Does One Treatment Fit All? Effectiveness of a Multicomponent Cognitive Behavioral Therapy Program in Data-Driven Subtypes of Perinatal Depression

Background: Current diagnostic systems of mental disorders are criticized for their poor validity and reliability, owing to the within disorder heterogeneity and between disorder homogeneity. The issue is important if treatments for mental disorders are to be tailored to individual needs. There is little information in this area on perinatal depression (PND), a highly prevalent condition globally.Aims: i) Quantify heterogeneity attributable to the polythetic diagnostic framework for PND and, ii) present evidence for the effectiveness of a multicomponent and low-intensity cognitive behavioral Thinking Healthy Programme (THP) across the heterogeneous presentations of PND.Methods: This investigation presents secondary analyses of a cluster randomized controlled trial, conducted in Kallar Syedan, Pakistan. A total of 903 pregnant women were randomized to an intervention group receiving the THP intervention or control group receiving enhanced usual care. Principal component analyses and clustering algorithm were utilized to identify heterogenous subtypes of PND. Linear mixed effects models were used to assess effectiveness of the intervention across the identified subtypes of PND.Results: Four different clusters of PND were identified: mixed anxiety-depression, somatic depression, mild depression, and atypical depression. All clinical phenotypes responded well to the THP intervention. Compared to their counterparts in the control group, mothers with mild depression in the treatment group yielded lowest risk ratios 0.24 (95% CI: 0.15 to 0.37), followed by mothers with anxiety-depression 0.50 (95% CI: 0.37 to 0.68), atypical depression 0.51 (95% CI: 0.27 to 0.99) and somatic depression 0.59 (95% CI: 0.42 to 0.83).Conclusion: The Thinking Healthy Programme was found to be effective in reducing severity of depressive symptoms and disability across the four subtypes of PND.

Prevalence and Clinical Features Associated with Unrecognized Bipolar Disorder among Outpatients with Depressive Disorder in Thailand

Objective: To determine the prevalence of unrecognized bipolar disorder and explore the clinical features of outpatients with depressive disorder associated with bipolar disorder. Materials and Methods: The present study was a cross-sectional study. One hundred six volunteer participants, diagnosed with depressive disorder at Naresuan University Hospital, Buddhachinaraj Phitsanulok Hospital, and Phichit Hospital participated in this study. Psychiatrists interviewed the participants to collect basic data and clinical characteristics to determine unrecognized bipolar disorder using the Thai version of the Mini International Neuropsychiatric Interview (MINI). Results: The results showed that the prevalence of unrecognized bipolar disorder was 18.9%. When multivariable logistic regression was used, it was found that there were two statistically significant factors associated with unrecognized bipolar disorder. These factors were a history of self-harm or suicide attempts (AOR 4.40, 95% CI 1.24 to 15.60), and atypical depression seen with overeating and hypersomnia (AOR 11.73, 95% CI 2.32 to 59.35). Conclusion: There are several misdiagnoses of patients with bipolar disorder because the patients are usually in a depressive state when they decide to consult a doctor. Therefore, doctors should further probe especially in patients with atypical depression, history of self-harm or attempted suicide. Keywords: Bipolar depression; Bipolar disorder; Diagnosis; Epidemiology; Prevalence

Case Report: Risperidone Induced Peripheral Edema

Risperidone is the first line of treatment for bipolar disorder, atypical depression, and Schizophrenia. We present a 55-year-old male with a history of schizoaffective disorder with bipolar type I presented with aggressive behavior and suicidal ideation. Our patient was treated with low-dose Risperidone; after that, he gradually developed leg pain and edema. His leg pain hampers his ambulation, which is clinically improved after a week of medication discontinuation; however, his leg edema did not resolve completely. In addition, we evaluated our patient's compliance with an empathic verbal interview that shows edema and leg pain hampers his quality of life. We have found that not informing edema as one of the possible side effects increases medication non-compliance in our case. There are several case reports about the side effect of Risperidone (such as leg edema) in combination with other medications, but there is no recommendation about patient counseling of forthcoming leg edema and mobility issues.

Heterogeneity in major depression and its melancholic and atypical specifiers: a secondary analysis of STAR*D

Objectives The melancholic and atypical specifiers for a major depressive episode (MDE) are supposed to reduce heterogeneity in symptom presentation by requiring additional, specific features. Fried et al. (2020) recently showed that the melancholic specifier may increase the potential heterogeneity in presenting symptoms. In a large sample of outpatients with depression, our objective was to explore whether the melancholic and atypical specifiers reduced observed heterogeneity in symptoms. Methods We used baseline data from the Inventory of Depression Symptoms (IDS), which was available for 3,717 patients, from the Sequenced Alternatives to Relieve Depression (STAR*D) trial. A subsample met criteria for MDE on the IDS (“IDS-MDE”; N =2,496). For patients with IDS-MDE, we differentiated between those with melancholic, non-melancholic, non-melancholic, atypical, and non-atypical depression. We quantified the observed heterogeneity between groups by counting the number of unique symptom combinations pertaining to their given diagnostic group (e.g., counting the melancholic symptoms for melancholic and non-melancholic groups), as well as the profiles of DSM-MDE symptoms (i.e., ignoring the specifier symptoms). Results When considering the specifier and depressive symptoms, there was more observed heterogeneity within the melancholic and atypical subgroups than in the IDS-MDE sample (i.e., ignoring the specifier subgroups). The differences in number of profiles between the melancholic and non-melancholic groups were not statistically significant, irrespective of whether focusing on the specifier symptoms or only the DSM-MDE symptoms. The differences between the atypical and non-atypical subgroups were smaller than what would be expected by chance. We found no evidence that the specifier groups reduce heterogeneity, as can be quantified by unique symptom profiles. Most symptom profiles, even in the specifier subgroups, had five or fewer individuals. Conclusion We found no evidence that the atypical and melancholic specifiers create more symptomatically homogeneous groups. Indeed, the melancholic and atypical specifiers introduce heterogeneity by adding symptoms to the DSM diagnosis of MDE.

Effect of neuropeptide Y antagonist BMS193885 on overeating and emotional responses induced by social isolation in rats

BACKGROUND: Chronic stress of social isolation is associated with an increased risk of mental illness, such as atypical depression, and is usually accompanied by hyperphagia and weight gain. We have previously shown that the NPY antagonist Y1R BMS193885 reduces the conditioned place preference of ethanol. The involvement of NPY receptors in non-chemical forms of addiction is assumed. AIM: Was to analyze the effects of NPY Y1R BMS193885 on emotional responses and elements of bindge eating in rats caused by rearing in social isolation. MATERIALS AND METHODS: We used the tests open field, elevated plus maze, Porsolts forced swimming test, resident intruder test and method of conditioned eating test in well-fed rats. RESULTS: The level of depression, negative emotionality and locomotor activity increased in rats reared in isolation. After intranasal administration of BMS193885 high locomotor activity was maintained, but investigating activity increased in isolated rats. Isolated animals showed an increase in body weight at the 6th week of life. By to the 9th week, the body weight of the isolated rats was significantly higher than in animals reared in the community (р 0.05). Intranasal administration of 20 g BMS193885 for 1 week caused a decrease in feed intake in both groups of animals (р 0.05). Isolated rats began to consume the same amount of food as animals reared in the community after administration of 0.9% NaCl solution. At the same time, elements of bindge eating were observed in the study of the conditioned food test in satiated isolated rats, which did not appear after 1 week of intranasal administration of 20 g of BMS193885. CONCLUSIONS: The data obtained prove that rats reared in isolation can be considered as a potential model for binge eating, the basis for metabolic imbalance caused by individual housing in rodents. These considerations are of particular relevance when evaluating the effectiveness of drugs, diet, or other interventions for metabolic health and depressive disorders.

Neurophysiological Subtypes of Depressive Disorders

Background: the clinical polymorphism of depressive disorders, together with the available data on the different responses of patients to treatment, motivate modern neuroscience to search for models that can explain such heterogeneity.Objective: to identify neurophysiological subtypes of depressive disorders.Patients and methods: 189 patients with moderate depression in the structure of a depressive episode (n = 42), recurrent depressive (n = 102) and bipolar affective disorders (n = 45); 56 healthy subjects. Clinical-psychopathological, psychometric, neurophysiological and statistical research methods were used in the work.The results: with the help of coherent EEG analysis, it is possible to identify at least 6 subtypes of the disorder, which characterize various branches of the pathogenesis of affective pathology, which go beyond the currently accepted nomenclature. The selected subtypes were determined by the profi les of dysfunctional interaction of various cortical zones in the alpha, beta and gamma ranges of the EEG. Subtype 1 was characterized by a decrease relative to the norm of imaginary alpha-coherence between the right parietal and left central, right parietal and left anterior temporal, as well as the right parietal and right anterior temporal EEG leads (P4-C3, P4-F7, P4-F8) and explained part of depressions, in the pathogenesis of which the leading role was played by violations of the promotion of positive and suppression of negative affect. Subtype 2 — an increase in beta-2-imaginary-coherence between the frontal leads of the left and right hemispheres, between the left frontal and right central cortex (F3-F4; F3-C4) and its decrease between the central cortical zones (C4-C3), in clinical terms this subtype was characterized by a persistent hedonic response and was associated with the clinical picture of atypical depression. Subtype 3 — an increase in imaginary alpha-coherence between the frontal (F4-F3) and its decrease between the central leads of the left and right hemisphere (C4-C3), correlated with the severity of depressive rumination. Subtype 4 — a decrease in imaginary alpha-coherence between the anterior temporal and frontal, as well as the anterior temporal and central cortex of the right hemisphere (F8-F4 and F8-C4), explained part of the depressions that developed against the background of avoidance personality disorder. Subtype 5 — a decrease in imaginary gamma coherence between the frontal and parietal, as well as the central and occipital cortical zones of the left hemisphere (F3-P3 and C3-O1), was associated with an outwardly oriented utilitarian style of thinking (alexithymia). Subtype 6 — a decrease in imaginary beta-1 coherence between the left central and right anterior temporal cortex (C3-F8), explained part of the depression with phobic and hypochondriacal disorders in the structure of recurrent depressive disorder. Such a clinical and biological typology seems new and promising in terms of searching for specifi c neurophysiological disorders in different types of depression and, accordingly, reaching differentiated therapeutic recommendations.

PIP5K2A (rs10828317) polymorphism in patients with alcohol dependence and affective disorders

Alcohol dependence (AD) and affective disorders (ADs) are serious medical and socio-economic problems of modern society. It is hypothesized that both disorders share a common neurobiological basis. Phosphatidylinositol-4-phosphate-5-kinase type 2 alpha (PIP5K2A) plays an essential role in neuronal phosphoinositide signaling pathways. Nonsynonymous rs10828317 mutation of the PIP5K2A gene leads to conformational changes of the PIP5K2A protein and a decrease in the functional activity of this enzyme. In this study, we assessed the possibility of using the rs10828317 polymorphic variant of the PIP5K2A gene as a marker of AD and ADs.Objective: to study the associations of the PIP5K2A (rs10828317) polymorphism with AD and ADs clinical course.Patients and methods. We enrolled 255 patients with AD and 325 patients with ADs. 126 patients with AD and 71 patients with ADs underwent a comprehensive clinical, clinical-dynamic, psychodiagnostic assessment using a set of clinical scales and tests, including Structured Interview Guide For The Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD), Alcohol Use Disorders Identification Test (AUDIT), The Obsessive-Compulsive Drinking Scale for craving in alcohol (OCDS).Results and discussion. PIP5K2A (rs10828317) polymorphism in patients with AD was associated with the OCDS mean score after the inpatient treatment; in patients with ADs - with the severity of atypical depression symptoms assessed by SIGH-SAD at the time of admission.Conclusion. The results of our pilot study indicate the involvement of PIP5K2A (rs10828317) polymorphism in the AD and ADs pathophysiology.

Dietary Patterns Are Differentially Associated with Atypical and Melancholic Subtypes of Depression

Diet has been associated with the risk of depression, whereas different subtypes of depression have been linked with different cardiovascular risk factors (CVRFs). In this study, our aims were to (1) identify dietary patterns with exploratory factor analysis, (2) assess cross-sectional associations between dietary patterns and depression subtypes, and (3) examine the potentially mediating effect of dietary patterns in the associations between CVRFs and depression subtypes. In the first follow-up of the population-based CoLaus|PsyCoLaus study (2009–2013, 3554 participants, 45.6% men, mean age 57.5 years), a food frequency questionnaire assessed dietary intake and a semi-structured interview allowed to characterize major depressive disorder into current or remitted atypical, melancholic, and unspecified subtypes. Three dietary patterns were identified: Western, Mediterranean, and Sweet-Dairy. Western diet was positively associated with current atypical depression, but negatively associated with current and remitted melancholic depression. Sweet-Dairy was positively associated with current melancholic depression. However, these dietary patterns did not mediate the associations between CVRFs and depression subtypes. Hence, although we could show that people with different subtypes of depression make different choices regarding their diet, it is unlikely that these differential dietary choices account for the well-established associations between depression subtypes and CVRFs.

Evidence for a specific regional association between lateral orbitofrontal cortex morphometry and increased appetite in major depression

Increased appetite and body weight are core features of atypical depression. While previous research has consistently highlighted the presence of distinct immunometabolic profiles in atypical depression, little is still known about the neural correlates of atypical symptoms in major depression. Even though obesity and increased body-mass index have frequently been associated with prefrontal brain structural alterations first and foremost in the orbitofrontal cortex (OFC) in healthy and depressed subjects, it is unclear if conceptually related atypical depressive symptoms are associated with similar neural signatures. Here we aimed to investigate associations between appetite and weight change in major depression and OFC morphometry using a multimodal structural neuroimaging approach. We found that increased appetite was associated with significantly lower cortical thickness and lower gray matter density specifically in the right lateral OFC. Further, Bayesian model comparison showed that appetite change was a more informative predictor for changes in cortical thickness and gray matter density compared to body mass index. No conclusive association between appetite change and white matter tracts connected to the right lateral OFC was found. Our findings highlight the relevance of the right lateral OFC for future investigation of the neurobiological underpinnings of the atypical depressive symptom dimensions appetite and weight gain.