Atypical Depression Research Articles

Differential effects of lifetime stressors on major depressive disorder severity: a longitudinal community-based cohort study.

Stressors across the lifespan are associated with the onset of major depressive disorder (MDD) and increased severity of depressive symptoms. However, it is unclear how lifetime stressors are related to specific MDD subtypes. The present study aims to examine the relationships between MDD subtypes and stressors experienced across the lifespan while considering potential confounders. Data analyzed were from the Zone d'Épidémiologie Psychiatrique du Sud-Ouest de Montréal (N = 1351). Lifetime stressors included childhood maltreatment, child-parent bonding, and stressful life events. Person-centered analyses were used to identify the clusters/profiles of the studied variables and multinomial logistic regression analyses were performed to examine the relationships between stressors and identified MDD subtypes. Intersectional analysis was applied to further examine how distal stressors interact with proximal stressors to impact the development of MDD subtypes. There was a significant association between proximal stressors and melancholic depression, whereas severe atypical depression and moderate depression were only associated with some domains of stressful life events. Additionally, those with severe atypical depression and melancholic depression were more likely to be exposed to distal stressors such as childhood maltreatment. The combinations of distal and proximal stressors predicted a greater risk of all MDD subtypes except for moderate atypical depression. MDD was characterized into four subtypes based on depressive symptoms and severity. Different stressor profiles were linked with various MDD subtypes. More specific interventions and clinical management are called to provide precision treatment for MDD patients with unique stressor profiles and MDD subtypes.

Comparative analysis of the identification efficacy of the bipolarity index and diagnostic and statistical manual of mental disorders, 5th edition, for bipolar disorder screening among college students

ObjectiveThis study aims to explore the differences in the identification efficacy of the Bipolarity Index (BPX) and the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), as screening approaches for bipolar disorder (BD). MethodsA total of 150 college students with depressive episodes who underwent outpatient and inpatient treatment at Central China Normal University Hospital and the Renmin Hospital of Wuhan University between January 2021 and December 2022 were selected as research participants. We used a self-developed general data questionnaire to collect comprehensive demographic and clinical data from all participants. This questionnaire covered various aspects including gender, age, occupation, education level, drinking habits, age at onset, disease duration, frequency and duration of the current episode, comorbidities, family history of genetic conditions, diagnosis and prognosis. Participants were evaluated using the BPX, the DSM-5 and the International Classification of Diseases, 10th Revision (ICD-10). Clinical diagnosis based on the ICD-10 served as the standard against which the BPX and DSM-5 were compared for sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). Additionally, we conducted a multivariate logistic regression analysis to evaluate risk factors associated with BD. ResultsThe sensitivity, specificity, accuracy, PPV and NPV were 85.34%, 81.90%, 84.00%, 87.21% and 79.69% for the BPX screening, and 72.73%, 90.32%, 80.00%, 91.43% and 70.00% for the DSM-5 screening, respectively. The study also identified significant clinical characteristics that differentiated those who screened positive for BD using the BPX. These characteristics included a younger average age at onset, a higher prevalence of atypical depression and more frequent prior affective episodes compared with those who did not meet the BPX criteria for BD. Risk factors associated with BD included atypical depression, history of suicide attempts, four or more previous affective episodes, borderline personality disorder, mixed states and a family history of BD. ConclusionIn conclusion, our findings suggest that the BPX exhibits superior sensitivity in screening for BD among college students compared with the DSM-5. Additionally, the study identifies significant risk factors (e.g., atypical depression, history of suicide attempts and multiple previous affective episodes), which are crucial for early detection and management.

The Association of Genetic Polymorphisms and Atypical Depression in Adults: A Systematic Review.

Atypical depression (AD) is a clinical subtype of depression characterised by mood reactivity and at least two of the following features: significant weight gain/increased appetite, hypersomnia, leaden paralysis, and/or interpersonal rejection sensitivity. The role of genetics in the development of depression remains a considerable level of interest among individuals. Due to the large number of breakthrough studies in genetics, there is currently a wealth of heterogeneous data on the existence of genetic markers for depression, including AD. However, it appears that there is a gap in the literature, as we were unable to identify any systematic reviews or meta-analyses that comprehensively describe these data. Therefore, our research aims to provide high-quality, solid evidence for further studies in this area. Electronic bibliographic databases (Scopus, MEDLINE) were systematically searched from inception to September 2023. We searched for any specific genetic markers that could be retrieved associated with AD. The quality of studies has been assessed by means of the Q-genie tool. Nine studies meeting the inclusion criteria were selected, which appeared to link genetic polymorphisms to atypical depression. Four studies examined genetic polymorphisms associated with the serotonin transporter gene (5-HTT), three studies examined genetic polymorphisms associated with endocrine regulation, two studies considered genetic polymorphisms associated with immune and/or cellular regulation, specifically the melanin-concentrating hormone receptor 2 (MCHR2), mineralocorticoid receptor (MR), and fat mass and obesity-associated protein (FTO) genes involved in the regulation of energy balance. The extracted data confirm that the atypical type of major depressive disorder is heritable to a certain extent. Individual risk markers for developing this type of depression may be identified in the future.

Are Methylation Patterns in the KALRN Gene Associated with Cognitive and Depressive Symptoms? Findings from the Moli-sani Cohort.

The KALRN gene (encoding kalirin) has been implicated in several neuropsychiatric and neurodegenerative disorders. However, genetic evidence supporting this implication is limited and targeted epigenetic analyses are lacking. Here, we tested associations between epigenetic variation in KALRN and interindividual variation in depressive symptoms (PHQ9) and cognitive (MoCA) performance, in an Italian population cohort (N = 2409; mean (SD) age: 67 (9) years; 55% women). First, we analyzed the candidate region chr3:124584826-124584886 (hg38), within the KALRN promoter, through pyrosequencing of 1385 samples. Then, we widened the investigated region by analyzing 137 CpGs annotated to the whole gene, rescued from epigenome-wide (Illumina EPIC) data from 1024 independent samples from the same cohort. These were tested through stepwise regression models adjusted for age, sex, circulating leukocytes fractions, education, prevalent health conditions and lifestyles. We observed no statistically significant associations with methylation levels in the three CpGs tested through pyrosequencing, or in the gene-wide association analysis with MoCA score. However, we observed a statistically significant association between PHQ9 and cg13549966 (chr3:124106738; β (Standard Error) = 0.28 (0.08), Bonferroni-corrected p = 0.025), located close to the transcription start site of the gene. This association was driven by a polychoric factor tagging somatic depressive symptoms (β (SE) = 0.127 (0.064), p = 0.048). This evidence underscores the importance of studying epigenetic variation within the KALRN gene and the role that it may play in brain diseases, particularly in atypical depression, which is often characterized by somatic symptoms.

Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status

BackgroundMajor Depressive Disorder (MDD) is a heterogenous and etiologically complex disease often presenting with divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) which are closely related to comorbidities, including cardiometabolic disorders. Hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of associated biological correlates of Hyperphagic and Hypophagic MDD remain fragmented. MethodsWe performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n = 7 and n = 13, respectively). ResultsAt baseline, we discovered an increased expression of TADA2B in hyperphagic MDD with the significant enrichment of 72 gene ontology pathways mainly related to inflammation. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD and discovered the upregulation of CCDC196 and the downregulation of SPATA33 in hyperphagic MDD. Gene ontology enrichment analysis after stress exposure showed pathways related to ribosomal activity. Limitations: The present findings are tempered primarily by the limited sample size, which requires independent replication of this exploratory study. However, stringent methods controlling for false positive findings mitigate the risk associated with sample size limitations. DiscussionLimitations notwithstanding, findings suggest that hyper- and hypophagic MDD is associated with divergent RNA expression profiles in peripheral blood that are amplified by exposure to a controlled stress test. Our findings in a well-controlled study provide evidence for peripheral markers of a relevant endophenotype of MDD.

The longitudinal patterns of depression subtypes and stressors in depression severity in the Canadian longitudinal study on aging (CLSA).

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.

Low-Grade Inflammation Associated with Major Depression Subtypes: A Cross-Sectional Study.

Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context.

Phenomenology and making sense of the DSM: situatedness in melancholic and atypical depression

Phenomenology and making sense of the DSM: situatedness in melancholic and atypical depression

The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight.

Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation. Both cortisol and inflammatory cytokines stimulate the production of plasminogen activator inhibitor-1 (PAI-1), a potent fibrinolysis inhibitor. Chronic anxiety, fear, and depression are among the many hypofibrinolytic conditions increasing the risk of oligo-anovulation, miscarriage, fetal growth restriction, and preeclampsia. Although significant, the impact of negative emotions on implantation is not as obvious as on ovulation or placentation. Other hypofibrinolytic conditions that may affect female reproduction through mechanisms dependent or independent of PAI-1 include metabolic disturbances (e.g., due to consumption of highly palatable foods, often used to alleviate negative affect), inflammation, hyperhomocysteinemia, hypothyroidism, hypercortisolism, antiphospholipid antibodies, and the 4G allele of the PAI-1 gene. Benzodiazepines and antidepressants should be used with caution in the first trimester as this combination may cause malformations. Also, selective serotonin reuptake inhibitors have fibrinolytic properties that increase the risk of bleeding after surgical procedures. Psychological interventions, especially group therapy, are effective in the prevention of reproductive disorders. Controlled trials are needed to test the hypothesis that female reproductive health depends on psychological well-being, a balanced diet and physical activity, suppression of inflammation and autoantibodies, and homocysteine and hormonal homeostasis.

Efficacy and tolerability of monoamine oxidase inhibitors for the treatment of depressive episodes in mood disorders: A systematic review and network meta-analysis.

Monoamine oxidase inhibitors (MAOIs) are considered third-line treatments for treatment resistant depression; however, they are underused in clinical practice. This study aimed to assess the efficacy, tolerability, and acceptability of MAOIs for the treatment of depression in comparison with other antidepressant treatments. A systematic review and network meta-analysis of randomised clinical trials was performed to compare the efficacy, tolerability and acceptability between MAOIs and other antidepressant treatments for the treatment of depressive episodes. A total of 83 double-blinded, randomised controlled trials were included in the analysis, with 7765 participants assigned to an active treatment and 1844 assigned to placebo. Several MAOIs, including isocarboxazid, phenelzine, tranylcypromine and moclobemide, showed significantly higher efficacy compared with placebo. The tolerability and acceptability of MAOIs was comparable to other antidepressants. A disproportionate number of studies investigating the most commonly used MAOIs, such as moclobemide and phenelzine, and a lack of specific studies focusing on treatment-resistant and atypical depression. MAOIs are similar in efficacy to other antidepressants for the treatment of depression. However, more studies are needed comparing MAOI treatment in people with treatment-resistant, atypical and bipolar depression.

Kleine Levin syndrome - presentation of five cases.

Kleine Levin syndrome (KLS) is a rare entity. It presents with subacute onset episodic hypersomnia, cognitive decline, altered perception, and occasional hyperphagia and hypersexuality with full recovery during the interepisodic period. Five cases presented with episodic hypersomnia and met the diagnostic criteria of KLS. The majority of the cases were females (3/5) in whom KLS is even rarer. The initial presentation was in the age range of 10-25 years. Cognitive dysfunction (5/5), derealization (4/5), viral prodrome (3/5), hyperphagia (3/5), and hypersexuality (2/5) were other clinical presentations. A differential diagnosis of atypical depression is the major challenge, and thorough history taking would help in differentiation. Treatment with stimulants (modafinil) and mood stabilizers (lithium) proved effective. A high degree of suspicion should be kept for cases of episodic hypersomnolence for early diagnosis and management of KLS.

Hypersomnia as a predictor of response to intravenous ketamine/intranasal esketamine in treatment resistant depression

BackgroundSleep disturbances are highly prevalent in depressive episodes and are linked to higher mood severity and suicidal behaviors. Slow wave sleep (SWS) and REM sleep are compromised in depression. Current evidence suggests that rapid antidepressant effects of intravenous (IV) ketamine in patients with treatment-resistant depression (TRD) is mediated by its effects on SWS and REM sleep. Sleep phenotypes may help predict ketamine response. MethodIn this observational study, we investigated differences in rates of response among sleep phenotypes defined by QIDS-SR in a cohort of patients with TRD (n = 52) treated with IV ketamine or intranasal (IN) esketamine. Also, we explored a neurovegetative symptoms of atypical depression (NVSAD) phenotype and its association between response and change in QIDS-SR following the treatment with IV ketamine/IN esketamine. Results94 % of patients reported sleep difficulties and 62 % reported more than one sleep phenotype with middle and early insomnia being the most prevalent. Individuals with baseline hypersomnia showed higher response rates and more pronounced improvements on their QIDS-SR score. Additionally, 15 % of patients presented with NVSAD phenotype; the majority of whom achieved response and had higher reductions on QIDS-SR. A trend towards faster response was identified for hypersomnia and atypical depression phenotypes. LimitationsObservational study design and lack of a placebo group. ConclusionsOur data indicate that patients with TRD who have baseline hypersomnia and atypical depression features experienced a more substantial reduction in depressive symptoms and are more likely to achieve response with ketamine/esketamine. This could serve as a future predictor for clinical response.

Features of the clinical picture of affective disorders in women during the menopausal transition and early postmenopause

To determine the clinical and psychopathological features of affective disorders in women in the perimenopausal and early postmenopausal periods. The study included 90 female patients receiving inpatient psychiatric care for affective disorders, among them 41 patients were perimenopausal (group 1) and 49 were early postmenopausal (group 2). Clinical and psychopathological, psychometric (the Hospital Anxiety and Depression Scale - HADS, the Hamilton Depression and Anxiety Scales - HAM-D and HAM-A, the Hypomania Checklist-32 - HCL-32, the Bipolarity Index (BI), the Insomnia Severity Index - ISI, the Pittsburgh Sleep Quality Index - PSQI) and statistical methods were used. Symptoms of atypical (63.4%) and anxious (87.8%) depression predominated among perimenopausal patients, and melancholic depression (59.2%) prevailed in early postmenopause. Patients in group 1 had higher anxiety scores on HADS and HAM-A compared to group 2 (p=0.003 and p=0.01). At the same time, early postmenopausal women had higher depression scores on the HADS and HAM-D (p=0.001). ISI and PSQI scores in postmenopause were significantly higher than in perimenopause (p=0.001 and p=0.009). The clinical features of affective disorders as well as severity and nature of the accompanying sleep disturbances vary depending on the stage of menopause, which must be considered when prescribing additional methods for examination and treatment of these disorders.

Methods for quantifying the heterogeneity of psychopathology

ObjectivesSpecifiers for a major depressive disorder (MDE) are supposed to reduce diagnostic heterogeneity. However, recent literature challenges the idea that the atypical and melancholic specifiers identify more homogenous or coherent subgroups. We introduce the usage of distance metrics to characterize symptom heterogeneity. We attempt to replicate prior findings and explore whether symptom heterogeneity is reduced using specifier subgroups.MethodsWe used data derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC Wave I; N = 5,749) and the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D; N = 2,498). We computed Hamming and Manhattan distances from study participants’ unique symptom profiles. Distances were standardized from 0-1 and compared by their within- and between-group similarities to their non-specifier counterparts for the melancholic and atypical specifiers.ResultsThere was no evidence of statistically significant differences in heterogeneity for specifier (i.e., melancholic or atypical) vs. non-specifier designations (i.e., non-melancholic vs. non-atypical).ConclusionReplicating prior work, melancholic and atypical depression specifiers appear to have limited utility in reducing heterogeneity. The current study does not support the claim that specifiers create more coherent subgroups as operationalized by similarity in the number of symptoms and their severity. Distance metrics are useful for quantifying symptom heterogeneity.

Cross-sectional analysis of depressive symptom profiles and serum C-reactive protein levels: data from the Northern Finland 1966 birth cohort

Purpose Individuals with depression exhibit significantly higher levels of systemic inflammation than those without depression, particularly among those with atypical depression. However, this association has been less convincing at the population level among individuals without a formal depression diagnosis but with suggestive symptoms. Our aim was to clarify this association. Materials and methods In a large birth cohort sample of the Finnish general population, we examined the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) levels in venous blood samples and atypical/non-atypical depressive symptoms using the Beck Depression Inventory-II to screen 5443 middle-aged participants. Results As expected, depressive symptoms associated to elevated hsCRP-levels compared to non-depressed. Participants with the atypical subtype of depressive symptoms (n = 84) had an odds ratio (OR) of 2.59 (95% CI 1.40–4.81) for elevated hsCRP levels compared to the non-depressed group. Similarly, our findings indicate that participants with non-atypical symptoms (n = 440) also showed an OR of 1.42 (95% CI 1.05–1.92) when compared to the non-depressed group (n = 4919). Conclusions These results provide additional support for previous research linking depression and inflammation and add to the field with a unique and sizeable study population. Furthermore, the current results support the notion that different types of depressive symptoms may be associated with inflammatory markers in slightly different ways.

A neuroimaging-based precision medicine framework for depression

BackgroundSymptom-based diagnostic criteria of depression leads to notorious heterogeneity and subjectivity. MethodsThe study was conducted in two stages at two sites: development of a neuroimaging-based subtyping and precise repetitive transcranial magnetic stimulation (rTMS) strategy for depression at Center 1 and its clinical application at Center 2. Center 1 identified depression subtypes and subtype-specific rTMS targets based on amplitude of low frequency fluctuation (ALFF) in a cohort of 238 major depressive disorder patients and 66 healthy controls (HC). Subtypes were identified using a Gaussian Mixture Model, and subtype-specific rTMS targets were selected based on dominant brain regions prominently differentiating depression subtypes from HC. Subsequently, one classifier was employed and 72 hospitalized, depressed youths at Center 2 received two-week precise rTMS. MRI and clinical assessments were obtained at baseline, midpoint, and treatment completion for evaluation. ResultsTwo neuroimaging subtypes of depression, archetypal and atypical depression, were identified based on distinct frontal-posterior functional imbalance patterns as measured by ALFF. The dorsomedial prefrontal cortex was identified as the rTMS target for archetypal depression, and the occipital cortex for atypical depression. Following precise rTMS, ALFF alterations were normalized in both archetypal and atypical depressed youths, corresponding with symptom response of 90.00% in archetypal depression and 70.73% in atypical depression. ConclusionsA precision medicine framework for depression was developed based on objective neurobiomarkers and implemented with promising results, actualizing a subtyping-treatment-evaluation closed loop in depression. Future randomized controlled trials are warranted.

Monoamine Oxidase Inhibitors and Clinically Relevant Drug Interactions: A Guide for Preventing Serotonin Toxicity and Hypertensive Reactions

This article describes and clarifies the two significant interactions encountered with monoamine oxidase inhibitors (MAOIs): serotonin toxicity and the tyramine pressor response. This is important because of the amount of inaccurate and misleading information (including in United States Food and Drug Administration-approved product information sheets and online resource and database systems) promulgated over the last few decades, which continues to cause confusion and undue concern. There are few if any clinically relevant CYP450 interactions with psychotropic drugs and no significant pharmacokinetic interactions. Serotonin toxicity is now well understood and only occurs in a problematic form when MAOIs are given in conjunction with serotonin reuptake inhibitors. Major prolonged elevations of blood pressure from tyramine are now less of a concern because of greatly reduced tyramine levels in foods. Therefore, MAOIs are safer and simpler to use in clinical practice than has usually been stated and should be considered earlier in the treatment algorithm for both atypical and melancholic depression. [ Psychiatr Ann . 2023;53(8):353–358.]

Characteristics of blood biomarkers and eating behavior among older community-dwelling adults with typical and atypical depression

Characteristics of blood biomarkers and eating behavior among older community-dwelling adults with typical and atypical depression

A Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD): study protocol for a randomized clinical trial and prognosis study

BackgroundMajor depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, closely associated with bipolar disorder (BD). However, there is still a lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about how to identify AFD, what is the appropriate individualized treatment for AFD, and what are the predictive biomarkers of conversion to BD.MethodsThe Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective, open-label study consisting of a 12-week randomized controlled trial (RCT) and a continued follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. Firstly, multivariate informatics analyses are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD, and patients with HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including “single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)”, “SSRI/SNRI combined with mood stabilizer,” “SSRI/SNRI combined with quetiapine (≥ 150 mg/day),” or “treatment as usual (TAU)” and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up until 4 years or switching to BD, to explore the risk factors of conversion from atypical depression to BD and eventually build the risk warning model of conversion to BD.DiscussionThe first enrolment was in August 2019. The iDoT-AFD study explores the clinical and biological markers for the diagnosis, treatment, and prognosis of AFD and further provides evidence for clinical guidelines of AFD.Trial registrationClinicalTrials.gov NCT04209166. Registered on December 19, 2019.

Characteristics and symptomatology of major depressive disorder with atypical features from symptom to syndromal level

ObjectiveTo explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative symptoms. MethodA 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). ResultsThe 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. LimitationsA cross-sectional design and a non-validated questionnaire were used. ConclusionsThe 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.