History Of Recurrent Major Depressive Disorder Research Articles

Identifying Depression Subtypes and Investigating their Consistency and Transitions in a 1-Year Cohort Analysis

Introduction Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.Objectives(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and(3) To examine how participants move between subtypes over time.Methods This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.ResultsWe identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).Image:Image 2:Conclusions We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.Disclosure of Interest C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research & Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared

Circulating microRNA associated with future relapse status in major depressive disorder.

Major depressive disorder (MDD) is an episodic condition with relapsing and remitting disease course. Elucidating biomarkers that can predict future relapse in individuals responding to an antidepressant treatment holds the potential to identify those patients who are prone to illness recurrence. The current study explored relationships between relapse risk in recurrent MDD and circulating microRNAs (miRNAs) that participate in RNA silencing and post-transcriptional regulation of gene expression. Serum samples were acquired from individuals with a history of recurrent MDD who were followed longitudinally in the observational study, OBSERVEMDD0001 (ClinicalTrials.gov Identifier: NCT02489305). Circulating miRNA data were obtained in 63 participants who relapsed (“relapsers”) and 154 participants who did not relapse (“non-relapsers”) during follow-up. The miRNA was quantified using the ID3EAL™ miRNA Discovery Platform from MiRXES measuring 575 circulating miRNAs using a patented qPCR technology and normalized with a standard curve from spike-in controls in each plate. The association between miRNAs and subsequent relapse was tested using a linear model, adjusting for age, gender, and plate. Four miRNAs were nominally associated with relapse status during the observational follow-up phase with a false discover rate adjusted p-value < 0.1. Enrichment analysis of experimentally validated targets revealed 112 significantly enriched pathways, including neurogenesis, response to cytokine, neurotrophin signaling, vascular endothelial growth factor signaling, relaxin signaling, and cellular senescence pathways. These data suggest these miRNAs putatively associated with relapse status may have the potential to regulate genes involved in multiple signaling pathways that have previously been associated with MDD. If shown to be significant in a larger, independent sample, these data may hold potential for developing a miRNA signature to identify patients likely to relapse, allowing for earlier intervention.

Anhedonia and increased evoked immune response

There is a growing body of evidence supporting the association between immune processes and psychopathology, including major depressive disorder (MDD). However, lack of diagnostic specificity has given rise to a search for specific symptom types, as opposed to more heterogeneous categorical diagnoses, linked to increased inflammation. One such symptom could be anhedonia, which is not only a key feature of MDD, but also a pervasive and persistent transdiagnostic symptom. To evaluate the specific role of anhedonia as well as categorical MDD diagnoses, we examined endotoxin-evoked immune responses in vitro in relation to current levels of anhedonia and history of recurrent MDD (rMDD) in a sample of adults recruited from the community. A total of 39 participants either had a history of rMDD (n ​= ​20) or no lifetime history of any MDD episodes (n ​= ​19). The average age of participants was 36.81 years and the majority were women (87.2%) and Caucasian (76.3%). We found that higher levels of current anhedonia, but not history of rMDD, were associated with increased lipopolysaccharide-stimulated levels of inflammatory markers even after we statistically adjusted for the potential influence of participants’ demographic (age, sex, ethnicity, income) and physiological (body temperature, BMI) characteristics, current symptoms of depression and anxiety, and the time of day of the sample collection. These findings highlight the relation of anhedonia specifically, rather than rMDD more generally, with inflammatory processes and identify endotoxin-stimulated cytokine production as a plausible biological marker of current anhedonia.

History of major depression is associated with neuropsychiatric symptoms but not systemic inflammation in a cross-sectional study in obese patients

Obesity is a major public health burden associated with neuropsychiatric comorbidities leading to social and occupational impairment. Given the growing prevalence of both obesity and mental disorders worldwide, understanding the risk factors of obesity-related neuropsychiatric comorbidities is crucial to develop preventive strategies and individualized treatments. Recent findings suggest that adiposity-driven inflammation contributes to neuropsychiatric comorbidities in obesity. However, not all obese subjects afflicted with chronic inflammation develop neuropsychiatric symptoms, suggesting additional risk factors. The aim of this study was to investigate the impact of personal history of major depressive disorder (MDD) on obesity-related inflammation and neuropsychiatric symptoms, and their relationship.A case-control study was conducted comparing 66 obese patients (body mass index > 35 kg/m2) and 22 healthy non-obese participants, free of any current neuropsychiatric diseases including MDD. Neuropsychiatric symptoms were assessed using the Neurotoxicity Rating Scale (NRS). Sociodemographic and clinical variables were gathered and blood was collected for the measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP). Multiple regression analyses were performed to assess the contribution of obesity and personal history of MDD to clinical outcomes and inflammatory status in study participants.Hs-CRP levels as well as NRS scores were significantly increased in the obese group. Overall, personal history of depression accounted for increased NRS scores but no significant association was found with inflammatory status. In addition, history of depression did not significantly modulate the relationship of obesity-related inflammation with NRS scores. Interestingly, obese individuals with history of recurrent MDD (n = 13) exhibited higher scores in the cognitive and sickness symptoms dimensions of the NRS compared to obese subjects with history of one depressive episode only.Findings indicate that history of depression contributes to neuropsychiatric symptoms, but not to systemic inflammation, in obese subjects free of current depressive episode. These results provide relevant information on the risk factors that may help identify obese subjects with increased risk of neuropsychiatric comorbidity.

Negative Self-Referential Processing Predicts the Recurrence of Major Depressive Episodes

Most individuals who develop Major Depressive Disorder (MDD) will experience a recurrent depressive episode; we know little, however, about cognitive mechanisms that increase the likelihood of recurrence. In the current study we examined whether negatively biased self-referential processing, negative life events, baseline depressive symptoms, and psychotropic medication use predicted the onset of a subsequent depressive episode in a longitudinal study of women with a history of recurrent MDD. Higher levels of depressive symptoms at baseline predicted experiencing a greater number of negative life events which, in turn, tended to predict recurrence of depression. Importantly, after accounting for other associations, negatively biased self-referential processing contributed unique variance to the likelihood of experiencing a depressive episode over the next three years. Thus, negatively biased self-referential processing appears to be a significant risk factor for the recurrence of depressive episodes and may be an important target for interventions aimed at preventing future episodes.

Cross-species evidence for the role of interleukin-33 in depression risk.

Extensive evidence highlights the role of inflammatory processes in major depressive disorder (MDD). However, most studies have examined a consistent set of inflammatory cytokines and there is evidence that other immune-derived products may play a role in MDD. In this article, we present data from 3 complimentary studies that support the role of a novel cytokine, interleukin-33 (IL-33), in depression risk. First, we show that a 2-SNP haplotype in the IL-33 gene (rs11792633 and rs7044343) moderated the link between women's history of childhood abuse and their history of recurrent MDD (rMDD), such that the link between childhood abuse and rMDD was stronger among women with fewer copies of the protective IL-33 CT haplotype. Second, linking these findings to differences in circulating cytokine levels, we show in a separate sample that those with a history of rMDD had higher peripheral levels of IL-33 and IL-1β compared with women with a single MDD episode or no history of MDD. Third, providing initial evidence of brain regions underlying these effects using archival rat brain tissue, we show that an acute stressor increased IL-33 expression in the paraventricular nucleus of the hypothalamus and, to a lesser extent, the prefrontal cortex, key brain regions underlying stress response and emotion regulation. These findings provide converging support for the potential role of IL-33 in risk for recurrent MDD. (PsycINFO Database Record

CHRONICITY OF DEPRESSION AND MOLECULAR MARKERS IN A LARGE SAMPLE OF HAN CHINESE WOMEN.

Major depressive disorder (MDD) has been associated with changes in mean telomere length and mitochondrial DNA (mtDNA) copy number. This study investigates if clinical features of MDD differentially impact these molecular markers. Data from a large, clinically ascertained sample of Han Chinese women with recurrent MDD were used to examine whether symptom presentation, severity, and comorbidity were related to salivary telomere length and/or mtDNA copy number (maximum N=5,284 for both molecular and phenotypic data). Structural equation modeling revealed that duration of longest episode was positively associated with mtDNA copy number, while earlier age of onset of most severe episode and a history of dysthymia were associated with shorter telomeres. Other factors, such as symptom presentation, family history of depression, and other comorbid internalizing disorders, were not associated with these molecular markers. Chronicity of depressive symptoms is related to more pronounced telomere shortening and increased mtDNA copy number among individuals with a history of recurrent MDD. As these molecular markers have previously been implicated in physiological aging and morbidity, individuals who experience prolonged depressive symptoms are potentially at greater risk of adverse medical outcomes.

Chronic and Episodic Stress in Children of Depressed Mothers

The goal of this study was to examine chronic and episodic stress in children of mothers with and without a history of major depressive disorder (MDD) during the children's lives. Participants were 255 mothers selected according to their history of MDD (present vs. absent during child's life) and their children (age 8–14; 53% girls, 81% Caucasian). Mothers' and children's histories of MDD were assessed using diagnostic interviews, and their depressive symptoms were assessed via self-report measures. Children's levels of chronic and episodic stress were assessed using a semistructured contextual threat interview. Children of mothers with a history of recurrent MDD, compared to single MDD or no depression, experienced more chronic stress within several domains including peers, mother–child relations, and other family member relations as well as greater episodic dependent interpersonal stress. Each of these group differences was maintained after excluding children with a history of MDD themselves and controlling for their current depressive symptoms. However, only the group difference in chronic peer stress was maintained when controlling for mothers' current depression. The results suggest that children exposed to recurrent maternal MDD experience higher levels of both chronic and episodic stress, at least some of which they contribute to themselves (dependent interpersonal stress) and which is at least partially independent of the effects of children's depression. In addition, much of this stress is associated primarily with current depression in the mother, though it appears that chronic peer stress may remain elevated even after the remission of maternal depression.

A Case of Major Depressive Disorder and Symptoms of Polycystic Ovary Syndrome Responding to Escitalopram

To the Editor: Despite wide-ranging clinical use of antidepressants to treat depression alone as well as depression associated with polycystic ovary syndrome (PCOS), there have been no reports to date on the use of serotonin reuptake inhibition with a successful outcome of both major depressive disorder (MDD) and PCOS symptomatology, such as oligomenorrhea/amenorrhea and hirsutism. Case report. Ms A, a 40-year-old married woman, had a 20-year history of recurrent MDD (DSM-IV). Her first episode began when she was 20 years old. Seven years ago, her depressive symptoms began to appear slowly, characterized by depressed mood, irritability, diminished interest in her usual activities, loss of appetite, weight loss, lack of energy, poor concentration, insomnia, and recurrent thoughts of death, such as “It would be nice not being alive.” These symptoms led to impaired work and social functioning. Her mother had a history of chronic depressive mood disorder. Ms A also had a 26-year history of PCOS, characterized by oligomenorrhea or amenorrhea, hirsutism, hyperandrogenism, and polycystic ovaries, confirmed by several laboratory tests and ultrasound, meeting the 2003 Rotterdam, or European Society for Human Reproduction/American Society for Reproductive Medicine (ESHRE/ASRM), criteria.1 Twenty years ago, her gynecologist suggested lifestyle changes such as exercises, nutritional guidance, low doses of oral contraceptive pills, cosmetic therapy, and laser therapy for hirsutism. With the use of oral contraceptive pills, Ms A experienced an improvement in her menstrual cycles, although she continued to have mood swings, irritability, and severe headaches, which were extremely distressing. She was switched to several oral contraceptive pills, but all showed severe side effects. She discontinued all oral contraceptive pills after a few months of use. In 2003, Ms A presented for treatment of MDD. Escitalopram—a selective serotonin reuptake inhibitor, not an oral contraceptive pill—was administered at 5 mg/d, with the dosage reaching 20 mg/d in 3 weeks. After 4 weeks of treatment, Ms A experienced clinically significant depressive symptomatic relief. Remission was achieved in 8 weeks. Over the next 18 months, she continued to receive escitalopram and experienced a return of regular menstrual cycles and improvement in hirsutism. She reported transient mild nausea at the beginning of treatment; no other side effects were reported. Remarkably, 2 months after antidepressant discontinuation, she started experiencing menstrual irregularity and hair growth. Ten months later, MDD recurred. During the next 4 years, she was on treatment with escitalopram at 20 mg/d and remained symptom-free. Meanwhile, she achieved notable menstrual cycle improvement and reduction in hirsutism. As Ms A was feeling well, she stopped taking the medication on her own and her menstrual complaints immediately recurred. She restarted escitalopram in 4 months, and her PCOS symptoms remitted again. This was the longest regular menstrual cycle period she had ever had with no use of oral contraceptive pills. Last year, her ultrasounds continued to show polycystic ovaries. Reports have revealed that hyperandrogenism, hormonal disturbances, obesity, ovarian dysfunction, hypothalamic pituitary abnormalities, and insulin resistance are implicated in the etiology of PCOS.2,3 Hormonal dysregulation is involved with both MDD and PCOS. As mood disorders and PCOS share some level of genetic and pathophysiologic mechanisms,4,5 the intervention on common metabolic changes can treat both conditions.

Structural brain changes in patients with recurrent major depressive disorder presenting with anxiety symptoms.

Major depressive disorder (MDD) presents with extensive clinical heterogeneity. In particular, overlap with anxiety symptoms is common during depressive episodes and as a comorbid disorder. The aim of this study was to test for morphological brain differences between patients having a history of recurrent MDD with, and without, anxiety symptoms (MDD+A and MDD-A). T1-weighted magnetic resonance images of age-, gender- and ethnically matched groups of MDD+A (n= 49) and MDD-A (n= 96) patients were available for voxel-based morphometry analysis of regional gray matter (GM) volume differences. Brain structural images were also contrasted with 183 age-, gender-, and ethnicity-matched healthy controls. MDD+A patients had greater GM volume (P(FWE) = .002) than MDD-A patients in the right temporal cortex extending from the mid-posterior superior temporal gyrus into the posterior middle and inferior temporal gyrus. The MDD patients together showed lower GM volume than healthy controls in the superior parietal lobe. Regional volume differences in patients are consistent with altered neuronal or glial microstructure. The temporolateral cortical differences distinguishing the 2 MDD groups suggest neurobiological differences related to the expression of anxiety symptoms in depression and provide further rationale for considering these groups independently for therapeutic outcomes studies.

Single versus recurrent depression history: Differentiating risk factors among current US smokers

Introduction The strong relationship between persistent tobacco use and Major Depressive Disorder (MDD) has motivated clinical trials of specialized treatments targeting smokers with a history of MDD. Meta-analyses suggest positive responses to specialized treatments have been observed consistently among smokers with history of recurrent rather than a single episode of MDD. Approximately 15% of current US smokers have a history of recurrent MDD. Little is known about the risk factors that contribute to persistent smoking and differentiate these at-risk smokers, US. Methods The National Comorbidity Survey – Replication (NCS-R) included a survey of 1560 smokers participants aged 18 and older in the United States. Lifetime history of MDD was categorized according to chronicity: no history (No MDD), single episode (MDD-S) and recurrent depression (MDD-R). The relationship between the chronicity of MDD, smoking characteristics, cessation history, nicotine dependence, comorbidity with psychiatric disorders, and current functional impairments were examined. Results MDD-R smokers reported fewer lifetime cessation efforts, smoked more cigarettes, had higher levels of nicotine dependence, had higher rates of comorbid psychiatric disorders and greater functional impairment than smokers with No MDD. MDD-S smokers were not consistently distinguished from No MDD smokers on cessation attempts, level of daily smoking, nicotine dependence or functional impairment indices. Conclusions The study highlights the importance of chronicity when characterizing depression-related risk of persistent smoking behavior. Although, clinical trials suggest MDD-R smokers specifically benefit from specialized behavioral treatments, these services are not widely available and more efforts are needed to engage MDD-R smokers in efficacious treatments.