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.

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.

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.

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.

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.

Ligand Exchange in the Synthesis of Metal-Organic Frameworks Occurs Through Acid-Catalyzed Associative Substitution.

The syntheses of metal-organic frameworks (MOFs) can be improved through modulated synthesis, synthesis employing precursors, and postsynthetic exchange (PSE) modifications, all of which share ligand exchange as a common and crucial reaction. To date, however, the mechanism of ligand exchange and the underlying principles governing it have remained elusive. Herein, we report energy landscapes for the ligand exchange processes of 1,4-benzenedicarboxylic acid and 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylic acid with Zr6O4(OH)4(OMc)12 (OMc = methacrylate), as calculated using density functional theory (DFT). The rate-limiting step of ligand exchange follows an associative-substitution mechanism catalyzed by protons, consistent with previous kinetic data. Our calculations suggest that the acid catalysis is dependent on the relative basicities of the incoming and outgoing ligands coordinated in the complex, allowing molecular-level rationalization of many seminal MOF syntheses that had previously been interpreted macroscopically. Our results provide new insights for MOF synthesis and new clues for the rational de novo synthesis of MOFs.

Homocysteine, rather than age of onset, is a better predictor for cognitive function in older adults with bipolar disorder.

OBJECTIVES: The association between older-age bipolar disorder and cognitive impairments may be mediated by vascular burden. The aim of the study was to examine the difference of cognitive function between older people with late-onset bipolar disorder (LOBD) and early-onset bipolar disorder (EOBD) by considering rigorous vascular risk burden evaluation, comprehensive cognitive tests, and relevant biochemistry data. METHODS: We recruited 95 outpatients aged over 55 with a DSM-IV-TR diagnosis of bipolar I disorder. Fifty had LOBD, defined by age of onset after 40. Cognitive function was evaluated through a battery of tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility. Vascular risk assessments included individual disorders, 10-year Framingham cardiovascular risk scores, and serum levels of homocysteine, vitamin B12, folate, and triiodothyronine. RESULTS: No differences were observed between LOBD and EOBD on any cognitive test after adjusting for potential confounders. In addition to age and educational years, multiple linear regression analyses indicated significantly negative associations between serum homocysteine levels and cognitive performances in attention, psychomotor speed, verbal memory, and executive function. CONCLUSIONS: Among older people with bipolar disorder, LOBD is not associated with more cognitive dysfunction in this study. However, higher serum homocysteine levels were significantly associated with worse cognitive performance in this particular group. Clinicians therefore have to pay attention to the cognitive function in older bipolar patients with higher levels of homocysteine.

Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics.

BACKGROUND: The aims of this study were to explore the relationship between early reduction in psychotic symptoms and the ultimate response in patients with schizophrenia treated by atypical antipsychotics, and to determine the best time to switch or maitain the regimen. We also explore the possible predictors for the clinical response. METHODS: One hundred eleven inpatients with acutely exacerbated schizophrenia were randomized to give optimal therapy of olanzapine, risperidone, and paliperidone in one-week run-in period and 12 weeks' intervention. All participants were assessed using Positive and Negative Syndrome Scale (PANSS). Early Response, defined as reduction of 25% in PANSS score, was examined at weeks 1, 2, 3, 4 and 8, and these ratings were used to predict ultimate response (25% PANSS reduction) at week 12. We hypothesized that early treatment response at Week 1 or 2 could predict Week 12's treatment outcome. RESULTS: The early treatment response at Week 2 had a greater negative prediction value (NPV, 93.6%) than did the response at Week 1 (NPV, 69.7%), Week 3 (NPV, 91.5%), Week 4 (NPV, 90.7%) and Week 8 (NPV, 87.2%). The positive predictive value became more acceptable (65%) until Week 4. There was no any other potential predictors, including types of antipsychotics medication and treatment dosage, were associated with ultimate response in this study. CONCLUSION: The treatment non-response at Week 2 optimally predicted the ultimate (Week 12) non-response, in terms of negative predictive value (NPV). These finding suggests that the revision of treatment strategy should be considered t if patients with schizophrenia was not responsive to them after 2 weeks' treatment, and for those who are responders at Week 2, another two weeks are needed to further evaluate whether they will be continuously responsive. TRIAL REGISTRATION: NCT03730857 at ClinicalTrial.gov . Date of registration: 30/Oct/2018.

Geometrical effects of phospholipid olefinic bonds on the structure and dynamics of membranes: A molecular dynamics study.

The trans isomers of fatty acids are found in human adipose tissue. These isomers have been linked with deleterious health effects (e.g., coronary artery disease). In this study, we performed molecular dynamics simulations to investigate the structures and dynamic properties of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and 1-palmitoyl-2-elaidoyl sn-glycero-3-phosphatidylcholine (PEPC) lipid bilayers. The geometry of the olefinic bond and membrane packing effects significantly influenced the conformations and dynamics of the two C-C single bonds adjacent to the olefinic bond. For the PEPC lipid, the two C-C single bonds adjacent to the olefinic bond adopted mainly nonplanar skew-trans and planar cis-trans motifs; although the cis conformation featured relatively strong steric repulsion, it was stabilized through membrane packing because its planar structure is more suitable for membrane packing. Moreover, membrane packing effects stabilized the planar transition state for conformational conversion to a greater extent than they did with the nonplanar transition state, thereby affecting the dynamics of conformational conversion. The rotational motions of the first neighboring C-C single bonds were much faster than those of typical saturated C-C single bonds; in contrast, the rotational motions of the second neighboring C-C single bonds were significantly slower than those of typical saturated torsion angles. The packing of PEPC lipids is superior to that of POPC lipids, leading to a smaller area per lipid, a higher order parameter and a smaller diffusion coefficient. The distinct properties of POPC and PEPC lipids result in PEPC lipids forming microdomains within a POPC matrix.

First-Principle Characterization of the Adsorption Configurations of Cyanoacrylic Dyes on TiO2 Film for Dye-Sensitized Solar Cells.

The loading of sensitizers on a semiconductor is crucial for determining the light-harvesting efficiency of dye-sensitized solar cells (DSSCs). The interfacial properties of dyes adsorbed on a TiO2 film, such as adsorption configurations and adsorption energy, can influence the total amount of dye sensitizers that loads and the stability of a DSSC device. Therefore, it is important to characterize the adsorption properties of sensitizers on TiO2 films atomically and electronically to ensure rational structure-based dye design for high-performance DSSCs. Due to the complex properties of interfacial dyes, previous works on the identification of adsorption configurations of dyes on TiO2 have sometimes been controversial, in particular, the essential IR band assignments. In this study, we employed density functional theory to investigate the adsorption energies, geometries, and vibrational frequencies of various adsorption configurations of 2-cyano-3-(thiophen-2-yl)acrylic acid adsorbed on TiO2. We performed a comparative assignment of the calculated vibrational peaks of tridentate and bidentate configurations to the experimental FT-IR spectra simultaneously. Our work backs up the coexistence of tridentate and bidentate bridging configurations, first proposed by Meng and co-workers. Moreover, our comparative IR mode assignments provide clues for further studies of the interfacial properties of dyes adsorbed on TiO2. Study of the transformation mechanisms between tridentate and bidentate modes suggests that the bidentate bridging configuration is a kinetically trapped adsorption mode and the tridentate configuration is thermodynamically the most stable one. Finally, we investigated the photophysical properties of a D-π-A dye in tridentate and bidentate adsorption configurations.

The Relationships of Obesity-Related Genetic Variants With Metabolic Profiles and Response to Metformin in Clozapine-Treated Patients With Schizophrenia.

Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia.

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.

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.

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.

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.

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.

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.

The relationship between serum uric acid concentration and metabolic syndrome in patients with schizophrenia or schizoaffective disorder.

Higher prevalence rates of metabolic syndrome (MetS) in patients with schizophrenia are getting more and more attention. Uric acid (UA) has been frequently reported to be associated with MetS in the general population. Sex difference in this relationship is inconsistent. As a selective antioxidant, UA has also been found to be reduced in patients with schizophrenia, and this effect may be prominent in men. With the inconsistent presentations, higher rate of MetS but possible lower UA concentrations, the aim of this study was to investigate the relationship by sexes between serum UA concentrations and prevalence of MetS in patients with schizophrenia or schizoaffective disorder. A total of 637 patients, 342 male and 295 female, were enrolled from 36 psychiatric rehabilitation institutions. Cross-sectional anthropometrical data, biochemical analysis, and serum UA were measured. Serum UA concentrations were divided into quartiles by sexes. Modified National Cholesterol Education Program Adult Treatment Panel III criteria for Asians were used as diagnosis of MetS. After adjustment, higher UA concentrations are associated with hypertriglyceridemia, low high-density lipoprotein cholesterol level, and high blood pressure in men and with hypertriglyceridemia in women. Significantly higher odds ratios for MetS in the UA third (4.02; 95% confidence interval, 1.33-12.1) and fourth quartiles (9.28; 95% confidence interval, 2.90-29.8) compared with the lowest quartile were found in men but not in women after adjustment. These results suggest that lower UA concentrations in male patients with schizophrenia or schizoaffective disorder are associated with lower risk of MetS.

Subjective memory impairment in older adults: aetiology, salience and help seeking.

BACKGROUND: Subjective memory impairment (SMI) is one of the key symptoms with which people with early cognitive impairment may present to health services. However, little research has investigated how older people view the symptom, its salience and how often help is sought. The objectives were to investigate (a) factors associated with SMI, (b) salience of SMI in comparison with other symptoms and (c) help seeking for SMI. METHOD: A cross-sectional survey was based in two Primary Care services in south London in which registered people aged 65+ were interviewed blind to the study objectives. Measurements included systematic ascertainment of SMI and other common symptoms/disorders. In each of these, concern and interference were quantified, and participants were asked to rank all reported symptoms/disorders in order of importance. RESULTS: Of 126 participants, any SMI was reported in 66.7%, and 31.0% reported SMI to a significant degree. SMI occupied a middling rank in terms of salience, being ranked as more concerning than angina, asthma, hypertension or a previous heart attack in around half of participants in whom these co-occurred. However, only one participant with SMI had sought help from their GP, making it the least likely symptom to be reported. CONCLUSION: Subjective memory impairment is common and appears to have functional and/or emotional significance for many older people. However, very few appear to seek medical attention for this symptom, which has implications for wider policy regarding prompt assessment and diagnosis of mild cognitive impairment or dementia.

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.