Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain.

BACKGROUND: Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD. METHODS: In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer's type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain. RESULTS: In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster. CONCLUSIONS: We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer's type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.

Cluster analysis exploring the impact of childhood neglect on cognitive function in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder related to neurocognitive deficits. Exposure to childhood trauma is associated with worse cognitive performance. Different compositions of childhood trauma in BD and their impacts on cognition are rarely reported. METHODS: We used the Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognitive performance and the Chinese version of the Short Form of the Childhood Trauma Questionnaire (C-CTQ-SF) to assess childhood trauma experience among 55 euthymic BD patients. Cluster analysis was applied to dissect their childhood trauma experiences, which revealed three distinct clusters: a low trauma group, neglect-focus group, and multiple-trauma-experience group. We compared the cognitive function between the three clusters and used a generalized linear model to evaluate the impact of childhood neglect on cognitive domains. RESULTS: The neglect-focus cluster showed prominent exposures to physical and emotional neglect (41.8%). BD patients in this cluster performed worse in BAC-A compared with patients in the multiple trauma cluster, especially in working memory and processing speed. The neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002) after adjusting sex, age, education year, BMI and total psychotropic defined daily dose. CONCLUSIONS: Distinct patterns of childhood trauma experience are seen in BD patients and are related with different cognitive profiles. Early exposure of neglect-focus trauma was associated with the worst cognitive performance in current study. Further studies investigating the intensity of the neglect, as well as individual resilience and coping mechanisms in BD, are warranted.

Efficacy of neuromodulation on the treatment of fibromyalgia: A network meta-analysis.

OBJECTIVE: Several types of neuromodulation have been investigated for the treatment of fibromyalgia, but they show varied efficacy on pain, functioning, comorbid depression and comorbid anxiety. Whether some types of neuromodulation or some factors are associated with a better response also awaits clarification. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials to evaluate the efficacy of neuromodulation in patients with fibromyalgia. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and PsycINFO before March 2022. We employed a frequentist random-effects network meta-analysis. RESULTS: Forty trials involving 1541 participants were included. Compared with sham control interventions, several types of transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) were associated with significant reduction of pain, depression, anxiety, and improvement in functioning. Many significantly effective treatment options involve stimulation of the primary motor cortex or dorsolateral prefrontal cortex. CONCLUSION: We concluded that several types of rTMS, tDCS and tRNS may have the potential to be applied for clinical purposes.

Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial.

BACKGROUND: Late-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. METHODS: A 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. RESULTS: A total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LIMITATIONS: Sample size is small with only marginal clinical effect. CONCLUSION: These findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.

Higher orexin-A levels are associated with treatment response to clozapine in patients with schizophrenia: A cross-sectional study.

BACKGROUND: Clozapine is the primary antipsychotic (APD) for treatment-resistant schizophrenia (TRS). However, only 40% of patients with TRS respond to clozapine, constituting a subgroup of clozapine-resistant patients. Recently, the neuropeptide orexin-A was shown to be involved in the pathophysiology of schizophrenia. This study evaluated the association of orexin-A levels with the clozapine response in patients with TRS. METHODS: We recruited 199 patients with schizophrenia, including 37 APD-free and 162 clozapine-treated patients. Clozapine-treated patients were divided into clozapine-responsive (n = 100) and clozapine-resistant (n = 62) groups based on whether they had achieved psychotic remission defined by the 18-item Brief Psychiatric Rating Scale (BPRS-18). We compared blood orexin-A levels among the three groups and performed regression analysis to determine the association of orexin-A level with treatment response in clozapine-treated patients. We also explored the correlation between orexin-A levels and cognitive function, assessed using the CogState Schizophrenia Battery. RESULTS: Clozapine-responsive patients had higher orexin-A levels than clozapine-resistant and APD-free patients. Orexin-A level was the only factor significantly associated with treatment response after adjustment. Orexin-A levels were negatively correlated with BPRS-18 full scale and positive, negative, and general symptoms subscale scores. We also observed a positive correlation between orexin-A levels and verbal memory, visual learning and memory, and working memory function. CONCLUSIONS: This cross-sectional study showed that higher levels of orexin-A are associated with treatment response to clozapine in patients with TRS. Future prospective studies examining changes in orexin-A level following clozapine treatment and the potential benefit of augmenting orexin-A signaling are warranted.

Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults.

Treating fibromyalgia with electrical neuromodulation: A systematic review and meta-analysis.

OBJECTIVE: Several types of electrical neuromodulation (such as transcranial direct current stimulation, tDCS; transcutaneous electrical nerve stimulation) have been applied in the treatment of fibromyalgia. These trials had different outcome measurements, such as subjective pain, pain threshold, depression, anxiety, and functioning. We intended to integrate data from different trials into a meta-analysis to clearly present the clinical value of electrical neuromodulation in fibromyalgia. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing the effect of all types of electrical neuromodulation in patients with fibromyalgia was conducted. The main outcome was subjective pain; the secondary outcomes included depression, anxiety, and functioning. RESULTS: Twenty-five studies and 1061 fibromyalgia patients were included in the quantitative analysis. Active electrical neuromodulation and active tDCS both showed significant effects on subjective pain, depression, and functioning. For different anode tDCS electrode positions, only F3-F4 revealed a significant effect on depression. Meta-regression tDCS effects on depression were significantly associated with age. CONCLUSIONS: Electrical neuromodulation is significantly effective in treating pain, depression, and functioning in patients with fibromyalgia. SIGNIFICANCE: The results may help clinicians to arrange effective treatment plans for patients with fibromyalgia, especially in those patients who reveal limited response to pharmacotherapy and psychotherapy.

Incidence, risk and protective factors for suicide mortality among patients with major depressive disorder.

AIM: Patients with major depression have greater suicide mortality, but there is no data on the standardised mortality ratio (SMR) and factors for suicide of major depression for Asian countries. This research estimates the SMR and the risk and protective factors for suicide mortality in patients with major depression in a large-scale Asian cohort. METHODS: Patients with major depression (N = 1978) admitted to a psychiatric hospital in Taiwan between 1985 and 2008 were enrolled as the study cohort. When the cohort was linked to the national mortality database, 415 deceased patients were identified. Of these 415 deaths, 107 were from suicide. Nested case-control with risk sampling was used, where each case was matched with two controls. Clinical information was collected through a standardised chart review process. The SMR for suicide mortality was estimated, and a conditional logistic regression analysis was performed to determine risk and protective factors for suicide. RESULTS: Patients with major depression had high all-cause and suicide mortality, with SMRs of 3.9 and 35.4, respectively. Agitation (adjusted risk ratio [aRR] = 2.85, P = 0.058), restlessness (aRR = 15.05, P = 0.045) and previous suicide attempts (aRR = 4.48, P = 0.004) were identified as risk factors for suicide mortality. By contrast, those with employment (aRR = 0.15, P = 0.003) or loss of interest (aRR = 0.32, P = 0.04) had lower risk. CONCLUSIONS: Patients with depression exhibited higher suicide mortality. Clinical staff should pay close attention to risk and protective factors to reduce suicide risk.

Characterization of clinical features and comorbidities between bipolar affective disorder with and without depressive episodes.

BACKGROUNDS: A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups. METHODS: This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups. RESULTS: The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups. CONCLUSIONS: Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.

The interactions between vitamin D and neurofilament light chain levels on cognitive domains in bipolar disorder.

BACKGROUND: Bipolar disorder is a chronic mental disorder related to cognitive deficits. Low serum vitamin D levels are significantly associated with compromised cognition in neuropsychiatric disorders. Although patients with bipolar disorder frequently exhibit hypovitaminosis D, the association between vitamin D and cognition in bipolar disorder, and their neuroaxonal integrity, is unclear. AIMS: To investigate the interaction effects between vitamin D and neurofilament light chain (NfL) levels on cognitive domains in bipolar disorder. METHOD: Serum vitamin D and NfL levels were determined in 100 euthymic patients with bipolar disorder in a cross-sectional study. Cognitive function was measured with the Brief Assessment of Cognition in Affective Disorders. We stratified by age groups and used general linear models to identify associations between vitamin D and NfL levels and their interaction effects on cognitive domains. RESULTS: The mean vitamin D and NfL levels were 16.46 ng/nL and 11.10 pg/mL, respectively; 72% of patients were vitamin D deficient. In the older group, more frequent hospital admissions and lower physical activity were identified in the group with versus without vitamin D deficiency. The age-modified interaction effect of vitamin D and NfL was associated with composite neurocognitive scores and verbal fluency in both age groups, and with processing speed domain in the younger group. CONCLUSIONS: We observed a high vitamin D deficiency prevalence in bipolar disorder. We identified the interaction of vitamin D and NfL on cognitive domains, and the effect was modified by age. Longitudinal or randomised controlled studies enrolling patients with various illness durations and mood statuses are required to validate our findings.

Therapeutic Drug Monitoring of Paliperidone in Patients With Schizophrenia in Taiwan.

BACKGROUND: The blood level of antipsychotics affects clinical responses to the drug; it can be influenced by race and several individual factors. This study analyzed the therapeutic plasma concentrations (Cps) of paliperidone for both oral and long-acting injectable (LAI) formulations in clinical samples from Taiwanese patients. METHODS: Patients diagnosed with schizophrenia and treated with either oral paliperidone for at least 4 weeks or LAI paliperidone for at least 6 months were enrolled. Blood samples were taken before the morning dose of oral paliperidone or the injection of LAI paliperidone to obtain the trough Cps. RESULTS: Among the patients in this study, 51 were taking oral paliperidone, and 26 were receiving LAI paliperidone. In the oral group, the mean Cps were 40.2 ± 19.8 ng/mL in patients taking 9 mg/d and 44.2 ± 15.9 ng/mL in those taking 12 mg/d. In the LAI group, the mean Cps were 32.9 ± 12.7 ng/mL in patients receiving 100 mg per 28 days and 49.9 ± 25.9 ng/mL in those receiving 150 mg per 28 days. The mean Cps per daily dose (Cps/DD) were 4.11 ± 1.99 ng/mL/mg in the oral group and 9.24 ± 3.78 ng/mL/mg in the LAI group. CONCLUSIONS: Under the suggested DD for oral and LAI paliperidone treatment, most Taiwanese patients with schizophrenia can reach the suggested therapeutic Cps range. Wide interindividual differences were observed in the Cps/DD for both the oral (7-fold) and LAI paliperidone (4-fold) groups. Compared with Western reports, no difference was observed in the body weight-adjusted Cps/DD.

The relationship of antipsychotic treatment with reduced brown adipose tissue activity in patients with schizophrenia.

BACKGROUND: Antipsychotic drug (APD) treatment has been associated with metabolic abnormalities. Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and secretes various metabolism-improving factors known as batokines. We explored the association of BAT activity with APD treatment and metabolic abnormalities in patients with schizophrenia by measuring the blood levels of bone morphogenetic protein 8b (BMP8b), a batokine secreted by mature BAT. METHODS: BMP8b levels were compared among 50 drug-free, 32 aripiprazole-treated, and 91 clozapine-treated patients with schizophrenia. Regression analysis was used to explore factors, including APD types, that might be associated with BMP8b levels and the potential effect of BMP8b on metabolic syndrome (MS). RESULTS: APD-treated patients had decreased BMP8b levels relative to drug-free patients. The difference still existed after adjustment for body mass index and Brief Psychiatric Rating Scale scores. Among APD-treated group, clozapine was associated with even lower BMP8b levels than the less obesogenic APD, aripiprazole. Furthermore, higher BMP8b levels were associated with lower risks of MS after adjustment for BMI and APD treatment. CONCLUSION: Using drug-free patients as the comparison group to understand the effect of APDs, this is the first study to show APD treatment is associated with reduced BAT activity that is measured by BMP8b levels, with clozapine associated a more significant reduction than aripiprazole treatment. BMP8b might have a beneficial effect against metabolic abnormalities and this effect is independent of APD treatment. Future studies exploring the causal relationship between APD treatment and BMP8b levels and the underlying mechanisms are warranted.

Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome.

BACKGROUND/PURPOSE: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. METHODS: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. RESULTS: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. CONCLUSION: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

Effect of Pharmacological and Neurostimulation Interventions for Cognitive Domains in Patients with Bipolar Disorder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis. METHODS: The PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044). RESULTS: Total 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00-1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03-1.13), and galantamine (SMD = 1.22, 95% CI = 0.10-2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined. CONCLUSION: Considerable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients' cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.

Associations of Genetic Variants of Methylenetetrahydrofolate Reductase and Serum Folate Levels with Metabolic Parameters in Patients with Schizophrenia.

The one-carbon metabolism pathway is a suitable candidate for studying the genetic and epigenetic factors contributing to metabolic abnormalities in patients with schizophrenia. We recruited 232 patients with schizophrenia and analyzed their serum folate, vitamin B12, and homocysteine levels and metabolic parameters to investigate the associations of genetic variants of methylenetetrahydrofolate reductase (MTHFR) and folate levels with metabolic parameters. MTHFR C677T and MTHFR A1298C were genotyped. Results showed that MTHFR 677T allele carriers had lower levels of total cholesterol and low-density lipoprotein cholesterol than those with the 677CC genotype. Metabolic parameters did not differ between MTHFR 1298C and 1298AA carriers. Patients with a low folate level had a lower high-density lipoprotein cholesterol level than those with a normal folate level, but the effect disappeared after adjustment for age, sex, and types of antipsychotics used. We found significant interactions between MTHFR A1298C and the folate level status (low vs. normal) in terms of body mass index and waist circumference. In conclusion, genetic variants in one-carbon metabolism might play a role in antipsychotic-induced metabolic abnormalities. Prospective studies on drug-naïve, first-episode patients with schizophrenia are warranted to identify key regions of DNA methylation changes accounting for antipsychotic-induced metabolic abnormalities.

The Heterogeneity of Longitudinal Cognitive Decline in Euthymic Bipolar I Disorder With Clinical Characteristics and Functional Outcomes.

We characterized the heterogeneity and risk factors of cognitive decline in euthymic bipolar disorder (BD), and their magnitude of associations with subjective daily functions. In this retrospective cohort, BD type I patients (N = 128) were followed for an average of 6.5 years. Intelligence quotient (IQ) at index date was recorded, and premorbid IQ was estimated. We used Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognition at follow-up. We evaluated current functions with World Health Organization Disability Assessment Schedule 2.0. Clinical and sociodemographic factors were examined for their independent effects on longitudinal cognitive decline. In addition, we employed multivariate adaptive regression spline to detect inflection points for the nature of slope changes in cognitive decline among BD patients. During follow-up years, 21 BD patients (16.4%) showed longitudinal cognitive decline. In cognitive decline group, all cognitive domains of BAC-A were significantly worsened. We found that density of episodes with psychotic features was an independent risk factor for cognitive decline after adjusted for age, gender and dose of mood stabilizer. After the age of 42 years, a steeper cognitive change was observed in the cognitive decline group. The correlation pattern between cognitive domains and functional outcomes differed between patients with and without cognitive decline. The present study characterized cognitive heterogeneity longitudinally in BD patients. As density of episodes play roles for cognitive decline, our results emphasize the importance of relapse prevention. Our findings provide hints for future personalized interventions and facilitating genetic and biological studies for dissecting the heterogeneity of bipolar illness.

Premenstrual dysphoric symptoms and lifetime suicide experiences in patients with mood disorder.

BACKGROUND: Premenstrual dysphoric symptoms (PMDS) commonly co-occurred with mood disorders and correlated with suicide experiences in women. This study aims to examine the associations between PMDS and lifetime suicide experiences in patients with mood disorders. METHODS: Participants were recruited from outpatient settings of two medical centers and one psychiatric hospital in Taiwan. Women aged 18-65 in non-acute state of major depressive disorder or bipolar affective disorder were recruited. PMDS and lifetime suicide experiences were defined by the Schedule for Affective Disorder and Schizophrenia-Lifetime. Lifetime suicide experiences were defined as no suicide experience, suicide plans only and suicide attempts. RESULTS: A total of 383 women participated in this study (54.8% of them were diagnosed with major depressive disorder), and 13.8% were diagnosed with PMDS. The prevalence of patients with lifetime suicide plans only and lifetime suicide attempts were 15.9% and 39.7%, respectively. In the univariate analysis, PMDS was correlated with lifetime suicide experience. After controlling for covariates, PMDS was a risk indicator for lifetime suicide attempts (OR: 3.46, 95% CI: 1.43-8.38) but not for suicide plans only (OR: 0.93, 95% CI: 0.28-3.11). CONCLUSIONS: PMDS correlated with lifetime suicide experiences in women with non-acute mood disorders. In particular, PMDS exhibited as an independent correlate for lifetime suicide attempts.

Trough Melatonin Levels Differ between Early and Late Phases of Alzheimer Disease.

OBJECTIVE: Melatonin has been considered to have an essential role in the pathophysiology of Alzheimer's disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn't show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits. METHODS: We enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment. RESULTS: In the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort. CONCLUSION: This study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies.

Comparison of cognitive function between early- and late-onset late-life depression in remission.

Differences in cognitive function have been suggested in people with late-life depression between those with early- (EOD) and late-onset (LOD), possibly reflecting different etiologies. The cutoff point for EOD and LOD was the first depressive episode before age 60 or later. However, depressive symptoms at the time of disorder are important confounders. The study aimed to compare cognitive function in older people with EOD and LOD in the euthymic state. A sample of 135 participants aged 60+ with a history of major depressive disorder in remission, received neuropsychological evaluation including tests of memory, attention, processing speed, visuospatial function, language, and executive function. Individual test scores and a derived composite score were investigated as dependent variables against age of onset using multiple linear regressions adjusted for potential confounders, including residual depressive symptoms. We found EOD (N = 67) and LOD (N = 68) groups did not differ significantly in overall composite cognitive scores after adjustment. Of individual test scores, only those for immediate recall were significantly lower in participants with EOD compared to LOD. In conclusion, the study found no associations between cognitive function and age of onset in this sample of people with depressive disorder in remission. Active or residual depressive symptoms might have confounded this relationship in previous research.