Profile Of Major Depressive Disorder Research Articles

0972 Rest-activity Rhythm Profiles in Major Depressive Disorder: A Cluster Analysis in Chinese Population

0972 Rest-activity Rhythm Profiles in Major Depressive Disorder: A Cluster Analysis in Chinese Population

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

Inflammatory signature of post-COVID-19 depression

IntroductionPersisting and disabling depressive symptomatology represent a prominent feature of the post-acute COVID-19 syndrome. Sars-CoV-2-induced immune system dysregulation mainly result in a cytokine storm. Once in the brain, inflammatory mediators negatively affect neurotransmission, microglia activation, and oxidative stress, possibly disrupting critical brain neurocircuits which underpin depressive symptoms. So far, only inflammatory markers based on leukocyte counts have been linked to depressive outcome in COVID survivors. However, an accurate immune profile of post-COVID depression has yet to be elucidated.ObjectivesIdentify inflammatory mediators that predict post-COVID depression among a panel of cytokines, chemokines, and growth factors, with a machine learning routine.Methods88 COVID age- and sex-matched survivors’ (age 52.01 ± 9.32) were screened for depressive symptomatology one month after the virus clearance through the Beck Depression Inventory (BDI-13), with 12.5% of the individuals scoring in the clinical range (BDI-13 ≥ 9). Immune assay was performed through Luminex system on blood sampling obtained in the same context. We entered 42 analytes into an elastic net penalized regression model predicting presence of clinical depression, applied within a 5-fold nested cross-validation machine learning routine running in MATLAB. Significance of predictors was evaluated according to variable inclusion probability (VIP), as returned by 5000 bootstraps. Socio-demographics, previous psychiatric history, hospitalization, time after discharge were used as covariates.ResultsThe model reached a balance accuracy of 73% and AUC of 77%, correctly identifying 73% of people suffering from clinically relevant depressive symptoms (Figure1). Depressive symptomatology was predicted by high levels of CCL17, ICAM-1, MIF, whereas CXCL13, CXCL12, CXCL10, CXCL5, CXCL2, CCL23, CCL15, CCL8, GM-CSF showed a protective effect (Figure2).Image:Image 2:ConclusionsThis is the first study highlighting a putative inflammatory signature of post-COVID depression. Consistently to the immune profile of Major Depressive disorder, upregulation of innate immunity mediators seems to foster depressive symptoms in the aftermath of COVID. Interestingly, recruiters of B and T cells promoting a physiological adaptive response to viral infection also mitigate its psychiatric sequelae. Understanding the biological basis of post-COVID depression could pave the way for personalized treatments capable of reducing its add-on burden.Disclosure of InterestNone Declared

Cognitive Impairment and Neurocognitive Profiles in Major Depression-A Clinical Perspective.

Increasingly, studies have investigated cognitive functioning from the perspective of acute state- to remitted phases of Major Depressive Disorder (MDD). Some cognitive deficits observed in the symptomatic phase persist in remission as traits or scars. The etiological origin and clinical consequences of the neurocognitive profiles reported in the literature are still unclear and may vary across populations. Deficits are suspected to influence the association between MDD and neurodegenerative disorders and could thus be of particular clinical consequence. The aim of this review is to describe the clinical neuropsychological profile in MDD and how it is related to research during the past decade on cognitive deficits in MDD from a state, trait, and scar perspective. This review, with a clinical perspective, investigates research from the past decade regarding cognitive functioning in MDD in a long-term perspective. We focus on the clinical manifestation of deficits, and the potential neurodegenerative consequences of the neurocognitive profile in MDD. Searches in Medline, PsycINFO and Embase were conducted targeting articles published between 2010 and 2020. Examination of the evidence for long-lasting neurocognitive deficits in major depression within the cognitive domains of Memory, Executive Functions, Attention, and Processing Speed was conducted and was interpreted in the context of the State, Scar and Trait hypotheses. Defining the neurocognitive profiles in MDD will have consequences for personalized evaluation and treatment of residual cognitive symptoms, and etiological understanding of mood disorders, and treatments could potentially reduce or delay the development of neurodegenerative disorders.

Cortisol in relation to problematic eating behaviours, adiposity and symptom profiles in Major Depressive Disorder

AimsMajor Depressive Disorder (MDD) is associated with an increased risk of chronic disease related to weight gain, problematic eating behaviours and neuroendocrine changes. MDD is frequently associated with altered hypothalamic-pituitary-adrenal axis activity and cortisol secretion, where cortisol has been implicated in regulating energy balance, food intake and depressogenic weight changes. However, little research has examined the relationships between cortisol, adiposity and depressogenic problematic eating behaviours. MethodPlasma cortisol concentrations were compared between 37 participants with MDD reporting appetite/weight loss, 43 participants with MDD reporting appetite/weight gain, and 60 healthy controls, by sex. Associations between cortisol, indices of adiposity and problematic eating behaviours were then assessed after accounting for demographic variables and depressive symptoms. Depressive symptoms were assessed using the Depression subscale of the Depression, Anxiety and Stress Scale, and eating behaviours with the Dutch Eating Behaviours Questionnaire and Yale Food Addiction Scale. ResultsParticipants with MDD reporting appetite/weight loss had higher cortisol compared to controls, and marginally higher cortisol than those with MDD reporting appetite/weight gain. Cortisol negatively and significantly accounted for unique variance in body mass index and waist circumference after accounting for variance associated with age, sex and depressive symptoms, however it was not a significant predictor of problematic eating behaviours, such as emotional eating or food addiction. Cortisol concentrations did not differ between sexes. ConclusionThe results indicate that cortisol is related to lower indices of adiposity and depressogenic symptoms of appetite/weight loss but is not related to problematic eating behaviours and appetite increases in MDD. These findings provide further evidence that the melancholic and atypical subtypes of MDD are associated with differential neuroendocrine and anthropometric indices, as well as behavioural and symptom profiles. Further research investigating the temporal nature of the identified relationships may assist in facilitating the development of improved interventions for individuals affected by weight changes in MDD.

Machine learning and bioinformatic analysis of brain and blood mRNA profiles in major depressive disorder: A case-control study.

This study analyzed gene expression messenger RNA data, from cases with major depressive disorder (MDD) and controls, using supervised machine learning (ML). We built on the methodology of prior studies to obtain more generalizable/reproducible results. First, we obtained a classifier trained on gene expression data from the dorsolateral prefrontal cortex of post-mortem MDD cases (n = 126) and controls (n = 103). An average area-under-the-receiver-operating-characteristics-curve (AUC) from 10-fold cross-validation of 0.72 was noted, compared to an average AUC of 0.55 for a baseline classifier (p = .0048). The classifier achieved an AUC of 0.76 on a previously unused testing-set. We also performed external validation using DLPFC gene expression values from an independent cohort of matched MDD cases (n = 29) and controls (n = 29), obtained from Affymetrix microarray (vs. Illumina microarray for the original cohort) (AUC: 0.62). We highlighted gene sets differentially expressed in MDD that were enriched for genes identified by the ML algorithm. Next, we assessed the ML classification performance in blood-based microarray gene expression data from MDD cases (n = 1,581) and controls (n = 369). We observed a mean AUC of 0.64 on 10-fold cross-validation, which was significantly above baseline (p = .0020). Similar performance was observed on the testing-set (AUC: 0.61). Finally, we analyzed the classification performance in covariates subgroups. We identified an interesting interaction between smoking and recall performance in MDD case prediction (58% accurate predictions in cases who are smokers vs. 43% accurate predictions in cases who are non-smokers). Overall, our results suggest that ML in combination with gene expression data and covariates could further our understanding of the pathophysiology in MDD.

Hot and cold cognitive disturbances in antidepressant-free patients with major depressive disorder: a NeuroPharm study.

Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals. We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time. The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity. We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.

Cognitive profiles in major depressive disorder: Comparing remitters and non-remitters to rTMS treatment

Major Depressive Disorder (MDD) is typically accompanied by cognitive impairment. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment for MDD involves stimulation of the dorsolateral prefrontal cortex which plays an important role in cognition. This study aimed to identify differences in cognitive profiles between remitters and non-remitters to rTMS at baseline and across treatment. 25 patients with MDD performed cognitive tasks at baseline and after 6, 12 and 30 sessions of rTMS. At baseline, there was no difference in simple reaction time (RT) between groups, but remitters (n = 13) showed faster RTs than non-remitters (n = 12) in the Switch and No-Switch conditions of Task Switching. Across sessions, remitters showed a decrease in 3-Back omission errors and RTs to 3-Back, Stroop's Congruent and Incongruent, and Task Switching's Switch and No-Switch conditions, whereas non-remitters only showed improvements in Stroop Congruent and Incongruent RTs. Baseline and final scores on the Hamilton Depression Rating Scale were positively correlated with Switch and No-Switch RTs. This study demonstrates that eventual remitters to rTMS treatment for MDD perform better in cognitive tasks requiring shifting attention, and this difference is observable prior to the start of treatment. Remitters also show improvement in both their mood and cognitive performance.

F107. Cortical Thickness Features Differentiate 16-Week Antidepressant Response Profiles in Major Depressive Disorder

F107. Cortical Thickness Features Differentiate 16-Week Antidepressant Response Profiles in Major Depressive Disorder

Cognitive profiles in major depressive disorder: Comparing remitters and non-remitters to rTMS treatment

Background: Major Depressive Disorder (MDD) is typically accompanied by cognitive impairment. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment for MDD involves the stimulation of the dorsolateral prefrontal cortex, an area of the brain known to play an important role in working memory and cognitive control.

Differences in the Clinical Profile of Adolescents and Young Adults with Major Depressive Disorder Across Parental History Groups

An important causal factor of depression is family history ¾ there is compelling evidence that Major Depressive Disorder (MDD) is familial. Although the connection between a maternal history of depression and offspring risk is well established, paternal history has been largely ignored in research thus far. The first goal of this study is to examine differences in the clinical profile of MDD across parental depression history groups (i.e., both-parent history versus maternal history only versus paternal history only versus no parental history). Based on previous findings, I predict that the severity of the clinical course of MDD (as operationalized by a higher severity of depression and anxiety symptoms, an increased likelihood of recurrence, and a greater likelihood of a comorbid anxiety disorder) will be highest for offspring with a both-parent history of depression, followed by those with a maternal history only, followed by individuals with a paternal history only, and lastly by offspring with no parental history of depression. The second goal is to determine if the group differences hypothesized above are further moderated by offspring sex. To date, very little is known about how parental history influences the clinical presentation of MDD in depressed offspring. This study will contribute to a limited body of research, and is unique in that it will include four parental history groups as well as offspring sex in its analyses. The study will use a quasi-archival sample of approximately 250 participants between 12 and 29 years of age, who have been diagnosed with MDD.

Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses.

Several microarray-based studies have investigated gene expression profiles in major depressive disorder (MDD), yet with highly variable findings. We examined blood-based genome-wide expression signatures of MDD, focusing on molecular pathways and networks underlying differentially expressed genes (DEGs) and behaviours of hypothesis-driven, evidence-based candidate genes for depression. Agilent human whole-genome arrays were used to measure gene expression in 14 medication-free outpatients with MDD who were at least moderately ill and 14 healthy controls matched pairwise for age and sex. After filtering, we compared expression of entire probes between patients and controls and identified DEGs. The DEGs were evaluated by pathway and network analyses. For the candidate gene analysis, we utilized 169 previously prioritized genes and examined their case-control separation efficiency and correlational co-expression network in patients relative to controls. The 317 screened DEGs mapped to a significantly over-represented pathway, the “synaptic transmission” pathway. The protein-protein interaction network was also significantly enriched, in which a number of key molecules for depression were included. The co-expression network of candidate genes was markedly disrupted in patients. This study provided evidence for an altered molecular network along with several key molecules in MDD and confirmed that the candidate genes are worthwhile targets for depression research.

Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder

BackgroundThis investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD).MethodsData were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The Composite Interview Diagnostic Instrument was used to diagnose MDD and GAD. Cognitive profiles were measured using the Leiden Index of Depression Sensitivity, the Anxiety Sensitivity Index, and the Penn State Worry Questionnaire.ResultsResults showed that differences in cognitive profiles between single MDD and single GAD subjects were present: scores on hopelessness/suicidality and rumination were significantly higher in MDD than GAD, whereas anxiety sensitivity for physical concerns and pathological worry were higher in GAD than MDD. The cognitive profile of comorbid MDD/GAD showed more extreme depression cognitions compared to single disorders, and a similar anxiety profile compared to single GAD subjects.ConclusionsDespite the commonalities in cognitive profiles in MDD and GAD, there are differences suggesting that MDD and GAD have disorder-specific cognitive profiles. Findings of this investigation give support for models like the cognitive content-specificity model and the tripartite model and could provide useful handles for treatment focus.

Preliminary analysis of age of illness onset effects on symptom profiles in major depressive disorder

Major depressive disorder (MDD) is prevalent across the lifespan, but relatively little is known about how age of illness onset impacts the cognitive and affective presentation of MDD. We explore depressive symptoms and cognition in 70 adults (30-89 years old) with MDD. Participants were divided into three groups on the basis of age of MDD onset: early (<30 years), midlife (30-49.9 years), and late (>50 years). Symptoms were assessed using the Hamilton Depression Rating Scale; principal component analysis was used to create symptom component scores. Cognitive functions were measured. The late-onset group were significantly older than the early-onset and midlife-onset groups. Analysis controlled for age and hemoglobin A1c levels, as some participants had diabetes. The late-onset group demonstrated greater weight loss and gastrointestinal symptoms compared with the early-onset group. Suicidal thoughts and sleep disturbance were higher in both the early-onset and late-onset groups compared with the midlife-onset group. Correlations between symptom components and cognitive domains varied by age-of-onset group. This preliminary analysis demonstrates cognitive and affective profiles that are both unique to age of onset and common across MDD. Symptom profiles may assist in identifying factors influencing depression and enhance the clinical evaluation and care of individuals struggling with the effects of depression across the lifespan.

Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients

Major depressive disorder (MDD) is a leading cause of disability worldwide and results tragically in the loss of almost one million lives in Western societies every year. This is due to poor understanding of the disease pathophysiology and lack of empirical medical tests for accurate diagnosis or for guiding antidepressant treatment strategies. Here, we have used shotgun proteomics in the analysis of post-mortem dorsolateral prefrontal cortex brain tissue from 24 MDD patients and 12 matched controls. Brain proteomes were pre-fractionated by gel electrophoresis and further analyzed by shotgun data-independent label-free liquid chromatography-mass spectrometry. This led to identification of distinct proteome fingerprints between MDD and control subjects. Some of these differences were validated by Western blot or selected reaction monitoring mass spectrometry. This included proteins associated with energy metabolism and synaptic function and we also found changes in the histidine triad nucleotide-binding protein 1 (HINT1), which has been implicated recently in regulation of mood and behavior. We also found differential proteome profiles in MDD with (n=11) and without (n=12) psychosis. Interestingly, the psychosis fingerprint showed a marked overlap to changes seen in the brain proteome of schizophrenia patients. These findings suggest that it may be possible to contribute to the disease understanding by distinguishing different subtypes of MDD based on distinct brain proteomic profiles.

Mood and anxiety disorders in females with the FMR1 premutation

Fragile X syndrome (FXS) is a model for studying the relative contributions of genetic and environmental factors to psychiatric disorders in mothers of children with disabilities. Here, we examine the frequency and predictors of mood and anxiety disorders in mothers with the FMR1 premutation. Ninety-three females with the FMR1 premutation were in the study and were compared to 2,159 women from the National Comorbidity Survey Replication (NCS-R) dataset. Mood and anxiety disorders were assessed using the SCID-I. Our data reflect elevated lifetime major depressive disorder (MDD), lifetime panic disorder without agoraphobia and current agoraphobia without panic disorder in the FMR1 premutation sample. Also, we found a low frequency of lifetime social phobia, specific phobia, and post-traumatic stress disorders and current specific phobia in the FMR1 premutation sample. The profile of MDD in the FMR1 premutation sample was not episodic or comorbid with an anxiety disorder, as in the NCS-R dataset. Never having been married and smaller CGG repeat length were associated with increased likelihood of MDD while increased children with FXS in the family and greater child problem behaviors were associated with increased likelihood of an anxiety disorder in the FMR 1 premutation group. Major depression in females with the FMR1 premutation may not be characterized as an episodically chronic recurrent disorder as it is in community samples and may have a genetic basis given the relationship with CGG repeat length and lack of association with all child and most demographic factors.

Interpersonal profiles in major depressive disorder

Although patients with mood disorders report interpersonal difficulties in addition to depression or anxiety, few studies have examined interpersonal patterns in those patients. Here the authors' goals were to (a) identify the interpersonal pattern in patients with major depressive disorder (MDD), (b) determine interpersonal differences between subgroups of MDD patients, and (c) examine the interpersonal patterns of comorbid MDD patients. One- hundred forty-one MDD adults participated in an ongoing randomized clinical trial of treatments for depression. Interpersonal profiles revealed that MDD patients were significantly more distressed by interpersonal problems than normative samples. Furthermore, MDD patients with depressive personality disorder reported more interpersonal distress than MDD-only patients report and were more likely to have interpersonal problems related to dominance and control than submissiveness.

Symptom Profile of Major Depressive Disorder in Women with Eating Disorders

Based on the well-documented association between eating disorders (EDs) and affective disorders, the patterns of comorbidity of EDs and major depressive disorder (MDD) were investigated. The temporal relation between EDs and MDD onset was analyzed to determine differences in the course and nature of MDD when experienced prior to versus after the onset of the ED. Lifetime MDD and depressive symptoms were assessed in 1371 women with a history of ED. The prevalence of MDD was first explored across ED subtypes, and ages of onset of MDD and EDs were compared. Depressive symptoms were examined in individuals who developed MDD before and after ED onset. The lifetime prevalence of MDD was 72.9%. Among those with lifetime MDD (n =963), 34.5% reported MDD onset before the onset of ED. Those who experienced MDD first reported greater psychomotor agitation (OR =1.53; 95%CI =1.14-2.06), and thoughts of own death (but not suicide attempts or ideation; OR =1.73; 95%CI =1.31-2.30). Among individuals who had MDD before ED, 26.5% had the MDD onset during the year before the onset of ED; 67% of individuals had the onset of both disorders within the same 3 year window. Clinicians treating individuals with new-onset ED or MDD should remain vigilant for the emergence of additional psychopathology, especially during the initial 3 year window following the onset of the first disorder.

Epidemiology of major depression in four cities in Mexico

Analyses were conducted to estimate lifetime and current prevalence of major depressive disorder (MDD) for four representative cities of Mexico, to identify variables that influence the probability of MDD, and to further describe depression in Mexican culture. A multistage probability sampling design was used to draw a sample of 2,509 adults in four different regions of Mexico. MDD was assessed according to DSM-IV criteria by using the Composite International Diagnostic Interview collected by trained lay interviewers. The prevalence of MDD in these four cities averaged 12.8% for lifetime and 6.1% for the previous 12 months. MDD was highly comorbid with other mental disorders. Women were more likely to have lifetime MDD than were men. Being divorced, separated, or widowed (compared to married or never married) and having experienced childhood trauma were related to higher lifetime prevalence but not to current prevalence. In addition, age and education level were related to current 12-month MDD. Data on the profile of MDD in urban Mexico are provided. This research expands our understanding of MDD across cultures.

Psychiatric disorders in the first-degree relatives of probands with bulimia nervosa.

Data from a family study of psychiatric disorders showed higher rates of major affective disorders, eating disorders, and alcoholism in first-degree relatives of 40 bulimic probands than in first-degree relatives of 24 control subjects. More importantly, the data showed higher rates of major affective disorders in relatives of bulimic probands who themselves had no history of major affective disorders than in relatives of control subjects. This significant finding indicates a familial relationship between bulimia nervosa and major affective disorders, which suggests the possibility of a common diathesis.