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Aim Methods Results Conclusions The current study aims to characterize the longitudinal patterns of depression subtypes and investigate the associations among the stability of depression subtypes, COVID‐19‐related stressors, and depression severity.The study utilized data from the Canadian Longitudinal Study on Aging, which is a national, long‐term study of Canadian adults aged 45 and older (n = 12,957). Latent profile analysis was used to identify latent depression subtypes. Latent transition analysis was then applied to assess the stability of these subtypes over time. Hierarchical multivariate linear regression was used to explore the relationships among these identified depression subtypes, COVID‐19‐related stressors, and depression severity among males and females, respectively.Distinct depression subtypes were identified. Except for atypical depression, other depression subtypes showed greater stability over time. We also found that melancholic depression (B = 9.432) and typical depression (B = 6.677) were strongly associated with depression severity during the pandemic. Health‐related stressors (B = 0.840), conflict (B = 3.639), difficulties accessing resources (B = 0.927), separation from family (B = 0.840), and caregiving experience (B = 0.764), were significantly associated with increased depression severity. Sex‐specific analyses also revealed differences in the associations between stressors and depression severity between males and females.This study contributes valuable insights into the latent clustering of depression subtypes and their stability. Stressors were associated with increased depression severity, with distinct associations observed among males and females. These findings have implications for targeted early interventions and integrated clinical management strategies by providing the evidence base for tailored mental health care during and after the pandemic. [ABSTRACT FROM AUTHOR]

Recent studies showed that immunometabolic dysregulation is related to unipolar major depressive disorder (MDD) and that it more consistently maps to MDD patients endorsing an atypical symptom profile, characterized by energy-related symptoms including increased appetite, weight gain, and hypersomnia. Despite the documented influence of the microbiome on immune regulation and energy homeostasis, studies have not yet investigated microbiome differences among clinical groups in individuals with MDD. Fifteen MDD patients with atypical features according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)-5, forty-four MDD patients not fulfilling the DSM-5 criteria for the atypical subtype, and nineteen healthy controls were included in the study. Participants completed detailed clinical assessment and stool samples were collected. Samples were sequenced for the prokaryotic 16S rRNA gene, in the V3-V4 variable regions. Only samples with no antibiotic exposure in the previous 12 months and a minimum of >2000 quality-filtered reads were included in the analyses. There were no statistically significant differences in alpha- and beta-diversity between the MDD groups and healthy controls. However, within the atypical MDD group, there was an increase in the Verrucomicrobiota phylum, with Akkermansia as the predominant bacterial genus. Cross-sectional data, modest sample size, and significantly increased body mass index in the atypical MDD group. There were no overall differences among the investigated groups. However, differences were found at several taxonomic levels. Studies in larger longitudinal samples with relevant confounders are needed to advance the understanding of the microbial influences on the clinical heterogeneity of depression. • Human microbiome affects immunometabolism that connects to atypical depressive symptoms. • We explored microbiome across atypical vs. typical vs. healthy controls. • Depressive subtypes and the healthy controls do not differ across alpha and beta diversity. • Distinct taxonomic differences were present within individuals with atypical depression. [ABSTRACT FROM AUTHOR]

Background: Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models. Methods: We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later. Results: The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave. Conclusions: The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles. [ABSTRACT FROM AUTHOR]

Summary: Background & Aims: Depression is receiving increase attention for its relation to lifestyle-related diseases. We aim to assess differences in blood biomarkers and dietary habit between individuals with typical and atypical depression. Methods: We gathered data from 804 older Japanese individuals. Participants with diagnosed depression were further grouped into typical or atypical subtypes. Dietary habits were measured by a dietary variety score. Considering the small sample size, descriptive analysis and logistic regression analysis adjusted by propensity score were used to evaluate the associations of blood biomarkers and dietary habits with typical and atypical depression. Results: Via interviews, 777 participants were confirmed to not be depressed, with the remaining 27 individuals having either typical (n = 18) or atypical (n = 9) depression. Weight, BMI, HbA1c levels, and the proportion of never drinkers were higher in the depressed group than in the non-depressed group (P = 0.04, P = 0.02, P = 0.04, P < 0.01, respectively). The habit of fruit intake was lower in the depression group (P = 0.01). Atypical depression was positively associated with weight and BMI (odds ratio: OR 1.06, P = 0.02, OR 1.20, P = 0.01), while typical depression had a positive relation to HbA1c (OR 1.76, P = 0.01). As for eating habit, atypical depression was negatively associated with fruit intake (OR 0.38, P < 0.01). Conclusions: Depression in older individuals was positively associated with weight (atypical type), BMI (atypical type), HbA1c (typical type), and low fruit intake (atypical type).

Introduction: Among treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines. Method: Out of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity -- QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning -- GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st - 3rd quartile) of 4 (1-9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11-33) months after remission. Results: At the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38-66%]). After DATA step 2, 37 patients were in remission (77% [65--89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78-97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62-95%]). Conclusion: These results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s). [ABSTRACT FROM AUTHOR]

To explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative symptoms. A total of 3187 patients who met DSM-IV TR criteria for MDD were enrolled. Demographics and symptomatology covering multiple symptom domains were assessed and compared between three groups of cases: those who met DSM criteria for atypical specifier (the DAD group), those who had at least one reversed vegetative symptoms (hypersomnia or hyperphagia) (the SAD group) without meeting DSM atypical specifier criteria, and those without any reversed vegetative symptoms (the NAD group). The DAD and SAD group accounted for 4.4% and 14.4% of the participants, respectively. The DAD cases were characterized by a highest proportion of hospitalizations, longest duration of current episode and worst quality of life. The DAD and SAD cases were more likely to adopt unhealthy behaviors (smoking and alcohol drinking). Most depressive symptoms related to higher illness severity and treatment resistance were more frequent in the DAD cases, followed by the SAD cases, and least frequent in the NAD cases. A cross-sectional design and a non-validated questionnaire were used. The findings support the role of DSM defined atypical depression as a valid MDD subtype and provide evidence for clinical utility of the simplified approach of defining atypical features based on only reversed vegetative symptoms. This has implications for illness screening, public health, suicide prevention and better treatment planning for depressed individuals with atypical features even below syndromal level. • Over 60% of participants with MDD endorsed at least one atypical symptom. • The DSM defined AD showed the most complex clinical presentation. • The simplified approach defined AD showed more complex clinical picture than MDD without any reversed vegetative symptoms. • The findings highlight the necessary for assessing atypical features even below syndromal level in patients with MDD. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate the associations of major depressive disorder (MDD) and its subtypes (atypical, melancholic, combined, unspecified) with actigraphy-derived measures of sleep, physical activity and circadian rhythms; and test the potentially mediating role of sleep, physical activity and circadian rhythms in the well-established associations of the atypical MDD subtype with Body Mass Index (BMI) and the metabolic syndrome (MeS). The sample consisted of 2317 participants recruited from an urban area, who underwent comprehensive somatic and psychiatric evaluations. MDD and its subtypes were assessed via semi-structured diagnostic interviews. Sleep, physical activity and circadian rhythms were measured using actigraphy. MDD and its subtypes were associated with several actigraphy-derived variables, including later sleep midpoint, low physical activity, low inter-daily stability and larger intra-individual variability of sleep duration and relative amplitude. Sleep midpoint and physical activity fulfilled criteria for partial mediation of the association between atypical MDD and BMI, and physical activity also for partial mediation of the association between atypical MDD and MeS. Our findings confirm associations of MDD and its atypical subtype with sleep and physical activity, which are likely to partially mediate the associations of atypical MDD with BMI and MeS, although most of these associations are not explained by sleep and activity variables. This highlights the need to consider atypical MDD, sleep and sedentary behavior as cardiovascular risk factors. • Atypical depression associated with later sleep midpoint and low physical activity. • Melancholic depression associated with low physical activity. • Later sleep midpoint associated with high BMI. • Physical activity associated with low BMI and decreased risk of metabolic syndrome. • Sleep midpoint and physical activity are partial statistical mediators. [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]

Introduction. Depression and metabolic syndrome (MetS) are important public health problems. This systematic review evaluated whether the atypical subtype of depression is associated with MetS, when compared to other depressive subtypes. Methods. Two independent reviewers searched in Medline, Lilacs, PsycInfo, Scopus and Web of Science databases, up to May 2021, without language restriction, including cross-sectional, case-control, and cohort studies, assessing adults. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. The PRISMA guidelines were adopted and this review was registered in PROSPERO (CRD42018109762). Results. The databases search identified 96 articles and 6 was included in this review. The methodological quality scores ranged from 7 to 10 points. The association between atypical depression and MetS was demonstrated in all publications, as well as the lack of association with melancholic and other subtypes. The prevalence of MetS was significantly higher among individuals with atypical depression. It is worth noting that only few studies assessing this comorbidity were conducted so far. Conclusions. MetS is associated with atypical depression, but not with melancholic or other subtypes. The identification of distinct depressive clinical features seems crucial to better understand its comorbidity with MetS and elucidate its pathophysiological pathways, both necessary to better guide prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

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Objective: to perform a comparative study of the clinical features of atypical depression (AtD) in affective disorders of various origins: in bipolar affective disorder (BAD), recurrent depressive disorder (RDR) and psychogenic depression (PD).Patients and methods. A sample of 250 depressed patients aged 18 to 65 years were examined, of which 77 participants (50 women and 27 men) with symptoms of AtD were included to the study. Group 1 included 35 patients with BAD, group 2 – 18 patients with RDR, and group 3 – 24 patients with diagnoses including PD. The patients' condition was assessed using the diagnostic criteria for affective disorders according to ICD-10 and DSM-5 with a Montgomery-Asberg Depression Rating Scale (MADRS).Results and discussion. AtD detection rate was 30.8%, including 45.4% in BAD, 23.4% – in RDR, and 31.2% – in PD. AtD manifested at the age of about 20 years, and was more common in women. AtD in BAD occurred more often in individuals with cycloid, hyperthymic, and hysterical features. Affective fluctuations before the disease onset, a significantly greater number of depressive episodes in history were characteristic. The most frequent typical depressive symptoms included: daily and seasonal mood fluctuations, morning deterioration of well-being, decreased appetite. High comorbidity with metabolic endocrine diseases was observed. AtD in RDR often began spontaneously in individuals with emotionally labile, psychasthenic, and hysterical features. The most common typical depressive symptoms included melancholy, derealization, weakness, ideas of self-accusation, suicidal thoughts and attempts. A high comorbidity with cardiovascular diseases was found. AtD in PD occurred more often in psychasthenic individuals. The most characteristic symptoms included: increased appetite, anxiety, asthenia, superficial night sleep, hypochondriacal inclusions. Comorbidity with skin and gastrointestinal diseases was observed.Conclusion. The identified features of the clinical picture and course of AtD in BAD, RDR, and PD can be used for earlier and more accurate evaluation of affective disorders and the adequate treatment administration.

Objective: to evaluate the treatment effectiveness for atypical depression (AtD) depending on its nosology: in bipolar affective disorder (BAD), recurrent depressive disorder (RDD) and psychogenic depression (PD).Patients and methods. A total of 250 patients with depression were screened, of which 77 patients with symptoms of AtD were enrolled in the study, 35 of them with BAD, 18 with RDD, and 24 with PD. Patients in all three groups received an antidepressant (AD) or a mood stabilizer (MS) monotherapy, or a combination of AD and antipsychotic (A), AD and A, MS and A, as well as a combination of AD, A and MS. The patients' condition was assessed clinically using a specially designed questionnaire and MADRS and CGI scales at the baseline and the 2nd, 3rd, 4th, 6th, 12th weeks of treatment. Quality of life satisfaction was assessed with the Q-LES-Q-SF (Scoring the Quality-of-Life Enjoyment and Satisfaction Questionnaire) scale at the treatment onset and after the 12th week of treatment.Results and discussion. Treatment regimens that included AD were the most eff in all groups of patients with AtD. The proportion of responders among those who received AD for bipolar disorder (75% or more) was significantly higher than among those who did not receive it (˂50%). In the RDD and PD groups, patients responded significantly better to AD monotherapy (RDD – 93.2%; PD – 91.5%) compared to other regimens. Agomelatine was the most frequently used (31.8%) and effective AD in all groups. Also, escitalopram, vortioxetine, and venlafaxine (p˂0.05) showed high efficacy, good tolerance, and absence of side effects that aggravate the main symptoms that characterize AtD. Among the antipsychotics in combination with AD, sulpiride was significantly more effective in patients with PD (p˂0.05). The highest rates of quality of life satisfaction were achieved in the BAD group, the lowest – in patients with PD (p˂0.05), which indirectly indicates the quality of remission, which is determined not only by the degree of reduction of depressive symptoms but also by the patients' subjective perception of their mental state.Conclusion. The inclusion of AD in the AtD treatment regimen significantly increases its effectiveness in patients of all groups, including BAD. AtD treatment should be administered not only taking into account its clinical signs and severity, but also depending on the nosology of the disease, the characteristics of its course. During drug administration, it is necessary to consider the spectrum of side effects, especially those that increase the symptoms of AtD itself.

Alessandro Gialluisi,1 Federica Santonastaso,2 Marialaura Bonaccio,1 Francesca Bracone,1 Nitin Shivappa,3,4 James R Hebert,3,4 Chiara Cerletti,1 Maria Benedetta Donati,1 Giovanni de Gaetano,1 Licia Iacoviello1,2 On behalf of the Moli-sani Investigators1Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy; 2Department of Medicine and Surgery, University of Insubria, Varese, Italy; 3Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 4Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USACorrespondence: Alessandro GialluisiDepartment of Epidemiology and Prevention, IRCCS Neuromed, Via dell´Elettronica, 86077, Pozzilli, ItalyTel +390865915244Email alessandro.gialluisi@gmail.comBackground: Depression is a mood disorder characterized by a high rate of resistance to pharmacological treatments, which has often been linked to chronic inflammation. This can be influenced by different environmental factors, in particular pro-inflammatory diets. However, a mediating role of circulating inflammation has never been observed.Aim: To test the association between a dietary inflammatory index (DII®) and continuous depressive symptoms (adapted version of PHQ9) in an Italian population cohort (N=13,301), along with potential explanatory effect of a composite index (INFLA-score) based on four circulating inflammatory biomarkers: C-reactive protein, granulocyte-to-lymphocyte ratio, platelet and white blood cell counts.Results: Significant positive associations were observed between DII and total depressive symptoms (standardized β (SE) = 0.038 (0.005), p < 0.001), and with two factors tagging somatic (0.012 (0.003), p < 0.001) and cognitive symptoms (0.012 (0.003), p < 0.001), after adjustment for different potential confounders (socioeconomic status, chronic health conditions and lifestyles). These associations were about twice as strong in women than in men. INFLA-score explained a small but significant proportion of the association with total depressive symptoms (0.90– 2.30%, p < 0.05), which was mainly driven by granulocyte-to-lymphocyte ratio (1.18– 1.65%). This effect was even stronger for the somatic (2.66– 4.66%) but not for the cognitive factor (0%).Conclusion: These findings support a strong link between inflammatory diet and depression, especially with somatic symptoms and within women. Moreover, they provide novel evidence for a potential explanatory role of circulating inflammation in this association, suggesting new paths for prevention and treatment of major and atypical depression.Keywords: dietary inflammatory index, depressive symptoms, atypical depression, circulating inflammation, granulocyte-to-lymphocyte ratio, white blood cells

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]

Introduction To improve the effectiveness of treatment for atypical depression, it is necessary to revise the accumulated experience, taking into account new knowledge and drugs. Objectives Comparative study of the efficacy and safety of therapy for atypical depression (AtD) in the structure of bipolar affective disorder (BAD), recurrent depressive disorder (RDR) and psychogenic depression (PD). Methods Clinical and clinical follow-up methods examined 77 patients with AtD, of which 35 - with bipolar disorder, 18 - with RDR and 24 - with PD. Patients in all three groups received monotherapy with an antidepressant or a mood stabilizer, or a combination of antidepressant and antipsychotic, antidepressant and mood stabilizer, mood stabilizer and antipsychotic, as well as a combination of antidepressant, antipsychotic and mood stabilizer. Results Agomelatine was the most frequently used (27.3%) and effective in reducing MADRS in all groups both in monotherapy and in combination with other drugs. Also in the PD group, escitalopram and vortioxetine were highly effective. Of the antipsychotics, when combined with antidepressants, sulpiride was found to be the most effective. When comparing the tolerance of antidepressants in all groups showed the best results (by the CGI scale), agomelatine and venlafaxine, in the BAR group is also vortioxetine. Conclusions The best strategy for effective and safe treatment of atypical depression is the use of modern antidepressant, which does not increase the symptoms of the atypical spectrum and, if necessary, can be supplemented with some antipsychotics. Disclosure No significant relationships.

Background: Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups. Methods: Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10−4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated. Results: ↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15–1.26), p = 2.37 × 10−14] and C-reactive protein [OR = 1.11 (1.06–1.17), p = 8.86 × 10−06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10−04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83–0.93), p = 1.04 × 10−05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively). Conclusions: ↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression. [ABSTRACT FROM AUTHOR]

The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to individuals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 individuals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of individual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, individuals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features. [ABSTRACT FROM AUTHOR]

Atypical depression (AtD) is contrasted with classical endogenous melancholic depression and is characterized by the presence of its uncharacteristic abnormalities, but the list of the latter varies from individual symptoms (increased appetite, weight gain, drowsiness, weakness, and anxiety) and their concurrence to syndromes accompanying depression (anxiety-phobic, obsessive-compulsive, panic attacks, derealization-depersonalization, hypochondriacal syndrome). In accordance with the DSM-5 diagnostic criteria, AtD is a symptom complex that includes mood reactivity and at least two of the following symptoms: hyperphagia, hypersomnia, lead-palsy, and personality sensitivity. AtD has been described within a variety of disorders: recurrent depressive disorder, bipolar affective disorder, dysthymia, cyclothymia, and psychogenic depression. The paper describes a clinical case of atypical depressive syndrome within the framework of type 2 bipolar disorder in a 51-year-old patient. AtD was concurrent with dermatitis herpetiformis (Dühring's disease) in some depressive episodes; it was accompanied by various somatic complaints in other cases. The latest episode of AtD occurred during the COVID-19 pandemic and included obvious reactive anxiety-phobic disorders. A detailed clinical and psychopathological analysis of history data, mental state, and ongoing therapy was carried out, which clearly reflects difficulties in the differential diagnosis of AtD and the use of adequate treatment.

Cushing’s syndrome may present with various psychiatric disorders which can lead to a misdiagnosis at the beginning, deterioration of the course of the disease and life-threatening complications. The most common psychiatric disorder is atypical depression. During the initial stages of the disease, the somatic symptoms of Cushing’s syndrome can be subtle, difficult to identify, especially when the psychiatric symptoms are dominant. Objective: The aim of the present article is to report a case of a 24-year-old woman with a Cushing’s syndrome, caused by the adrenal adenoma. The onset of the disease is a suicidal attempt. Family history is significant for psychiatry disorder. The belated diagnosis led to somatic and psychiatry complications of the disease – sepsis and persisting high suicidal risk. The dynamic change in the patient’s mental state – from a severe depressive episode with atypical symptoms to psychosis with single catatonic symptoms – correlated well with the gradual increase of the plasma cortisol levels. The antidepressant and subsequent antipsychotic medication turned out to be ineffective. The surgical treatment, followed by a normalization of the cortisol levels was a key to the successful outcome and the reduction of self-aggression risk. Conclusion: The early diagnosis and timely treatment of Cushing’s syndrome decrease the risk of multiple complications. The shift from atypical depression to psychosis with catatonic symptoms correlates with the worsening of the hormonal imbalance. The signs of atypical depression in Cushing's syndrome, resistant to the antidepressant medication, could be considered as relatively specific symptoms, guiding specialists to its somatogenic origin for the proper diagnosis.

The paper reviews Russian and foreign literature on atypical depression (AtD). It sets forth the historical aspects of identifying AtD among other depressive disorders: the authors have traced the path from depression with individual atypical manifestations to a syndrome with a clearly defined pattern and inclusion criteria in the international DSM-4 and DSM-5 classifications. The paper gives epidemiological indicators and shows their diversity due to various approaches to the determination and clinical assessment of AtD. It analyzes the results of studying AtD in the presence of various affective disorders, such as recurrent depressive disorder, bipolar affective disorder, and psychogenic depression, and notes their heterogeneity in both symptoms and genesis. The authors present approaches to treating AtD and the results of investigating drug (antidepressant) and non-drug (cognitive-behavioral psychotherapy, increased physical activity therapy) treatments.

Identifying additional noninvasive biomarkers for affective disorders, such as unipolar major depressive disorder (MDD) and bipolar disorder (BD), could aid in the diagnosis and treatment of these prevalent and debilitating neuropsychiatric conditions. One such candidate biomarker is the loudness dependence of the auditory evoked potential (LDAEP), an event-related potential that measures responsiveness of the auditory cortex to different intensities of sound. The LDAEP has been associated with MDD and BD, including therapeutic response to particular classes of antidepressant drugs, while also correlating with several other neuropsychiatric disorders. It has been suggested that increased values of the LDAEP indicate low central serotonergic neurotransmission, further implicating this EEG measure in depression. Here, we briefly review the literature on the LDAEP in affective disorders, including its association with serotonergic signaling, as well as with that of other neurotransmitters such as dopamine. We summarize key findings on the LDAEP and the genetics of these neurotransmitters, as well as prediction of response to particular classes of antidepressants in MDD, including SSRIs versus noradrenergic agents. The possible relationship between this EEG measure and suicidality is addressed. We also briefly analyze acute pharmacologic studies of serotonin and/or dopamine precursor depletion and the LDAEP. In conclusion, the existing literature suggests that serotonin and norepinephrine may modulate the LDAEP in an opposing manner, and that this event-related marker may be of use in predicting response to chronic treatment with particular pharmacologic agents in the context of affective disorders, such as MDD and BD, including in the presence of suicidality. [ABSTRACT FROM AUTHOR]

• Depression and metabolic disorders such as type 2 diabetes mellitus show frequent comorbidity. • Chronic low-grade inflammation plays a role in the pathogenesis of both conditions and their comorbidity. • Atypical features of depression such as overeating are associated with inflammation and metabolic disorders. • Depression and metabolic disorders share similar MRI-assessed brain patterns. Insulin resistance (IR) and related disorders, such as T2DM, increase the risk of major depressive disorder (MDD) and vice versa. Current evidence indicates that psychological stress and overeating can induce chronic low-grade inflammation that can interfere with glutamate metabolism in MDD as well as insulin signaling, particularly in the atypical subtype. Here we first review the interactive role of inflammatory processes in the development of MDD, IR and related metabolic disorders. Next, we describe the role of the anterior cingulate cortex in the pathophysiology of MDD and IR-related disorders. Furthermore, we outline how specific clinical features of atypical depression, such as hyperphagia, are more associated with inflammation and IR-related disorders. Finally, we examine the regional specificity of the effects of inflammation on the brain that show an overlap with the functional and morphometric brain patterns activated in MDD and IR-related disorders. [ABSTRACT FROM AUTHOR]

The present study examined associations between immunometabolic characteristics (IMCs) and depressive symptom profiles (DSPs) in probands with lifetime diagnoses of depression and/or anxiety disorders and their siblings. Data were from the Netherlands Study of Depression and Anxiety, comprising 256 probands with lifetime diagnoses of depression and/or anxiety and their 380 siblings. Measured IMCs included blood pressure, waist circumference, and levels of glucose, triglycerides, HDL cholesterol, CRP, TNF-α and IL-6. DSPs included mood, cognitive, somatic and atypical-like profiles. We cross-sectionally examined whether DSPs were associated with IMCs within probands and within siblings, and whether DSPs were associated with IMCs between probands and siblings. Within probands and within siblings, higher BMI and waist circumference were associated with higher somatic and atypical-like profiles. Other IMCs (IL-6, glucose and HDL cholesterol) were significantly related to DSPs either within probands or within siblings. DSPs and IMCs were not associated between probands and siblings. The results suggest that there is a familial component for each trait, but no common familial factors for the association between DSPs and IMCs. Alternative mechanisms, such as direct causal effects or non-shared environmental risk factors, may better fit these results. [ABSTRACT FROM AUTHOR]

Overeating is a complex behavioral phenotype in terms of both physiology and psychology. The mere transference of the diagnostic criteria for substance use disorders to define food addiction is too simplistic, for the following reasons: 1) a range of somatic and mental disorders require exclusion; 2) food addiction requires distinction from the physiological need to ingest sufficient calories to maintain a high body weight; 3) intentional weight loss can induce an eating behavior mimicking food addiction; 4) the concept lacks validation, especially in light of the high prevalence of "food addiction" in patients with anorexia nervosa; and 5) this construct has not led to novel and successful treatments for overeating and obesity. The concept of food addiction has the potential to distract from the need for focus on environmental influencers to combat the obesity pandemic. [ABSTRACT FROM AUTHOR]

Objective: Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery–Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using the Scale for Atypical Symptoms (SAS)). Methods: Data from 68 participants with treatment‐resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double‐blind, placebo‐controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic‐dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14 days postinfusion. Effect sizes were calculated for days 1 and 3 postinfusion. The primary measures of interest for this exploratory analysis were total MADRS, MADRS5, and SAS scores. Individual symptoms were also analyzed in an exploratory manner. Results: Scores improved significantly at Day 1 postinfusion (MADRS: Cohen's d = 0.64; MADRS5: Cohen's d = 0.61; SAS: Cohen's d = 0.41) and continued to be significantly improved over placebo at Day 3 (MADRS: Cohen's d = 0.49; MADRS5: Cohen's d = 0.43; SAS: Cohen's d = 0.39). Effect sizes were greater for typical/melancholic than atypical symptoms at Day 1 postinfusion. Conclusion: Ketamine appears to effectively treat both the typical/melancholic and atypical symptoms of depression, but may have early preferential effects for the former. [ABSTRACT FROM AUTHOR]

Background: The link between systemic inflammation and depression has been deeply investigated, but relatively few studies explored symptom-specific associations, mostly focusing on common inflammatory biomarkers like C-reactive protein (CRP) levels.Methods: We investigated associations of low-grade inflammation with depressive symptoms assessed through a reduced version of Patient Health Questionnaire 9 (PHQ-9) in a large population-based cohort of adult Italians (N = 13 301). We built logistic regressions between each depressive symptom and composite index of systemic inflammation based on four circulating biomarkers, namely CRP, Plt, WBC, and GLR (INFLA)-score, a composite blood-based inflammation index, and with its component biomarkers, namely CRP, platelets count (Plt), white blood cells count (WBC), and granulocyte-to-lymphocyte ratio (GLR).Results: We observed a strong association of the altered appetite/eating symptom with standardized INFLA-score (OR [95% CI] = 1.19 [1.12-1.26]; corrected p = 3.0 × 10-7 ), CRP (1.28 [1.20-1.36]; p = 1.9 × 10-13 ), and WBC (1.13 [1.06-1.20]; p = 2.3 × 10-3 ), and of tiredness/low energy with GLR (1.11 [1.05-1.17]; p = 9.4 × 10-3 ). These associations remained stable within nondepressed participants (PHQ-9 < 10), and after adjustment for the use of antidepressants, main chronic conditions, and lifestyle factors; while they were notably attenuated within depressed participants (PHQ-9 ≥ 10) and-for altered appetite only-by adjustment for obesity.Conclusions: This study provides a robust replication of the association previously reported between CRP and altered appetite in a large US population cohort, and supports a link between systemic inflammation, altered appetite, and tiredness. Moreover, it extends this evidence to inflammatory markers other than CRP and suggests new targets for the treatment of atypical depression. [ABSTRACT FROM AUTHOR]

Background: Depression is a heterogeneous disorder with multiple aetiological pathways and multiple therapeutic targets. This study aims to determine whether atypical depression (AD) characterized by reversed neurovegetative symptoms is associated with a more pernicious course and a different sociodemographic, lifestyle, and comorbidity profile than nonatypical depression (nonAD). Methods: Among 157 366 adults who completed the UK Biobank Mental Health Questionnaire (MHQ), N = 37 434 (24%) met the DSM-5 criteria for probable lifetime major depressive disorder (MDD) based on the Composite International Diagnostic Interview Short Form. Participants reporting both hypersomnia and weight gain were classified as AD cases (N = 2305), and the others as nonAD cases (N = 35 129). Logistic regression analyses were conducted to examine differences between AD and nonAD in depression features, sociodemographic and lifestyle factors, lifetime adversities, psychiatric and physical comorbidities. Results: Persons with AD experienced an earlier age of depression onset, longer, more severe and recurrent episodes, and higher help-seeking rates than nonAD persons. AD was associated with female gender, unhealthy behaviours (smoking, social isolation, low physical activity), more lifetime deprivation and adversity, higher rates of comorbid psychiatric disorders, obesity, cardiovascular disease (CVD), and metabolic syndrome. Sensitivity analyses comparing AD persons with those having typical neurovegetative symptoms (hyposomnia and weight loss) revealed similar results. Conclusions: These findings highlight the clinical and public health significance of AD as a chronic form of depression, associated with high comorbidity and lifetime adversity. Our findings have implications for predicting depression course and comorbidities, guiding research on aetiological mechanisms, planning service use and informing therapeutic approaches. [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: to study the clinical and psychopathological features of depressions with panic attacks.Patients and methods. A total of 100 in- and outpatients aged 18 to 60 years, who had been treated in the S.S. Korsakov Clinic of Psychiatry for mild and moderate depression with panic attacks, were clinically examined using the psychometric scales: the Montgomery–Asberg Depression Rating Scale, the Atypical Depression Diagnostic Scale, and the Sheehan Clinical Anxiety Rating Scale.Results. The clinical and psychopathological picture of depression with panic attacks differed significantly in three identified groups of patients with neurotic depression (ND), recurrent depressive disorder (RDD), and bipolar affective disorder (BAD). NDs with panic attacks were characterized by insignificant short-term symptoms of dreariness, indistinct anhedonia with the maximum manifestation of personality sensitivity, and a tendency to alcohol abuse. DDRs with panic attacks were inherent in melancholic and dreary symptoms, anhedonia, classical circadian mood fluctuations, and the most marked reactivity of mood. Depressions with panic attacks within BAD were typical of apathetic manifestations, hypersomnia, hyperphagia, and alcohol craving.Conclusion. Depressions with panic attacks have psychopathological features depending on whether they develop within ND, RDR, or BAD.

Dorota Łojko,1 Janusz K Rybakowski1,2 1Department of Adult Psychiatry, 2Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland Abstract: The history and present status of the definition, prevalence, neurobiology, and treatment of atypical depression (AD) is presented. The concept of AD has evolved through the years, and currently, in Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, the specifier of depressive episode with atypical feature is present for both diagnostic groups, that is, depressive disorders and bipolar and related disorders. This specifier includes mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity. Prevalence rates of AD are variable, depending on the criteria, methodology, and settings. The results of epidemiological studies using DSM criteria suggest that 15%–29% of depressed patients have AD, and the results of clinical studies point to a prevalence of 18%–36%. A relationship of AD with bipolar depression, seasonal depression, and obesity has also been postulated. Pathogenic research has been mostly focused on distinguishing AD from melancholic depression. The differences have been found in biochemical studies in the areas of hypothalamic–pituitary–adrenal axis, inflammatory markers, and the leptin system, although the results obtained are frequently controversial. A number of findings concerning such differences have also been obtained using neuroimaging and neurophysiological and neuropsychological methods. An initial concept of AD as a preferentially monoamine oxidase inhibitor-responsive depression, although confirmed in some further studies, is of limited use nowadays. Currently, despite numerous drug trials, there are no comprehensive treatment guidelines for AD. We finalize the article by describing the future research perspectives for the definition, neurobiology, and treatment. A better specification of diagnostic criteria and description of clinical picture, a genome-wide association study of AD, and establishing updated treatment recommendations for this clinical phenomenon should be the priorities for the coming years. Keywords: hypersomnia, hyperphagia, obesity, bipolar disorder, seasonal affective disorder

• „Conceptual endophenotypes" have been proposed as a means to identify subgroups of patients affected by stress-related disorders. • Neuropattern, based on conceptual endophenotypes, is a diagnostic instrument that integrates psychological and biological data. • MR gene variation was associated with the endophenotype CRF-hypoactivity , characterized by features of atypical depression. • MR gene variation might serve as a biomarker for subgrouping patients with stress-related disorders. Recently, the „conceptual endophenotype" approach has been proposed as a means to identify subgroups of patients affected by stress-related psychiatric disorders. Conceptual endophenotypes consist of patterns of psychological, biological, and symptomatic elements. We studied a sample of patients seeking help for psychosomatic and stress-related disorders (total N = 469), who were evaluated with a diagnostic instrument that integrates psychological and biological data to derive 13 endophenotypes, or Neuropattern. The goal of this study was to explore associations between common variations of the mineralocorticoid receptor gene (MR, NR3C2), and the 13 conceptual endophenotypes of Neuropattern, as well as with the respective biological and symptom measures. A common haplotype of the MR, comprised of two functional single nucleotide polymorphism (rs2070951 G/C & rs5522 A/G), was associated with the conceptual endophenotype CRF-hypoactivity, characterized by low cortisol levels at awakening and a symptom constellation often observed in atypical depression. Homozygous carriers of the G-A haplotype (haplotype 1), previously associated with reduced dispositional optimism, increased levels of rumination and higher risk for depression, more frequently endorsed this Neuropattern. In addition to the overall association between MR variation and CRF hypoactivity, we observed in the whole sample significant associations between MR haplotypes and cortisol awakening response patterns, as well as with symptoms that characterize the CRF hypoactivity endophenotype. If replicated, MR haplotype 1 might serve as a vulnerability marker for a disorder class characterized in biological terms by reduced cortisol levels, and in terms of symptom constellation by features often observed in atypical depression. [ABSTRACT FROM AUTHOR]

Highlights • BMI and overweight were associated with the atypical subtype of depression. • BMI/overweight in probands was associated with BMI/overweight in their relatives. • Atypical depression in probands was associated with BMI/overweight in relatives. Abstract Background We previously demonstrated the specificity of familial transmission of the atypical subtype of depression, primarily characterized by overeating and oversleeping. However, the specific components of this subtype that are familial have not been established. The aim of this paper is to examine whether the familial specificity of atypical depression can be attributed to the association between Body Mass Index (BMI) and overweight/obesity with mood disorders. Methods The sample included 293 probands recruited from the community and their 544 adult first-degree relatives. Diagnostic assignment was based on a direct semi-structured interview. Mixed effect models were employed to test the familial aggregation and the familial cross-aggregation of mood disorders and BMI/overweight. Results There were significant within-individual associations between overweight and the atypical subtype of depression (p -value = 0.003). There was also an association for BMI/overweight between probands and relatives (β = 0.23, p -value < 0.001; odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.02–2.43, respectively). Atypical depression in probands was significantly associated with BMI and overweight in relatives (β = 0.001, p -value = 0.040; OR = 2.79, 95%CI = 1.20–6.49, respectively). Limitations The cross-sectional design impedes our ability to evaluate the direction of these associations. Other potential risk factors, such as diabetes, physical activity and unhealthy diet were not considered. Conclusions These findings imply that overweight may be either a precursor or consequence of atypical depression rather than a manifestation of a common diathesis underlying depression in families. Clinicians should pay particular attention to this subtype that could be at increased risk for the development of cardiovascular risk factors and diseases. [ABSTRACT FROM AUTHOR]

Depression is highly prevalent (6% 1-year prevalence) and is the second leading cause of disability worldwide. Available treatment options for depression are far from optimal, with response rates only around 50%. This is most likely related to a heterogeneous clinical presentation of major depression disorder (MDD), suggesting different manifestations of underlying pathophysiological mechanisms. Poorer treatment outcomes to first-line antidepressants were reported in MDD patients endorsing an "atypical" symptom profile that is characterized by preserved reactivity in mood, increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity. In recent years, evidence has emerged that immunometabolic biological dysregulation is an important underlying pathophysiological mechanism in depression, which maps more consistently to atypical features. In the last few years human microbial residents have emerged as a key influencing variable associated with immunometabolic dysregulations in depression. The microbiome plays a critical role in the training and development of key components of the host's innate and adaptive immune systems, while the immune system orchestrates the maintenance of key features of the host-microbe symbiosis. Moreover, by being a metabolically active ecosystem commensal microbes may have a huge impact on signaling pathways, involved in underlying mechanisms leading to atypical depressive symptoms. In this review, we discuss the interplay between the microbiome and immunometabolic imbalance in the context of atypical depressive symptoms. Although research in this field is in its infancy, targeting biological determinants in more homogeneous clinical presentations of MDD may offer new avenues for the development of novel therapeutic strategies for treatment-resistant depression. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies". • Emerging evidence suggests that metabolic dysregulation and chronic low-grade inflammation are more consistently associated with a symptom profile often referred to as "atypical" depression. • A highly interconnected complex of adverse physiological adaptations are most likely common underlying biological substrates that dominate clinical presentations depending on individual predisposition and additional factors. • Accumulating evidence has identified human-associated microbes as a major player in the interplay between immune and energy dysregulation, linking atypical depressive symptoms to comorbid metabolic disorders. • Dysfunctional interplay among microbiome composition, immunity, and metabolism that predisposes to atypical depression and cardiometabolic disorders may occur early in development. • Dysbiosis of the oral microbiome facilitates the passage of pathogenic microbes and their metabolites across the blood-brain barrier and may affect neuronal function. [ABSTRACT FROM AUTHOR]

The lower reported prevalence of depression in men has been related to depression not being as well-recognised in men as it is in women. We sought to understand the clinical under-recognition of depression in men by reviewing some of the key evidence on male depression, concentrating on practices in the UK. Additionally, we aimed to draw conclusions that would contribute to the improvement of health promotion and of the diagnosis for male depression. Our perusal of the available evidence has revealed that some depressed men experience significant difficulties not only in disclosing but also in identifying their depression and that men often exhibit atypical symptoms such as anger. Furthermore, depressed men are often involved in attempts to self-manage their depressive symptoms. This stoic approach compromises the well-being of depressed men and it discourages them from accessing appropriate support resources. We conclude with suggestions for practice and research. [ABSTRACT FROM AUTHOR]

The lower reported prevalence of depression in men has been related to depression not being as well-recognised in men as it is in women. We sought to understand the clinical under-recognition of depression in men by reviewing some of the key evidence on male depression, concentrating on practices in the UK. Additionally, we aimed to draw conclusions that would contribute to the improvement of health promotion and of the diagnosis for male depression. Our perusal of the available evidence has revealed that some depressed men experience significant difficulties not only in disclosing but also in identifying their depression and that men often exhibit atypical symptoms such as anger. Furthermore, depressed men are often involved in attempts to self-manage their depressive symptoms. This stoic approach compromises the well-being of depressed men and it discourages them from accessing appropriate support resources. We conclude with suggestions for practice and research. [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]

Background: The link between the abnormalities of the Hypothalamic-pituitary-adrenal (HPA) axis and depression has been one of the most consistently reported findings in psychiatry. At the same time, multiple studies have demonstrated a stronger association between the increased activation of HPA-axis and melancholic, or endogenous depression subtype. This association has not been confirmed for the atypical subtype, and some researchers have suggested that as an antinomic depressive subtype, it may be associated with the opposite type, i.e. hypo-function, of the HPA-axis, similarly to PTSD. The purpose of this systematic review is to summarise existing studies addressing the abnormalities of the HPA-axis in melancholic and/or atypical depression.Method: We conducted a systematic review in the literature by searching MEDLINE, PsycINFO, OvidSP and Embase databases until June 2017. The following search items were used: "hypothalamic-pituitary-adrenal" OR "HPA" OR "cortisol" OR "corticotropin releasing hormone" OR "corticotropin releasing factor" OR "glucocorticoid*" OR "adrenocorticotropic hormone" OR "ACTH" AND "atypical depression" OR "non-atypical depression" OR "melancholic depression" OR "non-melancholic depression" OR "endogenous depression" OR "endogenomorphic depression" OR "non-endogenous depression". Search limits were set to include papers in English or German language published in peer-reviewed journals at any period. All studies were scrutinized to determine the main methodological characteristics, and particularly possible sources of bias influencing the results reported.Results: We selected 48 relevant studies. Detailed analysis of the methodologies used in the studies revealed significant variability especially regarding the samples' definition comparing the HPA axis activity of melancholic patients to atypical depression, including healthy controls. The results were subdivided into 4 sections: (1) 27 studies which compared melancholic OR endogenous depression vs. non-melancholic or non-endogenous depression or controls; (2) 9 studies which compared atypical depression or atypical traits vs. non-atypical depression or controls; (3) 7 studies which compared melancholic or endogenous and atypical depression subtypes and (4) 5 studies which used a longitudinal design, comparing the measures of HPA-axis across two or more time points. While the majority of studies did confirm the association between melancholic depression and increased post-challenge cortisol levels, the association with increases in basal cortisol and basal ACTH were less consistent. Some studies, particularly those focusing on reversed vegetative symptoms, demonstrated a decrease in the activity of the HPA axis in atypical depression compared to controls, but the majority did not distinguish it from healthy controls.Conclusions: In conclusion, our findings indicate that there is a difference in the activity of the HPA-axis between melancholic and atypical depressive subtypes. However, these are more likely explained by hypercortisolism in melancholia; and most often normal than decreased function in atypical depression. Further research should seek to distinguish a particular subtype of depression linked to HPA-axis abnormalities, based on symptom profile, with a focus on vegetative symptoms, neuroendocrine probes, and the history of adverse childhood events. New insights into the dichotomy addressed in this review might be obtained from genetic and epigenetic studies of HPA-axis related genes in both subtypes, with an emphasis on the presence of vegetative symptoms. [ABSTRACT FROM AUTHOR]

BackgroundLiterature has shown that obesity, metabolic syndrome and inflammation are associated with depression, however, evidence suggests that these associations are specific to atypical depression. Which of the atypical symptoms are driving associations with obesity-related outcomes and inflammation is unknown. We evaluated associations between individual symptoms of depression (both atypical and non-atypical) and body mass index (BMI), metabolic syndrome components and inflammatory markers.MethodsWe included 808 persons with a current diagnosis of depression participating in the Netherlands Study of Depression and Anxiety (67% female, mean age 41.6 years). Depressive symptoms were derived from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Univariable and multivariable regression analyses adjusting for sex, age, educational level, depression severity, current smoking, physical activity, anti-inflammatory medication use, and statin use were performed.ResultsIncreased appetite was positively associated with BMI, number of metabolic syndrome components, waist circumference, C-reactive protein and tumor necrosis factor-α. Decreased appetite was negatively associated with BMI and waist circumference. Psychomotor retardation was positively associated with BMI, high-density lipoprotein cholesterol and triglycerides, and insomnia with number of metabolic syndrome components.ConclusionIncreased appetite – in the context of a depressive episode – was the only symptom that was associated with both metabolic as well as inflammatory markers, and could be a key feature of an immuno-metabolic form of depression. This immuno-metabolic depression should be considered in clinical trials evaluating effectiveness of compounds targeting metabolic and inflammatory pathways or lifestyle interventions. [ABSTRACT FROM AUTHOR]