Cristiane Von Werne Baes

Assessment of the hypothalamic-pituitary-adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress - a systematic review

Objective: The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress. Methods: We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms: child abuse, depression, HPA axis, dexamethasone, prednisolone, fludrocortisone and spironolactone. Thirty-four papers were selected for this review. Results: Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress. Conclusions: The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

Emotional Abuse in Childhood Is a Differential Factor for the Development of Depression in Adults

Abstract We evaluate the association between subtypes of early life stress (ELS; sexual abuse, physical abuse, emotional abuse, physical neglect, and emotional neglect) and psychiatric disorders in adults. The sample was composed of 81 adult psychiatric patients treated at the Day Hospital Unit in Brazil. The patients were assessed using the Mini International Neuropsychiatric Interview according to diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The presence of ELS was confirmed by the Childhood Trauma Questionnaire, which investigates abuse and neglect subtypes. The patients were also evaluated for the severity of psychiatric symptoms through self-report questionnaires. A total of 71.6% of the patients experienced some type of severe ELS compared with 28.4% of the patients without ELS. Of these, 55.5% reported having experienced emotional abuse; 48.1%, physical neglect; 45.7%, emotional neglect; 39.5%, physical abuse; and 27.2%, sexual abuse. Our data showed that, among the ELS subtypes, emotional abuse was positively associated with psychopathology in adults, particularly with mood disorders (p < 0.05). The patients with a history of emotional abuse had higher severity scores in all symptoms, such as depression, hopelessness, suicidal ideation, anxiety, and impulsivity. These data demonstrate the impact of ELS, especially in cases of emotional abuse, as a trigger for psychiatric disorders and indicate that the severity of ELS is associated with severity of psychiatric symptoms. Therefore, further studies are needed to assess the importance of emotional abuse as a risk factor of severe psychopathology in adults.

Effectiveness of psychoeducation for depression: A systematic review

Objective: Pharmacological treatment is considered indispensable to major depressive disorder. In spite of this, a significant number of patients do not respond adequately to treatment based only on medication, presenting high relapse and recurrence rates. Therefore, psychosocial interventions, such as psychoeducation, have been increasingly recognized as an essential component in the treatment of depression, associated with pharmacological strategies. Thus, the aim of the present systematic review was to evaluate the effectiveness of psychoeducation for patients with unipolar depression, analyzing the evidence from the literature. Method: Searches were undertaken from April to October 2012 in LILACS, PsycINFO, PubMed, SCOPUS and ISI Web of Knowledge with keywords including ‘psychoeducation’, ‘psychoeducational intervention’ and ‘depression’, with no restriction regarding publishing dates. Results: Fifteen studies were included in the review, 13 of which evaluated the effectiveness of psychoeducation for patients with depression: 10 papers evaluated in-person psychoeducation approaches and three papers evaluated long-distance approaches. In addition to these 13 papers, one evaluated psychoeducational interventions for patients’ families and patients’ responses and another evaluated psychoeducational interventions for patients’ families and families’ responses. Findings suggest that increased knowledge about depression and its treatment is associated with better prognosis in depression, as well as with the reduction of the psychosocial burden for the family. Conclusions: Psychoeducation is a psychosocial treatment that has been well documented as an adjunct to pharmacological therapy. However, there are only a few studies regarding its effectiveness on adult patients with major depressive disorder. Although the publications in this area are still very limited, the articles selected in this review suggest that psychoeducation is effective in improving the clinical course, treatment adherence, and psychosocial functioning of depressive patients.

Early life stress in depressive patients: HPA axis response to GR and MR agonist

Background: Evidence indicates that early life stress (ELS) can induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress in the adult life that leads to depression. These appear to be related to the impairment of HPA hormones through binding to glucocorticoid (GR) and mineralocorticoid receptors (MR). The aim of this study was to evaluate the impact of ELS in HPA axis response to challenges with GR and MR agonists in depressed patients. Methods: We included 30 subjects, 20 patients with current major depression (HAM-D21 ≥ 17). Patients were recruited into two groups according to ELS history assessed by the Childhood Trauma Questionnaire (CTQ). The cortisol measures in the saliva and plasma were evaluated after using (at 10:00 p.m.) placebo, fludrocortisone (MR agonist), or dexamethasone (GR agonist). Results: Depressed patients showed a significantly lower salivary cortisol upon waking after placebo compared with controls. Moreover, cortisol awakening responses (CAR) after MR agonist were found to be lower in depressed patients than in controls. With CTQ scores, HAM-D21, body mass index and CAR after placebo, GR agonist, MR agonist we found in a Linear Regression model that depressive patients with ELS (p = 0.028) show differences between placebo vs. MR agonist (R = 0.51; p < 0.05) but not after GR agonist; in depressive patients, without ELS the data show differences between placebo vs. MR agonist (R = 0.69; p < 0.05); but now as well placebo vs. GR agonist (R = 0.53; p < 0.05). Conclusion: Our findings indicate that MR activity is impaired in depressed patients compared with controls. Furthermore, in spite of the previous limitations described, in depressed patients with ELS, there was suppression by MR agonist, indicating that patients with ELS are sensitive to MR agonists. In contrast with depressed patients without ELS, we find suppression after both MR and GR agonist. These data suggested that in ELS an imbalance exists between MR and GR with MR dysfunction.

Early Life Stress in Depressive Patients: Role of Glucocorticoid and Mineralocorticoid Receptors and of Hypothalamic-Pituitary-Adrenal Axis Activity

Depression is a chronic, recurrent and long-term disorder characterized by high rates of impairment and several comorbidities. Early life stress (ELS) is associated with the increased risk for developing depression in adulthood, influences its clinical course and predicts a poorer treatment outcome. Stressful life events play an important role in the pathogenesis of depression, being well established as acute triggers of psychiatric illness. The vulnerability for developing depression is associated to changes in neurobiological systems related to stress regulation. The hypothalamic-pituitaryadrenal (HPA) axis responds to external and internal stimuli. Reported results indicate that stress in early phases of development can induce persistent changes in the response of the HPA axis to stress in adulthood, leading to a raised susceptibility to depression. These abnormalities appear to be related to the HPA axis deregulation in depression, partially due to an imbalance between glucocorticoid receptors (GR) and mineral ocorticoid receptors (MR). While most studies have consistently demonstrated that GR function is impaired in major depression (reduced GR-mediated feedback in HPA axis), data about the MR role in depression are still limited and contr oversial. Thus, in this review article we summarize the main reported findings about the consequences of ELS in HPA axis functioning and in the responsivity of MR/GR receptors in depression.

Genetic biomarkers for differential diagnosis of major depressive disorder and bipolar disorder: A systematic and critical review

&NA; Depressive symptoms are present in the depressive mood state of bipolar disorder (BPD) and major depression disorder (MDD). Often, in clinical practice, BPD patients are misdiagnosed with MDD. Therefore, genetic biomarkers could contribute to the improvement of differential diagnosis between BPD and MDD. This systematic and critical review aimed to find in literature reliable genetic biomarkers that may show differences between BPD and MDD. This systematic review followed the PRISMA‐P method. The terms used to search PubMed, Scopus, PsycINFO, and Web of Science were depress*, bipolar, diagnos*, genetic*, biomark*. After applying the selection criteria, N = 27 studies were selected, being n = 9 about biomarkers for BPD; n = 15, about MDD; and n = 3 for distinguishing MDD from BPD. A total of N = 3086 subjects were assessed in the selected studies (n = 486 in BPD group; n = 1212 in MDD group; and n = 1388, healthy control group). The articles were dated up to June 2017. Of the N = 27 studies, n = 16 assessed gene, n = 1 miRNA, n = 2 lcnRNA and n = 3 protein expressions, n = 4 methylation, and n = 4 polymorphisms. Some studies applied more than one of these genetic analyses. To find reliable genetic biomarkers we have taken into account the methodological care during the studies development and their validity. The genetic biomarkers selected are related to genes that play a fundamental role in synaptic plasticity, neurogenesis, mood control, brain ageing, immune‐inflammatory processes and mitochondrial respiratory chain. BDNF gene expression was one of the genetic biomarkers that highlighted because of its capacity of distinguishing BPD and MDD groups, and being adequately reproduced by more than one selected study.

Consequências da personalidade borderline na adesão ao tratamento de dores crônicas

O Transtorno da Personalidade Borderline (TPB) e tema recorrente em saude mental devido aos prejuizos acarretados aos aspectos emocionais, interpessoais, cognitivos, comportamentais e de identidade do paciente. O objetivo deste artigo radica em debater sobre a interferencia do TPB na adesao ao tratamento das dores cronicas e em como a Terapia Comportamental Dialetica pode ser aplicada neste caso. Para tanto, foi realizado um estudo de caso, decorrentes dos atendimentos de Karla, paciente com TPB e diagnostico de fibromialgia. Notou-se que a situacao de desregulacao, bem como a baixa adesao ao tratamento, foi elemento importante para o baixo rendimento do tratamento.