Remission Of Major Depressive Disorder Research Articles

Self-reported affective biases, but not all affective performance biases, are present in depression remission.

Individuals with active major depressive disorder (MDD) have shown affective biases in cognitive flexibility and memory, particularly for negatively valenced stimuli. We evaluated whether impairments in affective flexibility would remain even during remission (rMDD), potentially representing trait- or scar-like effects of illness. Participants completed the Emotion Card Sort Test (ECST), a measure of cognitive flexibility containing emotionally valenced stimuli, and the Emotion Word Stimulus Test (EWST), a measure of affective biases in delayed recall and recognition memory, and several self-report measures. Healthy controls (HCs; n=35) and individuals with rMDD (n=93) did not differ on performance for any of the three word types on the ECST or EWT. However, individuals with rMDD demonstrated greater negative bias on EWT recognition trials relative to HCs (d=.36). On self-report measures, individuals with rMDD exhibited greater levels of neuroticism, problems with attentional control, pessimistic attributional style, and negative automatic thoughts compared to HCs. These results provide initial evidence that some performance, but not self-reported, indices of affective bias may improve during remission from MDD. Results of this study could suggest that some components of affective bias may represent state feature of illness and others trait-like risk or scar features. This study suggests that self-reported affective biases may persist in remission of major depressive disorder (rMDD). Affective attentional biases and affective memory biases were not demonstrated in individuals with rMDD, with the exception of a bias for recognizing negatively versus neutrally valenced stimuli. A limitation of this study was its cross-sectional design. Under ideal conditions, the same individuals would be studied in both the active and remitted phases of illness. Another limitation of this study was the smaller number of healthy controls relative to individuals with rMDD.

RELATIONSHIP OF HAIR CORTISOL CONCENTRATION WITH HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND EVERYDAY FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSIVE DISORDER

Introduction Psychotic features are more prevalent in older adults with depression than in younger depressed adults. Psychotic major depressive disorder (PMD) is associated with poorer neuropsychological performance and poorer everyday functioning, in both acute and remitted states, compared with non-psychotic major depressive disorder (NPMD). In addition, PMD is also associated with more pronounced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including elevated cortisol levels, but it is not known whether this difference between PMD and NPMD persists in remission. The goal of this exploratory study was to test the hypothesis that a history of psychotic features, poorer neuropsychological performance, and poorer everyday functioning were associated with higher cortisol levels in sustained remission of major depressive disorder. If confirmed, it could suggest a possible mechanism for neuropsychological and functional impairment in remitted PMD. In order to examine the relationship between sustained HPA dysfunction in remission and the aforementioned variables, we measured hair cortisol concentration (HCC), a measure of longer-term cortisol exposure. Methods This study used a cross-sectional design and included 60 participants aged 50 years or older with a history of major depressive disorder (n = 17 with NPMD and n = 43 with PMD) in sustained remission and 36 non-psychiatric comparison participants. Hair samples were collected using standardized methods and cortisol concentrations were determined from the first 3-cm hair segment most proximal to the scalp, or from as much hair as was available for participants with shorter hair. This hair segment represents the hair growth over the 3-month period prior to the sampling. HCC was measured in a research laboratory with extensive experience in this analysis using a validated high sensitivity enzyme immunoassay (EIA) that is standard in the field. In order to examine the relationships between HCC and i) history of psychotic features, ii) neuropsychological performance (processing speed, executive function, and verbal memory), and iii) everyday functioning (participant-report general functioning and observer-rated IADL performance), we performed three sets of correlation analyses, one for each variable of interest (point biserial for psychosis history and HCC; Pearson's r for neuropsychological and functional measures). We calculated effect sizes and 95% confidence limits in order to compare HCC results between patient and non-psychiatric comparison groups. HCC data were highly skewed and were log transformed for all analyses. Results NPMD and PMD groups had mean (SD) HCCs of 18.86 (32.97) pg/mg and 12.48 (11.26) pg/mg, respectively. The correlation between HCC and history of psychosis was weak (r = -0.02), as were the correlations between HCC and the neuropsychological measures (r ranging between -0.11 and 0.1). The correlations between HCC and i) IADL performance (r = -0.04) and ii) general functioning (r = -0.074) were also weak. None of these correlations were statistically significant. The mean (SD) HCC for non-psychiatric comparison subjects was 13.86 (20.06) pg/mg. Both effect sizes for the difference between the clinical and non-psychiatric comparison groups were small (0.26 for NPMD versus Comparison group and 0.25 for PMD versus Comparison group). Conclusions This is the first study to assess HCC in PMD and to examine the relationship between HCC and cognition and between HCC and everyday functioning in MDD. We did not find a correlation between HCC and history of psychosis, neuropsychological performance, or functioning in later-life patients with MDD in sustained remission. Further, there was no substantial difference in mean HCC between the patient and non-psychiatric comparison group. There is variability in the literature regarding HCC in MDD and regarding the relationship between HPA-axis function and neuropsychological performance in remitted MDD. Our findings will be discussed in this context. This research was funded by This study was funded by a research grant from the University Health Network Centre for Mental Health ($14,000)

Rehabilitative compensatory mechanism of hierarchical subnetworks in major depressive disorder: A longitudinal study across multi-sites

BackgroundBrain structural connectome comprise of a minority of efficiently interconnected rich club nodes that are regarded as ‘high-order regions’. The remission of major depressive disorder (MDD) in response to selective serotonin reuptake inhibitor (SSRI) treatment could be investigated by the hierarchical structural connectomes’ alterations of subnetworks. MethodsFifty-five MDD patients who achieved remission underwent diffusion tensors imaging (DTI) scanning from 3 cohorts before and after 8-weeks antidepressant treatment. Five hierarchical subnetworks namely, rich, local, feeder, rich-feeder and feeder-local, were constructed according to the different combinations of connections and nodes as defined by rich club architecture. The critical treatment-related subnetwork pattern was explored by multivariate pattern analysis with support vector machine to differ the pre-/post-treatment patients. Then, relationships between graph metrics of discriminative subnetworks/ nodes and clinical variables were further explored. ResultsThe feeder-local subnetwork presented the most discriminative power in differing pre-/post- treatment patients, while the rich-feeder subnetwork had the highest discriminative power when comparing pre-treatment patients and controls. Furthermore, based on the feeder connection, which indicates the information transmission between the core and non-core architectures of brain networks, its topological measures were found to be significantly correlated with the reduction rate of 17-item Hamilton Rating Scale for Depression. ConclusionAlthough pathological lesion on MDD relied on abnormal core organization, disease remission was association with the compensation from non-core organization. These results suggested that the dysfunctions arising from hierarchical subnetworks are compensated by increased information interactions between core brain regions and functionally diverse regions.

Examining the Link Between Cardiovascular Risk Factors and Neuropsychiatric Symptoms in Mild Cognitive Impairment and Major Depressive Disorder in Remission.

Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified. Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms. We examined the distribution of NPS using the Neuropsychiatric Inventory (NPI) scores in three cohorts from the Prevention of Alzheimer's Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study: older patients with a lifetime history of major depressive disorder (MDD) in remission, patients with mild cognitive impairment (MCI), and patients with combined MCI and MDD. We also examined the link between individual NPS and CVRFs, Framingham risk score, and Hachinski ischemic score in a combined sample. Analyses were based on a sample of 140 subjects, 70 with MCI, 38 with MCI plus MDD, and 32 with MDD. There was no effect of age, gender, education, cognition, or CVRFs on the presence (NPI >1) or absence (NPI = 0) of NPS. Depression was the most prevalent affective NPS domain followed by night-time behaviors and appetite changes across all three diagnostic groups. Agitation and aggression correlated negatively while anxiety, disinhibition, night-time behaviors, and irritability correlated positively with CVRFs (all p-values <0.05). Other NPS domains showed no significant association with CVRFs. CVRFs are significantly associated with individual NPI sub-scores but not with total NPI scores, suggesting that different pathologies may contribute to different NPS domains.

Acceptance and present-moment awareness in psychiatric disorders: Is mindfulness mood dependent?

The aim of the present study was to determine 1) whether deficits in two mindfulness dimensions (present-centered awareness and acceptance) were present in individuals with different psychiatric conditions and 2) whether co-existing depressive symptoms affected the mindfulness-related capacities in these groups. A total of 246 individuals, both clinical and non-clinical participants, were included in this study. The clinical sample consisted of 162 individuals; of these, 43 had a diagnosis of cocaine dependence while the remaining 119met clinical criteria for eating disorders (n = 43), major depressive disorder in remission (n = 39), and borderline personality disorder (n = 45). A non-clinical (NC) community sample consisting of 76 individuals was included as a control group. All participants completed self-report instruments to assess present-centered awareness, acceptance, and depressive symptoms. Present-centered awareness scores were significantly associated with depressive symptoms but not with the diagnostic group. By contrast, a significant effect of depressive symptoms and diagnostic group was associated with acceptance scores, with all clinical groups presenting significantly lower scores than the NC sample. These findings suggest that the association between psychopathology, mindfulness, and depressive symptoms varies depending on the specific aspect of mindfulness aspect (i.e., awareness or acceptance) evaluated.

Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials.

To conducted a systematic review and meta-analysis of prospective, randomized controlled trials (RCTs) that examined pharmacogenetic-guided decision support tools (DSTs) relevant to depressive symptom remission in major depressive disorder (MDD). Random-effects meta-analysis was performed on RCTs that examined the effect of DSTs on remission rates in MDD. RCT quality was assessed using the Cochrane Collaboration Criteria. A total of 1737 eligible subjects from five RCTs were examined. Individuals receiving pharmacogenetic-guided DST therapy (n=887) were 1.71 (95% CI: 1.17-2.48; p =0.005) times more likely to achieve symptom remission relative to individuals who received treatment as usual (n=850). Pharmacogenetic-guided DSTs might improve symptom remission among those with MDD.

Divergent associations between ghrelin and neural responsivity to palatable food in hyperphagic and hypophagic depression

BackgroundThe neurobiological mechanisms involved in divergent appetitive phenotypes in major depressive disorder (MDD) are not well understood, although recent data suggest disruption in mesolimbic reward circuitry. Ghrelin, an orexigenic hormone, has been shown to modulate the reward circuitry. We aimed to investigate the relationship between acylated ghrelin levels and the neural response to food stimuli in individuals with hyperphagic and hypophagic MDD in remission. MethodsWomen with hyperphagic MDD (n = 10), hypophagic MDD (n = 18), and healthy controls (HC; n = 18) underwent fMRI scanning during which they viewed images of food. The fMRI session was followed by a standardized meal, appetite ratings, and serial blood draws. ResultsIn individuals with hyperphagic MDD, greater change in acylated ghrelin in response to a meal was associated with increased BOLD response to high-calorie food in the bilateral ventral tegmental area and left hypothalamus. In contrast, negative associations were observed between acylated ghrelin AUC and BOLD activity in the right hypothalamus in the hypophagic MDD group. LimitationsUnbalanced group sizes with a relatively small sample in the hyperphagic MDD group. ConclusionsIn the absence of differences in absolute ghrelin levels between the hyperphagic MDD and HC groups, results in hyperphagic MDD might suggest a ghrelinergic signaling mechanism for increased appetite during an MDD episode in this group. Our findings shed light on interactions between appetite hormones and mesolimbic circuitry which could contribute to development of therapeutic targets for opposing appetite phenotypes in depression.

Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant Treatment in Female Outpatients with Major Depressive Disorder.

ObjectiveSome clinical studies have found alterations in the levels of serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) after applying antidepressant treatment in patients with major depressive disorder (MDD). We evaluated the serum BDNF and GDNF levels before and after 12 weeks of antidepressant treatment in MDD outpatients. MethodsSerum BDNF and GDNF levels were measured in 23 female MDD outpatients at baseline and after 12 weeks of treatment. The severity of depression was measured with the Hamilton Depression Rating Scale-17 (HAMD-17). Remission of MDD to the treatment was defined as a posttreatment HAMD-17 score of <7. ResultsAmong MDD patients, 19 (82.6%) subjects were in mild to moderate depression. The whole MDD patients had significantly higher serum BDNF and GDNF levels at baseline than those after 12 weeks of antidepressant treatment. The baseline serum BDNF and GDNF levels did not significantly between the remission and nonremission groups. The significant alteration in both BDNF and GDNF levels after antidepressant treatment were observed in patients with remission. ConclusionThe present study suggests that the baseline serum BDNF and GDNF levels are higher than the posttreatment levels in some mild-to-moderate MDD outpatients and the significant alteration in BDNF and GDNF level after treatment were observed in patients with remission.

Child abuse potential in mothers with early life maltreatment, borderline personality disorder and depression.

Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.AimsOur study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology. The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables. ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child. History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.Declaration of interestNone.

5-HTTLPR and MTHFR 677C>T polymorphisms and response to yoga-based lifestyle intervention in major depressive disorder: A randomized active-controlled trial.

Background:There is growing evidence suggesting that both genetic and environmental factors modulate treatment outcome in, a highly heterogeneous, major depressive disorder (MDD). 5-HTTLPR variant of the serotonin transporter gene (SLC6A4) and MTHFR 677C>T polymorphisms have been linked to the pathogenesis of MDD, and antidepressant treatment response. The evidence is lacking on the clinical utility of yoga in patients with MDD who have 5-HTTLPR and MTHFR 677C>T polymorphisms and less likely to respond to medications (SSRIs).Aims:We aimed to examine the impact of YBLI in those who have susceptible 5-HTTLPR and MTHFR 677C>T polymorphisms and are less likely to drug therapy with SSRIs.Settings and Design:In a 12 week randomized active-controlled trial, MDD patients (n = 178) were randomized to receive YBLI or drug therapy.Methods:Genotyping was conducted using PCR-based methods. The clinical remission was defined as BDI-II score ≤ 9.Statistical Analysis Used:An intent-to-treat analysis was performed, and the association of genotype with treatment remission consisted of the logistic regression model. A P value of <0.05 was considered statistically significant.Results:Multivariate logistic regression models for remission including either 5-HTTLPR or MTHFR 677C>T genotypes showed statistically significant odds of remission in YOGA arm vs. DRUG arm. Neither 5-HTTLPR nor MTHFR 677C>T genotype showed any influence on remission to YBLI (P = 0.73 and P = 0.64, respectively). Further analysis showed childhood adversity interact with 5-HTTLPR and MTHFR 677C>T polymorphisms to decrease treatment response in DRUG treatment arm, but not in YOGA arm.Conclusions:YBLI provides MDD remission in those who have susceptible 5-HTTLPR and MTHFR 677C>T polymorphisms and are resistant to SSRIs treatment. YBLI may be therapeutic for MDD independent of heterogeneity in its etiopathogenesis.

Collaborative Care Management Associated With Improved Depression Outcomes in Patients With Personality Disorders, Compared to Usual Primary Care.

Background: The use of a collaborative care management (CCM) model can dramatically improve short- and long-term treatment outcomes for patients with major depressive disorder (MDD). Patients with comorbid personality disorder (PD) may experience poorer treatment outcomes for MDD. Our study seeks to examine the differences in MDD treatment outcomes for patients with comorbid PD when using a CCM approach rather than usual care (UC). Methods: In our retrospective cohort study, we reviewed the records of 9614 adult patients enrolled in our depression registry with the clinical diagnosis MDD and the diagnosis of PD (Yes/No). Clinical outcomes for depression were measured with Patient Health Questionnaire–9 (PHQ-9) scores at 6 months. Results: In our study cohort, 59.4% of patients (7.1% of which had comorbid PD) were treated with CCM, as compared with 40.6% (6.8% with PD) treated with UC. We found that the presence of a PD adversely affected clinical outcomes of remission within both groups, however, at 6 months patients with PD had significantly lower MDD remission rates when treated with UC as compared with those treated with CCM (11.5% vs 25.2%, P = .002). Patients with PD in the UC group were also noted to have an increased rate of persistent depressive symptoms (PHQ-9 score ≥10) at 6 months as compared with those in the CCM group (67.7% vs 51.7%, P = .004). Conclusions: In patients with comorbid MDD and PD, clinical outcomes at 6 months were significantly improved when treated with CCM compared with UC. This finding is encouraging and supports the idea that CCM is an effective model for caring for patients with behavioral concerns, and it may be of even greater benefit for those patients being treated for comorbid behavioral health conditions.

Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder

BackgroundMajor depressive disorder (MDD) is a debilitating mental illness and a major cause of lost productivity worldwide. MDD patients often suffer from lifelong recurring episodes of increasing severity, reduced therapeutic response, and shorter remission periods, suggesting the presence of a persistent and potentially progressive pathology. MethodsSubgenual anterior cingulate cortex postmortem samples from four MDD cohorts (single episode, n = 20; single episode in remission, n = 15; recurrent episode, n = 20; and recurrent episode in remission, n = 15), and one control cohort (n = 20) were analyzed by mass spectrometry–based proteomics (n = 3630 proteins) combined with statistical analyses. The data was investigated for trait and state progressive neuropathologies in MDD using both unbiased approaches and tests of a priori hypotheses. ResultsThe data provided weak evidence for proteomic differences as a function of state (depressed/remitted) or number of previous episodes. Instead it suggested the presence of persistent MDD effects, regardless of episodes or remitted state, namely on proteomic measures related to presynaptic neurotransmission, synaptic function, cytoskeletal rearrangements, energy metabolism, phospholipid biosynthesis/metabolism, and calcium ion homeostasis. Selected proteins (dihydropyrimidinase-related protein 1, synaptosomal-associated protein 29, glutamate decarboxylase 1, metabotropic glutamate receptor 1, and excitatory amino acid transporter 3) were validated by Western blot analysis. The findings were independent of technical, demographic (sex or age), or other clinical parameters (death by suicide and drug treatment). ConclusionsCollectively, the results provide evidence for persistent MDD effects across current episodes or remission, in the absence of detectable progressive neuropathology.

Increased neural and pupillary reactivity to emotional faces in adolescents with current and remitted major depressive disorder.

This study combined multiple levels of analysis to examine whether disrupted neural and pupillary reactivity to emotional faces serves as a state- or trait-like marker of adolescent major depressive disorder (MDD). The study examined differences in pupil dilation and the event-related potential (ERP) late positive potential (LPP) component to emotional faces before and after a negative mood induction between 71 adolescents (age 11–18 years) with (i) a current diagnosis of MDD, (ii) a past episode of MDD currently in full remission and (iii) no lifetime history of any Axis I disorder. Relative to healthy control (HC) youth, adolescents with current or remitted MDD exhibited an enhanced LPP and pupillary response to all emotional facial expressions (fearful, happy and sad). This difference in reactivity between remitted depressed and HC adolescents persisted following the negative mood induction. Results also revealed that LPP and pupillary responses to emotional faces were significantly related, but only among the currently depressed adolescents. This study suggests that increased physiological and neural activation in response to social-emotional stimuli may not only characterize currently depressed adolescents, but also remains following MDD remission, potentially serving as a mechanism of risk for future depression relapse.

Quality of Life and Functioning in Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder After Treatment With Citalopram Monotherapy.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) often have high comorbidity, consequently influencing patient-reported outcomes of depressive symptom severity, quality of life (QOL), and functioning. We hypothesized that the combined effects of concurrent PTSD and MDD would result in worse treatment outcomes, whereas individuals who achieved MDD remission would have better treatment outcomes. We analyzed 2280 adult participants who received level 1 treatment (citalopram monotherapy) in the Sequenced Treatment Alternatives to Relieve Depression study, including 2158 participants with MDD without comorbid PTSD and 122 participants with MDD with comorbid PTSD (MDD + PTSD). Post hoc analysis examined the proportion of participants whose scores were within normal or severely impaired for functioning and QOL. Remission status at exit from MDD was also determined. At entry, participants with MDD + PTSD experienced significantly worse QOL, functioning, and depressive symptom severity compared with participants with MDD without comorbid PTSD. Although both groups had significant improvements in functioning and QOL posttreatment, the participants with MDD + PTSD were less likely to achieve remission from MDD. Findings suggested that participants with MDD + PTSD are at a greater risk for severe impairment across all domains and less likely to achieve remission from MDD after treatment with citalopram monotherapy. As such, the use of patient-reported measures of QOL and functioning may inform practicing clinicians' and clinical trial researchers' abilities to develop appropriate interventions and monitor treatment efficacy. More importantly, we encourage clinicians and health care providers to routinely screen for PTSD in patients with MDD because this at-risk group requires tailored and specific pharmacotherapy and psychotherapy interventions beyond traditionally standard treatments for depression.

Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study.

Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Among remitters (n=95), there was a strong concordance (Kendall's τ-b=0.84, P=0.0001; Cohen's κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing.

Higher serum DHEA concentrations before and after SSRI treatment are associated with remission of major depression

BackgroundDehydroepiandrosterone (DHEA) and its sulfated ester DHEA-sulfate (DHEA-S), (together DHEA[S]), are the most abundant adrenal steroids in humans and are found in blood and the brain, where they function as neurosteroids with direct receptor affinities. Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear. MethodsMorning fasting serum DHEA(S) concentrations were determined in 36 healthy, unmedicated MDD adults with Hamilton Depression (HDRS) ratings ≥17, and 75 healthy controls. MDD participants then completed eight weeks of open-label SSRI treatment before DHEA(S) levels were re-sampled; those with post-treatment HDRS ratings ≤7 were classified as “Remitters.” Pre- and post-treatment DHEA(S) levels of Remitters and Non-remitters were compared, controlling for age, sex, and BMI. ResultsPre-treatment HDRS ratings did not differ between Remitters and Non-remitters (p=0.179). Baseline DHEA levels of Remitters were significantly higher than both Non-remitters (p=0.008) and controls (p=0.004); baseline DHEA-S levels of Remitters were also higher than Non-remitters (p=0.040) but did not significantly differ from controls (p=0.096). Non-remitters did not significantly differ from controls. Post-treatment DHEA(S) levels remained higher in Remitters compared to Non-remitters (DHEA: p=0.013; DHEA-S: p=0.040). ConclusionsThese data suggest that higher circulating DHEA(S) levels (while unmedicated and after eight weeks of SSRI treatment) predict SSRI-associated remission in MDD. This raises the possibility that endogenous DHEA(S) abundance is a physiological adjunct to SSRI efficacy, as suggested by prior preclinical and clinical studies.

The recovery index: A novel approach to measuring recovery and predicting remission in major depressive disorder

BackgroundClinicians view “recovery” as the reduction in severity of symptoms over time, whereas patients view it as the restoration of premorbid functioning level and quality of life (QOL). The main purpose of this study is to incorporate patient-reported measures of functioning and QOL into the assessment of patient outcomes in MDD and to use this data to define recovery. MethodUsing the STAR*D study of patients diagnosed with MDD, this present analysis grades patients' MDD severity, functioning level, and QOL at exit from each level of the study, as well as at follow-up. Using Item Response Theory, we combined patient data from functioning and QOL measures (WSAS, Q-LES-Q) in order to form a single latent dimension named the Recovery Index. ResultsRecovery Index – a latent measure assessing impact of illness on functioning and QOL – is able to predict remission of MDD in patients who participated in the STAR*D study. ConclusionsBy incorporating functioning and quality of life, the Recovery index creates a new dimension towards measuring restoration of health, in order to move beyond basic symptom measurement.

Reconfiguration of hub-level community structure in depressions: A follow-up study via diffusion tensor imaging

BackgroundThe role of abnormal communications among large-scale brain networks have been given increasing attentions in the pathophysiology of major depressive disorder (MDD). However, few studies have investigated the effect of antidepressant medication treatment on the information communication of structural brain networks, especially converged from the individual analysis. MethodsNineteen unipolar MDD patients completed two diffusion tensor imaging (DTI) scans before and after 8-week treatment with selective serotonin reuptake inhibitor. DTI data of 37 matched healthy controls were acquired. We focused on a hub-level community structure network, and investigated whether it had differences on the whole structure and which regions drove these differences in terms of modular affiliation and hub role shift. Data were analyzed by the novel permutation network framework, which appraised the topological consistency of hubs and reserved an individual information. ResultsCompared to the pre-treatment state, post-treatment patients exhibited increasing number of modular members in the modules that included the right medial superior frontal gyrus (SFGmed) or the thalamus. Moreover, the result suggested a hub role shift of the left insula from a provincial-hub before treatment to a connector-hub after treatment. Additionally, reduced inter-module degree in the right SFGmed was positively correlated with the reduced sum score of 17-item Hamilton depression rating scale at the follow-up. ConclusionsAntidepressant medication treatment might be associated with modular reconfigurations of hubs within the fronto-limbic circuit. Moreover, increased inter-module connections of the left insula might improve its integration ability, promoting the remission of MDD. The correlation results of the right SFGmed suggested it might be a valuable indicator for treatment response.

Anxious distress predicts subsequent treatment outcome and side effects in depressed patients starting antidepressant treatment

Evidence has shown that the DSM-5 anxious distress specifier captures a clinically valid construct that predicts a worse clinical course. Although of importance for treatment planning and monitoring, however, the specifier's ability to predict treatment outcome is unknown. This is the first study to examine the ability of the DSM-5 anxious distress specifier to predict treatment response and side effects in depressed patients who recently initiated antidepressant treatment. Patients were from the Netherlands Study of Depression and Anxiety, an ongoing longitudinal cohort study. Baseline, 1-year and 2-year follow-up data were used from 149 patients (18–65 years) with current Major Depressive Disorder (MDD) who recently started adequately dosed antidepressant medication. Five self-report items were used to construct the DSM-5 anxious distress specifier. Treatment outcomes were depression severity after 1 year and 2 years, remission of MDD after 2 years and antidepressant side effects during treatment. For comparison, analyses were repeated for comorbid DSM-IV-based anxiety disorders as a predictor. In depressed patients who received antidepressant treatment, the anxious distress specifier (prevalence = 59.1%) significantly predicted higher severity (1 year: B = 1.94, P = 0.001; 2 years: B = 1.63, P = 0.001), lower remission rates (OR = 0.44, P = 0.0496) and greater frequency of side effects (≥4 vs. 0: OR = 2.74, P = 0.061). In contrast, the presence of comorbid anxiety disorders did not predict these treatment outcomes. The anxious distress specifier significantly predicts poorer treatment outcomes as shown by higher depression severity, lower remission rates, and greater frequency of antidepressant side effects in patients with MDD on adequate antidepressant treatment. Therefore, this simple 5-item specifier is of potential great clinical usefulness for treatment planning and monitoring in depressed patients.

Comorbid Social Phobia and Major Depressive Disorder: the Influence of Remission from Depression on Quality of Life and Functioning

Social phobia (SP) and major depressive disorder (MDD) are frequently concurrent, which negatively affects quality of life (QOL), functioning, and depressive symptom severity. We hypothesized individuals with comorbid SP and MDD (MDD + SP) would have worse treatment outcomes than those with MDD alone (MDDnoSP), but that both groups would have significant responses to treatment, and those who achieved MDD remission would have the best increases in QOL and functioning. We analyzed data for 2280 adults who received citalopram monotherapy in phase 1 of the NIH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Participants (82 MDD + SP and 2198 MDDnoSP) with complete entry and exit scores across QOL, functioning, and depressive symptom severity were examined. MDD remission status following treatment was determined. Patient-reported QOL and functioning scores were classified as within-normal or severely-impaired. No significant between-group differences were observed across all outcomes at entry or exit. Both groups experienced significant improvements in QOL and functioning (all p values .77). Although non-significant, the MDD + SP group was more likely to achieve within-normal scores and MDD remission post-treatment. Findings were interesting as we initially expected the MDD + SP participants to have worse outcomes, yet those with MDD alone had a more chronic course. Regardless, participants who were able to achieve MDD remission post-treatment had significantly better improvements in QOL and functioning. Accordingly, researchers and clinicians should utilize QOL and functioning measures when examining treatment effectiveness, while also considering the role of remission from major depressive disorder on quality of life.