with favorable tolerability.

Incongruent Expression of Brain-Derived Neurotrophic Factor and Cortisol in Schizophrenia: Results from a Randomized Controlled Trial of Laughter Intervention.

OBJECTIVE: Schizophrenia has been associated with dysfunction of the hypothalamic-pituitary-adrenal axis. Furthermore, alterations in neurotrophic factors might contribute to the pathogenesis of schizophrenia. We aimed to evaluate the effects of a simulated laughter intervention on the levels of cortisol and BDNF and to determine whether the effects associated with simulated laughter could be sustained after discontinuation of the intervention. METHODS: In this randomized controlled study, patients with schizophrenia according to DSM-IV clinical criteria were randomly assigned to receive either 8-week-long simulated laughter intervention (n=32) or treatment-as-usual group (control group, n=27). The serum levels of BDNF and cortisol were measured at baseline, week 8, and four weeks after discontinuation (week 12) of the intervention program. RESULTS: After an 8-week simulated laughter intervention, the laughter group had significantly higher levels of BDNF; however, four weeks after discontinuation of the intervention, the levels of BDNF significantly dropped. Interestingly, the levels of cortisol did not change significantly at week 8, but they were significantly elevated at week 12. The levels of BDNF and cortisol in the control group did not change significantly between week 0 and week 8. CONCLUSION: These findings suggest that the simulated laughter intervention has an early effect on neurogenesis with a significant delayed effect on stress regulation in subjects with schizophrenia.

The role of interleukin-33 in patients with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains uninvestigated in clinical studies of Alzheimer's disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD. METHODS: A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) completed two Mini-Mental State Examinations (MMSEs) over a 1-year interval. In all 100 participants at the second MMSE, we examined the plasma levels of IL-33, IL-ß, IL-1 receptor agonist (IL-1RA), beta amyloid (Aß), and tau and apolipoprotein E (ApoE) genotyping; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. RESULTS: IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P < 0.001). Patients expressing IL-33 preserved their cognitive function compared with IL-33 non-expressing patients (1-year ΔMMSE, 0.16 ± 1.6 vs - 1.5 ± 2.6; P = 0.006). The cognitive preservation was not associated with the lower levels of Aß, tau, and ApoE ε4, while higher levels of ApoE ε4 and phosphorylated tau were indeed associated with cognitive decline. The aMCI patients with AD conversion during study period had higher proportion of IL-33(-) than non-AD converters (90.9% vs 53.3%, P = 0.04). CONCLUSIONS: IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD.

Tinnitus and risk of Alzheimer's and Parkinson's disease: a retrospective nationwide population-based cohort study.

Tinnitus has been implied as a "soft" sign of neurodegenerative disease, which is characterized by progressive loss of neuronal function, such as Alzheimer's disease (AD) and Parkinson's disease (PD). This study aimed to determine whether the risk of developing AD/PD increases after having tinnitus. We conducted a retrospective matched cohort study with 12,657 tinnitus patients and 25,314 controls from the National Health Insurance Research Database (NHIRD) in Taiwan with almost 10 years follow-up. Tinnitus-related risk on developing AD/PD followingly was determined by the Cox regression to identify potential confounding factors. Through the 10-year follow-up period, 398 individuals with tinnitus (3.1%) and 501 control individuals (2.0%) developed AD (P < 0.001), and 211 tinnitus patients (1.7%) and 249 control patients (1.0%) developed PD (P < 0.001). Compared with controls, patients with tinnitus were 1.54 times more likely to develop AD (95% confidence interval (CI) 1.34-1.78, P < 0.001) and 1.56 times more likely to develop PD (95% CI 1.29-1.89, P < 0.001), after adjusting confounding factors. Our results indicate an association between tinnitus and higher risk of developing AD and PD. Additional physical comorbidities may also increase the risk of developing AD and PD.

Indicators of rapid cognitive decline in amnestic mild cognitive impairment: The role of plasma biomarkers using magnetically labeled immunoassays.

Plasma levels of biomarkers change with the progression of Alzheimer's disease (AD), which involves the accumulation of pathological amyloid ß (Aß) and Tau protein tangles. However, few studies have investigated the association between plasma biomarkers and rapid cognitive decline in patients with amnestic mild cognitive impairment (aMCI) and AD. A total of 10 healthy controls, 24 patients with aMCI, and 19 patients with AD were enrolled. All participants underwent twice Mini-Mental State Examination (MMSE), with a mean 1.2 year interval. Immunomagnetic reduction was utilized to evaluate levels of plasma biomarkers, including amyloid ß 1-40 (Aß1-40), Aß1-42, total Tau protein, phosphorylated Tau protein (Threonine 181), and α-synuclein (α-Syn). The correlations between plasma levels of biomarkers and MMSE change were examined. Our analysis reveals that current higher plasma levels of Aß1-42 and α-Syn with the cut-off value of plasma Aß1-42 >17.26 pg/mL and α-Syn >105 fg/mL had a moderate-to-high discriminatory capacity (area under the curve >0.70) for identifying cognitive deterioration in patients with aMCI. Our results thus suggest that plasma levels of Aß1-42 and α-Syn may be considered as useful markers to assess the severity of global cognitive decline in patients with aMCI.

Associations between migraine occurrence and the effect of aura, age at onset, family history, and sex: A cross-sectional study.

INTRODUCTION: The relationships between family history, sex, age at onset, and migraine occurrence have been documented. However, the associations between these factors across different sexes and subgroups of patients have yet to be elucidated. This study evaluated the association between family history and migraine in male and female patients experiencing episodic and chronic migraine with and without aura. METHODS: This cross-sectional, case-control study included 299 headache-free controls and 885 patients receiving outpatient treatment for migraine. Participants were classified into episodic (1-14 days/month) and chronic (≥15 days/month) migraine groups. RESULTS: Positive family history was significantly more frequently observed in the episodic group than in the chronic group (49.5% vs. 26%; P < 0.001) in male patients, particularly in male patients without aura (50.3% vs. 21.9%; P = 0.003); it was less frequently observed (58.7% vs. 73.7%; P = 0.048) in female patients with aura. Family history was correlated with an earlier age at onset (20.7 years vs. 22.8 years; P = 0.002), particularly in patients without aura (21 years vs. 23.7 years; P = 0.002), who were women (20.9 years vs. 23.9 years; P = 0.002). CONCLUSIONS: Different patterns of association between family history and migraine can be observed between men and women. A positive family history of migraine is correlated with an earlier age at onset, particularly among female patients without aura.

The Risk of Sexually Transmitted Infections Following First-Episode Schizophrenia Among Adolescents and Young Adults: A Cohort Study of 220 545 Subjects.

Young people are disproportionately affected by sexually transmitted infections (STIs). The risk of STIs in young people following first-episode schizophrenia is unknown. This study using Taiwan's National Health Insurance Research Database enrolled 44 109 adolescents and young adults with first-episode schizophrenia and 176 436 age- and sex-matched controls without schizophrenia from 2001 through 2009 and followed to the end of 2011. New-onset STIs were identified. Survival analysis was performed. Cox regression analysis was used to examine the effects of comorbid substance use disorder (SUD), schizophrenia medications, and schizophrenia severity. The E value for causality of evidence was calculated. We found that young people had a higher risk of STIs following first-episode schizophrenia compared with controls without schizophrenia (hazard ratio [HR] = 2.35, 95% CI = 2.08-2.64); these STIs included human immunodeficiency virus (HIV) (3.70, 2.60-5.28) and syphilis (5.35, 3.96-7.23). They also showed a disproportionate distribution of STIs, with an increased proportion of syphilis (20.4% vs 8.2%) and HIV (9.1% vs 6.0%). When presenting with SUD, the risks of HIV (11.00, 7.02-17.25) and syphilis (9.11, 6.16-13.47) were further increased. The severe schizophrenia group had an extremely high risk of syphilis (41.26, 27.69-61.47) and HIV (7.50, 3.85-14.62). Schizophrenia medications may provide beneficial effects against contracting STIs (0.77, 0.68-0.89). We concluded that following first-episode schizophrenia, young patients are at higher risk of STIs, particularly HIV and syphilis. The risk further increased when subjects presented with SUD or severe schizophrenia. Importantly, antipsychotic treatment may lower the risk of STIs.

Subjective cognitive complaints and migraine characteristics: A cross-sectional study.

OBJECTIVES: Subjective cognitive complaints by patients with migraine have been associated with memory impairment. However, whether the severity of memory impairment relates to migraine characteristics, such as attack frequency and aura, remains undetermined. We investigated the relationship between subjective cognitive complaints and migraine characteristics. MATERIALS AND METHODS: This cross-sectional study recruited 669 clinic outpatients from Taiwan. We stratified them by migraine frequency and the presence or absence of aura, and we controlled the data for confounding variables. We performed multivariable linear and logistic regressions to investigate whether different migraine frequencies are associated with subjective cognitive complaints, which were evaluated by the subjective memory complaints scale and the Ascertain Dementia 8 (AD8) questionnaire. RESULTS: Total subjective memory complaints scores tended to increase with the migraine attack frequency (P = .022) in patients with migraine with aura; similar results were obtained for AD8 scores in women with migraine with aura. Poor sleep quality was associated with a higher total subjective memory complaint (B = 0.08, 95% confidence interval [CI] = 0.03-0.14) and AD8 (B = 0.07, 95% CI = 0.02-0.11) scores. In addition, more severe depression was associated with higher total subjective memory complaints and AD8 scores (B = 0.05, 95% CI = 0.02-0.09; B = 0.08, 95% CI = 0.05-0.11, respectively). CONCLUSIONS: Subjective cognitive complaints tend to increase with the frequency of migraines with aura, and this interrelation is substantially influenced by depression severity and sleep disturbances.

Associations between Plasma Biomarkers and Cognition in Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment: A Cross-Sectional and Longitudinal Study.

Brain degeneration in patients with Alzheimer's disease (AD) results from the accumulation of pathological amyloid- (Aß) plaques and tau protein tangles, leading to altered plasma levels of biomarkers. However, few studies have investigated the association between plasma biomarkers and cognitive impairment in patients with AD. In this cross-sectional study, we investigated correlations between mini-mental state examination (MMSE) scores and levels of plasma biomarkers in patients with amnestic mild cognitive impairment (aMCI) and AD. Thirteen individuals with normal cognition, 40 patients with aMCI, and 37 patients with AD were enrolled. Immunomagnetic reduction was used to assess the levels of plasma biomarkers, including amyloid A1-40, A1-42, total tau protein (t-Tau), and phosphorylated tau protein (threonine 181, p-Tau181). Our analysis revealed a significant negative correlation between MMSE and both measures of tau, and a trend toward negative correlation between MMSE and A1-42. In a longitudinal study involving three patients with aMCI and two patients with AD, we observed strong negative correlations (r < -0.8) between changes in MMSE scores and plasma levels of t-Tau. Our results suggest that plasma levels of t-Tau and p-Tau181 can be used to assess the severity of cognitive impairment in patients with AD. Furthermore, the results of our preliminary longitudinal study suggest that levels of t-Tau can be used to monitor the progression of cognitive decline in patients with aMCI/AD.

Distinct Inflammation Biomarkers in Healthy Individuals and Patients with Schizophrenia: A Reliability Testing of Multiplex Cytokine Immunoassay by Bland-Altman Analysis.

OBJECTIVE: Since the inflammatory process has been implicated in the pathophysiology of psychiatric disorder, an important issue emerging is to assess the test-retest reliability of cytokine measurement in healthy individuals and patients with schizophrenia. The objective of the present study was to investigate the test-retest reliability of bead-based multiplex immunoassay technology (BMIT) for cytokine measurement by using a Bland-Altman plot (BAP). METHODS: Twenty healthy individuals and twenty patients with schizophrenia were enrolled, and a 17-plex cytokine assay was used to measure inflammatory biomarkers at baseline and two weeks later. The test-retest reliability was examined by BAP, 95% limits of agreement (LOA), intraclass correlation coefficient (ICC), and coefficient of repeatability (CoR). RESULTS: In the healthy controls, only interleukin (IL)-2, IL-13, IL-10, IL-17, and macrophage inflammatory protein-1ß showed excellent ICC. The BAP with 95% LOA determined that 13 cytokines showed acceptable 95% LOA for a 2-week test-retest reliability, and only IL-1ß, IL-12 and tumor necrosis factor (TNF)-α had significant test-retest bias. The CoR of cytokines varied significantly, ranging from 1.72 to 218.1. Compared with healthy controls, patients with schizophrenia showed significantly higher levels of IL-5, IL-13, and TNF-α and significantly lower levels of IL-4, IL-12, and interferon-gamma (IFN-γ). Of these six cytokines, IL-12 and TNF-α were considered suboptimal reliability. CONCLUSION: The findings from ICC and CoR implied that the test-retest reliability of BMIT for cytokine measurement were suboptimal. However, the BAP with 95% LOA confirmed that BMIT can reliably distinguish schizophrenia from healthy individuals in cytokine measurement, while significant within-subject variation and between-group overlapping were evident in cytokine expression.

Risk of Depressive Disorders Following Myasthenia Gravis: A Nationwide Population-Based Retrospective Cohort Study.

The chronic autoimmune disease myasthenia gravis (MG) is characterized by fluctuating muscle weakness, which can lead to a large amount of stress in the patient. The current investigation plans to assess the risk of depressive disorders in MG patients. A retrospective cohort study of patients ageing 20 years and older and also newly diagnosed with MG between January 1, 2000, and December 31, 2008, was conducted from the National Health Insurance Research Database (NHIRD) in Taiwan. Observations of all 349 MG patients and 1,396 control individuals were made until a diagnosis of a depressive disorder by a psychiatrist, until death, or until December 31, 2013. A range of comorbidities were found, such as coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia, with cerebrovascular disease being reported more frequently in MG patients in comparison with control subjects. After adjustment of patients' sex, age, urbanization, comorbidities, and monthly income, results indicated that MG individuals are 1.94 times more at risk (95% confidence interval [CI], 1.15-3.27, P = 0.014) of developing depressive disorders than are controls. This showed an increased risk in the development of depressive disorders in people with MG. Thus, depressive symptoms in MG patients should be regularly assessed.

Association of Suicide Risk With Headache Frequency Among Migraine Patients With and Without Aura.

Background: Migraines with aura have been associated with suicide in adolescents and young adults, but the association between suicide and migraine frequency has not been determined. This study investigated suicidal ideation and suicide attempts among patients with varying frequencies of migraines, with and without auras. Methods: This cross-sectional study analyzed 528 patients aged between 20 and 60 years from a headache outpatient clinic in Taiwan. All patients completed a set of questionnaires, including a demographic questionnaire, the Migraine Disability Assessment questionnaire, the Hospital Anxiety and Depression Scale, the Beck Depression Inventory, and the Pittsburgh Sleep Quality Index. Suicide risk was evaluated by self-reported lifetime suicidal ideation and attempts. Patients were divided into low-frequency (1-4 days/month), moderate-frequency (5-8 days/month), high-frequency (9-14 days/month), and chronic (≥15 days/month) migraine groups. The association between migraine frequency and suicidality was investigated using multivariable linear regression and logistic regression. Results: The rates of suicidal ideation and suicide attempts were the highest for chronic migraine with aura (ideation: 47.2%; attempts: 13.9%) and lowest in migraine-free controls (2.8%). Migraine frequency was an independent risk factor for suicidal ideation and attempts in patients with aura (both P trend < 0.001), but not in patients without auras. Migraine aura and depression were associated with higher risks of suicidal ideation and suicide attempts in patients with migraine. Conclusion: High migraine frequency has a correlation with high suicide risk in patients who experience an aura, but not in other patients with migraine.

Benzodiazepines Associated With Acute Respiratory Failure in Patients With Obstructive Sleep Apnea.

Aims: Obstructive sleep apnea (OSA) and insomnia commonly coexist; hypnotics are broadly prescribed for insomnia therapy. However, the safety of hypnotics use in OSA patients is unclear. We conducted a retrospective case-control study to investigate the risk of adverse respiratory events in hypnotics-using OSA patients. Methods: We obtained data from the Taiwan National Health Insurance Database from 1996 to 2013. The case group included 216 OSA patients with newly diagnosed adverse respiratory events, including pneumonia and acute respiratory failure. The control group included OSA patients without adverse respiratory events, which was randomly frequency-matched to the case group at a 1:1 ratio according to age, gender, and index year. Hypnotics exposure included benzodiazepines (BZD) and non-benzodiazepines (non-BZD). A recent user was defined as a patient who had taken hypnotics for 1-30 days, while a long-term user was one who had taken hypnotics for 31-365 days. Results: Multivariable adjusted analysis showed recent BZD use is an independent risk for adverse respiratory events (OR = 2.70; 95% CI = 1.15-6.33; P < 0.001). Subgroup analysis showed both recent and long-term BZD use increased the risk of acute respiratory failure compared to never BZD use (OR = 28.6; 95% CI = 5.24-156; P < 0.001, OR = 10.1; 95% CI = 1.51-67.7; P < 0.05, respectively). Neither BZD nor non-BZD use increased the risk of pneumonia in OSA patients. Conclusion: BZD use might increase the risk of acute respiratory failure in OSA patients.

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.