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1.
Curr Opin Psychiatry ; 36(6): 443-448, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37781973

RESUMO

PURPOSE OF REVIEW: Studies increasingly show the importance of reward processing in binge eating and provide evidence of associated changes in the neurobiological reward system. This review gives an up-to-date overview of the neurobiological substrates of reward processing subconstructs in binge eating. Neural findings are linked to different behavioral theories and the clinical relevance is discussed. RECENT FINDINGS: Increased neural responses in the orbitofrontal cortex, anterior cingulate cortex as well as striatum during anticipation and receipt of food rewards are found in association to binge eating. Increased model-free learning is also found and associated with altered brain reward reactivity. Data in rest report reduced striatal dopamine release and lower frontostriatal connectivity. Mechanisms of onset of binge eating are less clear, but specific personality traits, related to frontostriatal dysconnectivity, probably increase the risk of binge eating onset. SUMMARY: Both structural and task-based imaging studies show differences in the neurobiological reward system in binge eating. These changes are linked to specific reward processing, such as altered reward responsiveness to food cues, reinforcement learning, and habitual behavior. Findings are lined with different behavioral theories of binge eating, and a staging model is described, from onset to full illness development. Understanding the specific underlying aberrant reward mechanism in binge eating, associated with different stages of the illness, enables caregivers to focus their treatment more precisely.


Assuntos
Transtorno da Compulsão Alimentar , Humanos , Recompensa , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Corpo Estriado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
2.
J Eat Disord ; 11(1): 191, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884972

RESUMO

OBJECTIVE: This protocol proposes investigating the effects of short-chain fatty acids (SCFAs)-namely acetate, propionate, and butyrate-as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs are produced by bacterial fermentation of dietary fiber in the gut and have recently been proposed as crucial mediators of the gut microbiota's effects on the host. Emerging evidence suggests that SCFAs impact human psychobiology through endocrine, neural, and immune pathways and may regulate stress responses and eating behavior. METHOD: We will conduct a randomized, triple-blind, placebo-controlled trial in 92 patients with AN. Patients will receive either a placebo or a mixture of SCFAs (acetate propionate, butyrate) using pH-dependent colon-delivery capsules for six weeks. This clinical trial is an add-on to the standard inpatient psychotherapeutic program focusing on nutritional rehabilitation. HYPOTHESES: We hypothesize that colonic SCFAs delivery will modulate neuroendocrine, cardiovascular, and subjective responses to an acute laboratory psychosocial stress task. As secondary outcome measures, we will assess alterations in restrictive eating behavior and nutritional status, as reflected by changes in body mass index. Additionally, we will explore changes in microbiota composition, gastrointestinal symptoms, eating disorder psychopathology, and related comorbidities. DISCUSSION: The findings of this study would enhance our understanding of how gut microbiota-affiliated metabolites, particularly SCFAs, impact the stress response and eating behavior of individuals with AN. It has the potential to provide essential insights into the complex interplay between the gut, stress system, and eating behavior and facilitate new therapeutic targets for stress-related psychiatric disorders. This protocol is prospectively registered with ClinicalTrials.gov, with trial registration number NCT06064201.

3.
J Psychopathol Clin Sci ; 132(5): 621-633, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37104790

RESUMO

Studies suggest that negative affect (NA) can trigger binge eating (BE) in patients with bulimia nervosa (BN). Important factors in this relation between NA and BE could be craving (an intense desire for a BE episode) and negative urgency (the tendency to act rashly when NA is high). Therefore, this study wants to firstly explore the relations between NA, craving, rash action, and BE in daily life and secondly whether craving and rash action mediate the relationship between NA and BE. A sample of 70 female patients with BN and 76 female healthy controls (HC) took part in an experience sampling study where they reported on momentary NA, craving, rash action, and eating behaviors in daily life in a burst-measurement design over a period of 12 months. Assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of 3 weeks, all separated by 5-week periods of no assessment. First, NA predicted subsequent rash action in the whole sample but this was more pronounced in patients with BN. Second, NA predicted subsequent craving in patients with BN, but not in HC. Third, rash action and craving predicted subsequent BE in patients with BN. Fourth, NA had competing effects on eating in patients with BN, predicting subsequent BE through rash action and craving, but also predicting subsequent not eating. These results suggest that NA can lead to BE in daily life through rash action and craving, but that NA can also lead to dietary restriction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Transtorno da Compulsão Alimentar , Bulimia Nervosa , Bulimia , Humanos , Feminino , Fissura , Afeto
4.
Front Psychiatry ; 13: 1022298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311512

RESUMO

Background: Chronic stress and depressive symptoms have both been linked to increased heart rate (HR) and reduced HR variability. However, up to date, it is not clear whether chronic stress, the mechanisms intrinsic to depression or a combination of both cause these alterations. Subclinical cases may help to answer these questions. In a healthy working population, we aimed to investigate whether the effect of chronic stress on HR circadian rhythm depends on the presence of depressive symptoms and whether chronic stress and depressive symptoms have differential effects on HR reactivity to an acute stressor. Methods: 1,002 individuals of the SWEET study completed baseline questionnaires, including psychological information, and 5 days of electrocardiogram (ECG) measurements. Complete datasets were available for 516 individuals. In addition, a subset (n = 194) of these participants completed a stress task on a mobile device. Participants were grouped according to their scores for the Depression Anxiety Stress Scale (DASS) and Perceived Stress Scale (PSS). We explored the resulting groups for differences in HR circadian rhythm and stress reactivity using linear mixed effect models. Additionally, we explored the effect of stress and depressive symptoms on night-time HR variability [root mean square of successive differences (RMSSD)]. Results: High and extreme stress alone did not alter HR circadian rhythm, apart from a limited increase in basal HR. Yet, if depressive symptoms were present, extreme chronic stress levels did lead to a blunted circadian rhythm and a lower basal HR. Furthermore, blunted stress reactivity was associated with depressive symptoms, but not chronic stress. Night-time RMSSD data was not influenced by chronic stress, depressive symptoms or their interaction. Conclusion: The combination of stress and depressive symptoms, but not chronic stress by itself leads to a blunted HR circadian rhythm. Furthermore, blunted HR reactivity is associated with depressive symptoms and not chronic stress.

5.
Int J Mol Sci ; 23(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35955407

RESUMO

The gut microbiota encodes a broad range of enzymes capable of synthetizing various metabolites, some of which are still uncharacterized. One well-known class of microbiota-derived metabolites are the short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate and valerate. SCFAs have long been considered a mere waste product of bacterial metabolism. Novel results have challenged this long-held dogma, revealing a central role for microbe-derived SCFAs in gut microbiota-host interaction. SCFAs are bacterial signaling molecules that act directly on host T lymphocytes by reprogramming their metabolic activity and epigenetic status. They have an essential biological role in promoting differentiation of (intestinal) regulatory T cells and in production of the anti-inflammatory cytokine interleukin-10 (IL-10). These small molecules can also reach the circulation and modulate immune cell function in remote tissues. In experimental models of autoimmune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis or diabetes, a strong therapeutic potential of SCFAs through the modulation of effector T cell function was observed. In this review, we discuss current research activities toward understanding a relevance of microbial SCFA for treating autoimmune and inflammatory pathologies from in vitro to human studies.


Assuntos
Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Bactérias/metabolismo , Butiratos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Humanos
6.
Int J Eat Disord ; 55(11): 1421-1458, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35841198

RESUMO

OBJECTIVE: Changes in reward processing are hypothesized to play a role in the onset and maintenance of binge eating (BE). However, despite an increasing number of studies investigating the neurobiological reward system in individuals who binge eat, no comprehensive systematic review exists on this topic. Therefore, this review has the following objectives: (1) identify structural and functional changes in the brain reward system, either during rest or while performing a task; and (2) formulate directions for future research. METHODS: A search was conducted of articles published until March 31, 2022. Neuroimaging studies were eligible if they wanted to study the reward system and included a group of individuals who binge eat together with a comparator group. Their results were summarized in a narrative synthesis. RESULTS: A total of 58 articles were included. At rest, individuals who binge eat displayed a lower striatal dopamine release, a change in the volume of the striatum, frontal cortex, and insula, as well as a lower frontostriatal connectivity. While performing a task, there was a higher activity of the brain reward system when anticipating or receiving food, more model-free reinforcement learning, and more habitual behavior. Most studies only included one patient group, used general reward-related measures, and did not evaluate the impact of comorbidities, illness duration, race, or sex. DISCUSSION: Confirming previous hypotheses, this review finds structural and functional changes in the neurobiological reward system in BE. Future studies should compare disorders, use measures that are specific to BE, and investigate the impact of confounding factors. PUBLIC SIGNIFICANCE STATEMENT: This systematic review finds that individuals who binge eat display structural and functional changes in the brain reward system. These changes could be related to a higher sensitivity to food, relying more on previous experiences when making decisions, and more habitual behavior. Future studies should use a task that is specific to binge eating, look across different patient groups, and investigate the impact of comorbidities, illness duration, race, and sex.


OBJETIVO: Se plantea la hipótesis de que los cambios en el procesamiento de la recompensa desempeñan un papel en el inicio y mantenimiento de los atracones (BE). Sin embargo, a pesar de un número creciente de estudios que investigan el sistema de recompensa neurobiológica en individuos que comen en atracones, no existe una revisión sistemática exhaustiva sobre este tema. Por lo tanto, esta revisión tiene los siguientes objetivos: (1) identificar cambios estructurales y funcionales en el sistema de recompensa cerebral, ya sea en reposo o mientras se realiza una tarea; (2) formular direcciones para futuras investigaciones. MÉTODOS: Se realizó una búsqueda de artículos publicados hasta el 31 de marzo de 2022. Los estudios de neuroimagen eran elegibles si querían estudiar el sistema de recompensa e incluían a un grupo de individuos que comían en atracón junto con un grupo de comparación. Sus resultados se resumieron en una síntesis narrativa. RESULTADOS: Se incluyeron un total de 58 artículos. En reposo, los individuos que comen en atracón mostraron una menor liberación de dopamina estriatal, un cambio en el volumen del cuerpo estriado, la corteza frontal y la ínsula, así como una menor conectividad frontostriatal. Al realizar una tarea, hubo una mayor actividad del sistema de recompensa cerebral al anticipar o recibir alimentos, más aprendizaje de refuerzo sin modelos y un comportamiento más habitual. La mayoría de los estudios sólo incluyeron un grupo de pacientes, utilizaron medidas generales relacionadas con la recompensa y no evaluaron el impacto de las comorbilidades, la duración de la enfermedad, la raza o el sexo. DISCUSIÓN: Confirmando hipótesis anteriores, esta revisión encuentra cambios estructurales y funcionales del sistema de recompensa neurobiológica en BE. Los estudios futuros deben comparar los trastornos, utilizar medidas que sean específicas para el comer en atracones e investigar el impacto de los factores de confusión.


Assuntos
Transtorno da Compulsão Alimentar , Bulimia Nervosa , Humanos , Transtorno da Compulsão Alimentar/diagnóstico por imagem , Recompensa , Neuroimagem , Encéfalo/diagnóstico por imagem
7.
Front Psychiatry ; 13: 869608, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509881

RESUMO

Past research links depression and blunted cardiac vagal reactivity to chronic stress. Yet, to our knowledge no experiment investigates heart rate (variability) responses to a repeated laboratory stressor in patients with depression. Repeated exposure may provide valuable information on stress reactivity in depression. Fifty-nine women (30 inpatients diagnosed with depression and 29 matched controls) underwent two consecutive runs of a mental arithmetic stress paradigm consisting of one baseline and two exposures to control, stress, and recovery phases of 5 min each, in a case-control design. Subjective stress and electrocardiography were recorded. Variance of heart rate (HR) and root mean square of successive RR interval differences (RMSSD) were analyzed using linear mixed models. Overall, physiological parameters (HR and RMSSD) and subjective stress showed a strong group effect (all p < 0.001). In both groups, subjective stress and HR increased in response to stress, but the subjective stress levels of patients with depression did not return to baseline levels after the first stressor and for the remainder of the experiment (all p < 0.004 compared to baseline). Patients' HR reactivity responded oppositely: while HR recovered after the first stress exposure, no reactivity was observed in response to the second exposure. These findings may suggest that the often-reported blunted HR/HRV response to stressors results from exhaustion rather than an incapacity to react to stress. The altered HR reactivity could indicate allostatic (over-) load in depression.

8.
Eat Weight Disord ; 27(3): 857-865, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34091875

RESUMO

Numerous studies addressed the topic of behavioral and symptomatic changes in eating disorders. Rates of transition vary widely across studies, ranging from 0 to 70.8%, depending on the diagnoses taken into account and the study design. Evidence shows that the specific transition from restrictive-type anorexia nervosa (AN-R) to disorders involving binging and purging behaviors (BPB) is related to a worsening of the clinical picture and worse long-term outcomes. The aim of this systematic review and meta-analysis is to focus on this specific transition, review existing literature, and summarize related risk factors. Medline and PsycINFO databases were searched, including prospective and retrospective studies on individuals with AN-R. The primary outcome considered was the rate of onset of BPB. Twelve studies (N = 725 patients) were included in the qualitative and quantitative analysis. A total of 41.84% (95% CI 33.58-50.11) of patients with AN-R manifested BPB at some point during follow-up. Risk factors for the onset of BPB included potentially treatable and untreatable factors such as the family environment, unipolar depression and higher premorbid BMI. These findings highlight that patients with AN-R frequently transition to BPB over time, with a worsening of the clinical picture. Existing studies in this field are still insufficient and heterogeneous, and further research is needed. Mental health professionals should be aware of the frequent onset of BPB in AN-R and its risk factors and take this information into account in the treatment of AN-R. LEVEL OF EVIDENCE: Evidence obtained from a systematic review and meta-analysis, Level I.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Anorexia Nervosa/psicologia , Transtorno da Compulsão Alimentar/psicologia , Humanos , Estudos Prospectivos , Estudos Retrospectivos
10.
Front Psychiatry ; 12: 696170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393856

RESUMO

Background: Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression. Methods: A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers. Results: Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response (r = 0.55, p = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine. Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Conclusion: Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study. Clinical trial registration: EUDRACT number 2016-001715-21.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34171401

RESUMO

BACKGROUND: The macrophage theory of depression states that macrophages play an important role in Major Depressive Disorder (MDD). METHODS: MDD patients (N = 140) and healthy controls (N = 120) participated in a cross-sectional study investigating the expression of apoptosis/growth and lipid/cholesterol pathway genes (BAX, BCL10, EGR1, EGR2, HB-EGF, NR1H3, ABCA1, ABCG1, MVK, CD163, HMOX1) in monocytes (macrophage/microglia precursors). Gene expressions were correlated to a set of previously determined and reported inflammation-regulating genes and analyzed with respect to various clinical parameters. RESULTS: MDD monocytes showed an overexpression of the apoptosis/growth/cholesterol and the TNF genes forming an inter-correlating gene cluster (cluster 3) separate from the previously described inflammation-related gene clusters (containing IL1 and IL6). While upregulation of monocyte gene cluster 3 was a hallmark of monocytes of all MDD patients, upregulation of the inflammation-related clusters was confirmed to be found only in the monocytes of patients with childhood adversity. The latter group also showed a downregulation of the cholesterol metabolism gene MVK, which is known to play an important role in trained immunity and proneness to inflammation. CONCLUSIONS: The upregulation of cluster 3 genes in monocytes of all MDD patients suggests a premature aging of the cells, i.e. mitochondrial apoptotic dysfunction and TNF "inflammaging", as a general feature of MDD. The overexpression of the IL-1/IL-6 containing inflammation clusters and the downregulation of MVK in monocytes of patients with childhood adversity indicates a shift in this condition to a more severe inflammation form (pyroptosis) of the cells, additional to the signs of premature aging and inflammaging.


Assuntos
Transtorno Depressivo Maior/genética , Expressão Gênica , Inflamação , Mitocôndrias/metabolismo , Monócitos/metabolismo , Piroptose , Adulto , Experiências Adversas da Infância/psicologia , Estudos Transversais , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Microglia/metabolismo
12.
Eat Behav ; 41: 101505, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33831813

RESUMO

OBJECTIVE: The impact of COVID-19 lockdown measures on patients with an eating disorder remains unclear, but preliminary results indicate that some patients could be more vulnerable to experience an increase in eating disorder pathology than others. To provide possible directions for future research, this report explored the impact of the Belgian COVID-19 lockdown measures on patients with bulimia nervosa (BN). METHODS: The data of 15 female patients with BN from an ongoing experience sampling method study were analyzed. Mixed effects models compared surroundings, social context, negative affect (NA), positive affect (PA) and binge eating before and after the implementation of the lockdown measures. RESULTS: After the implementation of the lockdown measures, significant changes in surroundings and social context were found as well as an increase in NA and decrease in PA. Patients who experienced a higher binge eating frequency during the lockdown also experienced a stronger change in NA and PA. CONCLUSIONS: Future research should also look at changes in surroundings, social context, affect and how these interact with factors such as personality traits and coping styles when investigating why some patients are more susceptible to the negative effects of lockdown measures than others.


Assuntos
Transtorno da Compulsão Alimentar , Bulimia Nervosa , COVID-19 , Controle de Doenças Transmissíveis , Avaliação Momentânea Ecológica , Feminino , Humanos , SARS-CoV-2
13.
Clin Psychol Psychother ; 28(5): 1181-1193, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33590556

RESUMO

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the International Classification of Diseases (ICD-11) proposed a dimensional approach to the assessment of personality disorders (PDs). Both models dictate that the clinician first determines PD severity before assessing maladaptive traits, invoking the level of personality functioning (LPF) construct. We consider LPF a promising dimensional construct for translational research because of its clinical importance and conceptual overlap with the Research Domain Criteria (RDoC) Social Processes. We aim to identify biomarkers that co-vary with fluctuations in LPF in adulthood, ultimately to predict persistent decrease in LPF, associated with suicidality and morbidity. However, a theoretical framework to investigate stress-related oscillations in LPF is currently missing. In this article, we aim to fill this hiatus with a critical review about stress and LPF. First, we discuss acute stress and LPF. We briefly present the basics of the neurophysiological stress response and review the literature on momentary and daily fluctuations in LPF, both at a subjective and physiological level. Second, we review the effects of chronic stress on brain function and social behaviour and recapitulate the main findings from prospective cohort studies. This review underlies our suggestions for multimethod assessment of stress-related oscillations in LPF and our theoretical framework for future longitudinal studies, in particular studies using the experience sampling method (ESM).


Assuntos
Transtornos da Personalidade , Personalidade , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Transtornos da Personalidade/diagnóstico , Inventário de Personalidade , Estudos Prospectivos
14.
Eat Weight Disord ; 26(2): 475-481, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32080821

RESUMO

INTRODUCTION: Epidemiologic information on sociodemographic and clinical characteristics in eating disorders in Western European countries are scarce. PURPOSE: In this study, we report demographic and clinical characteristics of eating disorder (ED) patients undergoing treatment in five specialized ED centers in Flanders (Belgium). METHOD: Data from 642 ED patients were collected by means of a structured questionnaire. RESULTS: Data show that 93.8% of patients are female, with an average age of 22.6 years. The largest subgroup in our sample suffers from anorexia nervosa, namely 52.8%. Bulimia nervosa (BN), binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS) account for 17.7%, 10.7% and 18.8% of the sample, respectively. Mean age of onset was 17 years. Mean duration of illness was 5.6 years, but 20.2% of patients had their illness for over 8 years. Anorexia nervosa patients of the restricting type (AN-R) have the shortest duration of illness. BED patients stood out because they were older on average, more often in a relationship and more often in ambulatory treatment. 70% of patients over 20 years old completed higher education, but one-third of this group was unemployed and/or disabled. Remarkably, ED patients grow more up in intact families compared to the general population. CONCLUSIONS: Epidemiology of ED patients in treatment in Flanders (Belgium) seems to resemble worldwide findings. The long duration of illness, the common evolution towards chronicity and the early work impairment underline the severe personal and societal impact of ED and call to the need for early detection and treatment of these patients. LEVEL OF EVIDENCE: Level V: cross-sectional descriptive study.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Adulto , Bélgica/epidemiologia , Estudos Transversais , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , Humanos , Masculino , Adulto Jovem
15.
Neurobiol Stress ; 13: 100272, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33344725

RESUMO

BACKGROUND: Epigenetic changes are considered the main mechanisms behind the interplay of environment and genetic susceptibility in major depressive disorder (MDD). However, studies focusing on epigenetic dysregulation of the HPA axis stress response in MDD are lacking. Our objective was to simultaneously asses DNA methylation of the glucocorticoid receptor gene (NR3C1) and serotonin transporter gene (SLC6A4) and HPA axis response to stress in MDD. METHODS: We recruited 80 depressed inpatients and 58 gender and age matched healthy controls. All participants underwent the Trier Social Stress Test (TSST) and salivary cortisol was repeatedly measured to assess HPA axis reactivity. DNA methylation of the NR3C1 (exon 1 F) and SLC6A4 CpG islands was quantified from whole blood DNA. In the MDD group, clinical assessment was repeated at 8-week follow-up to test the predictive potential of DNA methylation for symptom improvement. RESULTS: Depressed patients had blunted cortisol reactivity to TSST compared to healthy controls (p = 0.01). In addition, they presented with increased average SLC6A4 (p = 0.003) and NR3C1 methylation (p = 0.03), as well as methylation of two individual NR3C1 CpG loci overlapping with the NGFI-A-binding sites (CpG12 and CpG20). Methylation of one of these two loci (CpG20) predicted lower symptom improvement at the follow-up (p = 0.007). Both, average NR3C1 and SLC6A4 methylation were associated with lower cortisol reactivity in the MDD group and explained about 16% of variability in cortisol response to TSST. CONCLUSIONS: We provide evidence of the role of NR3C1 and SLC6A4 DNA methylation in HPA axis dysregulation in MDD, which needs to be further explored.

16.
Transl Psychiatry ; 10(1): 296, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839428

RESUMO

Circulating monocytes contribute to inflammatory processes. We here validate abnormal expression of inflammation-related genes in monocytes of a large and well-characterised group of MDD patients, and relate the outcomes to pertinent clinical characteristics. Thirty-two genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD, and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene- expression data were related to age, sex, BMI, depression severity, childhood adversity (CA) and suicide risk (SR). Three distinct gene profiles were identified within the MDD group (downregulated, mixed upregulated and strongly upregulated genes). Patients in the merged upregulated groups had a significantly higher prevalence of CA and high SR. Using hierarchical clustering of the genes, we found a cluster of mainly cytokine (production)-related genes; patients with SR had a significantly higher expression of this cluster than patients without SR (particularly for IL-6, IL1A and IL1B). Such difference did not emerge for patients with and without CA. A downregulated gene profile was found for patients not exposed to CA and without SR (particularly for glucocorticoid-signalling genes NR3C1a and HSPA1/B). No inflammatory changes were observed for healthy controls exposed to CA. Our data show that inflammatory activation in MDD is not uniform, and that immunologically discernible phenotypes of depression can be linked to CA and high SR. The absence of monocyte inflammatory activation in healthy controls exposed to CA suggests an inflammatory involvement in MDD-prone individuals exposed to early stressors, but not healthy controls.


Assuntos
Transtorno Depressivo Maior , Suicídio , Depressão/genética , Transtorno Depressivo Maior/genética , Expressão Gênica , Humanos , Monócitos , Fenótipo
17.
Brain Behav Immun ; 87: 603-609, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32061905

RESUMO

BACKGROUND: Previous research has demonstrated a strong link between immune system abnormalities and Major Depressive Disorder (MDD). High suicide risk is a major complication of MDD and has recently been linked to strong (neuro-)immune alterations, but little is known on the link between circulating immune cell composition and suicidal risk status. METHODS: Here, we assessed percentages of circulating peripheral blood mononuclear cells with focus on T helper cell subsets (memory T helper cells, Th1, Th2, Th17 and T regulatory cells) in a large and well-matched cohort of 153 patients diagnosed with MDD and 153 age and sex matched controls. We explored the association of these cell populations with suicide risk while accounting for age, sex, BMI, depression severity and childhood trauma. RESULTS: Patients with MDD had reduced percentages of NK cells, and higher percentages of B and T cells in line with current literature. Further exploration of T-cells revealed a robustly elevated number of memory T helper cells, regardless of age group. Patients at high risk for suicide had the highest memory T helper cells and additionally showed a robust increase of Th17 cells compared to other suicide risk groups. CONCLUSIONS: The higher abundance of memory T helper cells points towards premature aging of the immune system in MDD patients, even during young adulthood. Patients at high risk for suicide show the clearest immune abnormalities and may represent a clinically relevant subtype of depression.


Assuntos
Senilidade Prematura , Transtorno Depressivo Maior , Suicídio , Adulto , Envelhecimento , Criança , Depressão , Humanos , Leucócitos Mononucleares , Linfócitos T Reguladores , Células Th1 , Células Th17 , Células Th2 , Adulto Jovem
18.
Eur Eat Disord Rev ; 28(3): 309-317, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32080958

RESUMO

BACKGROUND: Binge eating disorder (BED) is commonly associated with a history of trauma. Yet, there is little insight into the potential effect that trauma, dissociation, and depressive symptoms may have on the outcome of treatment interventions. METHODS: A total of 142 treatment-seeking patients admitted with a diagnosis of DSM-5 BED (88% female; mean age = 38.7; SD = 10.8) took part in a 6-month, protocolized, group cognitive behavioural therapy (CBT). Self-report questionnaires were administered to assess lifetime traumatic experiences, dissociation, and depression. Body mass index and the number of binges per week (BPW) were measured throughout treatment. The main outcomes were the percentage reduction in BPW and remission (i.e., less than one BPW; cf. DSM-5). RESULTS: Most BED patients (91.5%) reported a history of trauma, with two in three patients reporting three or more traumatic experiences. Whereas the number of traumatic experiences was not significantly associated with a reduction in BPW or remission, a higher traumatic impact score significantly decreased the likelihood of obtaining remission at the end of treatment (OR = 0.96; 95% CI [0.92, 0.99]). Higher levels of dissociative symptoms partially mediated this prospective association. CONCLUSIONS: The impact of traumatic experiences, as opposed to the number of traumatic experiences experienced, negatively predicts remission after 6 months of CBT. These findings highlight the importance of addressing trauma and dissociative features in the CBT treatment of BED.


Assuntos
Transtorno da Compulsão Alimentar/psicologia , Transtorno da Compulsão Alimentar/terapia , Terapia Cognitivo-Comportamental , Transtornos Dissociativos/psicologia , Trauma Psicológico/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psicoterapia de Grupo , Autorrelato , Resultado do Tratamento
19.
Int J Eat Disord ; 53(3): 339-348, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868255

RESUMO

BACKGROUND: Binge eating and purging behaviors (BPB) are common among college students, but evidence is scant on prevalence and associations of BPB with mental health problems and objective academic performance. This study aims to investigate: (a) 12-month prevalence of BPB among college first-year students, (b) comorbidity patterns of BPB with various mental health problems, and (c) the association of BPB with objective academic functioning. METHODS: Using data from the Leuven College Surveys (Belgium), as part of the World Mental Health Surveys International College Student initiative, we cross-sectionally assessed 12-month BPB and mental health problems among college first-year students (n = 4,889; response rate = 73.2%) at the beginning of the academic year. Objective measures of academic functioning (final grades, expressed in academic year percentage "AYP" [0-100%] and academic failure) were obtained from administrative records at the end of the academic year. RESULTS: Twelve-month prevalence of BPB was 7.6% (7.3%binge eating and 1.0%purging), with higher rates among females than males. Bivariate models showed an association between BPB and numerous mental health problems (ORs = 3.4-18.4). Multivariate models showed associations with non-suicidal self-injury, post-traumatic stress, internalizing/externalizing problems and suicidal ideation. After controlling for sociodemographic characteristics and comorbid mental health problems, BPB were still associated with lower AYP (-4.1 to -11.2% range) and elevated odds of academic year failure (ORs = 1.4-4.2). CONCLUSIONS: BPB (especially binge eating) are relatively common and associated with mental health problems, comparatively low academic performance, and higher risk of academic failure among college first-year students. Further study is needed to examine the causal dynamics underlying these associations.


Assuntos
Desempenho Acadêmico/psicologia , Transtorno da Compulsão Alimentar/epidemiologia , Estudantes/psicologia , Adolescente , Adulto , Transtorno da Compulsão Alimentar/psicologia , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Inquéritos e Questionários , Universidades , Adulto Jovem
20.
BMJ Open ; 9(9): e028284, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492781

RESUMO

INTRODUCTION: Smoking prevalence continues to be high over the world and smoking-induced diseases impose a heavy burden on the medical care system. As believed by many researchers, a promising way to promote healthcare and well-being at low cost for the large vulnerable smoking population is through eHealth solutions by providing self-help information about smoking cessation. But in the absence of first-hand knowledge about smoking habits in daily life settings, systems built on these methods often fail to deliver proactive and tailored interventions for different users and situations over time, thus resulting in low efficacy. To fill the gap, an observational study has been developed on the theme of objective and non-biased monitoring of smoking habits in a longitudinal and ambulatory mode. This paper presents the study protocol. The primary objective of the study is to reveal the contextual and physiological pattern of different smoking behaviours using wearable sensors and mobile phones. The secondary objectives are to (1) analyse cue factors and contextual situations of smoking events; (2) describe smoking types with regard to users' characteristics and (3) compare smoking types between and within subjects. METHODS AND ANALYSES: This is an observational study aimed at reaching 100 participants. Inclusion criteria are adults aged between 18 and 65 years, current smoker and office worker. The primary outcome is a collection of a diverse and inclusive data set representing the daily smoking habits of the general smoking population from similar social context. Data analysation will revolve around our primary and secondary objectives. First, linear regression and linear mixed model will be used to estimate whether a factor or pattern have consistent (p value<0.05) correlation with smoking. Furthermore, multivariate multilevel analysis will be used to examine the influence of smokers' characteristics (sex, age, education, socioeconomic status, nicotine dependence, attitudes towards smoking, quit attempts, etc), contextual factors, and physical and emotional statuses on their smoking habits. Most recent machine learning techniques will also be explored to combine heterogeneous data for classification of smoking events and prediction of craving. ETHICS AND DISSEMINATION: The study was designed together by an interdisciplinary group of researchers, including psychologist, psychiatrist, engineer and user involvement coordinator. The protocol was reviewed and approved by the ethical review board of UZ Leuven on 18 April 2016, with an approval number S60078. The study will allow us to characterise the types of smokers and triggering events. These findings will be disseminated through peer-reviewed articles.


Assuntos
Telefone Celular/instrumentação , Monitorização Ambulatorial/métodos , Fumar/epidemiologia , Dispositivos Eletrônicos Vestíveis , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Projetos de Pesquisa , Abandono do Hábito de Fumar/métodos , Adulto Jovem
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