Leaden Paralysis Research Articles

USING (GEN)OMICS TO DISENTANGLE DEPRESSION'S HETEROGENEITY

Psychiatric disorders are heterogeneous conditions with diverse symptom and course profiles. This complicates pathophysiology studies as different biological and environmental mechanisms could lead to the same disorders. Unravelling this heterogeneity is important to be able to provide precision medicine. Penninx focuses on further unravelling the heterogeneity of depression using genomics (DNA, RNA, epigenetics) as well as other ‘-omics’ (metabolomics, proteomics). In her Netherlands Study of Depression and Anxiety, detailed phenotyping is combined with biobanking in seven waves covering 15 years of data collection. Using these rich resources, it has been shown that about one-third of all depressed patients illustrates an immunometabolic depression profile, where atypical, energy-related symptoms (fatigue, hypersomnia, weight increase, leaden paralysis) are predominant and co-occur with higher (genetic vulnerabilities for) immunometabolic dysregulations. The other two-thirds of all depressed patients can be characterized by a more typical depression profile, with e.g. melancholia, and pathophysiology that is more characterized by HPA-axis dysregulations, adverse life events and a genetic vulnerability that is more overlapping with e.g. schizophrenia. Penninx's work illustrates that genomics in combination with other detailed phenotyping contributes to further disentangle the heterogeneity of mental disorders, paving the way towards personalized medicine.

The impact of comorbid premenstrual syndrome or premenstrual dysphoric disorder on the clinical characteristics of bipolar disorder among Han Chinese women.

Bipolar disorder (BD) is commonly comorbid with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). However, little is known about their relationship. This study aimed to assess the impact of comorbid PMS or PMDD on the clinical characteristics of BD. A cross-sectional study was conducted on 262 women with BD. PMS and PMDD were screened with the Premenstrual Symptoms Screening Tool (PSST). Symptomatic features were assessed with Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS), and atypical features by the depressive episode section of SCID-I/P. The rates of PMS and PMDD among BD were 57.6% and 20.6% according to PSST. No significant difference in the rates of PMS and PMDD was found between BD I, BD II, and BD-NOS. Compared to BD patients without PMS or PMDD, patients with comorbid BD and PMS or PMDD were younger, more educated, had a higher risk of OCD, had an earlier age of onset, scored higher on HAMD-17 and its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and were more likely to have increased appetite and leaden paralysis. In addition, patients with comorbid BD and PMDD were less likely to experience traumatic life events, more likely to have family history of mental disorders and have inflammatory or autoimmune disease, scored higher on HMAD-17, particularly in its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and sleep disturbance. Compared with BD without PMS or PMDD, BD with PMS or PMDD might be a specific subtype of BD characterized with earlier onset age, heavier genetic load, increased symptom severity, and atypical features.

Metabolomics signatures of depression: the role of symptom profiles

Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an “atypical/energy-related” symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An ‘AES profile’ score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = −0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature—commonly linked to cardiometabolic disorders—associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression’s detrimental impact on health.

Immunometabolic depression: from conceptualization towards implementation

AbstractThe burden on society by depression is undisputable, partly due to a chronic course pattern and depression’s large heterogeneity that contributes to non-response to standard treatments. Using data from the Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl), Penninx will illustrate both points. When examining the course of depression, especially when also considering the transitions into other affective disorders over time, chronicity is clearly more the rule than the exception (Verduijn et al. BMC Med 2017). Considering depression’s heterogeneity could lead to precision psychiatry approaches that help reduce depression’s chronicity. Immuno-metabolic dysregulations seem to vary as a function of depression heterogeneity: dysregulations map more consistently to “atypical” neurovegetative symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis). Findings are confirmed when utilizing genome-wide gene expression as well as DNA information (Milaneschi et al. Biol Psychiatry 2020). Preliminary treatment studies suggest that the presence of immuno-metabolic dysregulations in depression moderates antidepressant effects of standard or novel (immunomodulatory) interventions. An immuno-metabolic depression dimension could dissect depression’s heterogeneity and potentially match depressed subgroups to treatments with higher likelihood of clinical success.Disclosure of InterestNone Declared

Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial

IntroductionAs the role of (neuro)inflammation in depression pathophysiology is emerging, augmentation of antidepressant treatments with anti-inflammatory drugs have shown beneficial results, but not consistently across all studies. Inconsistencies may be due to depression biological and clinical heterogeneity. Immuno-Metabolic Depression (IMD) has been put forward as a form of depression characterized by the clustering of low-grade inflammation, metabolic dysregulations and atypical, energy-related symptoms (overeating, weight gain, hypersomnia, fatigue and leaden paralysis). IMD features are present in ∼30% of patients with Major Depressive Disorder (MDD). By selecting these specific patients, directly targeting inflammation may reduce depressive symptoms. Methodsand analysis INFLAMED is a double-blind randomized controlled trial. 140 MDD patients with IMD characteristics (MDD with Inventory of Depressive Symptomatology (IDS) ≥ 26, IDS atypical, energy related symptoms ≥6, C-Reactive Protein (CRP) > 1 mg/L) will receive either 400 mg celecoxib per day or matching placebo for a period of 12 weeks. Biological, physical and interview data will be collected after 2, 6 and 12 weeks of starting the intervention. Questionnaires will be sent out bi-weekly during the study period. The main study outcome is the IDS (30-item self-report) total score during 12-week follow-up. Secondary study outcomes include response, remission, adverse side effects, symptom profiles (atypical, energy-related symptoms), fatigue, food craving, sleep, anxiety symptoms, functioning, pain, and optionally, microbiome composition. Explorative analyses will be performed on the role of CRP, IL-6, TNF-α, cholesterol, triglycerides, glucose, BMI, waist and hip circumference. Ethics and disseminationThis protocol has been approved by the Medical Ethics Review Board of the Amsterdam UMC, location VUmc (2022.0015) on 2-6-2022, as well as by the competent authority in The Netherlands: CCMO, on 3-8-2022. Registration detailsTrail registration numbers NCT05415397, EudraCT 2021-003850-21

The association between adiposity and atypical energy-related symptoms of depression: A role for metabolic dysregulations

BackgroundAdiposity has been shown to be linked with atypical energy-related symptoms (AES) of depression. We used genomics to separate the effect of adiposity from that of metabolic dysregulations to examine whether the link between obesity and AES is dependent on the presence of metabolic dysregulations. MethodData were from NEO (n = 5734 individuals) and NESDA (n = 2238 individuals) cohorts, in which the Inventory of Depressive Symptomatology (IDS-SR30) was assessed. AES profile was based on four symptoms: increased appetite, increased weight, low energy level, and leaden paralysis. We estimated associations between AES and two genetic risk scores (GRS) indexing increasing total body fat with (metabolically unhealthy adiposity, GRS-MUA) and without (metabolically healthy adiposity, GRS-MHA) metabolic dysregulations. ResultsWe validated that both GRS-MUA and GRS-MHA were associated with higher total body fat in NEO study, but divergently associated with biomarkers of metabolic health (e.g., fasting glucose and HDL-cholesterol) in both cohorts. In the pooled results, per standard deviation, GRS-MUA was specifically associated with a higher AES score (β = 0.03, 95%CI: 0.01; 0.05), while there was no association between GRS-MHA and AES (β = −0.01, 95%CI: −0.03; 0.01). ConclusionThese results suggest that the established link between adiposity and AES profile emerges in the presence of metabolic dysregulations, which may represent the connecting substrate between the two conditions.

Major depressive disorder subtypes and depression symptoms in multiple sclerosis: What is different compared to the general population?

ObjectiveTo compare and characterize major depressive disorder (MDD) subtypes (i.e., pure atypical, pure melancholic and mixed atypical-melancholic) and depression symptoms in persons with multiple sclerosis (PwMS) with persons without MS (Pw/oMS) fulfilling the DSM-5 criteria for a past 12-month MDD. MethodsMDD in PwMS (n = 92) from the Swiss Multiple Sclerosis Registry was compared with Pw/oMS (n = 277) from a Swiss community-based study. Epidemiological MDD diagnoses were based on the Mini-SPIKE (shortened form of the Structured Psychopathological Interview and Rating of the Social Consequences for Epidemiology). Logistic and multinomial regression analyses (adjusted for sex, age, civil status, depression and severity) were computed for comparisons and characterization. Latent class analysis (LCA) was conducted to empirically identify depression subtypes in PwMS. ResultsPwMS had a higher risk for the mixed atypical-melancholic MDD subtype (OR = 2.22, 95% CI = 1.03–4.80) compared to Pw/oMS. MDD in PwMS was specifically characterized by a higher risk of the two somatic atypical depression symptoms ‘weight gain’ (OR = 6.91, 95% CI = 2.20–21.70) and ‘leaden paralysis’ (OR = 3.03, 95% CI = 1.35–6.82) and the symptom ‘irritable/angry’ (OR = 3.18, 95% CI = 1.08–9.39). ConclusionsMDD in PwMS was characterized by a higher risk for specific somatic atypical depression symptoms and the mixed atypical-melancholic MDD subtype. The pure atypical MDD subtype, however, did not differentiate between PwMS and Pw/oMS. Given the high phenomenological overlap with MS symptoms, the mixed atypical-melancholic MDD subtype represents a particular diagnostic challenge.

Integrating proteomic, sociodemographic and clinical data to predict future depression diagnosis in subthreshold symptomatic individuals

Individuals with subthreshold depression have an increased risk of developing major depressive disorder (MDD). The aim of this study was to develop a prediction model to predict the probability of MDD onset in subthreshold individuals, based on their proteomic, sociodemographic and clinical data. To this end, we analysed 198 features (146 peptides representing 77 serum proteins (measured using MRM-MS), 22 sociodemographic factors and 30 clinical features) in 86 first-episode MDD patients (training set patient group), 37 subthreshold individuals who developed MDD within two or four years (extrapolation test set patient group), and 86 subthreshold individuals who did not develop MDD within four years (shared reference group). To ensure the development of a robust and reproducible model, we applied feature extraction and model averaging across a set of 100 models obtained from repeated application of group LASSO regression with ten-fold cross-validation on the training set. This resulted in a 12-feature prediction model consisting of six serum proteins (AACT, APOE, APOH, FETUA, HBA and PHLD), three sociodemographic factors (body mass index, childhood trauma and education level) and three depressive symptoms (sadness, fatigue and leaden paralysis). Importantly, the model demonstrated a fair performance in predicting future MDD diagnosis of subthreshold individuals in the extrapolation test set (AUC = 0.75), which involved going beyond the scope of the model. These findings suggest that it may be possible to detect disease indications in subthreshold individuals up to four years prior to diagnosis, which has important clinical implications regarding the identification and treatment of high-risk individuals.

Curt Richter Award Plenary: Inside the effects of exercise: from cellular to psychological benefit: Time: Thursday, 06/Sep/2018: 7:15pm–8:00pm

Variety of evidence suggests that low-grade inflammation may be involved in the pathophysiology of bipolar disorder (BD). However, the conclusion regarding the relationship between inflammation and BD has been inconsistent. In this study, we aimed to survey the prevalence of low-grade inflammation in a large Han Chinese population with BD and assess its impact on the clinical features of BD.430 eligible cases were drawn from patients who were admitted or had ever been admitted for BD to the inpatient service of the psychiatric department of the Third Hospital of Sun Yat-sen University. Subjects with current active physical diseases or white blood count (WBC) >19.0 × 109/L (2 times the upper reference) were excluded. Serum C-reactive protein (CRP) levels and WBC were measured with fast blood sample. Low-grade inflammation was defined as CRP>3 mg/L or WBC > 9.5 × 109/L(the upper reference). Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education.If defined as CRP>3 mg/L, the prevalence of low-grade inflammation among BD was 10.1% (41/404), it was positively associated with BMI (p = 0.012), comorbidity of glycolipid metabolic diseases(p = 0.018). After adjusting for BMI, it was found to be positively related to recent suicide attempt (p = 0.03), initiation with (hypo)manic episode(p = 0.047), leaden paralysis (p = 0.037) and family history of mental disorders(p = 0.012), while the association between comorbidity of glycolipid metabolic diseases and low-grade inflammation disappeared (p = 0.330). If defined as WBC > 9.5 × 109/L, the prevalence of low-grade inflammation was 8.1% (33/409), it was positively associated with psychotic features (p = 0.011) and adverse life events before the onset of illness(p < 0.001), but was not significantly influenced by BMI (p = 0.077).A much lower prevalence of low-grade inflammation in BD is found among Han Chinese population than among western population. Low-grade inflammation of different definition impacts differentially on the clinical features of BD.

The association between low-grade inflammation and the clinical features of bipolar disorder in Han Chinese population

Variety of evidence suggests that low-grade inflammation may be involved in the pathophysiology of bipolar disorder (BD). However, the conclusion regarding the relationship between inflammation and BD has been inconsistent. In this study, we aimed to survey the prevalence of low-grade inflammation in a large Han Chinese population with BD and assess its impact on the clinical features of BD.430 eligible cases were drawn from patients who were admitted or had ever been admitted for BD to the inpatient service of the psychiatric department of the Third Hospital of Sun Yat-sen University. Subjects with current active physical diseases or white blood count (WBC) >19.0 × 109/L (2 times the upper reference) were excluded. Serum C-reactive protein (CRP) levels and WBC were measured with fast blood sample. Low-grade inflammation was defined as CRP>3 mg/L or WBC > 9.5 × 109/L(the upper reference). Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education.If defined as CRP>3 mg/L, the prevalence of low-grade inflammation among BD was 10.1% (41/404), it was positively associated with BMI (p = 0.012), comorbidity of glycolipid metabolic diseases(p = 0.018). After adjusting for BMI, it was found to be positively related to recent suicide attempt (p = 0.03), initiation with (hypo)manic episode(p = 0.047), leaden paralysis (p = 0.037) and family history of mental disorders(p = 0.012), while the association between comorbidity of glycolipid metabolic diseases and low-grade inflammation disappeared (p = 0.330). If defined as WBC > 9.5 × 109/L, the prevalence of low-grade inflammation was 8.1% (33/409), it was positively associated with psychotic features (p = 0.011) and adverse life events before the onset of illness(p < 0.001), but was not significantly influenced by BMI (p = 0.077).A much lower prevalence of low-grade inflammation in BD is found among Han Chinese population than among western population. Low-grade inflammation of different definition impacts differentially on the clinical features of BD.

S.03.02 - Clinical heterogeneity in major depressive disorder

S.03.02 - Clinical heterogeneity in major depressive disorder

Atypical depression: current perspectives.

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.

Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression

Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central functional resistance) may affect mood. However, evidence for leptin dysregulation in major depressive disorder (MDD) is conflicting. Inconclusive findings may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the relationship of leptin with MDD, its common subtypes (typical and atypical), and clinical features. The sample consisted of participants (aged 18 to 65 years) from the Netherlands Study of Depression and Anxiety with current (n = 1062) or remitted (n = 711) MDD and healthy control subjects (n = 497). Diagnoses of MDD and subtypes were based on DSM-IV symptoms. Additional symptoms were measured with the Inventory of Depressive Symptomatology. Blood levels of leptin and adiposity indexes (body mass index and waist circumference) were assessed. As compared to control subjects, higher leptin was associated with the atypical MDD subtype both for remitted (n = 144, odds ratio = 1.53, 95% confidence interval = 1.16-2.03, p = .003) and current (n = 270, odds ratio = 1.90, 95% confidence interval = 1.51-2.93, p = 5.3e-8) cases. This association was stronger for increasing adiposity levels (leptin by body mass index interaction, p < .02), strengthening the hypothesis of the involvement of leptin resistance. No association with leptin was found for overall MDD or the typical subtype. Among currently depressed patients, higher leptin was associated with key symptoms identifying the atypical subtype, such as hyperphagia, increased weight, and leaden paralysis. Leptin dysregulation (resistance) may represent an underlying mechanism connecting obesity and MDD with atypical features. Development of treatment effectively targeting leptin resistance may benefit patients with atypical depression characterized by obesity-related metabolic alterations.

Atypical features in depression: Association with obesity and bipolar disorder

ObjectivesDepression with atypical features amounts to a significant proportion of depressed patients. Studies have shown its association with bipolarity and, recently, with obesity. In this study, we investigated atypical features of depression in relation to overweight/obesity in three diagnostic categories: unipolar depression, bipolar depression and dysthymia. MethodsOut of 512 depressed patients screened, we recruited 182 research subjects, consisting of 91 pairs, matched by age, gender and diagnosis, in which one member of the pair was within the normal weight range (BMI≤25) and the other was either overweight or obese (BMI>25). There were 35 pairs with unipolar depression, 27 with bipolar depression and 29 with dysthymia. Symptoms of atypical depression, such as increased appetite, hypersomnia, leaden paralysis, longstanding pattern of interpersonal rejection sensitivity, and, a significant weight gain in the past 3 months, were assessed. ResultsAll the symptoms of atypical depression were significantly more pronounced in those depressed patients with a BMI>25, compared with depressed subjects with a normal weight. Except for hypersomnia, these symptoms scored significantly higher in women compared to men. Among the diagnostic categories, symptoms of atypical depression were significantly higher in patients with bipolar disorder compared with both major depressive disorder and dysthymia. LimitationsThe preponderance of women, the assessment of atypical depression by adaptation of the DSM criteria, entirely Polish population, specificity of selection criteria. ConclusionsThe results demonstrated a higher intensity of atypical depression's symptoms in overweight/obese depressed patients. They also confirm the association between obesity and bipolarity.

Locomotor Microactivities Associated with Therapeutic Responses in Patients with Seasonal Affective Disorders

Background: Psychomotor retardation, leaden paralysis and fatigue are often used to describe patients with depressive disorders. However, there is limited understanding of their meaning and how they are objectively manifested in the physical world. Patients with seasonal affective disorder (SAD) are characteristically hypoactive and experience restoration of energy during effective treatment with bright light. In this study, we attempt to identify quantitative metrics of psychomotor activity that correspond to the clinical perceptions of hypoactivity and to the early activating effects of treatment. Methods: Novel means of assessing the microstructure of activity was employed using wavelets and Hurst exponents to indicate the proclivity of subjects to persist at higher and lower levels of activity. This was assessed using actigraphs in 16 unmedicated patients with SAD before and following 2 weeks of bright light therapy. Results: Two weeks of phototherapy had no significant effect on mean levels of diurnal activity, but altered the microstructure of the activity. Specifically, phototherapy produced a significant reduction in inertial resistance in patients who had a ≥50% reduction in the Hamilton Depression Scale scores (n = 8), as reflected in a reduced tendency to persist at low levels of activity. There was also a strong correlation between ratings of fatigue and measures of persistence at high versus low activity in initial responders, but not in initial nonresponders. Conclusion: These findings suggest that light therapy alters the nature of diurnal activity troughs in early responsive patients, reducing their tendency to persist at low levels, possibly reflecting an alleviation of psychomotor retardation.

Treatment Challenges of Atypical Depression: A Case Report

Symptoms such as mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity are classified as atypical features of a major depressive episode. If these symptoms are concurrent with an episode of hypomania, the patient would be diagnosed with having a depressive episode in the continuum of bipolar II disorder. Because patients may have subsequent depressive episodes for years without any symptoms of hypomania, and because they can function unequivocally within the community due to the nature of the disorder, the diagnosis of a bipolar disorder often gets misclassified as one of a unipolar etiol ogy. Most evidence-based literature states the complexity of this diagnosis due to the subtlety of the presenting symptoms, and it is usually only with a thorough patient history that a clinician can diagnose a patient with bipolar II disorder when the chief complaint is atypical depression. An integrative approach to classifying the depression in terms of polarity requires the clinician to consider the longitudinal course of the patient’s illness; the tendency for depression to recur; the onset, prominence, and severity of depressive episodes; and whether there is a family history of bipolar disorder. It is essential to distinguish between unipolar and bipolar depression in order to treat current episodes and prevent further depressive episodes. The firstline treatment for unipolar depression with atypical features is monoamine oxidase inhibitors (MAOIs), whereas first-line treatment for bipolar depres sion is a mood stabilizer that may be augmented with an antidepressant. CASE

The validation of atypical depression among Chinese outpatients with depressive episodes in general hospital

Objective to evaluate the validation of among Chinese outpatients with depressive episodes and explore the role of atypical depressive symptoms in distinguishing bipolar depression from unipolar depression. Methods Structural clinical interviews with self-compiled questionnaires were performed on 276 outpatients with current depressive episode, then comparison of clinical characteristics including age of onset, gender proportion, seasonality, comorbidity of anxiety disorder, bipolar property, psychotic features, number of depressive episodes, and maximum duration of depressive episode were conducted between atypical (defined by DSM-Ⅳ-TR) and nonatypical depression. then the rate of atypical depressive symptoms were compared between unipolar depression and bipolar depression. Results The proportion of atypical depression among all the participants was 23.9%.Compared to nonatypical depression, psychotic features were more likely seen in atypical depression (20.0% vs 9.1%, P<0.05), but no difference was found in other clinical features between atypical and nonatypical depression. Except mood reactivity, atypical symptoms including oversleeping(45.5% vs 26.0%), overeating(22.7% vs 15.4%), weight gain(24.1% vs 14.6%), leaden paralysis(56.6% vs 47.2%), interpersonal rejection sensitivity(66.7% vs 34.2%) were more likely to occur in bipolar depression than in unipolar depression, the difference was statistically significant for oversleeping and interpersonal rejection sensitivity (P<0.05). Patients with mood reactivity differed little from those without mood reactivity in other clinical features. No association was found between mood reactivity, leaden paralysis and other criteria symptoms of atypical depression. Conclusion Atypical depression might be a useful concept, but its diagnostic criteria needs further validation among Chinese population. Key words: Atypical depression; Validation

Untreated major depressive disorder with and without atypical features: A clinical comparative study

Aims and methodA comparative study of major depression with and without atypical features (as per DSM IV TR criteria) was planned to assess illness characteristics, resulting dysfunction and co-morbidities, which can have important implications in its management. Serially, 107 newly registered patients with depression not taking any treatment for at least a month were included. Patients with psychotic features in present or past, known bipolar disorder and likely organic aetiology were excluded. They were interviewed using SCID I (Structured clinical interview for DSM IV axis I disorders). Impulsiveness, suicidal ideation and functioning in various spheres was also assessed and compared between those with and without atypical features. ResultsAtypical features were seen in a significant number (55.14%) of patients especially from urban and semi-urban areas. Interpersonal sensitivity and leaden paralysis were the commonest atypical features apart from mood reactivity. Presence of hypersomnia and/or hyperphagia documented in 36 (33.65%) of 107 patients. Comparison of patients with and without atypical features revealed no significant difference in illness characteristics including suicidal ideation. However, they differed in level of impulsiveness and associated psychiatric co-morbidities. Also, deterioration of functioning with rising HDRS was more significant in patients without atypical features. Clinical implicationsPresence of atypical features is common in patients with major depressive disorder. These patients should be vigilantly assessed and managed in view of equal morbidity but different co-morbidities like anxiety and soft bipolar disorders than those without atypical features.

Depressed Older Patients With the Atypical Features of Interpersonal Rejection Sensitivity and Reversed-Vegetative Symptoms are Similar to Younger Atypical Patients

The atypical depression (AD) subtype has rarely been examined in older patients. However, younger AD patients have been characterized as having more severe and chronic symptoms of depression compared with non-AD patients. Secondary data analysis by using analyses of variance and Growth Curve Modeling. Clinical Research Center for the study of depression in later life. Depressed older patients (N = 248) followed over 2 years. In a longitudinal study, we examined depression severity and chronicity in patients with major depression with some features of AD, specifically rejection sensitivity and reversed-vegetative symptoms (e.g., hyperphagia and hypersomnia), or leaden paralysis, and compared them to non-AD patients. The Diagnostic Interview Schedule (DIS) was used to assess depressive symptoms and history. Depression severity and chronicity were assessed every 3 months by using the Montgomery Asberg Depression Rating Scale. The AD symptom group reported more DIS depressive symptoms, more thoughts about wanting to die, earlier age of onset, poorer social support, and double the number of lifetime episodes than non-AD patients. Growth curve analyses revealed that, compared with non-AD patients, the AD symptom group had more residual symptoms of depression during the first year of follow-up but not during the second year. Characteristics of older patients with features of AD are similar to younger patients. Assessment of atypical symptoms, in particular, rejection sensitivity and reversed-vegetative symptoms, is essential and should be considered in treatment plans.

Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis?

The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperament accounted for much of the relationship between atypical depression and BPD, predicting 6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability (among BPD patients) and interpersonal sensitivity (among atypical depressive patients) appear to be related as part of an underlying cyclothymic temperamental matrix.