Major Depressive Disorder In Relation Research Articles

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.

The more you need, the less you get: Intersectionality and the inverse care law in the Brazilian depression care cascade

ABSTRACT Substantial research has shown that the population distribution of major depressive disorder (MDD) is strongly influenced by race, gender, and socioeconomic position. However, a deeper understanding of inequities in access to care for MDD according to these social markers is yet to be reached. We use data from the 2019 Brazilian National Health Survey, which includes 87,187 respondents aged 18 years and over, to test two hypotheses derived from the inverse care law: women, Black, and low-education respondents have higher frequencies of MDD, but lower access to each step of the depression care cascade, including diagnosis by a health professional, regular healthcare visits, and access to specialised treatment (H1); low-education Black women show the highest MDD frequency and the lowest access to care across the entire cascade (H2). Partially supporting H1 and H2, our results reveal a bottleneck in the first step of the depression care cascade. While no racial inequities were observed in the MDD prevalence, Black individuals were less likely than whites to be diagnosed by a health professional (OR 0.74). Women (OR 2.64) and low-education (OR 1.18) were more likely to have probable MDD in relation to men and high-education respondents, respectively, but only women (OR 1.58) were more likely to be diagnosed. Low-education Black women were equally more likely to have probable MDD (OR 3.11) than high-education white men. Conversely, high-education white women emerged as the most likely to be diagnosed with MDD (OR 1.63). Our findings suggest the inverse care law applies to the depression care cascade in Brazil through indication that its healthcare system perpetuates a multilayered system of oppression that overlooks multiply marginalised individuals. We also show that adequate screening by health care professionals should mitigate the complex patterns of inequity revealed by our study.

The Interplay of Childhood Maltreatment and Maternal Major Depressive Disorder in Relation to Youth’s Neural Reward Responsiveness

Neural reward system deficits represent one possible mechanistic pathway linking maternal major depressive disorder (MDD) to youth depression vulnerability. However, many youth exposed to maternal depression do not exhibit problematic reward functioning styles, suggesting that other factors exacerbate risk patterns. One subgroup at risk for reward processing deficits is youth exposed to childhood maltreatment; however, no studies have examined the interplay between early life adversity and maternal MDD in predicting reward processing deficits in youth. The current study examined whether childhood maltreatment moderated the link between maternal MDD and children's neural reward reactivity, assessed via the reward positivity (RewP) event-related potential (ERP) component.

Transdiagnostic emotion regulation processes explain how emotion-related factors affect co-occurring PTSD and MDD in relation to trauma

BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder (MDD) co-occur at high rates and greater disorder severity. Studies examining the contributions of specific emotion regulation (ER) processes and negative affect (NA) to PTSD and MDD co-occurrence are scarce. This study investigated a transdiagnostic understanding of the nature of PTSD and MDD co-occurrence by examining the roles of NA, ER processes, and negative mood regulation (NMR) expectancies in PTSD and MDD in relation to trauma. MethodsStructural equation modeling was used to examine the roles of emotionality, PTSD, and MDD constructs in 200 individuals with primary PTSD. ResultsER processes fully mediated the relationships between NA and PTSD (β = .40, p < .001) and MDD (β = .48, p < .001), and NMR expectancies and PTSD (β = −.31, p < .001) and MDD (β = −.37, p < .001). ConclusionsNA and NMR expectancies exert their effects on PTSD and MDD almost entirely through ER processes. ER appears to be a transdiagnostic process, partly accounting for the co-occurrence between PTSD and MDD. Co-occurrence models could benefit by incorporating ER processes to inform diagnostic classification and criteria and clinical intervention improved by specifically targeting ER processes.

Familial aggregation of major depressive disorder in an African-American community.

African Americans (AAs) with major depressive disorder (MDD) experience more impairment and poorer treatment outcomes relative to Whites, yet are underrepresented in family studies of MDD. This is the first study to investigate the familial aggregation of major depression among AAs. Participants' reports of depression from clinical and family history (FH) interviews were used to examine depression rates among 435 first-degree relatives and half-siblings of 63 depressed cases and 222 relatives of 33 nondepressed controls. Binary logistic regression was used to compute odds ratios (ORs) for FH of MDD and level of trauma exposure (high and low) in cases versus controls. Poisson regression models with generalized estimating equations were used to assess MDD in relatives of cases versus relatives of controls. Cases and controls did not differ in either FH of MDD (OR=1.2, 95% confidence interval [CI]=0.5-2.9), or prevalence of MDD in relatives (relative risk [RR]=1.5, 95% CI=0.8-2.5). However, exposure to high trauma was associated with increased risk of MDD (OR=3.0, 95% CI=1.22-7.17) and the combined effect of FH and trauma was greater than expected under an additive model. Similarly, the RR for MDD among relatives of cases with high-trauma levels was 2.2 (1.24-4.2), compared to relatives of controls with low trauma. The effect of FH of MDD appears to be exacerbated among individuals exposed to high trauma. Replication and further research on the chronology and subtypes of trauma and MDD, and their interactions, remain essential in AA populations.

The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review.

Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs.

Quality of life, family burden and associated factors in relatives with obsessive–compulsive disorder

ObjectiveThe aim of this study is to assess the quality of life (QoL), family burden and psychiatric disorders in first-degree relatives of patients with obsessive–compulsive disorder (OCD) and to compare them with healthy controls and their relatives. MethodsForty patients with OCD and 47 of their first-degree relatives as well as 40 healthy subjects and 45 of their first-degree relatives were recruited in this study. OCD and comorbid anxiety or mood disorders were determined by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Comorbid Axis II disorders were diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition Personality Disorders. Type and severity of obsessive–compulsive symptoms were assessed with the Yale–Brown Obsessive–Compulsive Scale, and the disability of patients with OCD was evaluated with the WHO DAS II. Family burden and QoL in the relatives were evaluated with the Zarit Burden Interview (ZBI) protocol and the World Health Organization Quality of Life Assessment—Brief, respectively. ResultsThe mean ZBI score of family members of OCD patients was higher than the control relatives. Linear regression analysis indicated that the independent factors associated with ZBI were duration of OCD, comorbid major depressive disorder and poorer insight. Compared with those of control relatives, the QoL of relatives of patients with OCD was significantly lower in all domains. While the diagnosis of major depressive disorder in relatives of OCD patients was significantly higher than the control relatives, the diagnosis of any anxiety disorder did not differ. ConclusionsOur study provides evidence that OCD not only affects the lives of patients but also their family members.

Is depression a disconnection syndrome? Meta- analysis of diffusion tensor imaging studies in patients with MDD

Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI. A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms "DTI" or "diffusion tensor;" "whole brain" or "voxel-based;" and "depress*." Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region. We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum. The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences. Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This isstrong evidence for the involvement of these neural circuits in the pathology of MDD.

Differences in temperament and character dimensions of personality between patients with Hwa-byung, an anger syndrome, and patients with major depressive disorder

This study examined differences in temperament and character dimensions of personality between patients with Hwa-byung (HB) and those with major depressive disorder (MDD). Of 144 participants, 96 completed the Korean version of the Temperament and Character Inventory-Revised Short (TCI-RS) and the Hwa-byung Scale. We diagnosed participants according to the DSM-IV and the Research Diagnostic Criteria for Hwa-byung. We compared TCI scores between the HB group (with or without MDD; N=55) and the MDD-only group (N=41) and correlated them with the total scores on six HB-specific symptoms (global HB severity) on the Hwa-byung Scale. Compared to patients with only MDD, patients with HB with or without MDD exhibited significantly higher scores on Impulsiveness; Harm Avoidance (HA) and its subscales of Anticipatory Worry; and Self-Transcendence (ST), with its subscale of Self-Forgetfulness. However, HB patients had lower scores on Self-Directedness, with its subscales of Responsibility, and Self-Acceptance; and Acceptance. Moreover, Global HB Severity had significant, positive correlations with ST, its subscale Self-Forgetfulness, and Anticipatory Worry but negative correlations with Attachment and Compassion. Our data are cross-sectional and self-reported, so they are subject to personal perceptual bias. The number of participants may be too low for us to generalize the results. These results suggest that HB is a different clinical entity from MDD in relation to personality traits, and that symptoms unique to HB are closely correlated with ST.

Brain volume abnormalities in major depressive disorder: A meta‐analysis of magnetic resonance imaging studies

So far, there have been no attempts to integrate the growing number of all brain volumetric magnetic resonance imaging studies in depression. In this comprehensive meta-analysis the magnitude and extent of brain volume differences between 2,418 patients with major depressive disorder and 1,974 healthy individuals from 64 studies was determined. A systematic research was conducted for volumetric magnetic resonance imaging studies of patients with major depressive disorder in relation to healthy control subjects. Studies had to report sufficient data for computation of effect sizes. For each study, the Cohen's d was calculated. All analyses were performed using the random effects model. Additionally, meta-regression analyses were done to explore the effects of potential sources of heterogeneity. Patients showed large volume reductions in frontal regions, especially in the anterior cingulate and orbitofrontal cortex with smaller reductions in the prefrontal cortex. The hippocampus, the putamen and caudate nucleus showed moderate volume reductions. This is the first comprehensive meta-analysis in major depressive disorder demonstrating structural brain abnormalities, particularly in those brain areas that are involved in emotion processing and stress-regulation.

Clinical characteristics of Major Depressive Disorder run in families – A community study of 933 mothers and their children

The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother–offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children’s sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.

Familial aggregation of depression in fibromyalgia: a community-based test of alternate hypotheses

Numerous studies report that fibromyalgia (FM), a syndrome characterized by widespread pain and generalized tender points, is comorbid with major depressive disorder (MDD). The current study tests two alternate explanations for their comorbidity using a family study methodology. The first is that FM is a depression spectrum disorder. The second is that depression is a consequence of living with FM. We recruited potential probands by initially screening by telephone for FM and MDD among women in the NY/NJ metropolitan area, randomly selecting telephone numbers from a list of households with women. Eligible women were invited for second stage physical examinations for FM diagnosis and psychiatric interviews for MDD diagnosis. All available adult, first-degree relatives received psychiatric interviews. Relatives of probands were divided into four groups on the basis of the probands' FM and MDD diagnoses (FM+/MDD+ ( n=156), FM+/MDD− ( n=51), FM−/MDD+ ( n=351) and FM−/MDD− ( n=101)). Results indicated that rates of MDD in the relatives of probands with FM but without personal histories of MDD were virtually identical to rates of MDD in relatives of probands with MDD themselves. This outcome is consistent with the hypothesis that FM is a depression spectrum disorder, in which FM and MDD are characterized by shared, familially mediated risk factors. The implications of these findings for a stress-vulnerability model of FM are discussed.

Myofascial pain and fibromyalgia: Familial aggregation of depression in fibromyalgia: A community-based test of alternate hypotheses

Numerous studies report that fibromyalgia (FM), a syndrome characterized by widespread pain and generalized tender points, is comorbid with major depressive disorder (MDD).The current study tests two alternate explanations for their comorbidity using a family study methodology. The first is that FM is a depression spectrum disorder. The second is that depression is a consequence of living with FM. We recruited potential probands by initially screening by telephone for FM and MDD among women in the NY/NJ metropolitan area, randomly selecting telephone numbers from a list of households with women. Eligible women were invited for second stage physical examinations for FM diagnosis and psychiatric interviews for MDD diagnosis. All available adult, firstdegree relatives received psychiatric interviews. Relatives of probands were divided into four groups on the basis of the probands FM and MDD diagnoses, FM /MDD (n 160), FM /MDD-(n 53), FM-/MDD (n 351) and FM-/MDD(n 103). Results indicated that rates of MDD in the relatives of probands with FM but without personal histories of MDD were virtually identical to rates of MDD in relatives of probands with MDD themselves. This outcome is consistent with the hypothesis that FM is a depression spectrum disorder, in which FM and MDD are characterized by shared, familially-mediated risk factors. The implications of these findings for a stress-vulnerability model of FM are discussed.

Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder

To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD had at least one comorbid anxiety disorder. Early age at onset (<10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants.

The influence of age on gender differences in depression: further population-based evidence on the relationship between menopause and the sex difference in depression.

This study tests the hypothesis that gender differences in depression diminish after menopause (around the age of 55). Methods Using the 1994 National Population Health Survey, we examine the relationship between age and gender on major depressive disorder in relation to sociodemographic and social covariates using contingency table analyses and multivariate logistic regression. Contingency table and multivariate analyses identify significantly higher rates of depression among women before and after the age period associated with menopause. A series of multivariate analyses controlling for a broad array of social factors also does not lead to any convergence in differences of rates of depression between males and females. Hormone replacement therapy (HRT) does not have a significant impact on these observed relationships. These findings are at odds with a recent study that has identified menopause as a point where gender differences in depression diminish. Further research is required to address this inconsistency.

Clinical features of major depressive disorder in adolescents and their relatives: Impact on familial aggregation, implications for phenotype definition, and specificity of transmission.

Three questions were addressed using family study data from a community sample: (a) Which clinical features of major depressive disorder (MDD) in adolescents are associated with elevated rates of MDD in relatives? (b) Which features of MDD in relatives distinguish family members of depressed adolescents from relatives of adolescents without mood disorders (NMD)? and (c) Do depressed adolescents with particular features have higher proportions of depressed relatives with the same features? Participants included 268 MDD adolescents, 401 NMD adolescents, and their 2,202 first-degree relatives. Rates of MDD were highest among relatives of depressed adolescents with recurrent episodes and greater impairment. Depression severity best distinguished the relatives of depressed adolescents from relatives of controls. Specific clinical features did not aggregate in families.

Adult onset of major depressive disorder in relation to early life violent victimisation: a case-control study

Major depressive disorder is a significant cause of morbidity among women in the USA. Women are twice as likely as men to be diagnosed with major depressive disorder, yet no known risk factors can account for this sex difference. We aimed to assess violent victimisation as a risk factor for depression in women. We undertook a case-control study to assess the association between violent victimisation early in life and major depressive disorder in women. We randomly selected a population-based sample of women, aged 36-45 years, from the greater Boston area. In 1999, 236 cases and 496 controls (n=732) completed a self-administered questionnaire designed to ascertain a lifetime history of exposure to violent victimisation. Our main outcome measure was major depressive disorder, assessed by structured clinical interview for Diagnostic Statistical Manual IV (DSM-IV) criteria. 363 (50%) of 732 respondents reported experience or fear of abuse as a child or adolescent. 68 were excluded because they reported violence as an adult only. Compared with women who reported no abuse, risk of depression was increased in women who reported any abuse as a child or adolescent (relative risk 2.5, 95% CI 1.9-3.0), physical abuse only (2.4, 1.8-3.0), sexual abuse only (1.8, 1.2-2.8), and both physical and sexual abuse (3.3, 2.5-4.1). Severity of abuse had a linear dose-response relation with depression. Our results suggest a positive association between violent victimisation early in life and major depressive disorder in women.

Family study of panic disorder

Family studies have demonstrated that genetic factors are involved in panic and other anxiety disorders. In order to investigate these factors, 25 probands with panic disorder (PD) were compared with three other groups (age and sex matched): patients with generalized anxiety disorder (GAD), major depressive disorder (MDD), and normal subjects. About 75% of all first-degree relatives were personally interviewed. Age-corrected morbidity risk (MR) was calculated according to the Stromgren method. The distribution of psychopathology in first-degree relatives showed significantly greater MR for PD in the relatives of PD probands in comparison with all groups. For all anxiety disorders and various psychiatric disorders, relatives of PD patients also showed greater MR than controls. The frequency of GAD and MDD in relatives did not discriminate between the groups. The results of this study validate PD as a separate illness from GAD, the differentiation of PD from MDD, and support the hypothesis of a genetic contribution to the predisposition of PD.

Prediction of postdexamethasone cortisol levels by serum sodium levels in patients with major depression.

The authors analyzed the dexamethasone suppression test (DST) results of 54 patients with major depressive disorder in relation to their pre-DST levels of cholesterol, sodium, potassium, and blood glucose, which are thought to have adrenocorticotrophic links. Discriminant analysis revealed that sodium alone was a significant predictor of nonsuppression. Validation of the predictive power of sodium could minimize the need for DST administration.

Breast-feeding

<h3>Abstract</h3> <h3>Background</h3> Major depressive disorder (MDD) is characterized by elevated activity of peripheral neuro-immune and neuro-oxidative pathways, which may cause neuro-affective toxicity by disrupting neuronal circuits in the brain. No study has explored peripheral indicators of neuroaxis damage in MDD in relation to serum inflammatory and insulin resistance (IR) biomarkers, calcium, and the physio-affective phenome consisting of depressive, anxious, chronic fatigue, and physiosomatic symptoms. <h3>Methods</h3> Serum levels of phosphorylated tau protein 217 (P-tau217), platelet-derived growth factor receptor beta (PDGFR), neurofilament light chain (NF-L), glial fibrillary acidic protein (GFAP), C-reactive protein (CRP), calcium and the HOMA2-insulin resistance (IR) index were measured in 94 MDD patients and 47 controls. <h3>Results</h3> 61.1% of the variance in the physio-affective phenome (conceptualized as a factor extracted from depression, anxiety, fatigue and physiosomatic symptoms) is explained by the regression on GFAP, NF-L, P-tau2017, PDGFRβ and HOMA2-IR (all positively associated), and decreased calcium. In addition, CRP and HOMA2-IR predicted 28.9% of the variance in the neuroaxis index. We observed significant indirect effects of CRP and calcium on the physio-affective phenome which were partly mediated by the four neuroaxis biomarkers. Annotation and enrichment analysis revealed that the enlarged GFAP, P-tau217, PDGFR, and NF-L network was enriched in glial cell and neuronal projections, the cytoskeleton and axonal transport, including a mitochondrion. <h3>Conclusions</h3> Peripheral inflammation and IR may damage the astroglial and neuronal projections thereby interfering with mitochondrial transport. This toxicity, combined with inflammation, IR and lowered calcium, may, at least in part, induce the phenome of MDD.