Chronic Major Depressive Disorder Research Articles

Serum L-selectin levels as predictive markers for chronic major depressive disorder progression

BackgroundMajor depressive disorder (MDD) exhibits a recurrence rate of up to 70%. Frequent recurrence can lead to chronic depression, which has considerable personal and societal consequences. This study aims to identify a serum protein biomarker to predict MDD recurrence and progression to chronicity.MethodsSerum samples from the MDD with single episode group (MDD-S), MDD with recurrence group (MDD-R), and a healthy control group were collected. Non-targeted analysis of the serum proteome was conducted using liquid chromatography–tandem mass spectrometry. Statistically significant common proteins when comparing the three groups were chosen. The selected marker candidates were subsequently validated through multiple response monitoring (MRM), incorporating a healthy control, MDD-S, MDD-R(2) (two episodes), and MDD-R(> 2) (more than two episodes) groups.ResultsL-selectin levels showed an upward trend in the MDD-R group compared to the healthy control and MDD-S groups. MRM validation revealed a decreased tendency for L-selectin in the MDD-R(> 2) group, indicative of a chronic state, versus the healthy control and MDD-S groups. The receiver operating characteristic analysis highlighted L-selectin as the chosen biomarker due to its classification efficacy for the MDD-R(> 2) group.ConclusionL-selectin emerged as a predictive biomarker for MDD recurrence and its potential evolution into chronic depression. This marker offers insights into changes in leukocyte-mediated inflammatory responses characteristic of chronic depression. Consequently, it may forecast the transition from acute to chronic inflammation in depressive patients.

Neurobiological mechanisms in the kynurenine pathway and major depressive disorder.

Major depressive disorder (MDD) is a prevalent psychiatric disorder that has damage to people's quality of life. Tryptophan is the precursor to serotonin, a critical neurotransmitter in mood modulation. In mammals, most free tryptophan is degraded by the kynurenine pathway (KP), resulting in a range of metabolites involved in inflammation, immune response, and neurotransmission. The imbalance between quinolinic acid (QA), a toxic metabolite, and kynurenic acid (KynA), a protective metabolite, is a relevant phenomenon involved in the pathophysiology of MDD. Proinflammatory cytokines increase the activity of the enzyme indoleamine 2,3-dioxygenase (IDO), leading to the degradation of tryptophan in the KP and an increase in the release of QA. IDO activates proinflammatory genes, potentiating neuroinflammation and deregulating other physiological mechanisms related to chronic stress and MDD. This review highlights the physiological mechanisms involved with stress and MDD, which are underlying an imbalance of the KP and discuss potential therapeutic targets.

Depressive Illness among Chronic Liver Disease Patients: A Cross-Sectional Study

OBJECTIVES This study investigated the association between chronic liver disease and major depressive disorder (MDD) in Pakistani adults. The prevalence of MDD among chronically ill patients admitted to a medical unit was examined, focusing on the impact of age, income, education level, and comorbidities on depression severity. METHODOLOGY A descriptive cross-sectional survey was conducted over two months at the Khyber Teaching Hospital in Peshawar. A total of 410 patients with chronic liver disease were included. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9). Data analysis was performed using SPSS version 25, utilizing statistical tests such as Pearson correlation, ANOVA. and chi-square.RESULTSThe study investigated depression severity among 410 patients with chronic liver disease, focusing on demographic characteristics and comorbidities. The mean age of participants was 54.244 years, with a moderate level of depressive symptoms indicated by a mean PHQ-9 score of 10. Income showed a weak but significant negative correlation with depression severity (-0.138, p = 0.005), while age did not show a significant correlation (-0.053, p = 0.288).CONCLUSIONThis study enhances the understanding of the intricate relationship between chronic liver disease and major depressive disorder (MDD). The results indicate that income level, education level, and the presence of comorbidities significantly influence the manifestation of depression in this population. Healthcare professionals can leverage these insights to identify high-risk patients and tailor interventions to enhance mental well-being and treatment outcomes for individuals with chronic liver disease.

Reporting Psychiatric Disease Characteristics in Post-Mortem- and Biological Research.

Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 ("don't eat me signals") located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after "psychological autopsy") selected by an experienced clinician.

Script-driven imagery of socially salient autobiographical memories in major depressive disorder

Cues of social rejection and affiliation represent proximal risk and protective factors in the onset and maintenance of depression. Such cues are thought to activate an evolutionarily primed neuro-cognitive alarm system, alerting the agent to the benefits of inclusion or the risk of social exclusion within social hierarchies focused on ensuring continued access to resources. In tandem, autobiographical memory is thought to be over-general and negatively biased in Major Depressive Disorder (MDD) which can contribute to maintenance and relapse. How memories of social rejection and affiliation are experienced and processed in MDD remains unexplored. Eighteen participants with recurrent and chronic MDD and 18 never-depressed controls listened to and vividly revisited autobiographical social experiences in an ecologically valid script-driven imagery paradigm using naturalistic memory narratives in an fMRI paradigm. Memories of Social Inclusion and Social Rejection broadly activated a common network of regions including the bilateral insula, thalamus and pre/postcentral gyrus across both groups. However, having a diagnosis of MDD was associated with an increased activation of the right middle frontal gyrus irrespective of memory type. Changes in positive affect were associated with activity in the dorsal ACC in the MDD group and in the insular cortex of the Control group. Our findings add to the evidence for complex representations for both positive and negative social signals in MDD and suggest neural sensitivity in MDD towards any socially salient information as opposed to selective sensitivity towards negative social experiences.

Major depressive disorder and chronic gastritis: A bidirectional two-sample Mendelian randomization study

ObjectiveObservational studies have posited a strong correlation between chronic gastritis (CG) and major depressive disorder (MDD), but the nature of this association remains uncertain, owing to the challenges of establishing the temporal sequence. The present study sought to elucidate the elusive relationship between CG and MDD by employing a bidirectional two-sample Mendelian randomization (MR) approach. MethodsWe extracted instrumental variants for MDD and CG from published genome-wide association study data, focusing on individuals of primarily European descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. ResultsFor MDD and CG, 221 and 5 genetic variants, respectively, were selectively extracted as instrumental variants. The results suggest that MDD is causally associated with an elevated risk of CG (IVW: 23andMe, OR = 1.33; 95% CI = 1.15–1.54; p = 1.06 × 10–4); conversely, no strong evidence was found to corroborate that CG exerts a causal effect on the incidence of MDD (IVW: OR = 1.01; 95% CI = 0.95–1.07; p = 0.68). ConclusionsThese findings provide novel insights into the causal relationship between CG and MDD, which may have implications for clinical decision-making in patients with MDD and CG.

Cerebellum and hippocampus abnormalities in patients with insomnia comorbid depression: a study on cerebral blood perfusion and functional connectivity.

Chronic insomnia disorder and major depressive disorder are highly-occurred mental diseases with extensive social harm. The comorbidity of these two diseases is commonly seen in clinical practice, but the mechanism remains unclear. To observe the characteristics of cerebral blood perfusion and functional connectivity in patients, so as to explore the potential pathogenesis and biological imaging markers, thereby improving the understanding of their comorbidity mechanism. 44 patients with chronic insomnia disorder comorbid major depressive disorder and 43 healthy controls were recruited in this study. The severity of insomnia and depression were assessed by questionnaire. The cerebral blood perfusion and functional connectivity values of participants were obtained to, analyze their correlation with questionnaire scores. The cerebral blood flow in cerebellum, vermis, right hippocampus, left parahippocampal gyrus of patients were reduced, which was negatively related to the severity of insomnia or depression. The connectivities of left cerebellum-right putamen and right hippocampus-left inferior frontal gyrus were increased, showing positive correlations with the severity of insomnia and depression. Decreased connectivities of left cerebellum-left fusiform gyrus, left cerebellum-left occipital lobe, right hippocampus-right paracentral lobule, right hippocampus-right precentral gyrus were partially associated with insomnia or depression. The connectivity of right hippocampus-left inferior frontal gyrus may mediate between insomnia and depression. Insomnia and depression can cause changes in cerebral blood flow and brain function. Changes in the cerebellar and hippocampal regions are the result of insomnia and depression. They reflect abnormalities in sleep and emotion regulation. That may be involved in the pathogenesis of comorbidity.

HMGB1/STAT3/p65 axis drives microglial activation and autophagy exert a crucial role in chronic Stress-Induced major depressive disorder

IntroductionNeuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. ObjectivesHere, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. MethodsBioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. ResultsThe differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. ConclusionOur study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.

Correlates of chronic depression in the general population: results from the CoLaus|PsyCoLaus study

PurposePrevious population-based studies have partially provided inconsistent results regarding the co-variates of chronic depression, which were likely to be attributable to methodological limitations. The present paper that compared people with chronic major depressive disorder (MDD), non-chronic MDD and no mood disorder in the community focused on specific atypical and melancholic depression symptoms and subtypes of MDD, family history (FH) of mood disorders, measured physical cardio-vascular risk factors (CVRF), personality traits, coping style and adverse life-events.MethodsData stemmed from a population-based cohort including 3618 participants (female 53%, n=1918; mean age 50.9 years, s.d. 8.8 years). Among them 563 had a lifetime history of chronic MDD, 1060 of non-chronic MDD and 1995 of no mood disorder. Diagnostic and FH information were elicited through semi-structured interviews, CVRF were assessed through physical investigations.ResultsThe major findings were that chronic MDD was associated with increase in appetite/weight and suicidal ideation/attempts during the most severe episode, higher exposure to life-events in adulthood, higher levels of neuroticism, lower levels of extraversion and lower levels of informal help-seeking behavior but less frequent FH of MDD compared to non-chronic MDD.ConclusionChronic MDD is associated with a series of potential modifiable risk factors which are accessible via psychotherapeutic approaches that may improve the course of chronic MDD.

Clinical efficacy and immune effects of acupuncture in patients with comorbid chronic pain and major depression disorder: A double-blinded, randomized controlled crossover study

BackgroundDepression and pain are highly comorbid and share biological mechanisms. Acupuncture is commonly used to manage both pain and depression, but the choice of acupoints for specific disorders differs. This study aimed to investigate whether specific acupuncture intervention on pain- and depression-acupoints would have specific efficacy and immune effects in patients with comorbid chronic pain and major depressive disorder (MDD). MethodsWe performed a subject- and assessor-blinded, crossover, and randomized controlled clinical trial of depression- and pain-specific acupuncture intervention and measured clinical responses and proinflammatory cytokines in patients with comorbid chronic pain and MDD. Specific acupoints for pain and depression were used in random order with a washout interval.Forty-seven patients were enrolled and randomly assigned to two groups: (1) the depression–pain group (23 patients who were treated with depression-specific acupoints and then the pain-specific acupoints after the washout) and (2) pain–depression group (24 patients with the reverse order). ResultsThe pain-specific acupoints for pain did not reduce Brief Pain Inventory scores to a significantly greater degree (-0.97 ± 1.69) than the depression-specific acupoints (-0.28 ± 1.88); likewise, the depression-specific acupoints did not significantly ameliorate Hamilton Depression Rating Scale (-4.59 ± 6.02) than the pain-specific acupoints (-6.69 ± 6.61). The pain-specific acupoints improved Beck Depression Inventory-Second Edition (-6.74 ± 9.76) even better than the depression-specific acupoints (-1.92 ± 10.74). The depression-specific acupoints did not significantly decrease the depression-related interleukin (IL)-6 level (-1.24 ± 6.67) than the pain-specific acupoints (-0.60 ± 4.36). The changed levels of IL-1β, tumor necrosis factor (TNF)-α between the depression-specific acupoints (-37.41 ± 194.49; −12.53 ± 54.68) and the pain-specific acupoints (-15.46 ± 87.56; −7.28 ± 27.86) could not reach significantly different, too. ConclusionThis study rejected our hypothesis that the pain-specific acupoints might produce superior analgesic effects than the depression-specific acupoints and vice versa. The cytokine results might imply that pain and depression share common biological mechanisms. (trial registration: https://www.clinicaltrials.gov: NCT03328819).

Validity of biopsychosocial model of intervention in contemporary medical practice: Walking a few extra miles

Validity of biopsychosocial model of intervention in contemporary medical practice: Walking a few extra miles

Quantifying Deviations of Brain Structure and Function in Major Depressive Disorder Across Neuroimaging Modalities

Identifying neurobiological differences between patients with major depressive disorder (MDD) and healthy individuals has been a mainstay of clinical neuroscience for decades. However, recent meta-analyses have raised concerns regarding the replicability and clinical relevance of brain alterations in depression. To quantify the upper bounds of univariate effect sizes, estimated predictive utility, and distributional dissimilarity of healthy individuals and those with depression across structural magnetic resonance imaging (MRI), diffusion-tensor imaging, and functional task-based as well as resting-state MRI, and to compare results with an MDD polygenic risk score (PRS) and environmental variables. This was a cross-sectional, case-control clinical neuroimaging study. Data were part of the Marburg-Münster Affective Disorders Cohort Study. Patients with depression and healthy controls were recruited from primary care and the general population in Münster and Marburg, Germany. Study recruitment was performed from September 11, 2014, to September 26, 2018. The sample comprised patients with acute and chronic MDD as well as healthy controls in the age range of 18 to 65 years. Data were analyzed from October 29, 2020, to April 7, 2022. Primary analyses included univariate partial effect size (η2), classification accuracy, and distributional overlapping coefficient for healthy individuals and those with depression across neuroimaging modalities, controlling for age, sex, and additional modality-specific confounding variables. Secondary analyses included patient subgroups for acute or chronic depressive status. A total of 1809 individuals (861 patients [47.6%] and 948 controls [52.4%]) were included in the analysis (mean [SD] age, 35.6 [13.2] years; 1165 female patients [64.4%]). The upper bound of the effect sizes of the single univariate measures displaying the largest group difference ranged from partial η2 of 0.004 to 0.017, and distributions overlapped between 87% and 95%, with classification accuracies ranging between 54% and 56% across neuroimaging modalities. This pattern remained virtually unchanged when considering either only patients with acute or chronic depression. Differences were comparable with those found for PRS but substantially smaller than for environmental variables. Results of this case-control study suggest that even for maximum univariate biological differences, deviations between patients with MDD and healthy controls were remarkably small, single-participant prediction was not possible, and similarity between study groups dominated. Biological psychiatry should facilitate meaningful outcome measures or predictive approaches to increase the potential for a personalization of the clinical practice.

25(OH)D levels are decreased in patients with difficult-to-treat depression

ObjectivesThe aims of the study are i) to compare 25-hydroxyvitamin D (25(OH)D) levels between clinically depressed individuals with insufficient treatment response and healthy controls and ii) to test the association between 25(OH)D levels and different affective disorder diagnoses (i.e., major depressive disorder (MDD) single episode, MDD recurrent episode, chronic MDD, and dysthymia), as well as grade of suicidal ideation. MethodWe quantified serum 25(OH)D in 202 individuals with difficult-to-treat depression (DTD) and 41 healthy controls. Patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR). ANCOVA was used to test differences in mean 25(OH)levels between depressed and controls, adjusting for sex, age, smoking, sampling season, ethnicity, somatic illness, and body mass index (BMI). Binary logistic regression models were used to test the association between depression and 25(OH)D levels. ResultsPatients with difficult-to-treat depression had significantly lower levels of 25(OH)D compared to healthy controls (ANCOVA, F = 4.89; p = 0.03). Thirty percent of the depressed patients were 25(OH)D deficient (<50 nmol/L) compared to 5% of the controls (Chi-squared test, χ2 = 11.38; p < 0.01). The odds for being depressed decreased significantly with 17% per 10 nmol/L increase of 25(OH)D (Binary logistic regression, p < 0.05). LimitationsThe cross-sectional design of the study precludes any conclusions about causality. A large part of the patients took psychotropic drugs and/or had somatic illnesses, which might have affected the results. ConclusionThe results of the present study add to the body of evidence linking 25(OH)D deficiency and depression. Further investigations are warranted to better understand any clinical implications of this association.

One-carbon and energy metabolism in major depression compared to chronic depression in adolescent outpatients: A metabolomic pilot study

While considered less severe than major depressive disorder (MDD), chronic depression has a devastating effect on people's lives. Metabolic alterations related to chronicity are still widely unknown. We investigated metabolic alterations in patients with depression and compared the episodic and chronic forms. The study participants comprised 76 adolescent outpatients (33 MDD, 43 chronic depression). Patients’ serum samples were analyzed with targeted metabolite analysis, yielding results for 102 metabolites associated, for example, with amino acid, energy, lipid, and one-carbon metabolism. After controlling for background factors, the chronic depression group had higher levels of choline (Cohen's d = 0.52 and unadjusted 95% confidence interval [0.05, 0.98]), glutamine (d = 0.42 [-0.04, 0.88]), glycine (d = 0.41 [-0.04, 0.87]), glycine betaine (d = 0.48 [0.02, 0.94]), guanidinoacetic acid (d = 0.23 [-0.23, 0.68]), octanoylcarnitine (d = 0.60 [0.13, 1.06]), phosphoethanolamine (d = 0.34 [-0.12, 0.79]) and succinate (d = 0.61 [0.14, 1.07]), and lower levels of glutamate (d = -0.66 [-1.12, -0.18]) when compared to the MDD group, although these differences did not remain after correction for multiple testing. The sample size was small for targeted metabolomic analysis, and the study did not include a healthy control group. These preliminary results indicate putative differences in one-carbon metabolism and energy metabolism between chronic depression and MDD, possibly due to long-term chronic stress. Metabolic profiles appear to have the potential firstly to identify and distinguish different types of depression, and secondly to help in personalizing treatments in the future.

Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients

Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.

Duration of medical home participation and quality of care for patients with chronic conditions

To examine whether the length of participation in a patient-centered medical home (PCMH), an evidence-based practice, leads to higher quality care for Medicaid enrollees with multiple co-morbid chronic conditions and major depressive disorder (MDD). This analysis uses a unique data source that links North Carolina Medicaid claims and enrollment data with other administrative data including electronic records of state-funded mental health services, a state psychiatric hospital utilization database, and electronic records from a five-county behavioral health carve-out program. This retrospective cohort study uses generalized estimating equations (GEEs) on person-year-level observations to examine the association between the duration of PCMH participation and measures of guideline-concordant care, including the receipt of minimally adequate care for MDD, defined as 6 months of antidepressant use or eight psychotherapy visits each year. Adults with two or more chronic conditions reflected in administrative data, including MDD. We found a 1.7 percentage point increase in the likelihood of receiving guideline-concordant care at 4 months of PCMH participation, as compared to newly enrolled individuals with a single month of participation (p < 0.05). This effect increased with each additional month of PCMH participation; 12 months of participation was associated with a 19.1 percentage point increase in the likelihood of receiving guideline-concordant care over a single month of participation (p < 0.01). The PCMH model is associated with higher quality of care for patients with multiple chronic conditions and MDD over time, and these benefits increase the longer a patient is enrolled. Providers and policy makers should consider the positive effect of increased contact with PCMHs when designing and evaluating initiatives to improve care for this population.

Mismatch negativity in patients with major depressive disorder: A meta-analysis

ObjectiveDeficits of mismatch negativity (MMN), a general index of echoic memory function, have been documented in patients with schizophrenia. However, it remains controversial whether patients with major depressive disorder (MDD) demonstrate MMN defects compared with healthy controls (HC). MethodsAfter screening 41 potential studies identified in PubMed and Medline, 13 studies consisting of 343 HC and 339 patients with MDD were included in the present meta-analysis. The effect sizes (Hedges’s g) with a random-effect and inverse-variance weighted model were estimated for the MMN amplitudes and latencies. The effects of different deviant types (i.e., frequency and duration) and of different illness stages (i.e., acute and chronic) on MMN were also examined. ResultsWe found that 1) MMN amplitudes (g = 1.273, p < 0.001) and latencies (g = 0.303, p = 0.027) to duration, but not frequency deviants, were significantly impaired in patients with MDD compared to HC; 2), acute patients exhibited lower MMN amplitudes (g = 1.735, p < 0.001) and prolonged MMN latencies (g = 0.461, p = 0.007) for the duration deviants compared to HC. Only the attenuated duration MMN amplitudes were detected in patients with chronic MDD (g = 0.822, p = 0.027); and 3) depressive symptoms did not significantly correlate with MMN responses. ConclusionsPatients with MDD demonstrated abnormal MMN responses to duration deviants compared to HC. SignificanceDuration MMN may constitute an electrophysiological indicator to differentiate HC from patients with MDD, particularly those in the acute stage.

Impact of childhood maltreatment on outcomes of antidepressant medication in chronic and/or recurrent depression

BackgroundWhile childhood maltreatment (CMT) is associated with higher rates of chronicity and recurrence in depression, whether CMT results in poorer outcomes with antidepressant medication remains unclear. MethodsWe performed secondary analyses with data from the large, representative, multisite trial Combining Medications to Enhance Depression Outcomes (CO-MED). CO-MED was a randomized, single-blinded, placebo-controlled study with 665 individuals (663 assessed for CMT) with chronic and/or recurrent Major Depressive Disorder (MDD). CMT was determined by a brief self-reported questionnaire assessing the four types of CMT defined by the Centers for Disease Control and Prevention: sexual abuse, emotional abuse, physical abuse, and neglect. Repeated measures and logistic regression analyses were used. ResultsIndividuals with CMT did not have a differential improvement of depressive symptoms when compared to those without CMT (adjusted p=.203 for continuous analysis; adjusted p=.320 for remission rates). Neither type of antidepressant medication (adjusted p=.302) nor the age at which CMT occurred (adjusted p=.509) affected depressive symptom outcomes. There was no difference in functional improvement between individuals with and without CMT (adjusted p=.228). A history of CMT was associated with greater antidepressant side effects (p=.009). LimitationsThis study investigated treatment-seeking individuals with chronic and/or recurrent MDD. Intensity and duration of CMT were not assessed. ConclusionIn a sample of treatment-seeking outpatients with chronic and/or recurrent MDD, a history of CMT was not associated with differential symptomatic or functional response to pharmacological treatment. However, those with CMT reported greater antidepressant side effect burden.

Economic Burden of Treatment-Resistant Depression among Adults with Chronic Non-Cancer Pain Conditions and Major Depressive Disorder in the US.

Major depressive disorder (MDD) and chronic non-cancer pain conditions (CNPC) often co-occur and exacerbate one another. Treatment-resistant depression (TRD) in adults with CNPC can amplify the economic burden. This study examined the impact of TRD on direct total and MDD-related healthcare resource utilization (HRU) and costs among commercially insured patients with CNPC and MDD in the US. The retrospective longitudinal cohort study employed a claims-based algorithm to identify adults with TRD from a US claims database (January 2007 to June 2017). Costs (2018 US$) and HRU were compared between patients with and without TRD over a 12-month period after TRD/non-TRD index date. Counterfactual recycled predictions from generalized linear models were used to examine associations between TRD and annual HRU and costs. Post-regression linear decomposition identified differences in patient-level factors between TRD and non-TRD groups that contributed to the excess economic burden of TRD. Of the 21,180 adults with CNPC and MDD, 10.1% were identified as having TRD. TRD patients had significantly higher HRU, translating into higher average total costs (US$21,015TRD vs US$14,712No TRD) and MDD-related costs (US$1201TRD vs US$471No TRD) compared with non-TRD patients (all p< 0.001). Prescription drug costs accounted for 37.6% and inpatient services for 30.7% of the excess total healthcare costs among TRD patients. TRD patients had a significantly higher number of inpatient (incidence rate ratio [IRR] 1.30, 95% CI 1.14-1.47) and emergency room visits (IRR 1.21, 95% CI 1.10-1.34) than non-TRD patients. Overall, 46% of the excess total costs were explained by differences in patient-level characteristics such as polypharmacy, number of CNPC, anxiety, sleep, and substance use disorders between the TRD and non-TRD groups. TRD poses a substantial direct economic burden for adults with CNPC and MDD. Excess healthcare costs may potentially be reduced by providing timely interventions for several modifiable risk factors.

Using a machine learning approach to investigate factors associated with treatment-resistant depression among adults with chronic non-cancer pain conditions and major depressive disorder

Objective Presence of chronic non-cancer pain conditions (CNPC) among adults with major depressive disorder (MDD) may reduce benefits of antidepressant therapy, thereby increasing the possibility of treatment resistance. This study sought to investigate factors associated with treatment-resistant depression (TRD) among adults with MDD and CNPC using machine learning approaches. Methods This retrospective cohort study was conducted using a US claims database which included adults with newly diagnosed MDD and CNPC (January 2007–June 2017). TRD was identified using a clinical staging algorithm for claims data. Random forest (RF), a machine learning method, and logistic regression was used to identify factors associated with TRD. Initial model development included 42 known and/or probable factors that may be associated with TRD. The final refined model included 20 factors. Results Included in the sample were 23,645 patients (73% female mean age: 55 years; 78% with ≥2 CNPC, and 91% with joint pain/arthritis). Overall, 11.4% adults (N = 2684) met selected criteria for TRD. The five leading factors associated with TRD were the following: mental health specialist visits, polypharmacy (≥5 medications), psychotherapy use, anxiety, and age. Cross-validated logistic regression model indicated that those with TRD were younger, more likely to have anxiety, mental health specialist visits, polypharmacy, and psychotherapy use with adjusted odds ratios (AORs) ranging from 1.93 to 1.27 (all ps < .001). Conclusion Machine learning identified several factors that warrant further investigation and may serve as potential targets for clinical intervention to improve treatment outcomes in patients with TRD and CNPC.