17-item Hamilton Depression Rating Scale Research Articles

In perspective of specific symptoms of major depressive disorder: Functional connectivity analysis of electroencephalography and potential biomarkers of treatment response

BackgroundThe symptom variability in major depressive disorder (MDD) complicates treatment assessment, necessitating a thorough understanding of MDD symptoms and potential biomarkers. MethodsIn this prospective study, we enrolled 54 MDD patients and 39 controls. Over the course of weeks 1, 2, and 4 participants underwent evaluations, with electroencephalograms (EEG) recorded at baseline and week 1. Our investigation considered five previously identified syndromal factors derived from the 17-item Hamilton Depression Rating Scale (17-item HAMD) for assessing depression: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. We assessed treatment response and EEG characteristics across all syndromal factors and total scores, all of which are based on the 17-item HAMD. To analyze the topology of brain networks, we employed functional connectivity (FC) and a graph theory-based method across various frequency bands. ResultsThe healthy control group had notably higher values in delta band EEG FC compared to the MDD patient group. Similar distinctions were observed between the responder and non-responder patient groups. Further exploration of baseline FC values across distinct syndromal factors revealed significant variations among the core, psychomotor-insight, and anorexia subgroups when using a specific graph theory-based approach, focusing on global efficiency and average clustering coefficient. LimitationsDifferent antidepressants were included in this study. Therefore, the results should be interpreted with caution. ConclusionsOur findings suggest that delta band EEG FC holds promise as a valuable predictor of antidepressant efficacy. It demonstrates an ability to adapt to individual variations in depressive symptomatology, offering insights into personalized treatment for patients with depression.

Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis

ObjectiveTo evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding.DesignSystematic review...

Electroconvulsive therapy modulates loudness dependence of auditory evoked potentials: a pilot MEG study.

Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study aims to investigate changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, in patients undergoing ECT. High-resolution magnetoencephalography (MEG) was utilized to measure LDAEP in nine depressed patients receiving right unilateral ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Depression severity and cognitive performance were assessed using the 24-item Hamilton Depression Rating Scale (HDRS24) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Contrary to our hypothesis, findings indicated a significant increase in LDAEP post-ECT (t 8 = 3.17, p = .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance. The observed increase in LDAEP suggests a more complex interaction between ECT and neurobiological systems, rather than a direct reflection of serotonergic neurotransmission. Potential mechanisms for this increase include ECT's impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammatory modulators such as TNF-α. Our results highlight the multifaceted effects of ECT on brain function, necessitating further research to elucidate these interactions.

Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder

BackgroundBrain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HT4R levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment. MethodsNinety patients with moderate to severe depression underwent molecular brain imaging to measure 5-HT4R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT4R binding was assessed for its ability to predict treatment outcome at weeks 4, 8, or 12. In 40 patients who were rescanned 8 weeks posttreatment, change in cerebral 5-HT4R binding was correlated with change in verbal memory and with change in depressive symptoms, as evaluated by the 6-item Hamilton Depression Rating Scale. ResultsAfter 8 weeks of serotonergic intervention, neostriatal 5-HT4R binding was reduced by 9%. Global change in 5-HT4R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT4R binding did not predict clinical recovery status at week 8 and was not associated with change in the 6-item Hamilton Depression Rating Scale scores. ConclusionsIn patients with moderate to severe MDD, treatment with selective serotonin reuptake inhibitors downregulated neostriatal 5-HT4R levels, which is consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT4R levels were downregulated after selective serotonin reuptake inhibitors, the more verbal memory improved, highlighting the potential importance of 5-HT4R as a treatment target in MDD. The findings offer insights into mechanisms that underlie antidepressant effects and point to new directions for precision medicine treatments for MDD.

Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models.

Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account. Depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). HAMD-17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)-logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis. The rate of depressive symptom in patients with PBC (n=162) was higher than in healthy controls (n=180) (52.5%vs. 16.1%; p<.001). HAMD-17 score was negatively associated with C4 levels and positively associated with levels of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TB), Immunoglobulin (Ig) G, and IgM (r=-0.162, 0.197, 0.355, 0.203, 0.182, 0.314, p<.05). In Lasso-logistic regression analysis, HAMD-17 score, human leukocyte antigen (HLA)-DRB1*03:01 allele, age, ALP levels, and IgM levels (odds ratio [OR]=1.087, 7.353, 1.075, 1.009, 1.005; p<0.05) were independent risk factors for cirrhosis. Elevated HAMD-17 score was also a discriminating factor for high risk of cirrhosis in patients with PBC in decision tree model. Depressive symptoms were associated with disease severity. Elevated HAMD-17 score was a risk factor for cirrhosis in patients with PBC.

Attenuated frontotemporal brain activation during cognitive tasks is associated with lower succinate dehydrogenase protein levels in patients with major depressive disorder

BackgroundPrevious studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism. MethodsFifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay. ResultsActivation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD. ConclusionsMDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD. LimitationsThe sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.

Sleep Problems and Gambling Disorder: Cross-Sectional Relationships in a Young Cohort.

To investigate the potential association between gambling disorder and symptoms of sleep problems (including insomnia and excessive daytime sleepiness). It was hypothesised that, compared to controls, individuals with gambling disorder would have significantly greater disturbance of sleep, as indicated by increased scores in: (1) sleep items on the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D); (2) total score on the HAM-A and HAM-D; and (3) the Epworth Sleepiness Scale (ESS). Secondary analysis of previously published data from 152 young adults, aged 18-29 years. Individuals were stratified into three groups: controls, those at risk of gambling disorder, and those with gambling disorder. One-way ANOVAs with post-hoc tests were conducted to determine whether groups differed significantly in sleep item scores and total scores of the HAM-A and HAM-D, and the ESS. HAM-D scale insomnia item scores were significantly higher in the disorder group, when compared to controls, this being particularly marked for middle and late insomnia. The HAM-A item score indicated significantly worse sleep quality in the disorder group, compared to at risk and control groups. Total HAM-A and HAM-D scores were significantly higher in the disorder group, but ESS scores did not differ significantly. Measures of disruptions in sleep were significantly higher in gambling disorder than controls. Anxiety and depressive symptom severity was also significantly higher in the gambling disorder group. Further research could have implications for identification and treatment of sleep disorders and psychiatric comorbidities in gambling disorder.

Alterations in electroencephalographic functional connectivity in individuals with major depressive disorder: a resting-state electroencephalogram study.

Major depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC). In this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4-8 Hz; alpha, 8-12 Hz; beta1, 12-16 Hz; beta2, 16-24 Hz; and beta3, 24-40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17). During the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked. Our study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression. The study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD.

Serum lipid level as a biomarker in depressive disorder: A cross-sectional case control study

Objectives: This study investigates the potential of serum lipids as markers for depression, specifically focusing on symptoms such as suicidal ideation and anhedonia. In the context of advancing psychiatric biomarker research, this study aims to identify lipid-related markers and their underlying biological connections to depression, offering valuable insights for clinical practice and patient outcomes. Material and Methods: This case-control observational study was conducted over 18 months at a tertiary care center. The study enrolled patients aged 18–60 years diagnosed with depression attending outpatient and inpatient departments, totaling 100 subjects, including 100 cases and 100 controls, with gender and body mass index (BMI)-matched controls. Inclusion criteria for cases required depression diagnosis using the International Classification of Diseases-10-Diagnostic Criteria for Research criteria, while controls comprised healthy individuals within the same age range. Exclusion criteria encompassed comorbid psychiatric illnesses, substance use disorders (except tobacco), unstable medical conditions, lipid-lowering agent use, and a BMI over 30. Clinical assessments, including the Hamilton Depression Rating Scale-17 item scale, Modified Scale for Suicidal Ideation, and Snaith-Hamilton Pleasure Scale-Clinician administered, were administered. Serum lipid parameters, including triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL)-cholesterol, were measured. Results: In a cross-sectional case-control study (n = 200), we examined serum lipids as potential depression biomarkers. Cases (n = 100) matched controls in age, BMI, and gender. Cases had lower TC (153.27 mg/dL vs. 171.34 mg/dL, P &lt; 0.01*). Serum TG and low-density lipoprotein also varied significantly with depression severity (P &lt; 0.01*). However, HDL levels remained consistent. No significant associations were found between suicidal ideation and anhedonia, and post hoc analyses revealed significant differences (P ≤ 0.05) in lipid parameters across various depression severity levels. Conclusion: These findings suggest a complex relationship between serum lipids and depression, with potential implications for understanding the biological underpinnings of depression and its severity. However, there was no such relationship that was observed between serum lipids and anhedonia or suicidal ideation. These insights could inform clinical practices and improve patient outcomes in depression management.

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites

BackgroundWhile theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. MethodsThirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3–4 days posttreatment (T1) and 10–11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. ResultsAlthough the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LimitationsThe modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10–11 days, whereas similar studies usually follow up for at least one month. ConclusionMore research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study

BackgroundCognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients.MethodsIn this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients’ cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients’ depressive symptoms at baseline and week 2.ResultsAfter 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups.ConclusionsrTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients.Trial registrationChinese Clinical Trial Registry (ChiCTR2100052122).

Combined Effect of Red Wine and Mocha Pot Coffee in Mild Vascular Cognitive Impairment

ObjectivesModerate daily mocha pot coffee intake has been associated with better mood and cognition in patients with mild vascular cognitive impairment (VCI). Similarly, moderate red wine consumption has shown protective effects on cognitive disorders, including Alzheimer's disease and vascular dementia. The aim of this study was to explore the synergistic relation between red wine and coffee intake on mood and cognitive status in mild VCI patients at risk for dementia. MethodsA total of 300 non-demented older patients with mild VCI were asked for coffee and red wine consumption and administered with the 17-items Hamilton Depression Rating Scale (HDRS), the Mini Mental State Examination (MMSE), and the Stroop Color-Word Interference Test (Stroop T), as well as the Activities of Daily Living (ADL) and the Instrumental ADL to measure their mood status, cognitive performance, and functional independence. Linear regression models were used to test the association between variables. ResultsModerate wine drinkers tended to show the best Stroop T score at any level of coffee consumption; conversely, heavy wine consumers performed worse at the Stroop T, especially in patients reporting high coffee intake. Moderate drinkers of both coffee and wine showed the lowest HDRS scores. Finally, a progressive increase in MMSE score was evident with increasing coffee consumption, which peaks when combined with a moderate wine consumption. ConclusionsDaily mocha pot coffee and red wine intake seem to be synergistically associated with global cognition, executive functioning, and mood status in patients with mild VCI; the association was not linear, resulting in a protective direction for moderate intake and detrimental for heavy consumption. Future studies are needed to further corroborate the present findings and the potential long-term protective effects of these dietary compounds over time.

Serum brain derived neurotrophic factor levels and post-stroke depression in ischemic stroke patients

BackgroundBrain-derived neurotrophic factor (BDNF) is crucial for neuronal survival and may be implicated in the pathophysiological process of depression. This study aimed to prospectively investigate the association between serum BDNF and post-stroke depression (PSD) at 3 months in a multicenter cohort study. MethodsA total of 611 ischemic stroke patients with serum BDNF measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Depression Rating Scale to assess depression status at 3 months after ischemic stroke, and PSD was defined as a score of ≥8. ResultsBaseline serum BDNF was inversely associated with the risk of depression after ischemic stroke. The multivariable-adjusted odds ratio of PSD for the highest tertile of BDNF was 0.53 (95 % confidence interval, 0.34–0.82; P for trend = 0.004) compared with the lowest tertile. Multivariable-adjusted spline regression model also showed a linear does-response association between serum BDNF levels and PSD at 3 months (P for linearity = 0.006). In addition, adding serum BDNF to conventional risk factors significantly improved the risk reclassification of PSD (net reclassification improvement: 16.98 %, P = 0.039; integrated discrimination index: 0.93 %, P = 0.026). LimitationsAll patients in this study were Chinese, so our findings should be applied to other populations cautiously. ConclusionsHigher serum BDNF levels at baseline were significantly associated with a decreased risk of PSD at 3 months, suggesting that BDNF might be a valuable predictive biomarker and potential therapeutic target for PSD among ischemic stroke patients.

The safety and efficacy of escitalopram and sertraline in post-stroke depression: a randomized controlled trial

ObjectivesThis study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice.MethodsWe recruited 60 patients (aged 40–89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann–Whitney U test, the chi-square test (χ2), or Fisher’s exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables.ResultsSignificant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05).ConclusionEscitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.

High-definition transcranial direct current stimulation (HD-tDCS) in major depressive disorder with anxious distress—a study protocol for a double-blinded randomized sham-controlled trial

BackgroundComorbid anxiety disorders and anxious distress are highly prevalent among individuals with major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. Few studies have evaluated the therapeutic effects of High-definition transcranial direct current stimulation (HD-tDCS) on depressive and anxiety symptoms among MDD patients with ADS. The current randomized controlled trial aims to assess the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects of MDD with ADS.MethodsMDD patients with ADS will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response, and the remission rate as measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before and after the intervention and at the 2nd and 6th week after the completed intervention. Secondary outcome measures include anxiety symptoms, cognitive symptoms, disability assessment, and adverse effects.DiscussionThe HD-tDCS applied in this trial may have treatment effects on MDD with ADS and have minimal side effects.Trial registrationThe trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2300071726. Registered 23 May 2023.

Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder.

To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=-4.169, p<0.001), and lower level of sestrin-2 (Z=-2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=-0.590, p=0.001) and wake time (r=-0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=-0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=-0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=-0.257, p=0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (r=0.270, p=0.033). The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.

Sex-differential cognitive performance on MCCB of youth with BD-II depression

BackgroundRecent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression.MethodThis cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted.Result​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression.ConclusionOur study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

Executive function deficits in patients with the first episode of late-life depression before and after SSRI treatment: A pilot fMRI study.

Executive function deficits (EFD) in late-life depression (LLD) has been reported to be associated with antidepressant treatment resistance, increased disability, and poor quality of life. However, the underlying neutral mechanisms of EFD in patients with the first episode of LLD remains unclear. A total of 27 patients with first-episode, drug-naive LLD and 27 non-depressed controls (NC) were recruited for the present research. Participants underwent the Trail Making Test, the 17-item Hamilton depression rating scale (HAMD-17) test, and task-state functional magnetic resonance imaging scans under the neutral Stroop task. LLD patients' executive functions, depressive symptoms, and brain activity were examined again after 6months of antidepressant treatment. Of the 27 LLD patients, 16 cases completed 6-month follow-ups. Patients in the LLD baseline group spent more time on the Trail Making Test A test than those in the NC group (p<0.05). In the presence of an incongruency between the word color and meaning, the accuracy rate of the neutral Stroop task in the LLD baseline group was lower, and the reaction time was greater than that in the NC group, with statistically significant difference (p<0.05). The HAMD-17 score in the LLD follow-up group was significantly lower than that in the LLD baseline group (p<0.05). More activated brain regions were present in the LLD baseline group than in the NC group when performing the neutral Stroop task. Compared with the LLD baseline group, abnormal activation of relevant brains in the cingulate-prefrontal-parietal network of LLD patients still existed in the LLD follow-up group. LLD patients engaged more brain areas than the NC group while performing the neutral Stroop task. Abnormal activation of the cingulate-prefrontal-parietal network could be a contributing factor to EFD in LLD. ChiCTR, ChiCTR2100042370 (Date of registration: 21/01/2021). We didn't enroll enough first-episode, LLD patients, the robustness of the findings need to be confirmed by large sample clinical trials.

The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway

There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18–65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [F(3,72) = 11.73,p < .001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = –229.44, t = -3.82,p < .001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium.

Latent Profile Analysis of Suicidal Ideation in Chinese Individuals with Bipolar Disorder.

Individuals with bipolar disorder (BD) have a greater suicide risk than the general population. In this study, we employed latent profile analysis (LPA) to explore whether Chinese individuals with different phases of BD differed at the levels of suicidal ideation. We recruited 517 patients. Depressive symptoms were measured using the 24-item Hamilton Depression Rating Scale (HAMD-24), and manic symptoms were evaluated using the Young Mania Rating Scale (YMRS). The extent of suicidal thoughts was determined through the Beck Scale for Suicide Ideation (BSSI). The scores of HAMD and YMRS were used to perform LPA. LPA categorized participants into three classes: one exhibiting severe depressive and mild manic symptomatology, another showing severe depressive and severe manic symptomatology, and the third one displaying severe depressive and intermediate manic symptomatology. Suicidal ideation levels were found to be remarkably elevated across all three classes. Additionally, the three classes showed no significant differences in terms of suicidal ideation. Our research confirms the link between depressive symptoms and suicide, independent of the manic symptoms. These findings carry meaning as they provide insight into the suicide risk profiles within different phases of BD.