Major Depressive Disorder Symptom Severity Research Articles

Circadian preference and sleep quality in healthy controls and psychiatric inpatients with major depressive disorder – An actigraphy study incorporating morning and evening mood assessments

ABSTRACT Major depressive disorder (MDD) is frequently accompanied by sleep disturbance. Regarding diurnal preference (chronotype), sleep problems and low mood have been associated with evening orientation. Considering diurnal preference, we investigated subjective restorative value of sleep and actigraphy sleep parameters together with mood assessments twice a day, i.e. in the morning and evening, during weekdays and weekends in MDD psychiatric inpatients and healthy controls (HCs). The restorative value of sleep was higher during the weekend in HC, and bedtimes and risetimes were delayed during the weekend compared to weekdays in HC and MDD. Morning mood affected subjective sleep ratings in both groups, while association with symptom severity (BDI) in MDD remained insignificant. In HC, better evening mood was associated with later bedtimes. Regarding the chronotype in HC, evening orientation was associated with relatively low restorative value of sleep during weekdays, and morning orientation was associated with relatively higher actigraphy sleep efficiency during weekdays compared to weekend. In MDD, an association of evening orientation with later rise times could be observed, while no chronotype dependent effect emerged regarding the restorative value of sleep or sleep efficiency. Our results emphasize that research on sleep in MDD should incorporate weekdays as well as weekends, chronotype assessment, and measures of morning and evening mood, as these can be associated with ratings of the subjective restorative value of sleep (i.e. in our study, better morning mood was associated with higher restorative values), but also with behavioral sleep parameters (i.e. in our study, more positive evening mood was associated with later bedtimes). Potentially, the restorative value of sleep in MDD evening types can be improved by maintaining a regular sleep schedule, which needs to be investigated in an experimental design.

Periodontal status and the efficacy of the first-line treatment of major depressive disorder.

ObjectivesThe efficacy of treatment of major depressive disorder (MDD) is not satisfactory. Systemic inflammation may play an important role in MDD pathogenesis and treatment outcomes. Periodontal disease is the systemic inflammatory condition. Its prevalence may be as high as 45%. We aimed to assess the association of periodontal status with the outcome of 3‐month first‐line treatment of MDD with selective serotonin reuptake inhibitors.Material and MethodsWe performed the prospective cohort study during 2018/2019 at Psychiatric Hospital “Sveti Ivan,” Croatia, on a consecutive sample of 43 patients. The outcome was the MDD symptoms severity measured using the Hamilton Depression Rating Scale‐17. The periodontal status was indicated by the clinical attachment loss (CAL).ResultsBaseline periodontal status had a nonlinear significant and clinically relevant association with the MDD treatment outcome (R 2 change of the quadratic term = 0.12; p = 0.027). In patients with good baseline periodontal status the severity of MDD symptoms was significantly improved. When the value of CAL was ≥4.44 mm, indicating the worse periodontal status, further increase in baseline CAL was associated with the worsening of MDD treatment outcomes independently of the baseline depression severity and 14 sociodemographic and clinical predictors of treatment outcome.ConclusionsPeriodontal healthcare is accessible, and should be utilize in an integrative, multidisciplinary approach not only for the sake of psychiatric patients' quality of life and prevention of periodontal disease, but for the sake of the outcomes of psychiatric treatment as well.

Fatmisia and Clinical Counseling Decision-Making in Master’s-Level Counselor Trainees

The Centers for Disease Control and Prevention and the World Health Organization have documented an increase in fat people in recent decades, which is being met with a backlash of anti-fat biases, or fatmisia. Fatmisia is prevalent in most aspects of society, especially among fat people who have internalized fatmisia. Utilizing a diagnostic questionnaire in combination with the Fat Phobia Scale–Short Form and the Weight Bias Internalization Scale, this study explored the relationship between client body size, the presence of a major depressive disorder (MDD) diagnosis, and if applicable, the severity of MDD symptoms assigned by counselor trainees (N = 113). Results were analyzed using one-way analysis of variance and covariance. This sample (N = 113) significantly differed in diagnoses assigned to obese clients by assigning more severe MDD. Study limitations and implications are discussed.

Uncovering microglial pathways driving sex-specific neurobiological effects in stress and depression

Women suffer from major depressive disorder (MDD) more often than men and report greater MDD symptom severity. Mounting evidence suggests that sex differences in MDD may be driven, in part, by sex-specific neurobiological mechanisms. Chronic stress is a significant risk factor in MDD, and preclinical rodent models show differential patterns of stress-induced neural remodeling and cognitive-behavioral dysfunction in males and females. For instance, chronic stress leads to synapse loss in the medial prefrontal cortex in male rodents yet has either no effect on- or increases-synapse number in females. Recent reports have implicated microglia, the immune cells of the brain, in MDD, and findings demonstrate sex-specific microglial signatures in both preclinical stress models and MDD patients. Given that microglia can remodel neural architecture, modulate synaptic transmission, and affect subsequent changes in behavior, it is plausible that microglial pathways contribute to differential stress effects on neuroplasticity and function in males and females. As such, this review examines the evidence for sex-specific microglia-neuron interactions in preclinical stress models and in patients with MDD. Discoveries highlighted herein demonstrate divergent microglial contributions in males and females and suggest that future studies investigating stress-linked disorders should be guided by sex-dependent neurobiological and behavioral findings. Examining these pathways represents a clear avenue toward both a richer understanding of brain, behavior, and immunity, and innovative psychoneuroimmunology-based applications in personalized medicine.

Plasma androgens and the presence and course of depression in a large cohort of men

BackgroundHypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms. MethodsIn 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography–tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years. ResultsNone of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms. ConclusionsThese results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.

Evaluation of depression and anxiety control in greek patients with major depressive disorder with/without generalized anxiety disorder and cardiovascular disease–pronoi study

IntroductionPatients with depression are likely to eventually develop Cardiovascular disease(CVD) and have a higher mortality rate than general population. In addition, anxiety disorders, especially Generalized Anxiety Disorder (GAD), may be associated with mortality and other adverse cardiac outcomes.ObjectivesEvaluation of depression and anxiety control in Greek patients with Major Depressive Disorder (MDD) with/without GAD and CVD, under 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin.Methods565 patients with MDD with/without GAD, enrolled in this observational, study (NCT03317262). The subgroup of 133(24%) patients had CVD. Severity of MDD and GAD symptoms was evaluated using the HAM-D and HAM-A Scores at baseline (V1) and after 6 months (V3) respectively.ResultsMean HAM-D score in patients with CVD without GAD, at V1 and V3 was 23.94±7.51 and 8.14±4.65 respectively (p<0.0001). Similar results were observed in patients without CVD without GAD (HAM-D score 26.67±8.79 at V1 and 7.44±4.40 at V3). Mean HAM-A score in patients with CVD and GAD at V1 and V3 was 25.64±6.38 and 8.98±3.93, respectively (p<0.0001). Same magnitude reduction in HAM-A score was observed in patients without CVD and GAD, 26.27±8.16 at V1 and 9.28±6.48 at V3 (p<0.0001). Patients’ depression symptoms with/without CVD and GAD showed also a significant reduction between V1 and V3.ConclusionsMDD patients with CVD without GAD, had a marginally lower baseline HAM-D score versus patients with GAD. After 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin the improvement of depressive and anxiety symptoms was almost equal between MDD patients with/without GAD regardless of the presence of coexisting CVD.DisclosureEmployee of ELPEN Pharmaceutical Co. Inc.

Selective Serotonin Reuptake Inhibitor Pharmaco-Omics: Mechanisms and Prediction.

Selective serotonin reuptake inhibitors (SSRIs) are a standard of care for the pharmacotherapy of patients suffering from Major Depressive Disorder (MDD). However, only one-half to two-thirds of MDD patients respond to SSRI therapy. Recently, a “multiple omics” research strategy was applied to identify genetic differences between patients who did and did not respond to SSRI therapy. As a first step, plasma metabolites were assayed using samples from the 803 patients in the PGRN-AMPS SSRI MDD trial. The metabolomics data were then used to “inform” genomics by performing a genome-wide association study (GWAS) for plasma concentrations of the metabolite most highly associated with clinical response, serotonin (5-HT). Two genome-wide or near genome-wide significant single nucleotide polymorphism (SNP) signals were identified, one that mapped near the TSPAN5 gene and another across the ERICH3 gene, both genes that are highly expressed in the brain. Knocking down TSPAN5 and ERICH3 resulted in decreased 5-HT concentrations in neuroblastoma cell culture media and decreased expression of enzymes involved in 5-HT biosynthesis and metabolism. Functional genomic studies demonstrated that ERICH3 was involved in clathrin-mediated vesicle formation and TSPAN5 was an ethanol-responsive gene that may be a marker for response to acamprosate pharmacotherapy of alcohol use disorder (AUD), a neuropsychiatric disorder highly co-morbid with MDD. In parallel studies, kynurenine was the plasma metabolite most highly associated with MDD symptom severity and application of a metabolomics-informed pharmacogenomics approach identified DEFB1 and AHR as genes associated with variation in plasma kynurenine levels. Both genes also contributed to kynurenine-related inflammatory pathways. Finally, a multiply replicated predictive algorithm for SSRI clinical response with a balanced predictive accuracy of 76% (compared with 56% for clinical data alone) was developed by including the SNPs in TSPAN5, ERICH3, DEFB1 and AHR. In summary, application of a multiple omics research strategy that used metabolomics to inform genomics, followed by functional genomic studies, identified novel genes that influenced monoamine biology and made it possible to develop a predictive algorithm for SSRI clinical outcomes in MDD. A similar pharmaco-omic research strategy might be broadly applicable for the study of other neuropsychiatric diseases and their drug therapy.

Balance Problems, Paralysis, and Angina as Clinical Markers for Severity in Major Depression.

Major depressive disorder (MDD) is a heterogeneous disorder. Our hypothesis is that neurological symptoms correlate with the severity of MDD symptoms. One hundred eighty-four outpatients with MDD completed a self-report questionnaire on past and present medical history. Patients were divided into three roughly equal depression severity levels based on scores from the APA Severity Measure for Depression—Adult (n = 66, 58, 60, for low, medium, high severity, respectively). We saw a significant and gradual increase in the frequency of “muscular paralysis” (1.5–5.2–16.7%) and “balance problems” (21.2–36.2–46.6%) from low to medium to high severity groups. We repeated the analysis using only the two most extreme severity categories: low severity (66 samples) vs. high severity (60 samples). High severity patients were also found to experience more “angina” symptoms than low severity patients (27.3 vs. 50%). The three significant clinical variables identified were introduced into a binary logistic regression model as the independent variables with high or low severity as the dependent variable. Both “muscular paralysis” and “balance problems” were significantly associated with increased severity of depression (odds ratio of 13.5 and 2.9, respectively), while “angina” was associated with an increase in severity with an odds ratio of 2.0, albeit not significantly. We show that neurological exam or clinical history could be useful biomarkers for depression severity. Our findings, if replicated, could lead to a simple clinical scale administered regularly for monitoring patients with MDD.

The association between alexithymia and two dimensions of major depressive disorder: cognitive and somatic-affective

Aim: To explore the association between alexithymia and two dimensions of major depressive disorder (MDD): cognitive and somatic-affective. Patients and methods. Unicentric, cross-sectional study included consecutive sample of 63 patients at the Department of Psychiatry (DoP), Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia. Target population included outpatients with diagnosed MDD (F32 and F33, according to ICD-10). Inclusion criteria were: confirmed MDD diagnosis, age between 18 and 65 years, both genders, outpatient treatment at the DoP. The main outcome was the association between alexithymia, measured by total score on 20-item Toronto-Alexithymia scale (TAS-20), with two dimensions of MDD, cognitive and somatic-affective, measured by Beck Depression Inventory-II (BDI-II). Results: Both dimensions of BDI-II and the total severity of MDD symptoms were statistically significantly, although low, associated with alexithymia, and the differences between these two correlations were not (statistically) significant. However, in the multivariable model, the cognitive dimension (b = 0.64; β = 0.48; p = 0.002; statistically significant at the false discovery rate of 0.05) was primarily associated with alexithymia, and the somatic-affective was not, after all cognitive aspects were controlled for (b = -0.19; β = 0-0.14; p = 0.491; not statistically significant, with the false discovery rate of 0.05). Conclusion: Alexithymia is primarily associated with a pure cognitive dimension of MDD after somatic-affective elements are excluded. Somatic-affective dimension of MDD is not associated with alexithymia after the cognitive elements were controlled for. Both dimensions, as well as the overall severity of MDD, are associated with alexithymia, but this association is relatively low.

Efficacy of Depression Management in an Integrated Psychiatric-Diabetes Education Clinic for Comorbid Depression and Diabetes Mellitus Types 1 and 2

ObjectivesPatients with type 1 and type 2 diabetes mellitus (DM) are 2 times as predisposed to developing mood disorders, such as major depressive disorder (MDD), compared with patients without diabetes. Management of comorbid MDD and DM remains a challenge because patients often suffer from poor medication compliance, lifestyle factors and refractory depression. Integration of psychiatric care into diabetes education clinics (DECs) has been suggested as an effective method of managing the comorbid conditions. As this strategy is being implemented into clinical care, its effectiveness in practice warrants further research. MethodsA retrospective chart review of 24 patients (10 men and 14 women) followed by an integrated psychiatry-DEC in Newmarket, Ontario, Canada, between April 2016 and July 2019 was performed. Depressive symptom severity at each appointment was assessed with the Patient Health Questionnaire-9 (PHQ-9) depression rating scale. ResultsThere was no significant change in PHQ-9 depression rating scale scoring between the first and most recent appointments (paired t test, p=0.356); however, patients who had improved PHQ-9 scoring were more likely to have more clinic visits (analysis of variance, p=0.0271). A significant negative correlation was found between both number of visits (Pearson coefficient, −0.56; p=0.005) and overall time the patients were followed by DEC (Pearson coefficient, −0.42; p=0.040) and PHQ-9 score changes between the first and most recent appointments. PHQ-9 change between individual appointments also displayed a positive correlation with time between appointments (Pearson coefficient, 0.26; p=0.027). ConclusionsRegular follow up in a psychiatry-DEC service might be beneficial in managing MDD symptom severity for comorbid MDD and DM.

PMH51 WHAT ARE THE ATTRIBUTES THAT PSYCHIATRISTS CONSIDER IN THE DECISION TO DISCHARGE ADULTS WITH MAJOR DEPRESSIVE DISORDER WHO HAVE BEEN HOSPITALIZED WITH ACTIVE SUICIDAL IDEATION WITH INTENT?

To ascertain the relative importance of various attributes that US-based psychiatrists consider when deciding to discharge adults hospitalized with major depressive disorder and active suicidal ideation with intent (MDSI). A choice-based conjoint (CBC) analysis was conducted via online survey among psychiatrists actively managing patients with MDSI. Potential attributes and levels within each attribute were identified through literature review with expert consultation and validated through qualitative interviews with 10 US-based psychiatrists. In the final CBC analysis, psychiatrists assessed which of three patients in hypothetical scenarios (in which levels for each attribute varied across patients) were most appropriate for discharge. A hierarchical Bayesian multinomial-logit analysis using a Markov Chain Monte Carlo algorithm was used to calculate model parameters (utilities). Ranges of utilities were used to determine the relative importance of attributes (scaled to sum to 100). 100 psychiatrists completed the survey; 48% were affiliated with a teaching/university hospital, and participants reported a mean of 14.5 years (standard deviation: 8.5) in practice. The relative importance of attributes considered in determining appropriateness for discharge were (from most to least important): current major depressive disorder (MDD) severity (24.8 [95% confidence interval: 23.3, 26.3]); clinician assessment of current suicidal ideation (SI) (20.8 [18.5, 23.0]); previous history of suicide attempts (16.7 [15.9, 17.6]); psychosocial support at discharge (13.0 [11.7, 14.4]); post-discharge outpatient follow-up plan (immediacy and frequency of visits) (9.8 [8.8, 10.8]); current length of hospital stay (9.2 [8.1, 10.3]); and clinician assessment of SI at admission (5.7 [4.8, 6.6]). Current level of symptoms of MDD, including overall depression severity and SI, were the most important attributes that psychiatrists reported considering when discharging patients hospitalized with MDSI. Further research should be conducted to determine whether treatment approaches targeting modifiable attributes (e.g. MDD symptom severity and SI) could reduce length of stay for these patients.

Structural MRI at 7T reveals amygdala nuclei and hippocampal subfield volumetric association with Major Depressive Disorder symptom severity

Subcortical volumetric changes in major depressive disorder (MDD) have been purported to underlie depressive symptomology, however, the evidence to date remains inconsistent. Here, we investigated limbic volumes in MDD, utilizing high-resolution structural images to allow segmentation of the hippocampus and amygdala into their constituent substructures. Twenty-four MDD patients and twenty matched controls underwent structural MRI at 7T field strength. All participants completed the Montgomery-Asberg Depression Rating Scale (MADRS) to quantify depressive symptomology. For the MDD group, volumes of the amygdala right lateral nucleus (p = 0.05, r2 = 0.24), left cortical nucleus (p = 0.032, r2 = 0.35), left accessory basal nucleus (p = 0.04, r2 = 0.28) and bilateral corticoamygdaloid transition area (right hemisphere p = 0.032, r2 = 0.38, left hemisphere p = 0.032, r2 = 0.35) each displayed significant negative associations with MDD severity. The bilateral centrocortical (right hemisphere p = 0.032, r2 = 0.31, left hemisphere p = 0.032, r2 = 0.32) and right basolateral complexes (p = 0.05, r2 = 0.24) also displayed significant negative relationships with depressive symptoms. Using high-field strength MRI, we report the novel finding that MDD severity is consistently negatively associated with amygdala nuclei, linking volumetric reductions with worsening depressive symptoms.

Cortisol, oxytocin, and quality of life in major depressive disorder.

Quality of life (QoL) is greatly impaired in major depressive disorder (MDD). These impairments are not fully accounted for by symptom severity, may persist beyond depressive episodes, and are a risk factor for poor outcomes. MDD is often associated with prominent neuroendocrine changes and increased risk of chronic disease. However, there is a lack of research examining whether biological factors are related to QoL in MDD. This research examined relationships between cortisol, oxytocin, symptom severity, and QoL in MDD. Sixty adults meeting DSM-5 criteria for MDD and 60 healthy controls provided morning plasma samples which were analysed for cortisol and oxytocin levels, and completed measures of QoL and psychopathology. Participants with MDD had lower QoL than controls. Cortisol correlated negatively with overall QoL and all QoL domains. Oxytocin correlated positively with overall QoL, and Psychological and Social-Relationships domains. Additionally, cortisol levels were inversely related to psychological QoL, and oxytocin was positively related to social QoL, after controlling for symptom severity and demographic variables. This study provides novel evidence linking neuroendocrine pathways to particular domains of QoL in MDD. The results indicate that activity of the hypothalamic-pituitary-adrenal axis is linked to poor psychological QoL, and that oxytocin is important to social QoL, independently of severity of psychopathology. Biopsychosocial approaches to QoL associated with mental health conditions may lead to greater understanding of the underlying mechanisms and to improved, tailored interventions.

Hormonal Dynamics Effect of Serum Insulin-Like Growth Factor I and Cortisol/Dehydroepiandrosterone Sulfate Ratio on Symptom Severity of Major Depressive Disorder.

Insulin-like growth factor I (IGF-I) is a neurotrophic factor produced by the hypothalamic-pituitary-somatotropic axis and is considered a potential contributor to the pathology of major depressive disorder (MDD). Although it is known that the hypothalamic-pituitary-adrenal axis and cortisol are involved in the pathology of MDD, the association with dehydroepiandrosterone sulfate (DHEAS) remains unclear. The current study sought to clarify the relationship between these hormones and the pathology of MDD. Subjects were 91 Japanese patients with a diagnosis of MDD. Serum IGF-I, cortisol, and DHEAS were measured. Samples were taken before breakfast after overnight fasting. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). Subjects included 59 men and 32 women with an average age of 44.1 ± 13.1 years (mean ± SD). The blood IGF-I level was 152.0 ± 50.0 ng/mL, the cortisol level was 10.1 ± 4.6, and the DHEAS level was 201.3 ± 112.7 μg/dL. The mean HAM-D score was 13.9 ± 9.0. Serum IGF-I levels were not correlated with cortisol. Higher IGF-I, cortisol, and cortisol/DHEAS ratios were associated with higher HAM-D scores (adjusted R = 0.240, P < 0.001), and higher IGF-I and cortisol were associated with higher melancholic or suicide subscores (adjusted R = 0.200, P < 0.001; adjusted R = 0.273, P < 0.001). Our findings suggest that hormonal dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-somatotropic axes may be related to the symptom severity of MDD, melancholia, and suicide-related factors.

Differences in Perceptions of Major Depressive Disorder Symptoms and Treatment Priorities Between Patients and Health Care Providers Across the Acute, Post-Acute, and Remission Phases of Depression

Limited data exist on concordance between patients’ and health care providers’ (HCPs) perceptions regarding symptoms of major depressive disorder (MDD) and treatment priorities, particularly across disease phases. This study examined concordance during the acute, post-acute, and remission phases of MDD. In an online survey, 2,008 patients responded based on their experience with MDD, and 1,046 HCPs responded based on their clinical experience treating patients with MDD. Questions included symptom frequency and severity, treatment priorities, and impact on psychosocial functioning. Patients reported more frequently mood, physical, and cognitive symptoms than HCPs in the post-acute and remission phases and greater impact on psychosocial functioning. Patients reported that all these symptoms require high treatment priority across the phases of MDD, generally to a greater extent than HCPs. Patients also gave high emphasis to addressing impairment in psychosocial functioning early in the treatment course. A substantial difference in the effectiveness of treating symptoms of MDD between patients and HCPs was observed. This is the first study to quantify, broadly, differences in perceptions of MDD symptom prevalence, severity, and treatment priorities across MDD phases, and the study findings highlight a need for improved communication between patients and HCPs about symptoms, their impact on psychosocial functioning, and treatment priorities across phases.

Patient Perspective of Cognitive Symptoms in Major Depressive Disorder: Retrospective Database and Prospective Survey Analyses.

BackgroundMajor depressive disorder (MDD) is a common and burdensome condition. The clinical understanding of MDD is shaped by current research, which lacks insight into the patient perspective.ObjectiveThis two-part study aimed to generate data from PatientsLikeMe, an online patient network, on the perception of cognitive symptoms and their prioritization in MDD.MethodsA retrospective data analysis (study 1) was used to analyze data from the PatientsLikeMe community with self-reported MDD. Information on patient demographics, comorbidities, self-rated severity of MDD, treatment effectiveness, and specific symptoms of MDD was analyzed. A prospective electronic survey (study 2) was emailed to longstanding and recently active members of the PatientsLikeMe MDD community. Study 1 analysis informed the objectives of the study 2 survey, which were to determine symptom perception and prioritization, cognitive symptoms of MDD, residual symptoms, and medication effectiveness.ResultsIn study 1 (N=17,166), cognitive symptoms were frequently reported, including “severe” difficulty in concentrating (28%). Difficulty in concentrating was reported even among patients with no/mild depression (80%) and those who considered their treatment successful (17%). In study 2 (N=2525), 23% (118/508) of patients cited cognitive symptoms as a treatment priority. Cognitive symptoms correlated with depression severity, including difficulty in making decisions, concentrating, and thinking clearly (rs=0.32, 0.36, and 0.34, respectively). Cognitive symptoms interfered with meaningful relationships and daily life tasks and had a profound impact on patients’ ability to work and recover from depression.ConclusionsPatients acknowledge that cognitive dysfunction in MDD limits their ability to recover fully and return to a normal level of social and occupational functioning. Further clinical understanding and characterization of MDD for symptom prioritization and relapse risk due to residual cognitive impairment are required to help patients return to normal cognitive function and aid their overall recovery.

Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-Coil in treatment of major depressive disorder; A randomized clinical trial

Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment option for major depressive disorder (MDD). However, comparisons of efficacy between the two FDA-approved protocols of rTMS modalities are lacking. The aim of this industry-independent, randomized-controlled, single-blind trial was to evaluate clinical outcome of the two FDA-approved rTMS protocols delivered by H1-coil and the figure-8-coil, in MDD patients. A total of 228 MDD patients were randomized to 20 sessions of H1-coil or 8-coil as an adjunct to standard-of-care pharmacotherapy, or standard-of-care pharmacotherapy alone. Baseline MDD symptom severity was almost the same in the three groups. Hamilton depression rating scale (HAM-D17) mean score was 17 (5.3) in H1-coil, 17 (5.4) in 8-coil, and 19 (6.1) in control group. The primary outcome was the proportion of patients achieving remission defined as HAM-D17 score ≤7 at end-of-treatment at week-4. In the intention-to-treat analysis odds ratio for remission was 1.74 (CI95% 0.79–3.83) in H1-coil compared to the 8-coil group. The difference between two rTMS protocols was not significant. Remission rate was significantly greater in both HF-rTMS groups compared to the control: 60% (CI95% 48–71%), 43% (CI95% 31–55%) and 11% (CI95% 5–20%) respectively. The response was significantly better in H1-coil, than in 8-coil group OR = 2.33; CI95% 1.04–5.21 (P = 0.040). The HAM-D17 was lowered by 59% in the H1-coil, 41% in the 8-coil (P = 0.048), and 17% in the control group (P < 0.001 vs H1-coil; P = 0.003 vs 8-coil). Safety, tolerability, and the changes in quality of life were comparable. We confirmed the safety and efficacy of both FDA-approved protocols as adjunctive treatments of MDD. Better response rate and greater reduction of depression severity were observed in the H1-coil group, but without a significant difference in the remission rate between the two rTMS modalities. Clinical trials registrationClinicaltrials.govNCT02917499

Disagreement and factors between symptom on self-report and clinician rating of major depressive disorder: A report of a national survey in China

BackgroundMeasurement-based care (MBC) is a popular strategy of clinical management for patients with major depressive disorder (MDD). The consistency of self-report and clinical measurements is of importance, but whether individual symptom severity is in agreement for both self-report and clinician rating in MDD has not been comprehensively tested. This study aimed to test whether individual symptom severity of MDD was in agreement between self-report and clinician rating, and to explore factors affecting the agreement. MethodsIn the National Survey on Symptomatology of Depression (NSSD) of China, 3275 patients with a major depressive episode were evaluated by both self-report and a clinician-rated version of 62 questions. ResultsOn average, 59% of all patients reached absolute agreement with their research clinicians. Among all questions, 73% returned with moderate positive strength of correlation, followed by 27% with low positive correlation. In 77% of the total questions, there was a tendency to rate higher in the self-report version compared with the clinician-rated version. After classifying the symptoms by six major domains, it was found that patients and clinicians showed more consistent answers in history and somatic questions (81% and 65% reached agreement), and that there were more differences in mood, energy, and anxiety questions (up to 56% in full agreement). “Outpatient”, “high financial status”, “poor working condition”, and “high education level” were found to be significant positive predictors for patients rating higher than clinicians or patients and clinicians reaching agreement as opposed to clinicians rating higher than patients. LimitationsThe cross-sectional nature of our study undermines the interpretation of the results across the MDD treatment course. ConclusionsIt is sufficient to use the self-report version of a questionnaire to screen, monitor, and detect remission for MDD symptoms. Complete assessment of depression severity should take both clinician-rated scales and self-reported measures into consideration. Factors other than source of admission, financial status, working condition, and education level should be further investigated for the discrepancy between self-report and clinician rating.

Positive Affect as a Buffer between Chronic Stress and Symptom Severity of Emotional Disorders.

Research has demonstrated that stressors play a critical role in the development of generalized anxiety disorder (GAD), social anxiety disorder (SAD), and major depressive disorder (MDD). Separately, deficits in positive affect (PA) have been identified in GAD, SAD, and MDD. While previous research has linked the buffering effects of PA in chronic illness, such effects have yet to be investigated for chronic stressors and emotional disorder-related symptom severity. The purpose of the present study was to examine PA as a moderator of chronic interpersonal and non-interpersonal stress on GAD, SAD, and MDD symptom severity. Using a multilevel statistical approach with a sample of adolescents and young adults (N=463), PA was found to significantly moderate the relationship between chronic interpersonal stress and symptom severity for MDD and SAD. Findings suggest that in times of chronic interpersonal stress, higher PA may serve as a buffer from development of SAD and MDD symptoms.

The associations of TAC1 gene polymorphisms with major depressive disorder

Substance P, which is encoded by tachykinin precursor 1 gene (TAC1), has been implicated in the regulation of stress responses and the pathogenesis of major depressive disorder (MDD). We evaluated the association of 10 SNPs on TAC1 with MDD susceptibility in 111 patients with MDD and 79 control subjects, and with 17-item Hamilton depression rating scale (HAMD17) score in MDD patients. In all subjects, haplotype (ht) 2 homozygous individuals showed higher plasma substance P levels than subjects carrying one or no copy of ht2. The minor allele frequency of rs1397202 was higher in patients with MDD than that in control subjects. Patients homozygous for the minor allele of rs1397202 showed significantly lower HAMD17 scores than patients carrying the common allele. Our results suggest a possible involvement of genetic variants of TAC1 with the plasma level of substance P and symptom severity of MDD.