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.

A meta-analysis on the therapeutic efficacy of repetitive transcranial magnetic stimulation for cognitive functions in attention-deficit/hyperactivity disorders.

BACKGROUND: Therapeutic efficacies of repetitive transcranial magnetic stimulation (rTMS) for improving cognitive functions in patients with deficit/hyperactivity disorder (ADHD) remained unclear. The aim of this meta-analysis was to investigate the therapeutic efficacy of rTMS focusing on different cognitive performances. METHODS: Major databases were searched electronically from inception to February 2023 by using keywords mainly "rTMS" and "ADHD" to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of rTMS for improving cognitive functions assessed by standardized tasks in patients with ADHD. The overall effect size (ES) was calculated as standardized mean difference (SMD) based on a random effects model. RESULTS: Meta-analysis of five RCTs with 189 participants (mean age of 32.78 and 8.53 years in adult and child/adolescent populations, respectively) demonstrated that rTMS was more effective for improving sustained attention in patients with ADHD compared with the control groups (SMD = 0.54, p = 0.001).Our secondary analysis also showed that rTMS was more effective for improving processing speed than the control groups (SMD = 0.59, p = 0.002) but not for enhancing memory or executive function. CONCLUSIONS: Our results supported the therapeutic efficacy of rTMS for improving sustained attention and processing speed. However, the limitation of available data warrants further studies to verify these findings.

Can Heart Rate Variability be Viewed as a Biomarker of Problematic Internet Use? A Systematic Review and Meta-Analysis.

Heart rate variability (HRV) has been used to explore the parasympathetic activity of individuals with problematic Internet use (PIU), but the results are controversial. We conducted a systematic review and meta-analysis of studies comparing HRV in PIU individuals and healthy participants from several databases. HRV was analyzed according to the parasympathetic activity in hierarchical order (primary analysis), and the total variability (secondary analysis). The baseline HRV and HRV reactivity were both considered. Of the 106 studies screened, 12 were included in the quantitative analysis. Significant differences were observed for baseline HRV in PIU individuals compared to the controls. Regarding HRV reactivity, PIU individuals did not have a significantly lower HRV value during pleasant or unpleasant stimuli. In summary, PIU individuals and healthy subjects had significantly different resting state parasympathetic activity. The finding of HRV reactivity in PIU individuals awaits further investigation.

The efficacy of non-invasive, non-convulsive electrical neuromodulation on depression, anxiety and sleep disturbance: a systematic review and meta-analysis.

The effects of non-invasive, non-convulsive electrical neuromodulation (NINCEN) on depression, anxiety and sleep disturbance are inconsistent in different studies. Previous meta-analyses on transcranial direct current stimulation (tDCS) and cerebral electrotherapy stimulation (CES) suggested that these methods are effective on depression. However, not all types of NINECN were included; results on anxiety and sleep disturbance were lacking and the influence of different populations and treatment parameters was not completely analyzed. We searched PubMed, Embase, PsycInfo, PsycArticles and CINAHL before March 2021 and included published randomized clinical trials of all types of NINCEN for symptoms of depression, anxiety and sleep in clinical and non-clinical populations. Data were pooled using a random-effects model. The main outcome was change in the severity of depressive symptoms after NINCEN treatment. A total of 58 studies on NINCEN were included in the meta-analysis. Active tDCS showed a significant effect on depressive symptoms (Hedges' g = 0.544), anxiety (Hedges' g = 0.667) and response rate (odds ratio = 1.9594) compared to sham control. CES also had a significant effect on depression (Hedges' g = 0.654) and anxiety (Hedges' g = 0.711). For all types of NINCEN, active stimulation was significantly effective on depression, anxiety, sleep efficiency, sleep latency, total sleep time, etc. Our results showed that tDCS has significant effects on both depression and anxiety and that these effects are robust for different populations and treatment parameters. The rational expectation of the tDCS effect is 'response' rather than 'remission'. CES also is effective for depression and anxiety, especially in patients with disorders of low severity.

Dehydroepiandrosterone status and efficacy of dehydroepiandrosterone supplementation for bone health in anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN. METHOD: Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta-analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed. RESULTS: Meta-analysis of 15 cross-sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01-545.25) and reduced DHEAS levels (MD = -24.90 µg/dl; 95% CI, -41.72 to -8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study. DISCUSSION: Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA. PUBLIC SIGNIFICANCE: This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia nervosa.

OBJETIVO: Este estudio fue diseñado para determinar el estado de la dehidroepiandrosterona (DHEA) en mujeres con anorexia nerviosa (AN) y para evaluar la eficacia de la suplementación con DHEA como tratamiento para la salud ósea en mujeres con AN. MÉTODO: Los estudios se obtuvieron de las bases de datos PubMed, Embase, Cochrane library, MEDLINE y Scopus desde su inicio hasta el 14 de febrero de 2022. Se incluyeron estudios observacionales que compararon los niveles séricos de DHEA entre mujeres que padecen AN y controles sanos para el metanálisis, y se revisaron los ensayos controlados aleatorios (ECA) que evaluaron los efectos de la suplementación con DHEA sobre la masa ósea. RESULTADOS: El metanálisis de 15 estudios transversales reveló que los pacientes que padecen AN tenían niveles séricos significativamente elevados de DHEA (diferencia de medias [DM] = 311,63 ng/dL; intervalo de confianza [IC] del 95%, 78,01-545,25) y niveles reducidos de DHEAS (DM = -24,90 µg/dL; IC del 95%, -41,72 a -8,07) en comparación con los controles sanos. La revisión sistemática de siete ECA encontró que la monoterapia con DHEA no mejora la densidad mineral ósea (DMO) en comparación con placebo después de ajustar el aumento de peso. Si bien la combinación de DHEA y anticonceptivos orales conjugados ha llevado a un aumento de la fuerza ósea y una disminución de la pérdida ósea, el efecto beneficioso parece limitarse a adolescentes mayores y adultos con placas de crecimiento cerradas. En un estudio se identificaron posibles efectos perjudiciales sobre la DMO en adolescentes más jóvenes con placas de crecimiento abiertas. DISCUSIÓN: Debido a la falta de beneficio aparente de la DHEA en mujeres que padecen AN y su posible efecto perjudicial sobre la DMO en pacientes jóvenes que padecen AN, la evidencia actual no apoya el uso de la DHEA.

Heart rate variability in patients with dementia or neurocognitive disorders: A systematic review and meta-analysis.

OBJECTIVE: Heart rate variability, a quantitative measure of mainly parasympathetic activity, has been applied in evaluating many types of psychiatric and neurological disorders, including dementia (or neurocognitive disorders). However, although dementia patients often showed significantly lower heart rate variability (various indices) than healthy controls, and different types of dementia had distinct heart rate variability features, the results were not identical across studies. We designed a systematic review and meta-analysis for incorporating data from different studies. METHODS: We gathered studies comparing heart rate variability in patients with dementia and in healthy controls. Heart rate variability was analysed in several ways: parasympathetic function in hierarchical order (main analysis), total variability, comparison of heart rate variability between different subtypes of dementia, specific indices of heart rate variability and heart rate variability reactivity. RESULTS: In the initial search, we found 3425 relevant articles, from which 24 studies with a total of 1107 dementia patients and 1017 control participants finally entered the main meta-analysis. The dementia patients had a significantly lower resting heart rate variability for parasympathetic function (Hedges' g = -0.3596, p = 0.0002) and total variability (Hedges' g = -0.3059, p = 0.0002) than the controls. For diagnostic subgroup analysis relative to the controls, heart rate variability was significantly lower in patients with mild cognitive impairment (Hedges' g = -0.3060) and in patients with dementia with Lewy bodies (Hedges' g = -1.4154, p < 0.0001). Relative to patients with Alzheimer's disease, heart rate variability in patients with dementia with Lewy bodies was significantly lower (Hedges' g = -1.5465, p = 0.0381). Meta-regression revealed that gender proportion was significantly associated with effect size. CONCLUSION: Our results show that dementia patients (especially those with dementia with Lewy bodies and mild cognitive impairment) have lower parasympathetic activity than healthy people. The influence of gender on the results should be carefully interpreted.

Heart rate variability in patients with anxiety disorders: A systematic review and meta-analysis.

AIMS: Patients with anxiety disorders (AD) have been found to have lower heart rate variability (HRV) than healthy individuals in some studies, but this was inconsistent. Furthermore, the influence of distinct diagnoses, study design, and demographic factors on the results was not comprehensively examined. METHODS: We gathered studies comparing HRV in patients with AD and in healthy controls. The parasympathetic activity in the hierarchical order principle was adopted in the main analysis. We adopted the random effects model to calculate the standardized mean difference. RESULTS: Of the 7805 screened studies, 99 were included in the quantitative analysis, with a total of 4897 AD patients and 5559 controls finally entered the meta-analysis. AD patients had a significantly lower resting-state HRV for parasympathetic activity compared to control (Hedges' g = -0.3897). For the diagnostic subgroup analysis relative to the controls, resting-state HRV was significantly lower in post-traumatic stress disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder patients. HRV reactivity (all reactivity data, data on physiological challenge, and psychological challenge) did not show significant inter-group differences between AD patients and healthy subjects. CONCLUSIONS: The results supported that patients with AD had significantly lower resting-state HRV than the healthy population, but no alterations were found for HRV reactivity.

Small molecule inhibitors and biologics in treating nail psoriasis: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. METHODS: Eligible studies in online databases were identified until March 10, 2020. To assess the efficacy of small molecule inhibitors and biologics, network meta-analyses with surface under the cumulative ranking curve of improvement in nail score at 10 to 16 and at 24 to 26 weeks, as well as 100% improvement of Nail Psoriasis Severity Index (NAPSI), were performed. RESULTS: Thirty-nine studies with a total of 13 treatment arms involving 15,673 patients with nail psoriasis were included. An network meta-analysis showed that tofacitinib (weighted mean difference, 56.67; 95% confidence interval [CI], 35.87-77.48) and ixekizumab (weighted mean difference, 59.40; 95% CI, 45.87-72.93) presented the most improvement of nail score at 10 to 16 weeks and 24 to 26 weeks, respectively. For 100% improvement of the Nail Psoriasis Severity Index, ixekizumab showed the best efficacy among all treatments (odds ratio, 2.98; 95% CI, 1.74-5.10). LIMITATIONS: Insufficiency of eligible data and no long-term follow-up data. CONCLUSION: Tofacitinib and ixekizumab presented the best efficacy for treating nail psoriasis in 10 to 16 weeks and 24 to 26 weeks, respectively.

Treating toxic epidermal necrolysis with systemic immunomodulating therapies: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been used to treat toxic epidermal necrolysis (TEN), but their efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) evaluating the effects of systemic immunomodulating therapies on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN. METHODS: A literature search was performed in online databases (from inception to October 31, 2019). Outcomes were mortality rates and Score of Toxic Epidermal Necrolysis (SCORTEN)-based standardized mortality ratio (SMR). A frequentist random-effects model was adopted. RESULTS: Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments showed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (odds ratio, 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms showed that corticosteroids and intravenous immunoglobulin combination therapy was the only treatment with significant survival benefits (SMR, 0.53; 95% CI, 0.31-0.93). LIMITATIONS: Heterogeneity and a paucity of eligible randomized controlled trials. CONCLUSIONS: Combination therapy with corticosteroids and IVIg may reduce mortality risks in patients with SJS/TEN overlap and TEN. Cyclosporine and etanercept are promising therapies, but more studies are required to provide clearer evidence.

The effect of vitamin D supplement on negative emotions: A systematic review and meta-analysis.

BACKGROUND: The several meta-analyses of the effect of vitamin D on depression have produced inconsistent results and studies dealing with anxiety were not incorporated. There has been no comprehensive analysis of how results are affected by the nature of the sample or the dosage and duration of supplementation. The study is aimed to investigate whether vitamin D supplementation reduces negative emotions and to analyze the possible influence of sample and regimen. METHOD: We conducted a systematic review and meta-analysis of randomized controlled trials comparing the effect of vitamin D and placebo on negative emotion. Databases were searched for relevant articles published before February 2019. RESULTS: The analysis covered 25 trials with a total of 7,534 participants and revealed an effect of vitamin D on negative emotion (Hedges' g = -0.4990, 95% CI [-0.8453, -0.1528], p = .0047, I2 = 97.7%). Subgroup analysis showed that vitamin D had an effect on patients with major depressive disorder and on subjects with serum 25(OH)D levels ≤50 nmol/L. The pooled data from trials of vitamin D supplementation lasting ≥8 weeks and dosage ≤4,000 IU/day indicated that vitamin D had an effect. CONCLUSIONS: Our results support the hypothesis that vitamin D supplementation can reduce negative emotions. Patients with major depressive disorder and individuals with vitamin D deficiency are most likely to benefit from supplementation. But to interpret the results with high heterogeneity should still be cautious.

Gabapentinoids for treatment of alcohol use disorder: A systematic review and meta-analysis.

OBJECTIVE: Gabapentin (GBP) and pregabalin (PGB) have been used to treat alcohol use disorder (AUD) and alcohol withdrawal, but with inconsistent results. In this meta-analysis, we explored the effects of GBP/PGB treatment on AUD and their effects on withdrawal, craving, depression, and sleep disturbance in AUD patients. METHODS: We carried out a systematic review and meta-analysis of randomized controlled trials comparing the effects of GBP/PGB on AUD with those of a placebo or control treatment. Electronic databases were searched for relevant articles published before September 2019. The primary outcome was defined as the efficacy measure on achieving abstinence or reducing alcohol consumption in a hierarchical order. We included 16 studies in our meta-analysis. RESULTS: Overall, GBP had no significant benefit comparing to placebo or control treatment (Hedges' g = 0.0725, p = 0.6743). For specific alcohol-related outcome, GBP had significant effect on percentage of heavy drink (Hedges' g = 0.5478, p = 0.0441) and alcohol withdrawal symptoms (Hedges' g = 0.2475, p = 0.0425). GBP/PGB did not have significant beneficial effect on craving, depressive symptoms, or sleep disturbance. Instability was shown in sensitivity analyses of some above results. CONCLUSIONS: GBP may be helpful to reduce AUD patients' heavy drinking behavior and withdrawal, but more studies are needed for drawing conclusions.

Effect of Apolipoprotein E ɛ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The apolipoprotein E ɛ4 (APOE ɛ4) genotype is the major genetic risk factor for Alzheimer's disease (AD). However, its effect on an individual's response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ɛ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ɛ4 carrier status. METHODS: Clinical studies with AD patients reporting APOE ɛ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). RESULTS: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ε4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ε4 carriers and APOE ε4 non-carriers (SMD = 0.022, 95% CI: -0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. CONCLUSIONS: APOE ɛ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ε4 carrier status.

Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis.

BACKGROUND: The relationship between isotretinoin treatment for acne and depression is controversial. Quantitative analysis has not yet been conducted. OBJECTIVE: To conduct a meta-analysis, evidence-based examination of the relationship between isotretinoin and depression. METHOD: A systematic review and meta-analysis of the literature published from inception to September 30, 2016, was conducted. Controlled or prospective non-controlled trials on ≥15 acne patients receiving isotretinoin treatment were included. The prevalence of depression and change in depression scores were calculated. RESULT: Thirty-one studies met the inclusion criteria. In the controlled studies, the change in depression scores from baseline was not significantly different between patients receiving isotretinoin treatment and those receiving an alternative treatment (standardized mean difference [SMD] -0.334, 95% confidence interval [CI] -0.680 to 0.011). The prevalence of depression after isotretinoin treatment significantly declined (relative risk [RR] 0.588, 95% CI 0.382-0.904). The mean depression scores significantly decreased from baseline (SMD -0.335, 95% CI -0.498 to -0.172). LIMITATIONS: No randomized controlled trials were reviewed; a large inter-study variation was observed. CONCLUSIONS: Isotretinoin treatment for acne does not appear to be associated with an increased risk for depression. Moreover, the treatment of acne appears to ameliorate depressive symptoms.

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.

Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis.

BACKGROUND: The efficacy of probiotics as a therapeutic alternative for attention-deficit hyperactivity disorder (ADHD) remain unclear. AIMS: To investigate the effectiveness of probiotics for symptoms of ADHD and identify possible factors affecting their efficacy. METHOD: Randomised placebo-controlled trials were identified through searching major databases from inception to April 2023, using the main keywords 'probiotics' and 'ADHD' without limitation on languages or geographic locations. The outcome of interest included improvement in total symptoms of ADHD, symptoms of inattention and hyperactivity/impulsivity, and drop-out rate. Continuous and categorical data were expressed as effect sizes based on standardised mean differences (SMDs) and odds ratios, respectively, with 95% confidence intervals. RESULTS: Meta-analysis of seven trials involving 379 participants (mean age 10.37 years, range 4-18 years) showed no significant improvement in total symptoms of ADHD (SMD = 0.25; P = 0.12), symptoms of inattention (SMD = 0.14; P = 0.3) or hyperactivity/impulsivity (SMD = 0.08; P = 0.54) between the probiotic and placebo groups. Despite non-significance on subgroup analyses, there was a large difference in effect size between studies using probiotics as an adjunct to methylphenidate and those using probiotics as supplementation (SMD = 0.84 v. 0.07; P = 0.16), and a moderate difference in effect size between studies using multiple strains of probiotics and those using single-strain regimens (SMD = 0.45 v. 0.03; P = 0.19). CONCLUSIONS: Current evidence shows no significant difference in therapeutic efficacy between probiotics and placebos for treatment of ADHD symptoms. However, albeit statistically non-significant, higher therapeutic efficacies associated with multiple-strain probiotics or combining probiotics with methylphenidate may provide direction for further research.

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.