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Anxious depression is a prevalent subtype of depression associated with adverse outcomes such as higher depression severity and higher rates of suicidality. This study leveraged a state-wide research registry of depressed and/or suicidal youth to compare the prevalence, clinical correlates, and symptom patterns of those with versus without anxious depression. We included baseline data from 797 participants (ages 8–20) with a diagnosis of a depressive disorder. A score on the Generalized Anxiety Disorder Scale (GAD-7) ≥ 10 was used to define individuals with and without anxious depression. A structured battery was used to capture psychiatric diagnostic status, depression/anxiety severity, suicide risk, history of trauma, functioning, and resilience. The prevalence of anxious depression among youth with depressive disorders was 59.5 % (n = 474). Youth with anxious depression had greater depression severity and anxiety symptoms, higher suicidality, and a higher prevalence of comorbid anxiety disorders than those without. Youth with anxious depression had greater impairment in functioning defined as worse pain interference, pain severity, fatigue, and social relationships compared to those without anxious depression. Youth with anxious depression also reported higher rates of depressive symptoms such as irritable mood, feelings of guilt, and psychomotor agitation compared to those without anxious depression. Anxious depression is associated with worse depression severity, higher suicidality, and lower functioning. Longitudinal work is needed to examine long-term courses of anxious depression to explore its stability as a diagnostic subcategory. • Anxious depression is a prevalent depression subtype primarily explored in adults. • In our sample of depressed youth (n = 747), 59.5 % had Anxious Depression. • It is associated with worse depression severity, suicidality, and functioning. • Longitudinal work is needed on the time-course and outcomes for Anxious Depression. [ABSTRACT FROM AUTHOR]

Introduction: The heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders. Methods: In this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category. Results: We identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled “Neurotic” (C1), “Extraverted” (C2), “Anxious to please” (C3), “Self-critical” (C4), “Conscientious” (C5). The non-clinical clusters were labeled “Self-confident” (N1), “Low endorsement” (N2), “Non-neurotic” (N3), “Neurotic” (N4), “High endorsement” (N5). The combined clusters were labeled “Self-confident” (NC1), “Externalising” (NC2), “Neurotic” (NC3), “Secure” (NC4), “Low endorsement” (NC5), “High endorsement” (NC6), “Self-critical” (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism. Discussion: Overall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications. [ABSTRACT FROM AUTHOR]

Background: Predicting the course and complications of perinatal depression through the identification of clinical subtypes has been previously undertaken using the Edinburgh Postnatal Depression Scale and has the potential to improve the precision of care and improve outcomes for women and their children. Methods: Edinburgh Postnatal Depression Scale scores were collected twice in pregnancy and twice in the postpartum in a sample of 360 women who met diagnostic criteria for perinatal depression using the Structured Clinical Interview for DSM disorder. These data were used to compare with previous, though conflicting, evidence from cross-sectional studies and extend this by undertaking longitudinal measurement invariance modelling to test the structural validity across the perinatal period. Latent profile and transition modelling was used to identify distinct subtypes of women and assess the utility of these subtypes and transition profiles to predict clinically meaningful outcomes. Results: Although our data supported one of the previously reported three-factor Edinburgh Postnatal Depression Scale structures used to compute subfactor totals for depressed mood, anxiety and anhedonia at both early pregnancy and 6 months postpartum, there was little value in using these Edinburgh Postnatal Depression Scale subfactor scores to identify subtypes predictive of clinically meaningful postpartum symptom subtypes, or of general health, pregnancy and neonatal outcomes. Conclusion: Our study does not support the use of the Edinburgh Postnatal Depression Scale to distinguish perinatal depressive subtypes for the purposes of predicting course and complications associated with perinatal depression. However, the results give guidance on alternative ways to study the value of personalised management in improved outcomes for women living with or at risk for perinatal depression. [ABSTRACT FROM AUTHOR]

IntroductionThe heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders.MethodsIn this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category.ResultsWe identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled “Neurotic” (C1), “Extraverted” (C2), “Anxious to please” (C3), “Self-critical” (C4), “Conscientious” (C5). The non-clinical clusters were labeled “Self-confident” (N1), “Low endorsement” (N2), “Non-neurotic” (N3), “Neurotic” (N4), “High endorsement” (N5). The combined clusters were labeled “Self-confident” (NC1), “Externalising” (NC2), “Neurotic” (NC3), “Secure” (NC4), “Low endorsement” (NC5), “High endorsement” (NC6), “Self-critical” (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism.DiscussionOverall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications.

Lack of energy, fatigue, debility are often seen in depression and hardly respond to treatment. Finding some biomarkers for these symptoms may be important for diagnosis and treatment. We aimed to investigate the possible relationship between depression and energy-related molecules irisin, adropin and preptin. There were 117 patients with depression and 59 healthy volunteers included in the study. Sociodemographic characteristics and clinical features of groups were evaluated, and depressed patients were divided into subtypes, then irisin, adropin, preptin levels were compared between depressive patients and healthy controls and between subtypes. Depression severity, quality of life, functionality and the relations with irisin, adropin and preptin levels and associations between depression subtypes were evaluated. Irisin, adropin, and preptin levels were lower in depression, positively correlated with quality of life, and negatively correlated with depression severity and functional impairment. Depression subtypes showed no difference in irisin, adropin and preptin levels. We found decreased serum irisin, adropin and preptin levels in depression. Our results may support investigation of irisin, adropin and preptin as biomarkers for depression but it might be more meaningful to evaluate these biomarkers in a long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Previous 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. Methods: Data 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. Results: The 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. Conclusion: Chronic 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. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Are the subtypes of major depressive disorder according to the diagnostic and statistical manual of mental disorders (DSM-IV) specifiers stable in advanced age and what is the influence of mild cognitive impairment on this stability? • What is the main finding of this study? Longitudinal stability into advanced age of the atypical and the combined subtypes but not of the melancholic subtype of major depressive disorder according to the DSM-IV specifiers and absence of the effect of mild cognitive impairment on this stability. • What is the meaning of the finding? Additional support for the validity of the atypical subtype of major depressive disorder according to the DSM-IV specifier in older age. To assess 1) the longitudinal stability of the atypical, melancholic, combined atypical-melancholic and the unspecified subtypes of major depressive disorder (MDD) according to the diagnostic and statistical manual of mental disorders (DSM –IV) specifiers in older adults, and 2) the effect of mild cognitive impairment (MCI) on the stability of these subtypes. Prospective cohort study with a 5.1 year-follow-up. Population-based cohort from Lausanne, Switzerland. A total of 1,888 participants (mean age: 61.7 years, women: 69.2%) with at least two psychiatric evaluations, one after the age of 65 years. Semistructured diagnostic interview to assess lifetime and 12-month DSM-IV Axis-1 disorders at each investigation and neuro-cognitive tests to identify MCI in participants aged 65 years and over. Associations between lifetime MDD status before and 12-month depression status after the follow-up were assessed using multinomial logistic regression. The effect of MCI on these associations was assessed by testing interactions between MDD subtypes and MCI status. 1) Associations between depression status before and after the follow-up were observed for atypical (adjusted OR [95% CI] = 7.99 [3.13; 20.44]), combined (5.73 [1.50; 21.90]) and unspecified (2.14 [1.15; 3.98]), but not melancholic MDD (3.36 [0.89; 12.69]). However, there was a certain degree of overlap across the subtypes, particularly between melancholic MDD and the other subtypes. 2) No significant interactions were found between MCI and lifetime MDD subtypes regarding depression status after follow-up. The strong stability of the atypical subtype in particular highlights the need for identifying this subtype in clinical and research settings, given its well-documented links to inflammatory and metabolic markers. [ABSTRACT FROM AUTHOR]

Clinical and etiological heterogeneity have hindered our understanding of depression, thus driving the studies of major depressive disorder (MDD) subtypes. Atypical depression (AD) is a subtype of MDD with atypical features. Cognitive impairment is one of the factors that contribute to the suffering of patients with MDD. Therefore, this study investigated the characteristics and differences in cognitive functioning of AD and non-atypical depression (non-AD) using the MATRICS Consensus Cognitive Battery (MCCB). A total of 101 patients with AD and 252 patients with non-AD were assessed with the MCCB and clinical scales. Propensity score matching (PSM) was used to balance confounders between groups. After PSM, between-group differences were compared for cognitive and clinical variables. In addition, multiple linear regression analyses were performed to explore the effects of cognitive and clinical variables on the quality of life. The AD group scored significantly lower in attention/vigilance and social cognition in all cognitive domains than the non-AD group. Attention/vigilance and social cognition were significant positive predictors of quality of life, whereas atypical symptoms and depressive severity were significant negative predictors. This study suggests significant differences in cognitive functions between the AD and non-AD subtypes. Atypical symptoms and impaired cognition have a negative impact on patients' quality of life. Attention/vigilance and social cognition are worse in AD than non-AD, which the atypical features of patients with AD may explain. The pathological mechanisms and treatment strategies of AD should be further explored in the future to promote individualized treatment strategies. • We used propensity score matching to control for covariates and reduce bias. • We compared the cognitive differences between MDD subtypes. • We included parental education and depression severity in the covariates. • AD scored lower in attention/vigilance and social cognition compared to non-AD. • Atypical feature is a negative predictor of quality of life. [ABSTRACT FROM AUTHOR]

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptomprofiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group. Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences. Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with themembership in the "pessimistic" group. Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency has been suggested to contribute to the onset of depression, but published results are inconsistent. The aims of this study were 1) to compare serum 25-hydroxyvitamin D (25(OH)D) levels in patients with depression and non-depressed controls and 2) to examine whether distinct subtypes and symptom severity of depression may vary in their association with 25(OH)D. Methods: The study involved cross-sectional data of n=1169 participants from the BiDirect Study (n=639 patients with clinically diagnosed major depressive disorder (MDD), n=530 controls). Serum 25(OH)D was measured via LS-MS/MS. We performed analysis of covariance to evaluate adjusted means of 25(OH)D levels and multinomial logistic regression to assess the association of depression and its clinical characteristics, namely distinct subtypes and symptom severity, with 25(OH)D status (adjusted for age, sex, education, season of blood sample collection, and lifestyle factors). Results: In total, 45.0% of the participants had adequate 25(OH)D levels (≥20 ng/ml), whereas 24.9% had a deficiency (<12 ng/ml). Patients with MDD had lower 25(OH)D levels than controls (16.7 vs. 19.6 ng/ml, p<0.001). Patients with atypical depression had the lowest levels (14.6 ng/ml). Symptom severity was inversely related to 25(OH)D. Moreover, patients with MDD had a more than 2-times higher odds of 25(OH)D deficiency than controls. Atypical depression showed the highest odds of deficiency. Conclusions: The results support that patients with depression have lower 25(OH)D concentrations than non-depressed individuals. Distinct subtypes, particularly the atypical subtype, may play a special role in this context. Therefore, depression heterogeneity should be considered in future research. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a serious mental illness characterized by mood changes and high suicide rates. However, no studies are available to support a blood test method for MDD diagnosis. The objective of this research was to identify potential peripheral blood biomarkers for MDD and characterize the novel pathophysiology. Methods: We accessed whole blood microarray sequencing data for MDD and control samples from public databases. Biological functions were analysed by GO and KEGG pathway enrichment analyses using the clusterprofile R package. Infiltrated immune cell (IIC) proportions were identified using the CIBERSORT algorithm. Clustering was performed using the ConsensusClusterPlus R package. Protein–protein interactions (PPI) were assessed by constructing a PPI network using STRING and visualized using Cytoscape software. Rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks to induce stress behaviour. Stress behaviour was evaluated by open field experiments and forced swimming tests. Flow cytometry was used to analyse the proportion of CD8+ T cells. The expression of the corresponding key genes was detected by qRT–PCR. Results: We divided MDD patients into CD8H and CD8L clusters. The functional enrichment of marker genes in the CD8H cluster indicated that autophagy-related terms and pathways were significantly enriched. Furthermore, we obtained 110 autophagy-related marker genes (ARMGs) in the CD8H cluster through intersection analysis. GO and KEGG analyses further showed that these ARMGs may regulate a variety of autophagy processes and be involved in the onset and advancement of MDD. Finally, 10 key ARMGs were identified through PPI analysis: RAB1A, GNAI3, VAMP7, RAB33B, MYC, LAMP2, RAB11A, HIF1A, KIF5B, and PTEN. In the CUMS model, flow cytometric analysis confirmed the above findings. qRT–PCR revealed significant decreases in the mRNA levels of Gnai3, Rab33b, Lamp2, and Kif5b in the CUMS groups. Conclusion: In this study, MDD was divided into two subtypes. We combined immune infiltrating CD8+ T cells with autophagy-related genes and screened a total of 10 ARMG genes. In particular, RAB1A, GNAI3, RAB33B, LAMP2, and KIF5B were first reported in MDD. These genes may offer new hope for the clinical diagnosis of MDD. [ABSTRACT FROM AUTHOR]

Abstract Background Although, the relation between inflammation and major depressive disorder (MDD) looks like firm, it may not exist in all patients with depression. Therefore, the main aim of this study was to compare serum C-reactive protein (CRP) level among clinical subtypes of MDD and its relation with suicidality. Results According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD, 98 patients included and categorized into five clinical subtypes groups: atypical, anxious, melancholic, psychotic, and unspecified depression with percent (11.2%, 31.6%, 19.4%, 15.3%, and 22.4%) respectively. Twenty-four (24.5%) of all patients had suicidal thoughts using Beck Scale for Suicidal Ideation (BSS) with statistically significant increase (P < 0.05*) in suicidality among atypical group. On assessing CRP level, there was highly statistical significant increase (P < 0.001**) among cases with atypical type and also cases with suicidal ideation. Also, logistic regression analysis found that the significant predictors for high CRP among the studied cases were smoking, suicidality, atypical depression, and suicide depression. Conclusions Higher level of CRP was found among patients with atypical MDD, and there was significant relationship between CRP and suicidality.

Background: Major depressive disorder (MDD) is a serious mental illness characterized by mood changes and high suicide rates. However, no studies are available to support a blood test method for MDD diagnosis. The objective of this research was to identify potential peripheral blood biomarkers for MDD and characterize the novel pathophysiology.Methods: We accessed whole blood microarray sequencing data for MDD and control samples from public databases. Biological functions were analysed by GO and KEGG pathway enrichment analyses using the clusterprofile R package. Infiltrated immune cell (IIC) proportions were identified using the CIBERSORT algorithm. Clustering was performed using the ConsensusClusterPlus R package. Protein–protein interactions (PPI) were assessed by constructing a PPI network using STRING and visualized using Cytoscape software. Rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks to induce stress behaviour. Stress behaviour was evaluated by open field experiments and forced swimming tests. Flow cytometry was used to analyse the proportion of CD8+ T cells. The expression of the corresponding key genes was detected by qRT–PCR.Results: We divided MDD patients into CD8H and CD8L clusters. The functional enrichment of marker genes in the CD8H cluster indicated that autophagy-related terms and pathways were significantly enriched. Furthermore, we obtained 110 autophagy-related marker genes (ARMGs) in the CD8H cluster through intersection analysis. GO and KEGG analyses further showed that these ARMGs may regulate a variety of autophagy processes and be involved in the onset and advancement of MDD. Finally, 10 key ARMGs were identified through PPI analysis: RAB1A, GNAI3, VAMP7, RAB33B, MYC, LAMP2, RAB11A, HIF1A, KIF5B, and PTEN. In the CUMS model, flow cytometric analysis confirmed the above findings. qRT–PCR revealed significant decreases in the mRNA levels of Gnai3, Rab33b, Lamp2, and Kif5b in the CUMS groups.Conclusion: In this study, MDD was divided into two subtypes. We combined immune infiltrating CD8+ T cells with autophagy-related genes and screened a total of 10 ARMG genes. In particular, RAB1A, GNAI3, RAB33B, LAMP2, and KIF5B were first reported in MDD. These genes may offer new hope for the clinical diagnosis of MDD.

Mineralocorticoid-receptor (MR) dysfunction as expressed by low systolic blood pressure and a high salivary aldosterone/cortisol ratio predicts less favorable antidepressant treatment outcome. Inhibition of peripheral 11-beta-hydroxysteroid-dehydrogenase type 2 (11betaHSD2) reverses these markers. We therefore tested the hypothesis that the 11betaHSD2 inhibitor glycyrrhizin affects treatment outcome via this mechanism. We administered Glycyrrhiza glabra (GG) extract containing 7–8 % of glycyrrhizin at a dose of 2 × 700 mg daily adjunct to standard antidepressants in hospitalized patients with major depression. These subjects were compared in an open-label fashion with patients, who did not receive GG (treatment as usual, TAU). Assessments were done at baseline and approximately 2 weeks after. Twelve subjects were treated with GG and compared to 55 subjects with TAU. At week 2, the Hamilton Depression Rating Scale (HAMD-21) change from baseline as well as the CGI-S change showed a significant time × treatment interaction (p < 0.03), indicating a possible therapeutic benefit of GG. Clinical benefit seems to be more pronounced in subjects with lower systolic blood pressure and significantly correlated with reduced sleep duration in the GG group. Our preliminary data show that treatment with the 11betaHSD2 inhibitor glycyrrhizin may possess a beneficial effect on antidepressant response, which may be specific to a defined depression subtype.

Mineralocorticoid-receptor (MR) dysfunction as expressed by low systolic blood pressure and a high salivary aldosterone/cortisol ratio predicts less favorable antidepressant treatment outcome. Inhibition of peripheral 11-beta-hydroxysteroid-dehydrogenase type 2 (11betaHSD2) reverses these markers. We therefore tested the hypothesis that the 11betaHSD2 inhibitor glycyrrhizin affects treatment outcome via this mechanism. We administered Glycyrrhiza glabra (GG) extract containing 7–8 % of glycyrrhizin at a dose of 2 × 700 mg daily adjunct to standard antidepressants in hospitalized patients with major depression. These subjects were compared in an open-label fashion with patients, who did not receive GG (treatment as usual, TAU). Assessments were done at baseline and approximately 2 weeks after. Twelve subjects were treated with GG and compared to 55 subjects with TAU. At week 2, the Hamilton Depression Rating Scale (HAMD-21) change from baseline as well as the CGI-S change showed a significant time × treatment interaction (p < 0.03), indicating a possible therapeutic benefit of GG. Clinical benefit seems to be more pronounced in subjects with lower systolic blood pressure and significantly correlated with reduced sleep duration in the GG group. Our preliminary data show that treatment with the 11betaHSD2 inhibitor glycyrrhizin may possess a beneficial effect on antidepressant response, which may be specific to a defined depression subtype. [ABSTRACT FROM AUTHOR]

Background: Melancholic depression (MD) is a subtype of Major Depression associated with more clinical severity and poorer prognosis that non-melancholic depression (NMD). The differentiation between depression subtypes is still clinical, although the identification of specific biomarkers could be useful for diagnosis and the development of new treatments. Purpose of the present manuscript is to review the biomarkers that have been associated with MD.Methods: We performed a bibliographic research on the main databases (PubMed, Embase, PsycInfo, Isi Web of Knowledge, Medscape, The Cochrane Library), in order to find studies that proposed biological markers for melancholic depression. A total of 14 studies met our inclusion criteria.Results: Most of studies focused on immune dysregulation. Subjects with MD show biological abnormalities than healthy controls (HC). MD might be characterized by specific biological changes and it could be associated to more severe abnormalities with respect to NMD; however especially about this latter point the available data are preliminary.Limitations: Most available data have not been replicated; the studies focused on different biomarkers. In addition, many articles report results on a limited sample size.Conclusions: Melancholic depression is a subtype of major depression that seems to be associated with specific alterations of different biological systems. Future studies with larger sample can confirm the results and hypothesis presented in this review. [ABSTRACT FROM AUTHOR]

Background: The heterogeneity of late-life depression hampers diagnosis and treatment. Data-driven methods have identified several subtypes of depression in older persons, but the longitudinal stability of these subtypes remains unknown.Methods: In total 111 older persons with a major depressive disorder both at baseline and 2-year follow-up from the Netherlands Study of Depression in Older persons (NESDO) were included. Latent class analysis was performed to identify subtypes of depression at baseline and at 2-year follow-up, and latent transition analysis was used to examine the stability of these subtypes over time. Transition rates between subtypes and characteristics of groups were examined.Results: Two subtypes were identified in both baseline (T0) and follow-up data (T1), including a 'melancholic' subtype (prevalence 80.2% (T0) and 62.2% (T1)), and an 'atypical' subtype (prevalence 19.8% (T0) and 37.8% (T1)). The melancholic subtype was characterized by decreased appetite and weight and had a stability of 0.86. The atypical subtype was characterized by increased appetite and weight and had a stability of 0.93, although the discriminating power of different symptoms had decreased at T1. Mean age and education differed significantly between stable and transitioning subgroups, other characteristics did not differ between subgroups.Limitations: Limited sample size might have hampered the analyses.Conclusions: Subtypes of late-life depression are relatively stable, but symptoms of depression (like weight loss) seem to blur with symptoms of (patho)physiological aging. This underlines the clinical relevance of depression subtyping, but also the importance of further research into subtypes and the influence of aging. [ABSTRACT FROM AUTHOR]

Objective: About half or more of treatment‐resistant depressed patients do not respond to ketamine, and few clinical predictors to gauge the most likely antidepressant response have been proposed. We explored whether depression subtypes are associated with response to ketamine. Method: Ninety‐seven participants with depression were administered six repeated‐dose intravenous ketamine and assessed for depression (Montgomery–Åsberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAMA), and suicidal ideation (Beck Scale for Suicidal Ideation, SSI) at baseline, 24 h after each infusion, and 2 weeks after the whole treatment. Participants were classified by melancholic/anxious subtype. Individuals who met criteria for neither or both subtypes were classified separately, resulting in four mutually exclusive groups. Results: Patients with melancholic or melancholic–anxious features were less likely to respond (e.g., day 13, melancholic–anxious vs. anxious, OR 0.138, 95% CI 0.032–0.584, P = 0.007) or remit (e.g., day 26, melancholic vs. no subtype, OR 0.182, 95% CI 0.035–0.960, P = 0.045) and took longer to achieve response/remission than those with anxious or no subtype features. Faster HAMA score reductions were observed in patients with anxious or melancholic–anxious features, and faster SSI score reductions were observed among those with melancholic–anxious features. Conclusion: Our study shows promising results for ketamine as a novel antidepressant preferentially for the treatment of non‐melancholic or anxious depression. [ABSTRACT FROM AUTHOR]

Background: Prior studies indicate that depression is a risk factor for type 2 diabetes (T2D), though there is considerable heterogeneity in reported estimates. Identifying homogeneous subgroups of depression strongly associated with T2D may be beneficial. This study examined associations between depression and anxiety comorbidity with the risk of T2D.Methods: 78,025 participants from the Lifelines Cohort Study (age range = 30-75 years) without diabetes at baseline were included in this study. The Mini-International Neuropsychiatric Interview assessed depressive and anxiety symptoms at baseline. Incident T2D was assessed by self-report or hemoglobin A1c levels during an approximately 3.8-year follow-up period. Risk of T2D was compared across four groups (no depressive or anxiety symptoms, depressive symptoms alone, anxiety symptoms alone, comorbid depressive/anxiety symptoms) using mixed effects logistic regression analyses adjusted for sociodemographic, lifestyle, and cardiometabolic characteristics.Results: 1,096 participants developed diabetes. Compared to those without depressive or anxiety symptoms (n = 74,467), those with comorbid depressive and anxiety symptoms (n = 743) were more likely to develop T2D (n = 28, OR = 2.12, 95% CI = 1.22-3.68). Depressive symptoms alone (n = 650) and anxiety symptoms alone (n = 2,165) were not significantly associated with T2D (n = 23 and n = 24, respectively, developed diabetes). Those with comorbid symptoms were also more likely to develop T2D compared to those with depressive symptoms alone (OR = 2.86, 95% CI = 1.25-6.54).Limitations: Depressive and anxiety symptom assessments were based on a screening tool. Hemoglobin A1c data were only available for a subset of participants.Conclusions: Depression with comorbid anxiety may be a subgroup of depression that is strongly associated with the risk of T2D. [ABSTRACT FROM AUTHOR]

Depression is a significant public health problem but symptom remission is difficult to predict. This may be due to substantial heterogeneity underlying the disorder. Latent class analysis (LCA) is often used to elucidate clinically relevant depression subtypes but whether or not consistent subtypes emerge is unclear. We sought to critically examine the implementation and reporting of LCA in this context by performing a systematic review to identify articles detailing the use of LCA to explore subtypes of depression among samples of adults endorsing depression symptoms. PubMed, PsycINFO, CINAHL, Scopus, and Google Scholar were searched to identify eligible articles indexed prior to January 2016. Twenty-four articles reporting 28 LCA models were eligible for inclusion. Sample characteristics varied widely. The majority of articles used depression symptoms as the observed indicators of the latent depression subtypes. Details regarding model fit and selection were often lacking. No consistent set of depression subtypes was identified across studies. Differences in how models were constructed might partially explain the conflicting results. Standards for using, interpreting, and reporting LCA models could improve our understanding of the LCA results. Incorporating dimensions of depression other than symptoms, such as functioning, may be helpful in determining depression subtypes. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that inflammatory and cortisol dysregulation are underlying pathophysiological mechanisms in the aetiology of major depressive disorder, particularly in younger adults. However, findings of biological disturbances in late-life depression have been divergent, probably due to the even greater heterogeneity of depression in older adults with aging processes influencing biological factors. Using empirically derived subtypes may enable the identification of biological disturbances underlying depression in older adults.Methods: Data were used from the Netherlands Study of Depression in Older Persons (NESDO) of 359 persons aged 60 years or older, with a current diagnosis of major depressive disorder (MDD). Depressive subtypes (severe atypical, severe melancholic, and moderate severe subtype) that were previously identified through latent class analysis (LCA), were examined on differences in inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL), as well as cortisol parameters.Results: No differences in measures for inflammation and cortisol across subtypes were observed in uncorrected or for putative confounders corrected models.Limitations: Several subjects had missing cortisol and inflammatory data, decreasing the power. However, results did not change after imputation analysis.Discussion: In this cohort of depressed older adults, no differences in inflammation and cortisol measures between depression subtypes were observed. This is probably due to the many (patho)physiological processes that are involved in aging, thereby clouding the results. [ABSTRACT FROM AUTHOR]

Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

The burden of depression in men is high. Current diagnostic criteria may not fully capture men’s experience with depression. Descriptions of the heterogeneity in depression among men are lacking. The purpose of the study was to characterize latent subtypes of major depression and changes in these subtypes among men receiving citalopram in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Latent transition analysis was applied to data from 387 men who completed baseline and Week 12 study visits in Level 1 of STAR*D. Items from the self-report version of the Quick Inventory of Depressive Symptomatology were used as indicators of latent depression subtypes. Four statuses were identified at baseline and Week 12. Baseline statuses were Mild (10% of men), Moderate (53%), Severe with Psychomotor Slowing (20%), and Severe with Psychomotor Agitation (17%). At Week 12, the statuses were Symptom Resolution (41%), Mild (36%), Moderate (18%), and Severe with Psychomotor Slowing (5%). Men in the Mild status were most likely to transition to Symptom Resolution (probability = 69%). Men in the Severe with Agitation status were least likely to transition to Symptom Resolution (probability = 0%). This work highlights the need to not focus solely on summary rating scores but to also consider patterns of symptoms when treating depression. [ABSTRACT FROM AUTHOR]

Objective: This study examined the associations of personality characteristics with both subtypes and symptom dimensions of depression in older adults.Methods: Three hundred and seventy-eight depressed older adults participated in the Netherlands Study of Depression in Older Persons. Personality characteristics were assessed by the NEO-Five Factor Inventory. Subtypes and symptom dimensions of depression were determined using the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology (IDS). Multinomial logistic regression analyses were performed to examine the associations between personality and atypical, melancholic, and unspecified subtypes of major depression. Linear regression analyses examined the associations between personality and the IDS mood, somatic, and motivation symptom dimensions. The analyses were adjusted for confounders and additionally adjusted for depression severity.Results: Neuroticism, Extraversion, Conscientiousness, and Agreeableness were associated with specified (atypical or melancholic) major depression compared with unspecified major depression in the bivariate analyses but lost their significance after adjustments for functional limitations and severity of depression. Neuroticism was positively associated with the IDS mood and motivation symptom dimensions, also in the adjusted models. Further, Extraversion and Agreeableness were negatively associated with the IDS mood symptom dimension, and Extraversion and Conscientiousness were negatively associated with the IDS motivation symptom dimension. None was associated with the IDS somatic symptom dimension.Conclusions: This study demonstrated the association of personality characteristics with mood and motivational symptoms of late-life depression. The lacking ability of personality to differentiate between melancholic and atypical depression seems to be largely explained by severity of depressive symptoms. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression. Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression. [ABSTRACT FROM AUTHOR]

Background: Clinical findings indicate heterogeneity of depressive disorders, stressing the importance of subtyping depression for research and clinical care. Subtypes of the common late life depression are however seldom studied. Data-driven methods may help provide a more empirically-based classification of late-life depression.Methods: Data were used from the Netherlands Study of Depression in Older People (NESDO) derived from 359 persons, aged 60 years or older, with a current diagnosis of major depressive disorder. Latent class analysis (LCA) was used to identify subtypes of depression, using ten CIDI-based depression items. Classes were then characterized using various sociodemographic and clinical characteristics.Results: The most prevalent class, as identified by LCA, was a moderate-severe class (prevalence 46.5%), followed by a severe melancholic class (prevalence 38.4%), and a severe atypical class (prevalence 15.0%). The strongest distinguishing features between the three classes were appetite and weight and, to a lesser extent, psychomotor symptoms and loss of interest. Compared with the melancholic class, the severe atypical class had the highest prevalence of females, the lowest mean age, the highest BMI, and highest prevalence of both cardiovascular disease, and metabolic syndrome.Limitations: The strongest distinguishing symptoms, appetite and weight, could be correlated. Further, only longitudinal studies could demonstrate whether the identified classes are stable on the long term.Discussion: In older persons with depressive disorders, three distinct subtypes were identified, similar to subtypes found in younger adults. The strongest distinguishing features were appetite and weight; moreover, classes differed strongly on prevalence of metabolic syndrome and cardiovascular disease. These findings suggest differences in the involvement of metabolic pathways across classes, which should be considered when investigating the pathogenesis and (eventually) treatment of depression in older persons. [ABSTRACT FROM AUTHOR]

Little is known about adherence to dietary recommendations and depression. Furthermore, dietary habits may differ among depression subtypes, which has not been evaluated previously. Two population-based Swiss studies, including 3620 individuals from PsyCoLaus and 11,032 individuals from the Swiss Health Survey 2012 (SHS), were used to examine the associations between adherence to common dietary guidelines and odds of depressive disorders. In both studies, depression was assessed by validated instruments. Adherence to dietary recommendations were assessed by a semi-quantitative food frequency questionnaire (PsyCoLaus) and by single item questions (SHS). Logistic regression analyses were used to assess the association of adhering to dietary recommendations with depression. For the analyses of diet with depression subtypes maximum-likelihood multinomial (polytomous) logistic regression analyses were conducted. No association of adherence to dietary recommendations with current major depressive disorder (MDD) was observed in any of the two study populations except for adherence to fish consumption, which was positively associated with MDD in the SHS. For depression subtypes, statistically significantly positive associations of vegetable consumption and adherence to the 5-a-day recommendation with current unspecified and current melancholic MDD were found. In conclusion, we don’t see consistent associations between adherence to dietary recommendations and MDD or subtypes of depression. [ABSTRACT FROM AUTHOR]

To investigate possible contributors to the inconsistent association between frontal lobe asymmetry (FLA) and depression, EEG data were collected across five frontal sites, and examined for their associations with four subtypes of depression (Depressed mood, Anhedonia, Cognitive depression, Somatic depression). One hundred community volunteers (54 males, 46 females) aged at least 18 yr completed standardized scales for depression and anxiety, and gave EEG data under Eyes Open and Eyes Closed conditions. Results indicated that, although there was no significant correlation between the differences in EEG power across each of the five pairs of frontal sites and total depression scores, there were several meaningful correlations (accounting for at least 10% of the variance) between specific EEG site differences data and each of the four depression subtypes. There were also different patterns of association between FLA and the depression subtypes according to sex, and total depression severity. These findings help to explain the apparent inconsistency in previous FLA-depression results, and argue for a more nuanced approach to this hypothesis. [Display omitted] • Frontal lobe asymmetry has been inconsistently associated with depression. • Although often measured as a single metric, depression is heterogeneous. • Frontal asymmetry was examined for four subtypes of depression. • Different frontal sites were associated with different depression subtypes. • Asymmetry-depression association was influenced by sex and depression severity. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features), has been identified as a distinct nosological entity in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We identified the predominant manic symptoms present at baseline in a multiregional, placebo-controlled trial involving 211 patients with MDD with mixed features ( Clinicaltrials.gov NCT01421134 ). Patients with 2 or 3 DSM-5 criteria defined manic symptoms were eligible for the study. At study baseline, increased talkativeness (pressure to keep talking) and flight of ideas (racing thoughts) were endorsed by approximately 65% of patients and a decreased need for sleep was endorsed by 40% of patients. Approximately 60% of patients also endorsed irritability and distractibility at baseline although these symptoms are not generally counted as part of the “mixed” depression diagnosis as they may overlap with criteria for MDD. Thus, five clinical symptoms characterized the manic presentation in the majority of patients diagnosed as having MDD with “mixed” features in this first placebo-controlled trial examining the use of a psychotropic medication (lurasidone) in this population. Our findings support the designation of MDD with mixed features specifier and suggest that this subpopulation of depressed patients may warrant additional medication beyond antidepressants. [ABSTRACT FROM AUTHOR]

We report the development procedure for a Spanish version of the CORE measure for subtyping melancholic depression and its psychometric properties. The sample comprised two subsets of depressive patients: 117 in-patients clinically assessed after admission and before discharge; and 34 in- and out-patients who were video-recorded, with each recording being rated by independent raters and re-rated six months later. The internal consistency of the Spanish version of the CORE was high, with Cronbach's alpha coefficient of 0.93 for the total CORE score. High intra-class correlation coefficient for the total score (0.96) and the three subscales (around 0.8) indicate high inter-rater reliability. Baseline and six-month ratings of video-recordings showed high test-retest reliability. Regarding construct validity, the correlation between the CORE and the Newcastle endogeneity scale scores was 0.64. A ROC curve generated an optimal cut-off of 10 to predict the definition of endogeneity/melancholia based on the Newcastle score >=6 and the DSM-IV-TR definition of melancholia. The comparison between the CORE scores at admission and at discharge revealed large differences, indicating demonstrable sensitivity to change. The Spanish version of the CORE system is a reliable and valid instrument for sub-typing depression in terms of melancholic versus non-melancholic sub-types. [ABSTRACT FROM AUTHOR]

Background: Depression is supposed to be associated with an unhealthy lifestyle including poor diet. The objective of this study was to investigate differences in diet quality between patients with a clinical diagnosis of depression and population-based controls. Additionally, we aimed to examine effects of specific depression characteristics on diet by analyzing if diet quality varies between patients with distinct depression subtypes, and if depression severity is associated with diet quality. Methods: The study included 1660 participants from the BiDirect Study (n = 840 patients with depression, n = 820 population-based controls). The psychiatric assessment was based on clinical interviews and a combination of depression scales in order to provide the classification of depression subtypes and severity. Diet quality scores, reflecting the adherence to a healthy dietary pattern, were calculated on the basis of an 18-item food frequency questionnaire. Using analysis of covariance, we calculated adjusted means of diet quality scores and tested differences between groups (adjusted for socio-demographic, lifestyle-, and health-related factors). Results: We found no differences in diet quality between controls and patients with depression if depression was considered as one entity. However, we did find differences between patients with distinct subtypes of depression. Patients with melancholic depression reported the highest diet quality scores, whereas patients with atypical depression reported the lowest scores. Depression severity was not associated with diet quality. Conclusions: Previous literature has commonly treated depression as a homogeneous entity. However, subtypes of depression may be associated with diet quality in different ways. Further studies are needed to enlighten the diet-depression relationship and the role of distinct depression subtypes. [ABSTRACT FROM AUTHOR]

• Early onset MDD may be a particular subset of patients with a particular inflammatory profile. • Higher TNFα and IL-1β levels are associated with the early-onset of the MDD. • Changes in inflammatory balance may be implicated in the severity of MDD and maybe progression. Major depressive disorder (MDD) is a common condition that affects the general population over a wide range of ages, regardless of gender and social background. Early-onset of MDD in adulthood, between ages of 18 and 30 years, is associated with worse outcomes and increased years of disability. Stress load and physical health have been associated with age of onset in MDD. We aim to investigate whether early onset MDD might be associated with changes in systemic inflammatory markers. We examined levels of following cytokines: IL-1β, IL-6, IL-10 and TNFα in 234 patients with MDD. Higher serum levels of TNFα and IL-1β are associated with the early onset of the disorder in patients with MDD. IL-6 levels were also higher in the early onset group and IL-10 levels were higher in the late onset group, but with no significant difference. Changes in the anti-inflammatory/pro-inflammatory balance have been described in mood disorders and may be implicated in its severity and pattern of progression. Our findings reinforce that higher serum levels of IL-1β and TNFα may be associated with the earlier onset subgroup of MDD patients. Future research that target inflammatory markers of immune modulation may be, key in the search for novel preventative therapeutics. [ABSTRACT FROM AUTHOR]

Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs. [ABSTRACT FROM AUTHOR]

Background.Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question.Method.Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes.Results.Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6–72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors.Conclusions.Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion. [ABSTRACT FROM AUTHOR]

Background Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. Methods/design This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. Discussion Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations. [ABSTRACT FROM AUTHOR]

Abstract: Depression is a severe psychiatric disorder, which is a huge burden on both the individual and society as a whole. Neurobiological studies of depression on humans are limited by ethics. Animal models established by stressor stimulation are currently effective tools for the neurobiological study of depression. In this study, we comparatively analyzed behavioral heterogeneity, gender, and individual differences in animal models reflecting early life stress, adverse events in adulthood, or combined early life stress and stressful events in adulthood. Results demonstrated that these three different stressors induced dissimilar depressive behaviors. Maternal deprivation (MD) induced severe anhedonia. Chronic unpredictable stress (CUPS) induced the most severe decrease in desperation behavior, moderate anhedonia, and moderate loss of interest in exploration of the surroundings. Dural stress (DS) exposure caused the most severe decline in interest in exploring the surroundings. Male rats all exhibited some form of depressive behavior after they were exposed to MD, CUPS and DS. In contrast, no depressive performance was observed in female rats after they were exposed to MD, and the CUPS only decreased the total distance the rats crawled in the open field test. Rats exhibited more obvious individual differences in floating time than in the vertical activity, total distance and sucrose preference rate when experiencing stress. Our study suggests that different stressors may induce different depression subtypes and that the observed differences in the prevalence of depression between genders in the clinic may be due to effect of psychosocial factors which affects humans more strongly than rats. Our study also suggests that individual difference is more obvious in desperation behaviors than that in exploratory interest and anhedonia when the individual experienced stress. [Copyright &y& Elsevier]

Objective: Melancholic versus non-melancholic depression dichotomy is perhaps the most widely accepted distinction in categorization of depression. This research aims to compare symptom based, severity based, and biology based categorization of depression. Methods: To achieve this, the cluster analysis was performed on a sample of 78 depressed patients, first by using 14 SCID-I depressive symptoms. Patients were clustered again with regard to post dexhametasone cortisol levels (suppressed vs non-suppressed groups), and lastly according to HDRS (Hamilton Depression Rating Sacale) scores (high vs low severity groups). Biological (thyroid stimulating hormone -TSH, basal and post dexhametasone cortisol levels), clinical (age, age of onset, severity of depression, psychosocial stressors, and personality disorder) and demographic variables of these categories were compared. Results: There was a high degree of accordance between the cluster analytically derived endogenous group and the DSM-IV diagnosis of melancholia. Cluster analytically generated endogenous group were older, more severely depressed, and had higher basal cortisol levels than non-endogenous depressive subtype. Severely depressed group according to HDRS scores had lower TSH levels. Only DST (dexamethasone suppression test) non-suppressive patients had more depressive disorders in their family. Conclusions: The results of our study partly support the hypothesis that endogenous and melancholic depression have distinct clinical and biological features. [ABSTRACT FROM AUTHOR]

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pain complaints commonly accompany major depressive disorder (MDD). However, whether patients with MDD and pain complaints differ from those without pain complaints is not well studied. Objective: The objective of this study was to compare depressed outpatients with and those without current pain complaints in terms of sociodemographic, clinical, and presenting symptom features. Methods: The baseline clinical and sociodemographic data of a large representative outpatient sample with nonpsychotic MDD (n=3745) enrolled in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study were collected. Baseline information on pain complaints was based on Item No. 25 (somatic pain) of the 30-item Inventory of Depressive Symptomatology–Clinician Rating (IDS-C30). Results: After adjusting for sex, depression severity (IDS-C30 less Item No. 25), and general medical comorbidities (as measured by the Cumulative Illness Rating Scale total score), we found clinically meaningful differences between patients with and those without pain complaints. Younger, African American, Hispanic, and less educated patients were more likely to report pain complaints. In addition, those with pain complaints were more likely to report anxious features with irritable mood, sympathetic nervous system arousal, and gastrointestinal problems as well as poorer quality of life. Neither a more chronic course of illness nor suicidal ideation was associated with pain. Conclusions: Pain complaints are common among outpatients with MDD and are associated with certain symptom features and poorer quality of life. However, the findings of this study suggest that depression accompanied by pain complaints does not increase the clinical psychiatric burden or chronicity of depression. [Copyright &y& Elsevier]

Although much depression may be dysfunctional, the capacity to experience normal depressive symptoms in response to certain adverse situations appears to have been shaped by natural selection, If this is true, then different kinds of situations may evoke different patterns of depressive symptoms that are well suited to solving the adaptive challenges specific to each situation. The authors called this the situation-symptom congruence hypothesis. They tested this hypothesis by asking 445 participants to identify depressive symptoms that followed a recent adverse situation. Guilt, rumination, fatigue, and pessimism were prominent following failed efforts; crying, sadness, and desire for social support were prominent following social losses. These significant differences were replicated in an experiment in which 113 students were randomly assigned to visualize a major failure or the death of a loved one. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although severe depression is dysfunctional, the capacity to experience normal low mood may be useful in certain fitness-threatening situations. Moreover, if specific kinds of situations recurred often enough in the course of evolution, natural selection may have shaped partially differentiated subtypes of low mood that are parallel to the subtypes of anxiety that protect against different kinds of danger. To test this hypothesis, we examined how symptoms of low mood differ depending upon the precipitating situation, and whether these differences match expectations of symptoms useful in each kind of situation. Method: 337 subjects who experienced a period of low mood within the last year wrote accounts describing perceived causes of their low mood and they filled out the CES-D depression inventory. Seven symptom scales were derived from analysis of CES-D data. Independent judges blindly coded the accounts into one of six precipitant categories. Results: Different untoward situations were associated with different symptoms that were predicted to be useful in those situations. Social losses (death of a loved one, romantic breakups, and social isolation) were associated with greater crying and arousal. Failure to reach a goal, stress, and winter seasons were associated with more fatigue and pessimism. Discussion: These results suggest that natural selection shaped not only a generic state of low mood but also partially differentiated subtypes shaped to cope with specific situations that were associated with fitness losses among our ancestors. [Copyright &y& Elsevier]

Background: Previously, we identified four depression subtypes defined by distinct functional connectivity alterations in depression-related brain networks, which in turn predicted clinical symptoms and treatment response. Optogenetic functional magnetic resonance imaging offers a promising approach for testing how dysfunction in specific circuits gives rise to subtype-specific, depression-related behaviors. However, this approach assumes that there are robust, reproducible correlations between functional connectivity and depressive symptoms-an assumption that was not extensively tested in previous work., Methods: First, we comprehensively reevaluated the stability of canonical correlations between functional connectivity and symptoms (N = 220 subjects) using optimized approaches for large-scale statistical hypothesis testing, and we validated methods for improving estimation of latent variables driving brain-behavior correlations. Having confirmed this necessary condition, we reviewed recent advances in optogenetic functional magnetic resonance imaging and illustrated one approach to formulating hypotheses regarding latent subtype-specific circuit mechanisms and testing them in animal models., Results: Correlations between connectivity features and clinical symptoms were robustly significant, and canonical correlation analysis solutions tested repeatedly on held-out data generalized. However, they were sensitive to data quality, preprocessing, and clinical heterogeneity, which can reduce effect sizes. Generalization could be markedly improved by adding L2 regularization, which decreased estimator variance, increased canonical correlations in left-out data, and stabilized feature selection. These improvements were useful for identifying candidate circuits for optogenetic interrogation in animal models., Conclusions: Multiview, latent-variable approaches such as canonical correlation analysis offer a conceptually useful framework for discovering stable patient subtypes by synthesizing multiple clinical and functional measures. Optogenetic functional magnetic resonance imaging holds promise for testing hypotheses regarding latent, subtype-specific mechanisms driving depressive symptoms and behaviors., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)