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BACKGROUND: Adverse childhood experiences (ACE) elevate the risk of both major depressive disorder (MDD) and metabolic diseases. The underlying pathophysiology might include alterations of adipokine levels as a consequence of ACE. In this study, we used a full-factorial design to investigate the levels of select adipokines in women with ACE-only (n = 23), MDD-only (n = 27), ACE+MDD (n = 25) and healthy controls (HC, n = 29) to identify metabolic makers associated with vulnerability and resilience of developing MDD after ACE exposure. METHODS: Serum levels of adiponectin, leptin, adiponectin-to-leptin (A/L) ratio, and retinol binding protein 4 (RBP4) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin levels did not differ between groups. Individuals with vs. without MDD showed higher leptin serum concentrations. As predicted, A/L ratio indicated lower values in individuals with vs. without ACE. RBP4 showed a more nuanced pattern with reduced levels in the ACE-only and MDD-only groups compared to HC. Furthermore, the ACE-only group showed lower RBP4 concentrations compared to ACE+MDD. These results were not accounted by BMI or medication status. CONCLUSION: Our results do not support the utility of adiponectin and leptin as predictors of vulnerability or resilience of developing MDD after ACE. In contrast, RBP4 might play a role in resilience towards the development of MDD following ACE. Further research on this more recently discovered adipokine seems warranted.
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Experiencias Adversas de la Infancia , Trastorno Depresivo Mayor , Humanos , Femenino , Adipoquinas/metabolismo , Leptina , Adiponectina/metabolismo , Proteínas Plasmáticas de Unión al RetinolRESUMEN
The glucocorticoid cortisol is the end product of the hypothalamic-pituitary-adrenal (HPA) axis and crucial for the stress response in humans. Cortisol regulates numerous biological functions by binding to two different types of receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Both receptors are found in the brain where they are crucially involved in various mental functions and in feedback inhibition of cortisol release. The precise role of both receptors in the human stress response is not completely understood. In this study, we examined the effects of pharmacological blockade of the MR or the GR on stress-induced cortisol release in a sample of 318 healthy young men (M = 25.42, SD = 5.01). Participants received the MR antagonist spironolactone (300 mg), the GR antagonist mifepristone (600 mg), or a placebo and were subjected 90 min later to a social-evaluative stressor (Trier Social Stress Test) or a non-stressful control condition. We found significantly higher stress-induced cortisol release in the spironolactone group, whereas participants after mifepristone administration did not differ from the control groups. These results suggest that MR blockade results in attenuated fast negative feedback processes and emphasize the important role of the MR during the early phase of the stress response.
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Mifepristona , Espironolactona , Masculino , Humanos , Espironolactona/farmacología , Espironolactona/metabolismo , Mifepristona/farmacología , Mifepristona/metabolismo , Hidrocortisona/metabolismo , Mineralocorticoides/metabolismo , Mineralocorticoides/farmacología , Receptores de Glucocorticoides/metabolismo , Antagonistas de Receptores de Mineralocorticoides/farmacología , Antagonistas de Receptores de Mineralocorticoides/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Receptores de Mineralocorticoides/metabolismo , Estrés Psicológico/tratamiento farmacológicoRESUMEN
Acute stress affects interoception, but it remains unclear if this is due to activation of the sympatho-adreno-medullary (SAM) or hypothalamic-pituitary-adrenocortical axis. This study aimed to investigate the effect of SAM axis activation on interoceptive accuracy (IAcc). Central alpha2-adrenergic receptors represent a negative feedback mechanism of the SAM axis. Major depressive disorder and adverse childhood experiences (ACE) are associated with alterations in the biological stress systems, including central alpha2-adrenergic receptors. Here, healthy individuals with and without ACE as well as depressive patients with and without ACE (n = 114; all without antidepressant medication) were tested after yohimbine (alpha2-adrenergic antagonist) and placebo. We assessed IAcc and sensibility in a heartbeat counting task. Increases in systolic and diastolic blood pressure after yohimbine confirmed successful SAM axis activation. IAcc decreased after yohimbine only in the healthy group with ACE, but remained unchanged in all other groups (Group × Drug interaction). This effect may be due to selective upregulation of alpha2-adrenergic receptors after childhood trauma, which reduces capacity for attention focus on heartbeats. The sympathetic neural pathway including alpha2-adrenergic circuitries may be essential for mediating interoceptive signal transmission. Suppressed processing of physical sensations in stressful situations may represent an adaptive response in healthy individuals who experienced ACE.
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Experiencias Adversas de la Infancia , Trastorno Depresivo Mayor , Interocepción , Humanos , Interocepción/fisiología , Receptores Adrenérgicos , Yohimbina/farmacologíaRESUMEN
RATIONALE: Major depressive disorder (MDD) is a severe mental disorder with affective, cognitive, and somatic symptoms. Mood congruent cognitive biases, including a negative attentional bias, are important for development, maintenance, and recurrence of depressive symptoms. MDD is associated with maladaptive changes in the biological stress systems such as dysregulations of central noradrenergic alpha2-receptors in the locus coeruleus-noradrenergic system, which can affect cognitive processes including attention. Patients with adverse childhood experiences (ACE), representing severe stress experiences in early life, might be particularly affected. OBJECTIVES: With an experimental design, we aimed to gain further knowledge about the role of noradrenergic activity for attentional bias in MDD patients with and without ACE. METHODS: We tested the effect of increased noradrenergic activity induced by the alpha2-receptor blocker yohimbine on attentional bias in a placebo-controlled repeated measures design. Four groups were included as follows: MDD patients with and without ACE, and healthy participants with and without ACE (total N = 128, all without antidepressant medication). RESULTS: A significant effect of MDD on attentional bias scores of sad face pictures (p = .037) indicated a facilitated attentional processing of sad face pictures in MDD patients (compared to non-MDD individuals). However, we found no such effect of ACE. For attentional bias of happy face pictures, we found no significant effects of MDD and ACE. Even though a higher increase of blood pressure and salivary alpha-amylase following yohimbine compared to placebo indicated successful noradrenergic stimulation, we found no significant effects of yohimbine on attentional bias of happy or sad face pictures. CONCLUSIONS: Our results are consistent with the hypothesis of a negative attentional bias in MDD patients. However, as we found no effect of ACE or yohimbine, further research is needed to understand the mechanisms by which ACE increases the risk of MDD and to understand the biological basis of the MDD-related negative attentional bias.
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Sesgo Atencional , Trastorno Depresivo Mayor , Depresión , Humanos , Norepinefrina , YohimbinaRESUMEN
Osteoporosis is characterized by low bone mass and damage to the bone tissue's microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.
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Susceptibilidad a Enfermedades , Vesículas Extracelulares/metabolismo , Osteoporosis/etiología , Osteoporosis/metabolismo , Estrés Psicológico , Animales , Biomarcadores , Remodelación Ósea/genética , Remodelación Ósea/inmunología , Regulación de la Expresión Génica , Humanos , MicroARNs/genética , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogénesis/genética , Osteoporosis/patologíaRESUMEN
Background: Adverse childhood experiences (ACE) are associated with an increased risk of major depressive disorder (MDD) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Within the HPA axis, corticotropin-releasing hormone and vasopressin (AVP) synergistically stimulate the release of adrenocorticotropic hormone, which promotes cortisol release. The cleavage product copeptin is produced during AVP synthesis and is a surrogate marker of AVP release. Children with ACE and young adults with depressive symptoms have higher levels of copeptin than healthy controls. Objective: To uncover the effects of MDD and ACE on copeptin levels in adult females. Methods: We recruited 94 women (mean age: 34.0 ± 3.6 years): 23 with MDD and ACE, 24 with MDD without ACE, 22 with ACE without MDD, and 25 healthy controls. ACE was defined as repeated sexual or physical abuse at least once a month over at least one year before the age of 18 years. MDD was defined by the DSM-IV criteria. Copeptin plasma levels were measured with an immunoluminometric assay. Results: The four groups did not differ in demographic variables. We found a significant negative correlation between body mass index (BMI) and copeptin plasma levels (r = -.21; p = .045). Copeptin plasma levels did not differ between the four groups after controlling for BMI. Conclusion: Neither MDD nor ACE was associated with altered plasma copeptin levels. Thus, copeptin does not seem to play a major role in MDD and ACE in adult females.
Antecedentes: Las experiencias adversas de la infancia (EAI) se asocian con un mayor riesgo de trastorno depresivo mayor (TDM) y desregulación del eje hipotalámico-pituitario-adrenal (HPA). Dentro del eje HPA, la hormona liberadora de corticotropina y la vasopresina (AVP) estimulan sinérgicamente la liberación de la hormona adrenocorticotrópica, que promueve la liberación de cortisol. El producto de escisión copeptina se produce durante la síntesis de AVP y es un marcador sustituto de la liberación de AVP. Los niños con EAI y los adultos jóvenes con síntomas depresivos tienen niveles más altos de copeptina que los controles sanos.Objetivo: Descubrir los efectos del TDM y la EAI en los niveles de copeptina en mujeres adultas.Métodos: Se reclutaron 94 mujeres (edad media: 34,0 ± 3,6 años): 23 con TDM y EAI, 24 con TDM sin EAI, 22 con EAI sin TDM y 25 controles sanos. La EAI se definió como abuso sexual o físico repetido al menos una vez al mes durante al menos un año antes de los 18 años. El TDM fue definido por los criterios del DSM-IV. Los niveles plasmáticos de copeptina se midieron con un ensayo inmunoluminométrico.Resultados: Los cuatro grupos no difirieron en las variables demográficas. Encontramos una correlación negativa significativa entre el índice de masa corporal (IMC) y los niveles plasmáticos de copeptina (r = −.21; p = .045). Los niveles plasmáticos de copeptina no difirieron entre los cuatro grupos después de controlar el IMC.Conclusión: Ni el TDM ni la EAI se asociaron con niveles alterados de copeptina plasmática. Por tanto, la copeptina no parece desempeñar un papel importante en el TDM y la EAI en mujeres adultas.
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Impaired cognitive functioning constitutes an important symptom of major depressive disorder (MDD), potentially associated with elevated cortisol levels. Adverse childhood experiences (ACE) enhance the risk for MDD and can contribute to disturbances in the stress systems, including cortisol and cognitive functions. In healthy participants, cortisol administration as well as acute stress can affect cognitive performance. In the current study, we tested cognitive performance in MDD patients with (N = 32) and without (N = 52) ACE and healthy participants with (N = 22) and without (N = 37) ACE after psychosocial stress induction (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST). MDD predicted lower performance in verbal learning and both selective and sustained attention, while ACE predicted lower performance in psychomotoric speed and working memory. There were no interaction effects of MDD and ACE. After stress, MDD patients were more likely to show lower performance in working memory as well as in selective and sustained attention compared with participants without MDD. Individuals with ACE were more likely to show lower performance in verbal memory after stress compared with individuals without ACE. Our results indicate negative effects of MDD and ACE on distinct cognitive domains. Furthermore, MDD and/or ACE seem to enhance susceptibility for stress-related cognitive impairments.
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Trastorno Depresivo Mayor , Niño , Cognición , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-SuprarrenalRESUMEN
Major depressive disorder (MDD) has been associated with changes in the biological stress systems, including the locus coeruleus-noradrenergic system. Accumulated evidence suggests an upregulation of central alpha2-receptors, leading to decreased noradrenergic activity on a central level in MDD patients. Adverse childhood experiences (ACE) such as physical or sexual abuse might contribute to those changes. Furthermore, noradrenaline can affect cognitive processes, e.g. learning and memory. Cognitive dysfunctions constitute an important symptom of MDD. We aimed to investigate the relationship of alpha2-receptor dysregulation with learning processes in MDD by conducting a differential fear conditioning paradigm after double-blind administration of the alpha2-receptor antagonist yohimbine versus placebo. To investigate the role of ACE systematically, we included four groups of healthy participants and MDD patients with and without ACE (MDD-/ACE-: Nâ¯=â¯44, MDD-/ACE+: Nâ¯=â¯26, MDD+/ACE-: Nâ¯=â¯24, MDD+/ACE+: Nâ¯=â¯24; without antidepressant medication). We found increased noradrenergic activity after yohimbine administration across groups as measured by alpha-amylase and blood pressure. Overall, fear responses were higher after yohimbine as indicated by skin conductance responses and fear-potentiated startle responses. While we found no significant MDD effect, ACE had significant impact on the ability to discriminate between both conditioned stimuli (CS+ predicting an aversive stimulus, CS- predicting none), depending on drug condition. After yohimbine, CS discrimination decreased in individuals without ACE, but not in individuals with ACE. Differences in the response to yohimbine might be explained by aberrant alpha2-receptor regulation in individuals with ACE. Impaired discrimination of threat and safety signals might contribute to enhanced vulnerability following ACE.
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Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Experiencias Adversas de la Infancia/tendencias , Condicionamiento Psicológico/efectos de los fármacos , Trastorno Depresivo Mayor/metabolismo , Miedo/efectos de los fármacos , Norepinefrina/metabolismo , Yohimbina/administración & dosificación , Adulto , Experiencias Adversas de la Infancia/psicología , Niño , Condicionamiento Psicológico/fisiología , Estudios Transversales , Trastorno Depresivo Mayor/psicología , Miedo/fisiología , Miedo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa/efectos adversos , alfa-Amilasas/metabolismoRESUMEN
BACKGROUND: Many depressed patients do not achieve response or remission despite adequate treatment. Identifying predictors of outcome can contribute to developing therapeutic algorithms for difficult-to-treat depression. Therefore, we examined clinical predictors of response and remission in a naturalistic inpatient sample undergoing multimodal treatment for depression. METHODS: Three hundred and fifty-one consecutive inpatients admitted to a tertiary care university hospital (specialized psychiatry unit for treatment of unipolar and bipolar depression) between January 2014 and December 2016 were characterized by a set of sociodemographic and clinical variables. The predictive value of these variables for response (≥ 50% decrease from baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score) and remission (MADRS score at discharge < 10) were explored using bivariate analysis and logistic regression. RESULTS: Greater symptom severity and fewer psychotropic medications at the time of admission predicted response. Remission rates were higher for patients with non-chronic depression, higher number of previous depressive episodes, fewer psychotropic medications and less severe depression at admission. LIMITATIONS: This was a retrospective study without a control group. The sample was drawn from a single inpatient ward specialized for difficult-to-treat depression. CONCLUSIONS: Greater baseline depression severity might be a proxy for a less chronic course of depression thereby explaining its association with greater response rates. Fewer episodes in the past and polypharmacy could indicate treatment-resistance and chronicity, contributing to lower remission rates. Therefore, preventing chronicity should be a central aim of depression treatment.
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Trastorno Bipolar/terapia , Trastorno Depresivo/terapia , Terapia Combinada , Femenino , Humanos , Pacientes Internos/psicología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
The influence of stress on executive functions has been demonstrated in numerous studies and is potentially mediated by the stress-induced cortisol release. Yet, the impact of cortisol on cognitive flexibility and task switching in particular remains equivocal. In this study, we investigated the influence of pharmacological glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) stimulation, two corticosteroid receptor types known to be responsible for cortisol effects on the brain. We conducted two experiments, each with 80 healthy participants (40 women and 40 men), and tested the effect of the unspecific MR/GR agonist hydrocortisone (Experiment I) and the more specific MR agonist fludrocortisone (Experiment II) on switch costs and task rule congruency in a bivalent, cued task switching paradigm. The results did not confirm our hypotheses; we found no significant effects of our manipulations on task switching capacity, although general switching and congruency effects were observed. We discuss the absence of MR/GR-mediated effects and propose alternative mechanisms that could explain stress induced effects on task switching.
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Función Ejecutiva/efectos de los fármacos , Fludrocortisona/farmacología , Hidrocortisona/farmacología , Receptores de Glucocorticoides/agonistas , Receptores de Mineralocorticoides/agonistas , Adolescente , Adulto , Señales (Psicología) , Técnicas de Diagnóstico Neurológico , Método Doble Ciego , Femenino , Glucocorticoides/farmacología , Voluntarios Sanos , Humanos , Hidrocortisona/metabolismo , Masculino , Mineralocorticoides/farmacología , Placebos , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
Alterations of the hypothalamic-pituitary-adrenal (HPA) axis such as altered glucocorticoid receptor sensitivity and increased immune reactivity might contribute to the pathogenesis of major depressive disorder (MDD). Exposure to adverse childhood experiences (ACE) precipitates vulnerability to MDD and might be associated with endocrine and immune alterations in the disorder. In order to disentangle the effects of ACE and MDD, we recruited 87 women: n = 23 with MDD and ACE as determined by clinical interview and questionnaires (Structured Clinical Interview for DSM-IV, Early Trauma Inventory, Childhood Trauma Questionnaire), n = 24 with MDD without ACE, n = 21 with ACE but no current or lifetime MDD, and n = 26 healthy women without either MDD or ACE. Glucocorticoid signaling and mitogen-stimulated proliferation were analyzed ex vivo in peripheral blood-derived mononuclear cells. Additionally, mRNA expression of the glucocorticoid and the mineralocorticoid receptor (GR / MR) was assessed. Peripheral GR sensitivity as well as GR and MR expression levels were not significantly different between groups. Women with ACE showed an increased immune response after mitogen stimulation independent of the presence of MDD. Our results provide evidence for a functionally altered ex-vivo immune response in cell cultures from women with a history of ACE. Thus, ACE might contribute to the pathogenesis of MDD through inflammatory pathways.
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Trastorno Depresivo Mayor/inmunología , Inmunidad Celular/fisiología , Receptores de Glucocorticoides/inmunología , Adulto , Experiencias Adversas de la Infancia , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/fisiopatología , Dexametasona/metabolismo , Femenino , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Persona de Mediana Edad , Mitógenos/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Saliva/metabolismo , Encuestas y CuestionariosRESUMEN
Cognitive function is often impaired in patients with major depressive disorder (MDD). Childhood trauma is a risk factor for developing MDD and is also associated with cognitive impairments in later life. We aimed to investigate the effects of childhood trauma on cognitive function in MDD. 68 medication-free MDD patients and 75 healthy controls (HC) participated. We tested cognitive function with the Autobiographical Memory Test, Auditory Verbal Learning Test (AVLT), Trail Making Test A and B, Rey-Osterrieth/Taylor Complex Figure Test, and Digit Span Backward. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Patients and HC did not differ with respect to age, sex, education. Mean CTQ sum scores differed significantly for depressed and HC with mean 47.8 (19.2) and 31.0 (6.8), respectively. Depressed patients and HC (without taking childhood trauma into account) differed only in AVLT performance. When childhood trauma was considered, this group difference disappeared. Subsequent regression analyses revealed that higher CTQ scores but not a diagnosis of MDD were associated with less specific autobiographical memories. Associations of CTQ with other cognitive domains failed significance after correction for multiple testing. Our results suggest that cognitive function is influenced by childhood trauma in MDD. However, the effects are small.
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Adultos Sobrevivientes de Eventos Adversos Infantiles/psicología , Disfunción Cognitiva/psicología , Trastorno Depresivo Mayor/psicología , Función Ejecutiva , Memoria Episódica , Adulto , Estudios de Casos y Controles , Niño , Cognición , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Aprendizaje VerbalRESUMEN
Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels. Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 ± 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse. Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93). Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of "inflammatory depression". Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies.
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The capacity to represent the emotional and mental states of others is referred to by the concept of empathy. Empathy further differentiates into an emotional and a cognitive subcomponent, which in turn is known to require a tacit perspective-taking process. However, whether the empathizer by himself needs to enter an affective state as a necessary precondition for emotional empathy remains a matter of debate. If empathy would require a vicarious emotional reaction, specific physiological markers of affective responding should be detectable in the empathizing person. In the present study, we investigated the relationship between self-reported empathy and psychophysiological responses in young, healthy participants. We assessed emotional and cognitive empathy with the Multifaceted Empathy Test on the one hand and the corresponding heart rate and skin conductance responses (SCR), affective startle modulation and heart rate variability on the other. We found a negative relationship between SCR and self-reported emotional empathy: higher SCR to emotional stimuli predicted lower empathy ratings. We conclude that physiological arousal is not necessary and might even diminish empathy for others.
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Nivel de Alerta/fisiología , Empatía/fisiología , Adolescente , Adulto , Electrocardiografía , Electromiografía , Femenino , Respuesta Galvánica de la Piel/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Recuerdo Mental/fisiología , Escalas de Valoración Psiquiátrica , Reflejo de Sobresalto , Autoinforme , Aprendizaje Espacial/fisiología , Adulto JovenRESUMEN
BACKGROUND: Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are a prominent finding in patients with major depressive disorder (MDD). Inconsistencies regarding a hyper- or hypoactive HPA axis may be explained by the moderating effect of childhood adverse experiences (ACE) which are associated with both HPA axis dysfunction and MDD in adulthood. We aimed to systematically disentangle the effects of ACE and MDD on HPA axis by comparing healthy women with and without childhood adversity and women with MDD with and without ACE. METHODS: The dexamethasone/corticotropin-releasing hormone (DEX/CRH) test was administered in 35 women with MDD and ACE as determined by a clinical interview (SCID, Early Trauma Inventory), 51 women with MDD without ACE, 21 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. RESULTS: There were no group differences in age, smoking, body mass index, and intake of oral contraceptives. Free salivary cortisol responses were not significantly different between the four groups. CONCLUSIONS: This study shows no evidence for a dysregulation of the HPA axis as measured by the DEX/CRH test in depressed women with and without childhood adversity as compared to mentally healthy women with or without early life stress. Our results do not support the assumption of distinct neuroendocrine endophenotypes in MDD with regard to ACE.
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Hormona Liberadora de Corticotropina/metabolismo , Trastorno Depresivo Mayor/metabolismo , Hormona Adrenocorticotrópica , Adulto , Hormona Liberadora de Corticotropina/análisis , Hormona Liberadora de Corticotropina/sangre , Depresión/metabolismo , Depresión/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Dexametasona/análisis , Dexametasona/sangre , Dexametasona/metabolismo , Femenino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Acontecimientos que Cambian la Vida , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/fisiopatología , Saliva/químicaRESUMEN
Adverse childhood experiences (ACE) enhance the risk for mental disorders, e.g. major depressive disorder (MDD). Increasing evidence suggests an association between ACE and impaired physical health, e.g. metabolic syndrome. The aim of this study was to assess several metabolic risk markers in healthy individuals with and without ACE and depressed patients with and without ACE. We examined glucose and insulin release in the oGTT in 33 women with MDD and ACE, 47 women with MDD without ACE, 21 women with ACE but no current or lifetime MDD and 36 healthy women without either MDD or ACE. Several metabolic markers such as triglycerides, cholesterol, LDL, HDL, HbA1c, BMI and waist to hip ratio were assessed. The four groups did neither differ in insulin release and glucose concentrations in the oGTT nor with respect to other metabolic variables. Depressed patients with and without psychotropic medication did not differ in any outcome variable, but there was a trend towards higher glucose concentrations in the oGTT in patients with current psychotropic medication. In this physically healthy sample neither ACE nor MDD were associated with metabolic risk factors. Thus, metabolic alterations might not directly be linked to ACE and depression.
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Adultos Sobrevivientes de Eventos Adversos Infantiles , Glucemia/análisis , Trastorno Depresivo Mayor/sangre , Insulina/sangre , Síndrome Metabólico/sangre , Adulto , Adultos Sobrevivientes de Eventos Adversos Infantiles/estadística & datos numéricos , Comorbilidad , Trastorno Depresivo Mayor/epidemiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Adulto JovenRESUMEN
Mood congruent alterations in information processing such as an impaired memory bias for emotional information and impaired inhibitory functions are prominent features of a major depressive disorder (MDD). Furthermore, in MDD patients hypothalamic-pituitary-adrenal axis dysfunctions are frequently found. Impairing effects of stress or cortisol administration on memory retrieval as well as impairing stress effects on cognitive inhibition are well documented in healthy participants. In MDD patients, no effect of acute cortisol administration on memory retrieval was found. The current study investigated the effect of acute cortisol administration on memory bias in MDD patients (N = 55) and healthy controls (N = 63) using the Directed Forgetting (DF) task with positive, negative and neutral words in a placebo controlled, double blind design. After oral administration of 10 mg hydrocortisone/placebo, the item method of the DF task was conducted. Memory performance was tested with a free recall test. Cortisol was not found to have an effect on the results of the DF task. Interestingly, there was significant impact of valence: both groups showed the highest DF score for positive words and remembered significantly more positive words that were supposed to be remembered and significantly more negative words that were supposed to be forgotten. In general, healthy participants remembered more words than the depressed patients. Still, the depressed patients were able to inhibit intentionally irrelevant information at a comparable level as the healthy controls. These results demonstrate the importance to distinguish in experimental designs between different cognitive domains such as inhibition and memory in our study.
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Antiinflamatorios/administración & dosificación , Sesgo , Trastorno Depresivo Mayor/complicaciones , Emociones/efectos de los fármacos , Hidrocortisona/administración & dosificación , Trastornos de la Memoria/tratamiento farmacológico , Administración Oral , Adulto , Método Doble Ciego , Femenino , Humanos , Inhibición Psicológica , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estadísticas no Paramétricas , Aprendizaje Verbal/efectos de los fármacos , Vocabulario , Adulto JovenRESUMEN
BACKGROUND: Adverse childhood experiences (ACE) increase the risk to develop major depressive disorder (MDD) and obesity or metabolic syndrome in adulthood. In addition, ACE may be associated with an exaggerated endocrine response to stress, which, in turn, may lead to enhanced food intake resulting in obesity and metabolic problems. METHODS: We systematically examined the stress response and consecutive food intake in 32 women with MDD and ACE as determined by a clinical interview (Early Trauma Inventory), 52 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. All participants underwent a psychosocial stress test (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST) before they were offered a buffet of snacks. Participants were not aware that the primary outcome variable was the amount of consumed kilocalories (kcal). RESULTS: The four groups did not differ in demographic variables. Stress resulted in higher cortisol release and higher blood pressure compared to the control condition. Patients with MDD without ACE had a significantly lower cortisol response to stress compared to controls. Across groups, we found higher kcal intake after stress compared to the control condition. Comparing high and low cortisol responders to stress, higher kcal intake after stress was only seen in those with low cortisol release. CONCLUSIONS: This study provides evidence that blunted rather than enhanced cortisol release to stress might lead to increased food intake, independent from MDD and ACE.
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Ingestión de Alimentos/psicología , Conducta Alimentaria/psicología , Adulto , Depresión/metabolismo , Trastorno Depresivo Mayor/metabolismo , Ingestión de Alimentos/fisiología , Femenino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Acontecimientos que Cambian la Vida , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/fisiopatología , Saliva , Estrés Psicológico/metabolismo , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: Many studies have shown disturbed glucocorticoid receptor (GR) in depressed patients. In contrast, only few studies targeted mineralocorticoid receptor (MR) function with inconclusive results. We examined the effects of the MR antagonist spironolactone on cortisol secretion in depressed patients and healthy individuals. METHODS: Forty-eight unmedicated depressed patients (mean age 41.6years) and 45 age- and sex-matched healthy participants (40.7years) received the MR antagonist spironolactone (300mg) or placebo with three days apart in a randomized, double-blind, within-subject cross-over design. We measured salivary cortisol before ingestion of study medication (baseline) as well as +60min, +90min, +120min, +150min and 180min after baseline. RESULTS: Repeated-measures ANOVA for area under the curve (AUCg) cortisol revealed a treatment effect with higher cortisol after spironolactone and a treatment by group interaction. Post-hoc analyses revealed higher cortisol in depressed patients compared to healthy participants in the placebo condition. In the spironolactone condition, the cortisol levels were not significantly different. CONCLUSIONS: Potentially, impaired MR or GR signaling could be responsible for higher cortisol levels in depressed patients in the placebo condition. However, after MR blockade that increased cortisol secretion across groups leading to higher GR occupation, we found no differences between depressed patients and healthy controls. Thus, our results argue for depression-associated alterations in MR signaling rather than disturbed GR-mediated feedback inhibition.
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Trastorno Depresivo Mayor/metabolismo , Receptores de Mineralocorticoides/metabolismo , Espironolactona/farmacología , Adulto , Análisis de Varianza , Área Bajo la Curva , Estudios de Casos y Controles , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hidrocortisona/metabolismo , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/farmacología , Escalas de Valoración Psiquiátrica , Saliva/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex and is involved in social cognition. We recently found that pharmacological stimulation of the MR enhances emotional empathy but does not affect cognitive empathy. In the current study, we examined whether blockade of the MR impairs empathy in patients with major depressive disorder (MDD) and healthy individuals. METHODS: In a placebo-controlled study, we randomized 28 patients with MDD without psychotropic medication and 43 healthy individuals to either placebo or 300 mg spironolactone, a MR antagonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. RESULTS: In the MET, we found no significant main effect of treatment or main effect of group for cognitive empathy but a highly significant treatment by group interaction (p < 0.01). Patients had higher cognitive empathy scores compared to controls in the placebo condition but not after spironolactone. Furthermore, in the spironolactone condition reduced cognitive empathy was seen in MDD patients but not in controls. Emotional empathy was not affected by MR blockade. In the MASC, no effect of spironolactone could be revealed. CONCLUSION: Depressed patients appear to exhibit greater cognitive empathy compared to healthy individuals. Blockade of MR reduced cognitive empathy in MDD patients to the level of healthy individuals. Future studies should further clarify the impact of MR functioning on different domains of social cognition in psychiatric patients.