Marcelo Feijó de Mello

Decreased Adrenocorticotropic Hormone and Cortisol Responses to Stress in Healthy Adults Reporting Significant Childhood Maltreatment

BACKGROUND Preclinical research findings suggest that exposure to stress and concomitant hypothalamus-pituitary-adrenal (HPA) axis activation during early development can have permanent and potentially deleterious effects. A history of early-life abuse or neglect appears to increase risk for mood and anxiety disorders. Abnormal HPA response to stress challenge has been reported in adult patients with major depressive disorder and posttraumatic stress disorder. METHODS Plasma adrenocorticotropin hormone (ACTH) and cortisol reactivity to the Trier Social Stress Test were examined in healthy adults (n = 50) without current psychopathology. Subjects with a self-reported history of moderate to severe childhood maltreatment (MAL) (n = 23) as measured by the Childhood Trauma Questionnaire were compared with subjects without such a history (CTL) (n = 27). RESULTS Compared with CTLs, MAL subjects exhibited significantly lower cortisol and ACTH baseline-to-peak deltas. A significant group effect was seen in the (repeated measures) cortisol response to the stress challenge, reflecting lower concentrations among MAL subjects. A significant group x time effect characterized the relatively blunted ACTH response of the MAL group. Emotional neglect (-.34, p = .02) and sexual abuse (.31, p = .03) strongly predicted maximal cortisol release. CONCLUSIONS In adults without diagnosable psychopathology, childhood maltreatment is associated with diminished HPA axis response to a psychosocial stressor. Possible explanations for the finding are discussed.

The Clinical Correlates of Reported Childhood Sexual Abuse: An Association Between Age at Trauma Onset and Severity of Depression and PTSD in Adults

This study investigated the relationship between the age of -self‐reported sexual abuse occurrence and the development of post-traumatic stress disorder and/or depressive symptoms in adulthood. Subjects were evaluated for the presence of post-traumatic stress disorder and/or depressive symptoms as well as for a self-reported history of sexual abuse before the age of 18. Results found that relative risk of having severe post-traumatic stress disorder symptoms was 10 times higher in patients reporting sexual abuse after age 12 than in those reporting sexual abuse before age 12. Relative risk of having severe depressive symptoms was higher for those abused before the age of 12 than for those abused after the age of 12. Findings suggest that the impact of reported sexual abuse at different stages of development may lead to distinct psychiatric symptoms in adulthood.

Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA) axis

Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA) axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology.

Temperament and hypothalamic–pituitary–adrenal axis function in healthy adults

BACKGROUND Traits such as behavioral inhibition and neuroticism have been linked to the development of mood and anxiety disorders. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, a manifestation of the stress response, is often seen in major depression and has also been demonstrated in animals and humans with inhibited temperaments. A recent study found HPA hyperactivity in adults with high levels of neuroticism. The present study investigated associations of temperament and HPA function in 31 healthy adults. METHODS AND MATERIALS Subjects completed diagnostic interviews, questionnaires, and the dexamethasone-/corticotropin-releasing hormone (Dex/CRH) test. Temperament was assessed using the Tridimensional Personality Questionnaire (TPQ). RESULTS Novelty Seeking was inversely related to plasma cortisol concentrations in the Dex/CRH test. Harm Avoidance and Reward Dependence were not significantly associated with cortisol responses in the Dex/CRH test. The results were not accounted for by psychiatric symptoms or a history of stress or childhood maltreatment. CONCLUSIONS These findings are consistent with previous reports associating temperament factors with HPA axis hyperactivity. Further work is needed to replicate these observations and determine whether HPA axis dysfunction might account for some of the previously reported association of personality factors with mood and anxiety disorders.

A systematic review on the effectiveness of cognitive behavioral therapy for posttraumatic stress disorder

Objective: Cognitive behavioral therapy (CBT) is the most common psychotherapy approach for the treatment of PTSD. Nevertheless, previous reviews on the efficacy of several types of psychotherapy were unable to detect differences between CBT and other psychotherapies. The purpose of this study was to conduct systematic review on the efficacy of CBT in comparison with studies that used other psychotherapy techniques. Method: Databases were searched using the following terms: posttraumatic stress disorder/stress disorder, treatment/psychotherapy/behavior cognitive therapy, randomized trials, and adults. Randomized clinical trials published between 1980 and 2005 and that compared CBT with other treatments for PTSD was included. The main outcomes were remission, clinical improvement, dropout rates and changes in symptoms. Results: The 23 clinical trials included in the review comprised 1,923 patients: 898 in the treatment group and 1,025 in the control group. CBT had better remission rates than EMDR (RR = 0.35; 95%CI: 0.16; 0.79; p = 0.01) or supportive therapies (RR = 0.43; 95%CI: 0.25; 0.74; p = 0.002, completer analysis). CBT was comparable to Exposure Therapy (ET) (RR = 0.90; 95%CI: 0.58; 1.40; p = 0.64), and cognitive therapy (CT) (RR = 1.01; 95%CI: 0.67; 1.51; p = 0.98) in terms of efficacy and compliance. Conclusions: These findings suggest that specific therapies, such as CBT, exposure therapy and cognitive therapy are equally effective, and more effective than supportive techniques in the treatment of PTSD.

The Impact of Epidemic Violence on the Prevalence of Psychiatric Disorders in Sao Paulo and Rio de Janeiro, Brazil

Background Violence and other traumatic events, as well as psychiatric disorders are frequent in developing countries, but there are few population studies to show the actual impact of traumatic events in the psychiatric morbidity in low and middle-income countries (LMIC). Aims To study the relationship between traumatic events and prevalence of mental disorders in São Paulo and Rio de Janeiro, Brazil. Methods Cross-sectional survey carried out in 2007–2008 with a probabilistic representative sample of 15- to 75-year-old residents in Sao Paulo and Rio de Janeiro, Brazil, using the Composite International Diagnostic Interview. Results The sample comprised 3744 interviews. Nearly 90% of participants faced lifetime traumatic events. Lifetime prevalence of any disorders was 44% in Sao Paulo and 42.1% in Rio de Janeiro. One-year estimates were 32.5% and 31.2%. One-year prevalence of traumatic events was higher in Rio de Janeiro than Sao Paulo (35.1 vs. 21.7; p<0.001). Participants from Rio de Janeiro were less likely to have alcohol dependence (OR = 0.55; p = 0.027), depression (OR = 0.6; p = 0.006) generalized anxiety (OR = 0.59; p = 0.021) and post-traumatic stress disorder (OR = 0.62; p = 0.027). Traumatic events correlated with all diagnoses – e.g. assaultive violence with alcohol dependence (OR = 5.7; p<0.001) and with depression (OR = 1.7; p = 0.001). Conclusion Our findings show that psychiatric disorders and traumatic events, especially violence, are extremely common in Sao Paulo and Rio de Janeiro, supporting the idea that neuropsychiatric disorders and external causes have become a major public health priority, as they are amongst the leading causes of burden of disease in low and middle-income countries. The comparison between the two cities regarding patterns of violence and psychiatric morbidity suggests that environmental factors may buffer the negative impacts of traumatic events. Identifying such factors might guide the implementation of interventions to improve mental health and quality of life in LMIC urban centers.

Evaluation of physical activity habits in patients with posttraumatic stress disorder.

OBJECTIVE In this study, we present data from a survey that aimed to assess the physical activity habits of adult Brazilian patients with Posttraumatic Stress Disorder. METHOD Fifty male and female patients with Posttraumatic Stress Disorder participated in this study. The mean age at onset was 37±12 years, and the mean time between diagnosis and follow-up was 3.6±4.2 years. RESULTS Substantial changes in physical activity habits were observed following the onset of PTSD. While more than half of the patients participated in physical activities prior to Posttraumatic Stress Disorder onset, there was a significant reduction in their participation afterwards. The justifications for stopping physical activities or sport participation were lack of time and lack of motivation. DISCUSSION Several studies have shown that physical exercise decreases reverts symptoms of psychiatric disorders such as depression, anxiety and social isolation. We could therefore hypothesize that patients with Posttraumatic Stress Disorder who exercise should experience the same benefits. CONCLUSION Our findings demonstrated that patients with Posttraumatic Stress Disorder have low levels of participation in sports or physical activities.

Candidate-Gene Approach in Posttraumatic Stress Disorder After Urban Violence: Association Analysis of the Genes Encoding Serotonin Transporter, Dopamine Transporter, and BDNF

Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case–control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3′UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3′UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20–2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.

Catechol-O-methyltransferase (COMT) val158met Polymorphism as a Risk Factor for PTSD After Urban Violence

PTSD is a psychiatric disorder that requires a traumatic event as diagnostic criteria. Brazil has high rates of violence, and it is expected that urban victims of violence would be at risk to the development of PTSD. Studies have associated the COMT val158met polymorphism with diminished stress resilience, reduced ability to extinguish conditioned fear, and the development of PTSD after multiple traumatic experiences. The aim of this study was to identify, in a case–control study, whether the val158met polymorphism (rs4860) is associated with the development of PTSD in a group of victims of urban violence. To our knowledge, this is the first study that examines the association between PTSD and urban violence. The polymorphism of COMT in PTSD patients (n = 65) as well as in victims of violence without PTSD (n = 34) and in a community control group (n = 335) were genotyped. We found a significant relationship between the met allele (p < 0.02) and PTSD among cases (PTSD+)and victims of violence without PTSD (PTSD−; OR 2.57) and between cases and community control group (p < 0.003) Further analysis with larger samples and another ethnic group should be necessary to confirm our findings.

Maus-tratos na infância e psicopatologia no adulto: caminhos para a disfunção do eixo hipotálamo-pituitária-adrenal

OBJECTIVE The aim of this paper was to examine the relationship between childhood maltreatment and adult psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. METHOD A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. RESULTS There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. DISCUSSION The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. CONCLUSION Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses.