HAMD Scores Research Articles

Association of reduced serum EGF and leptin levels with the pathophysiology of major depressive disorder: A case-control study.

Major depressive disorder (MDD) is a heterogeneous mental disorder having a very diverse course and causing a significant changes in daily life. Though the exact pathophysiology of depression is still not known, an alteration in the serum levels of cytokines and neurotrophic factors was seen in MDD subjects. In this study, we compared the serum levels of 'pro-inflammatory cytokine leptin and neurotrophic factor EGF' in healthy controls (HCs) and MDD patients. To make the findings more accurate, we eventually looked for a correlation between altered serum leptin and EGF levels and the severity of the disease condition. For this case-control study, about 205 MDD patients were enrolled from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, Dhaka, and about 195 HCs were enrolled from various parts of Dhaka. The DSM-5 was utilized to evaluate and diagnose the participants. The HAM-D 17 scale was used to measure the severity of depression. After collecting blood samples, they were centrifuged to produce clear serum samples. These serum samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits to measure serum leptin and EGF levels. We observed lowered serum EGF levels in MDD patients compared to HCs (524.70 ± 27.25 pg/ml vs. 672.52 ± 49.64 pg/ml, p = 0.009), and HAM-D score was elevated in MDD patients compared to HCs (17.17 ± 0.56 vs. 2.49 ± 0.43, p<0.001). But no correlation was established between serum EGF levels and the severity of depression. However, no significant differences were observed between MDD patients and HCs in the case of serum leptin levels (p = 0.231). Our study findings suggest that reduced serum EGF levels have an impact on the pathogenesis of depression. But as per our investigation, the severity of depression is not correlated with altered EGF levels. Our findings regarding the association of EGF with MDD would help to use EGF as a risk indicator of depression. We suggest further clinical investigations to determine the precise function of leptin and EGF in depression.

Equal remission rates and reduced length of hospital stay with twice-daily repetitive transcranial magnetic stimulation (rTMS) for major depression – A large naturalistic retrospective cohort association study

ObjectivesRepetitive transcranial magnetic stimulation (rTMS) is a level 1a evidence-based treatment for major depression, but high cost of care and limited effectiveness in naturalistic cohorts have been lingering criticisms. This naturalistic, retrospective cohort analysis compares the effect of once and twice daily treatment protocols of rTMS using quality assurance data collected at an Australian private psychiatric hospital. MethodsA total of 210 inpatients self-selected into two groups receiving up to 30 sessions of either daily (n = 101) or twice daily (n = 109) 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). The a priori primary outcome measure was remission rate as measured by pre and post treatment HAMD-17 scores. Length of hospital stay was a secondary post hoc outcome adopted due to the importance to cost of acute psychiatric care. ResultsRemission rates were similar across groups, with 44.9% and 45.4% for twice daily and daily rTMS groups respectively, although these may be confounded by patient expectations, other treatments and medication changes given the naturalistic setting. The length of hospital stay was 10.11 days and 18.44 days for twice daily and daily rTMS respectively – the twice daily rTMS length of hospital stay was 45.1% shorter 95% CI [38.7% - 51.56%]. Dropout rates were high; Twenty-seven (24.77%) twice daily participants dropped out before 20 sessions were completed, and 35 (34.65%) of daily participants. ConclusionsTwice daily 10 Hz left sided rTMS remission outcomes were similar to traditional once daily rTMS but required a shorter length of hospital stay. This finding has substantial cost of care implications. If these findings are independently replicated, twice daily rTMS may become the standard of care for inpatient rTMS.

Mood Disorders are Correlated with Autonomic Nervous Function in Chronic Insomnia Patients with OSA.

To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA). Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A. The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=-0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=-0.321, P =0.031, r =-0.449, p =0.002). OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.

Thyroid dysfunction in young, first-episode and drug-naïve patients with major depressive disorder: prevalence and associated clinical factors.

The incidence of thyroid dysfunction (TD) and major depressive disorder (MDD) is increasing year by year in the general population. However, the prevalence and correlates of TD in first-episode drug-naive (FEDN) MDD patients have not been explored. This study sought to fill this gap and examine the association between TD and MDD. We recruited 1,289 FEDN MDD patients aged 18 ~ 45 years. A total of 1,289 FEDN MDD outpatients were recruited. Demographical and suicide data were collected for each patient, and lipid profiles, thyroid function, and fasting blood glucose (FBG) levels were measured. The Hamilton Depression Scale 17 (HAMD-17) was assessed for depression. The prevalence of TD in young FEDN MDD patients was 64.86%. Compared with those without TD, patients with TD had longer duration of illness, greater HAMD score, higher BMI, TG, TC, and LDL-C levels, and higher suicide attempt rates, but lower HDL-C and FBG levels. Further logistic regression indicated that duration of illness, HAMD score, TC, HDL-C, BMI, and FBG levels were significantly associated with TD. No causal relationship can be drawn due to the cross-sectional design. TD is common in young FEDN MDD patients. So clinicians should monitor thyroid function in patients with MDD.

Association between peripheral orexin A/B levels and depression with childhood trauma

BackgroundOrexin dysfunction has previously been demonstrated to be associated with depression. However, no studies reported the different effects of orexin A/B on depression with and without childhood trauma (CT). In this study，we assessed the correlation between expression of orexin A/B and depression severity in major depressive disorder (MDD) patients and healthy controls. MethodsA total of 97 MDD patients and 51 healthy controls were recruited in this study. According to the total scores of childhood trauma questionnaire (CTQ), the MDD patients were further divided into two subgroups, MDD with CT and MDD without CT. The 17-item Hamilton Depression Scale (HAMD-17), and plasma orexin A and orexin B concentrations were measured in all participants using enzyme-linked immunosorbent assay. ResultsOrexin B plasma levels were significantly higher in MDD patients with CT and without CT than that in the healthy control group (P < 0.05), whereas there was no statistical difference between the two depression groups. After adjusting age and BMI for covariates, the LASSO regression revealed significant association between the plasma orexin B levels and the total scores of HAMD (β = 3.348), CTQ (β = 2.005). There was no difference in plasma orexin A levels among three groups (P > 0.05). ConclusionsAlthough peripheral orexin B levels are associated with the depression, rather than orexin A, CT appear to play a role in the association between orexin B levels and depression.China Clinical Trial Registration Center (Registration No.: ChiCTR2000039692).

Alterations in Gray Matter Morphology and Functional Connectivity in Adult Patients with Newly Diagnosed Untreated Hypothyroidism.

Background: Untreated adult hypothyroidism may be associated with cognitive and emotional impairment, but the precise underlying neuropathological mechanism is unknown. We investigated the brain morphological and functional abnormalities associated with cognition and emotion in hypothyroidism. Methods: This is a cross-sectional observational study. Forty-four newly diagnosed adult hypothyroid patients and 54 well-matched healthy controls (HCs) were enrolled. All participants underwent three-dimensional T1-weighted imaging and resting-state functional magnetic resonance imaging (MRI). Morphological and seed-based functional connectivity (FC) analyses were performed to compare the intergroup differences. Neuropsychological tests, including the Montreal Cognitive Assessment (MoCA) Scale, 24-item Hamilton Depression Rating Scale (HAMD-24), and Hamilton Anxiety Rating Scale (HAMA) were administered. Thyroid function test and blood lipid levels were measured. Correlations were computed between neuropsychological and biochemical measures with neuroimaging indices. Sensitive morphological or functional neuroimaging indicators were identified using receiver operating characteristic (ROC) analysis. Results: Compared with HCs, hypothyroid patients demonstrated lower total and subdomain scores on the MoCA and higher HAMD-24 and HAMA scores. Morphological analysis revealed the hypothyroid patients had significantly reduced gray matter (GM) volumes in the right superior frontal gyrus, superior temporal gyrus, left dorsolateral superior frontal gyrus, middle frontal gyrus, and supplementary motor area as well as significantly increased GM volumes in the bilateral cerebellar Crus I and left precentral gyrus. Furthermore, seed-based FC analysis of hypothyroid patients showed increased FC between the right cerebellar Crus I and left precentral gyrus, triangular part of the inferior frontal gyrus, and angular gyrus of the inferior parietal lobe. The language scores of the MoCA were positively correlated with Jacobian values of the left supplementary motor area (r = 0.391, p = 0.046) and precentral gyrus (r = 0.401, p = 0.039). ROC analysis revealed FC value between cerebellar Crus I and angular gyrus could differentiate groups with relatively high accuracy (sensitivity: 75%, specificity: 77.8%, area under the curve: 0.794 [CI 0.701-0.888], p < 0.001). Conclusions: Untreated adult-onset hypothyroidism may be associated with impaired cognition and anxiety or depression. GM morphological alterations and FC of the cerebellum with subregions of the frontal and parietal lobes may represent key neuropathological mechanisms underlying the cognitive deterioration and mood dysregulation observed in hypothyroid adults. Clinical Trial Registration Number: chiCTR2000028966.

Fast and accurate assessment of depression based on voice acoustic features: a cross-sectional and longitudinal study.

Depression is a widespread mental disorder that affects a significant portion of the population. However, the assessment of depression is often subjective, relying on standard questions or interviews. Acoustic features have been suggested as a reliable and objective alternative for depression assessment. Therefore, in this study, we aim to identify and explore voice acoustic features that can effectively and rapidly predict the severity of depression, as well as investigate the potential correlation between specific treatment options and voice acoustic features. We utilized voice acoustic features correlated with depression scores to train a prediction model based on artificial neural network. Leave-one-out cross-validation was performed to evaluate the performance of the model. We also conducted a longitudinal study to analyze the correlation between the improvement of depression and changes in voice acoustic features after an Internet-based cognitive-behavioral therapy (ICBT) program consisting of 12 sessions. Our study showed that the neural network model trained based on the 30 voice acoustic features significantly correlated with HAMD scores can accurately predict the severity of depression with an absolute mean error of 3.137 and a correlation coefficient of 0.684. Furthermore, four out of the 30 features significantly decreased after ICBT, indicating their potential correlation with specific treatment options and significant improvement in depression (p < 0.05). Voice acoustic features can effectively and rapidly predict the severity of depression, providing a low-cost and efficient method for screening patients with depression on a large scale. Our study also identified potential acoustic features that may be significantly related to specific treatment options for depression.

MiR-218-5p and miR-320a-5p as Biomarkers for Brain Disorders: Focus on the Major Depressive Disorder and Parkinson's Disease.

Depression is one of the early and most persistent non-motor symptoms of Parkinson's disease (PD), which remains ignored, resulting in the underdiagnosis of PD. Unfortunately, scarce studies and the non-availability of diagnostic strategies cause countless complications, highlighting the need for appropriate diagnostic biomarkers. Recently, brain-enriched miRNAs regulating vital neurological functions have been proposed as potent biomarkers for therapeutic strategies. Therefore, the present study is aimed to identify the brain-enriched miR-218-5p and miR-320-5p in the serum of the Chinese depressed PD patients (n = 51) than healthy controls (n = 51) to identify their potency as biomarkers. For this purpose, depressive PD patients were recruited based on HAMA and HAMD scores and miR-218-5p and miR-320-5p and IL-6, and S100B levels were analyzed using real-time PCR (qRT-PCR) and ELISA assay, respectively. In silico analysis was performed to identify key biological pathways and hub genes involved in the psychopathology of depression in PD. Here, we found significantly downregulated miR-218-5p and miR-320-5p following higher levels of IL-6 and S100B in depressed PD patients than in control (p < 0.05). The correlation analysis revealed that both miRNAs were negatively correlated with HAMA and HAMD, and IL-6 scores, along with a positive correlation with PD duration and LEDD medication. ROC analysis showed AUC above 75% in both miRNAs in depressed PD patients, and in silico analysis revealed that both miRNA's targets regulate key neurological pathways such as axon guidance, dopaminergic synapse, and circadian rhythm. Additional analysis revealed PIK3R1, ATRX, BM1, PCDHA10, XRCC5, PPP1CB, MLLT3, CBL, PCDHA4, PLCG1, YWHAZ, CDH2, AGO3, PCDHA3, and PCDHA11 as hub-genes in PPI network. In summary, our findings show that miR-218-5p and miR-320-5p can be utilized as future biomarkers for depression in PD patients, which may aid in the early diagnosis and treatment of Parkinson's disease.

Serum glial fibrillary acidic protein and neurofilament light chain in treatment-naïve patients with unipolar depression

BackgroundUnipolar depression has been associated with increased levels of glial dysfunction and neurodegeneration biomarkers, such as Glial Fibrillary Acidic Protein (GFAP) and Neurofilament light chain (NfL). However, previous studies were conducted on patients taking psychotropic medication and did not monitor longitudinal associations between disease status and GFAP/NfL. MethodsTreatment-naïve patients with unipolar depression (n = 110) and healthy controls (n = 33) were included. GFAP/NfL serum levels were analyzed by Single Molecule Array at baseline and 3-month follow-up. The primary endpoint was GFAP/NfL levels in patients with depression compared with healthy controls. The secondary endpoint was the associations between GFAP/NfL with depression severity and cognitive function. ResultsThe patients' mean HAM-D17 score was 18.9 (SD 3.9) at baseline and improved by 7.9 (SD 6.8) points during follow-up. GFAP/NfL was quantified in all individuals. At baseline, the adjusted GFAP levels were −16.8 % (95 % CI: −28.8 to −1.9, p = 0.03) lower among patients with depression compared to healthy controls, while NfL levels were comparable between the groups (p = 0.57). In patients with depression, mean NfL levels increased from baseline to follow-up (0.68 pg/ml, p = 0.03), while GFAP levels were unchanged (p = 0.24). We did not find consistent associations between NfL/GFAP with depression scores or cognitive function. ConclusionThis largest study of serum NfL/GFAP levels in patients with depression did not support previous findings of elevated GFAP/NfL in patients with depression or positive associations with depression severity. Although limited by a small control group, our study may support the presence of glial dysfunction but not damage to neurons in depression.

Predicting the fatigue in Parkinson's disease using inertial sensor gait data and clinical characteristics.

The study aimed to analyze the clinical features and gait characteristics of patients with Parkinson's disease (PD) who also suffer from fatigue and to develop a model that can help identify fatigue states in the early stages of PD. A total of 81 PD patients have been enrolled for the Parkinson's Fatigue Scale (PFS-16) assessment and divided into two groups: patients with or without fatigue. Neuropsychological assessments of the two groups, including motor and non-motor symptoms, were collected. The patient's gait characteristics were collected using a wearable inertial sensor device. PD patients who experienced fatigue had a more significant impairment of motor symptoms than those who did not, and the experience of fatigue became more pronounced as the disease progressed. Patients with fatigue had more significant mood disorders and sleep disturbances, which can lead to a poorer quality of life. PD patients with fatigue had shorter step lengths, lower velocity, and stride length and increased stride length variability. As for kinematic parameters, PD patients with fatigue had lower shank-forward swing max, trunk-max sagittal angular velocity, and lumbar-max coronal angular velocity than PD patients without fatigue. The binary logistic analysis found that Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS-I) scores, Hamilton Depression Scale (HAMD) scores, and stride length variability independently predicted fatigue in PD patients. The area under the curve (AUC) of these selected factors in the receiver operating characteristic (ROC) analysis was 0.900. Moreover, HAMD might completely mediate the association between Hamilton Anxiety Scale (HAMA) scores and fatigue (indirect effect: β = 0.032, 95% confidence interval: 0.001-0.062), with a percentage of mediation of 55.46%. Combining clinical characteristics and gait cycle parameters, including MDS-UPDRS-I scores, HAMD scores, and stride length variability, can identify PD patients with a high fatigue risk.

White matter abnormalities are associated with the declined ability of reasoning and problem-solving in major depressive disorder.

Executive function in people with depression is linked to the integrity of white matter fibers in the brain. We hypothesized that the maze tests in neuropsychological tests assessed reasoning and problem-solving abilities dependent on the integrity of brain white matter fibers, and assessed this relationship using diffusion tensor imaging (DTI) in depressed patients and healthy controls. Participants aged from 18 to 50 years were recruited from Zhumadian Second People's Hospital from July 2018 to August 2019. The sample included 33 clinically diagnosed individuals with major depressive disorder (MDD) and 24 healthy volunteers (HVs). All subjects underwent Neuropsychological assessment battery (NAB) maze tests and DTI. Tract-based spatial statistics technology in FSL software was used to process DTI data, and threshold-free cluster enhancement (TFCE) was used to perform multiple comparison corrections. The fractional anisotropy (FA) of white matter fibers in the MDD group and HVs group were compared and extracted. Pearson correlation was used to analyze the relationship between FA and NAB scores and HAMD scores. The mean NAB maze test score for the MDD group was lower than the HVs group, and the difference was statistically significant (F=11.265, p=.037). The FA value of the body of corpus callosum and cerebral peduncle right in the depression group was lower than that in the healthy control group, and the difference was statistically significant (p<.05). FA value of the body of corpus callosum was positively correlated with NAB score (r=0.400, p=.036), but not with the HAMD score (r=0.065, p=.723). The decreased ability of reasoning and problem-solving in MDD may be due to the decreased integrity of the white matter fibers of the body of the corpus callosum.

A Study of Quality of Life in Patients with Vitiligo in A Tertiary Care Centre in Marathwada Region

Introduction: Vitiligo is an acquired idiopathic skin disorder characterized by loss of inherited complexion of skin and mucosa resulting in white patches. Although there is no physical impairment, vitiligo may significantly affect quality of life and psychological well-being. Unpredictable course of vitiligo and uncertainty of treatment make patients more vulnerable to hopelessness and depression. Aim: To assess the quality of life and level of depression in patients suffering from vitiligo and its relation to various demographic and clinical parameters. Material and methods: A cross-sectional observational study, consisting 92 patients diagnosed as vitiligo, was carried out in outpatient department of Dermatology in a tertiary care centre, Aurangabad, Marathwada region. After noting demographic and clinical parameters, patients were asked to fill Vitiligo Impact Scale (VIS) and interviewed with Hamilton Depression Rating Scale (HAM-D) questionnaires. Mean VIS and HAM-D scores were compared with various demographic and clinical variables. Statistical analysis was done using SPSS20. Results: Our study revealed that younger and middle age patients suffered from more depression and had higher impact on quality of life. Women in general had greater impact on quality of life and level of depression. Education plays an important role in alleviating anxiety associated with disease. Generalized and progressive vitiligo was more distressing for patients. Conclusion: Objective scoring systems such as VIS and HAM-D should be used routinely to measure impairment of quality of life and to assess level of depression. These findings should be incorporated into therapeutic decision-making.

Aberrant brain entropy in posttraumatic stress disorder comorbid with major depressive disorder during the coronavirus disease 2019 pandemic.

Previously, neuroimaging studies on comorbid Posttraumatic-Major depression disorder (PTSD-MDD) comorbidity found abnormalities in multiple brain regions among patients. Recent neuroimaging studies have revealed dynamic nature on human brain activity during resting state, and entropy as an indicator of dynamic regularity may provide a new perspective for studying abnormalities of brain function among PTSD-MDD patients. During the COVID-19 pandemic, there has been a significant increase in the number of patients with PTSD-MDD. We have decided to conduct research on resting-state brain functional activity of patients who developed PTSD-MDD during this period using entropy. Thirty three patients with PTSD-MDD and 36 matched TCs were recruited. PTSD and depression symptoms were assessed using multiple clinical scales. All subjects underwent functional magnetic resonance imaging (fMRI) scans. And the brain entropy (BEN) maps were calculated using the BEN mapping toolbox. A two-sample t-test was used to compare the differences in the brain entropy between the PTSD-MDD comorbidity group and TC group. Furthermore, correlation analysis was conducted between the BEN changes in patients with PTSD-MDD and clinical scales. Compared to the TCs, PTSD-MDD patients had a reduced BEN in the right middle frontal orbital gyrus (R_MFOG), left putamen, and right inferior frontal gyrus, opercular part (R_IFOG). Furthermore, a higher BEN in the R_MFOG was related to higher CAPS and HAMD-24 scores in the patients with PTSD-MDD. The results showed that the R_MFOG is a potential marker for showing the symptom severity of PTSD-MDD comorbidity. Consequently, PTSD-MDD may have reduced BEN in frontal and basal ganglia regions which are related to emotional dysregulation and cognitive deficits.

A case of early‐onset familial Alzheimer’s disease caused by PSEN1 gene Y115C mutation in a Chinese pedigree

AbstractBackgroundAlzheimer’s disease is the most common cause of dementia, with approximately 0.9% associated with known genetic mutations. Presenilin 1(PSEN1) gene is one of the most common genes associated with early‐onset familial Alzheimer’s disease (EOFAD). We reported a case of EOFAD with Y115C mutation of PSEN1 gene which was the first report in China.MethodAn early‐onset Alzheimer’s patient from Beijing Tiantan Hospital, Capital Medical University and her family were enrolled as the research object. The clinical and imaging data of the proband were collected. The genomic DNA from peripheral venous blood of the proband was screened.ResultThere were 6 members with memory and working competence loss in this pedigree. The proband, whose age of onset was 42 years old, was manifested as memory loss for more than 1year. She became apathetic, lazy in housework but without abnormal mood and behavior. She was healthy in the past, denied smoking and drinking history. Her grandmother, mother, aunt, uncle and brother all showed memory loss. Her brother is now unable to complete the driver’s work. The physical examination showed poor memory, calculation, orientation, executive functions, slow reaction and poor comprehension. The MMSE score was 11, MoCA‐Beijing score was 5, ADL‐20 score was 28, HAMD score was 2, HAMA score was 1 and PSQI score was 5. Head MRI of the proband showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. The arterial spin labeling finding showed significantly reduced blood perfusion in the left cortex and hippocampus. A c.344A &gt; G (p. Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis.ConclusionWe reported this EOFAD case caused by Y115C mutation of PSEN1 gene in a Chinese family to enrich the genetic and clinical phenotypic characteristics in China. Gene detection plays an important role in the diagnosis of the early‐onset Alzheimer’s disease.

Incidence and risk factors of post-stroke cognitive impairment in convalescent elderly patients with first-episode acute ischemic stroke.

A total of 350 first-time AIS elderly patients (aged ≥60 years) were collected and analyzed. Multivariate Logistic regression analysis showed that the lesion site, frontal temporal, cerebral white matter degeneration, age ≥75 years, BMI ≥28, onset in autumn/winter, hospitalization expenses >20,000 yuan/month, high DBPV, high NIHSS score, and high HAMD score were risk factors for PSCI. Higher education level was a protective factor. In conclusion, the incidence of PSCI in elderly AIS patients was relatively high and related to the several factors, which indicated that more attention should be paid for such patients to prevent PSCI.

Multiple Complement Pathway-related Proteins Might Regulate Immunopathogenesis of Major Depressive Disorder

Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD. Plasma levels of C1q, C3, C3b/iC3b, C4, Factor B, Factor H, and properdin were assayed in 22 patients with MDD and 27 healthy controls by multiplex suspension assay. The patients with MDD were diagnosed as per DSM IV-TR. Hamilton Depression Rating Scale (HAM-D), Montgomery Depression Rating Scale and Clinical Global Improvement were used for clinical assessments of the patients. The plasma levels of these complement proteins were also correlated with various clinical scores and phenotypes of MDD. The patients with MDD and healthy controls did not differ in terms of age and gender (p > 0.1). The patients with MDD had a mean duration of illness of around 3 years, with average number of depressive episodes being 6 and the mean HAM-D score was 19. Of the seven complement components, the plasma levels of C1q, Factor B, and Factor H (p ≤ 0.05) were significantly elevated in MDD patients compared to healthy controls. However, the plasma levels of these complement proteins were not found to correlate with the clinical profile of MDD patients. Both Factor B and Factor H are crucial in the induction and regulation of the alternative pathway of complement activation. The alternative pathway also plays a critical role in inflammation. These findings suggest an important role of the alternative complement pathway in immuno-inflammation in MDD.

Down-regulated miR-16-2 in peripheral blood is positively correlated with decreased bilateral insula volume in patients with major depressive disorder

BackgroundThe downregulated microRNA-16-2-3p (miR-16-2) had been believed to be associated with major depressive disorder (MDD). This study aimed to investigate the potential of miR-16-2 as a biomarker for MDD by analysing its expression levels, furthermore, to explore the relationship between miR-16-2, clinical symptoms and alterations in grey matter volume (GMV) in MDD patients. MethodsReal-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of miR-16-2 in 48 drug-naïve patients with MDD and 50 healthy controls (HCs). We conducted ROC curve analysis to assess the diagnostic value of miR-16-2 in MDD, and evaluated its ability to predict antidepressant response by reassessing depressive and anxiety symptoms after treatment. Voxel-based morphometry was carried out to explore alterations in regional GMV that may be associated with MDD. Pearson analysis was used to explore the relationship between miR-16-2 expression, clinical symptoms, and altered GMV in the brains of MDD patients. ResultsWe found that MDD patients had significantly downregulated miR-16-2 expression, which was negatively correlated with HAMD-17 and HAMA-14 scores, and had great diagnostic value for MDD (AUC = 0.806, 95 % CI: 0.721–0.891). In addition, MDD patients had significantly lower GMV in the bilateral insula and left superior temporal gyrus (STG_L) than HCs. GMV reduction in the bilateral insula was found to be correlated with miR-16-2 expression. ConclusionsOur findings support the potential value of miRNA-16-2 as a biomarker for MDD. It also suggests that miRNA-16-2 may be associated with abnormal insula and involved in pathophysiological mechanisms of MDD.

Brain glucose metabolism on [18F]-FDG PET/CT: a dynamic biomarker predicting depression and anxiety in cancer patients.

To explore the correlation between the incidence rates of depression and anxiety and cerebral glucose metabolism in cancer patients. The experiment subjects consisted of patients with lung cancer, head and neck tumor, stomach cancer, intestinal cancer, breast cancer and healthy individuals. A total of 240 tumor patients and 39 healthy individuals were included. All subjects were evaluated by the Hamilton depression scale (HAMD) and Manifest anxiety scale (MAS), and were examined by whole body Positron Emission Tomography/Computed Tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG). Demographic, baseline clinical characteristics, brain glucose metabolic changes, emotional disorder scores and their relations were statistically analyzed. The incidence rates of depression and anxiety in patients with lung cancer were higher than those in patients with other tumors, and Standard uptake values (SUVs) and metabolic volume in bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were lower than those in patients with other tumors. We also found that poor pathological differentiation, and advanced TNM stage independently associated with depression and anxiety risk. SUVs in the bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were negatively correlated with HAMD and MAS scores. This study revealed the correlation between brain glucose metabolism and emotional disorders in cancer patients. The changes in brain glucose metabolism were expected to play a major role in emotional disorders in cancer patients as psychobiological markers. These findings indicated that functional imaging can be applied for psychological assessment of cancer patients as an innovative method.

Temporal Dynamic Alterations of Regional Homogeneity in Parkinson's Disease: A Resting-State fMRI Study.

Brain activity is time varying and dynamic, even in the resting state. However, little attention has been paid to the dynamic alterations in regional brain activity in Parkinson's disease (PD). We aimed to test for differences in dynamic regional homogeneity (dReHo) between PD patients and healthy controls (HCs) and to further investigate the pathophysiological meaning of this altered dReHo in PD. We included 57 PD patients and 31 HCs with rs-fMRI scans and neuropsychological examinations. Then, ReHo and dReHo were calculated for all subjects. We compared ReHo and dReHo between PD patients and HCs and then analyzed the associations between altered dReHo variability and clinical/neuropsychological measurements. Support vector machines (SVMs) were also used to assist in differentiating PD patients from HCs using the classification values of dReHo. The results showed that PD patients had increased ReHo in the bilateral medial temporal lobe and decreased ReHo in the right posterior cerebellar lobe, right precentral gyrus, and supplementary motor area, compared with controls. The coefficient of variation (CV) of dReHo was considerably higher in the precuneus in PD patients compared with HCs, and the CV of dReHo in the precuneus was found to be highly associated with HAMD, HAMA, and NMSQ scores. Multiple linear regression analysis controlling for demographic, clinical, and neuropsychiatric variables confirmed the association between altered dReHo and HAMD. Using the leave-one-out cross validation procedure, 98% (p < 0.001) of individuals were properly identified using the SVM classifier. These results provide new evidence for the aberrant resting-state brain activity in the precuneus of PD patients and its role in neuropsychiatric symptoms in PD.

Med Check: Zuranolone for Depression, Uzedy for Schizophrenia, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Zuranolone for Depression, Uzedy for Schizophrenia, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:25 May 2023https://doi.org/10.1176/appi.pn.2023.06.6.1Zuranolone Found to Quickly Reduce Major Depression SymptomsAdults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study published in May in The American Journal of Psychiatry (AJP) suggests. Zuranolone is an oral, once-daily neuroactive steroid that acts on GABA-A receptors.The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of major depressive disorder, had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM-D) score of at least 24 at screening and before they started taking the assigned study medication.The researchers randomized 534 participants to take either 14 days of treatment with zuranolone 50 mg/day or placebo in the evening. The researchers evaluated the participants 10 times over the course of the 42-day trial using such assessments as the HAM-D, the Columbia–Suicide Severity Rating Scale, the Clinical Global Impressions severity score, and more.Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study,” the researchers wrote.FDA Approves Uzedy for Treating SchizophreniaIn April the U.S. Food and Drug Administration (FDA) approved Uzedy (risperidone extended-release injectable suspension) for the treatment of schizophrenia in adults, Teva and MedinCell announced. Uzedy is a long-acting subcutaneous antipsychotic that may be given in one- or two-month dosing intervals.In the phase 3 RISE trial, 544 patients aged 13 to 65 years with schizophrenia were randomized to receive a subcutaneous injection of Uzedy (either once per month or once every two months) or placebo. Those who received Uzedy once per month or once every two months had a reduction of 80.0% and 62.5% in the risk to relapse compared with those who received placebo, respectively. Results were similar in the phase 3 SHINE trial, which examined the long-term safety of the drug for up to 56 weeks in 336 patients aged 13 to 65 years with schizophrenia.A companion survey of participants in the SHINE trial found that 89% of patients and 92% of health professionals rated administration of Uzedy as easy when asked how easy or difficult it was to receive or administer the medication in its current form. Further, 70% of patients reported that Uzedy provided a better injection experience than their previous long-acting injectables (LAIs).Abilify Asimtufii Approved for Schizophrenia, Bipolar I TreatmentAbilify Asimtufii (aripiprazole extended release injectable suspension) has been approved by the FDA for the treatment of schizophrenia in adults and as a monotherapy treatment of bipolar I disorder in adults, Otsuka and Lundbeck announced in April. Abilify Asimtufii is a long-acting subcutaneous atypical antipsychotic that may be given every two months.The approval was based on safety and efficacy data from trials of Abilify Maintena, which is for once monthly dosing, and on the results of a phase 1-2 study. In the phase 1-2 study, 266 adults with schizophrenia or bipolar I disorder were randomly assigned to receive either Abilify Asimtufii 960 mg every 56 days, for a total of four injections or Abilify Maintena 400 mg administered every 28 days for a total of eight injections. Treatment with Abilify Asimtufii resulted in similar aripiprazole plasma concentrations and efficacy to Abilify Maintena. ■ ISSUES NewArchived