The relationship between basal and acute HPA axis activity and aggressive behavior in adults

The hypothalamic–pituitary–adrenal (HPA) axis seems to play a major role in the development, elicitation, and enhancement of aggressive behavior in animals. Increasing evidence suggests that this is also true for humans. However, most human research on the role of the HPA axis in aggression has been focusing on highly aggressive children and adolescent clinical samples. Here, we report on a study of the role of basal and acute HPA axis activity in a sample of 20 healthy male and female adults. We used the Taylor Aggression Paradigm to induce and measure aggression. We assessed the cortisol awakening response as a trait measure of basal HPA axis activity. Salivary free cortisol measures for the cortisol awakening response were obtained on three consecutive weekdays immediately following awakening and 30, 45, and 60 min after. Half of the subjects were provoked with the Taylor Aggression Paradigm to behave aggressively; the other half was not provoked. Acute HPA axis activity was measured four times, once before and three times after the induction of aggression. Basal cortisol levels were significantly and negatively related to aggressive behavior in the provoked group and explained 67% of the behavioral variance. Cortisol levels following the induction of aggression were significantly higher in the provoked group when baseline levels were taken into account. The data implicate that the HPA axis is not only relevant to the expression of aggressive behavior in clinical groups, but also to a large extent in healthy ones

Standardisation framework for the Maudsley staging method for treatment resistance in depression

Background: Treatment-resistant depression (TRD) is a serious and relatively common clinical condition. Lack of consensus on defining and staging TRD remains one of the main barriers to understanding TRD and approaches to intervention. The Maudsley Staging Method (MSM) is the first multidimensional model developed to define and stage treatment-resistance in “unipolar depression”. The model is being used increasingly in treatment and epidemiological studies of TRD and has the potential to support consensus. Yet, standardised methods for rating the MSM have not been described adequately. The aim of this report is to present standardised approaches for rating or completing the MSM. Method: Based on the initial development of the MSM and a narrative review of the literature, the developers of the MSM provide explicit guidance on how the three dimensions of the MSM–treatment failure, severity of depressive episode and duration of depressive episode– may be rated. Result: The core dimension of the MSM, treatment failure, may be assessed using the Maudsley Treatment Inventory (MTI), a new method developed for the purposes of completing the MSM. The MTI consists of a relatively comprehensive list of medications with options for rating doses and provisions treatment for multiple episodes. The second dimension, severity of symptoms, may be assessed using simple instruments such as the Clinical Global Impression, the Psychiatric Status Rating or checklist from a standard diagnostic checklist. The standardisation also provides a simple rating scale for scoring the third dimension, duration of depressive episode. Conclusion: The approaches provided should have clinical and research utility in staging TRD. However, in proposing this model, we are fully cognisant that until the pathophysiology of depression is better understood, staging methods can only be tentative approximations. Future developments should attempt to incorporate other biological/ pathophysiological dimensions for staging

Cortisol, cognition and the ageing prefrontal cortex

The structural and functional decline of the ageing human brain varies by brain region, cognitive function and individual. The underlying biological mechanisms are poorly understood. One potentially important mechanism is exposure to glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with age in humans, and chronic exposure to high levels is hypothesised to result in cognitive decline via cerebral remodelling. However, studies of GC exposure in humans are scarce and methodological differences confound cross-study comparison. Furthermore, there has been little focus on the effects of GCs on the frontal lobes and key white matter tracts in the ageing brain. This thesis therefore examines relationships among cortisol levels, structural brain measures and cognitive performance in 90 healthy, elderly community-dwelling males from the Lothian Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and evening) and reactive profiles (before and after a cognitive test battery). Structural variables comprised Diffusion Tensor Imaging measures of major brain tracts and a novel manual parcellation method for the frontal lobes. The latter was based on a systematic review of current manual methods in the context of putative function and cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and volumetric accuracy when compared to both single- and multi-atlas parcellation at the lobar level. Cognitive ability was assessed via tests of general cognitive ability, and neuropsychological tests thought to show differential sensitivity to the integrity of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared considerable overlap with general cognitive ability, and cognitive scores correlated most consistently with the volumes of the anterior cingulate. This is discussed in light of the diverse connective profile of the cingulate and a need to integrate information over more diffuse cognitive networks according to proposed de-differentiation or compensation in ageing. Individuals with higher morning, evening or pre-test cortisol levels showed consistently negative relationships with specific regional volumes and tract integrity. Participants whose cortisol levels increased between the start and end of cognitive testing showed selectively larger regional volumes and lower tract diffusivity (correlation magnitudes <.44). The significant relationships between cortisol levels and cognition indicated that flatter diurnal slopes or higher pre-test levels related to poorer test performance. In contrast, higher levels in the morning generally correlated with better scores (correlation magnitudes <.25). Interpretation of all findings was moderated by sensitivity to type I error, given the large number of comparisons conducted. Though there were limited candidates for mediation analysis, cortisol-function relationships were partially mediated by tract integrity (but not sub-regional frontal volumes) for memory and post-error slowing. This thesis offers a novel perspective on the complex interplay among glucocorticoids, cognition and the structure of the ageing brain. The findings suggest some role for cortisol exposure in determining age-related decline in complex cognition, mediated via brain structure

Ajuste social em pacientes com transtorno afetivo bipolar, unipolar, distimia e depressão dupla Social disability in patients with bipolar and unipolar affective disorders, dysthymia and double depression

OBJETIVOS: Dados internacionais mostram que os transtornos afetivos têm uma prevalência de, aproximadamente, 11,3% da população. Além disso, são uma das doenças que mais geram perdas sociais e nos relacionamentos familiares. O objetivo deste trabalho foi avaliar o ajuste social e familiar de pacientes com transtornos afetivos (bipolar, unipolar, distimia e com depressão dupla), comparando o resultado entre as categorias diagnósticas, além de verificar quais variáveis estão associadas e conduzem ao pior ajuste. MÉTODOS: Foram feitos a caracterização socioeconômica e demográfica e um levantamento dos dados de evolução e de história da doença por meio de um questionário elaborado para essa finalidade. Para a avaliação de ajuste social, utilizou-se a Escala de Avaliação da Incapacitação Psiquiátrica (DAS/OMS, 1998). O relacionamento familiar foi avaliado pelo Global Assessment of Relational Functioning Scale (GARF/APA, 1994). Foram estudados 100 pacientes em tratamento, por pelo menos seis meses, no Ambulatório de Psiquiatria da Faculdade de Medicina Unesp, Botucatu, SP. RESULTADOS/CONCLUSÕES: Com predomínio de mulheres, a maioria dos pacientes tinha no mínimo dois anos de seguimento, idade acima de 50 anos, baixa escolaridade e nível socioeconômico baixo. Não houve diferença estatística significativa quanto aos dados socioeconômicos e demográficos. Na análise de regressão logística, o diagnóstico e o relacionamento familiar tiveram papel significativo no resultado de ajustamento social. Os pacientes unipolares e os distímicos tiveram melhores resultados no ajustamento social e no relacionamento familiar do que os bipolares e aqueles com depressão dupla.<br>OBJECTIVES: International data show that affective disorders have a prevalence of 11.3% in the general population. Besides that, they are responsible for social dysfunctioning and family relationship distress. The aim of this study was to assess social and family disability in affective disorder patients (bipolar and unipolar disorders, dysthymia, and double depression); and then compare the results among diagnostic groups to identify variables associated with an increased level of disability. METHODS: Socioeconomic and demographic data as well as evolution, outcome and disease history data were collected using a specific questionnaire. To assess social disability, the Disability Assessment Scale (DAS-WHO, 1988) was used. Family relationship distress was assessed through the Global Assessment of Relational Functioning Scale (GARF-APA, 1994). A hundred patients who were under treatment for at least 6 months at the university outpatient clinic were studied. RESULTS/CONCLUSIONS: Most of the patients were females, 50 years old or more, had at least 2 years of follow-up, and low educational and socioeconomic level. There was no statistical significant differences among demographic and socioeconomic levels and different diagnostic categories. Logistic regression analysis showed an important impact in social functioning due to the diagnosis and family relationship. Unipolar and dysthymic patients had better outcome in social and family functioning than bipolar and double depression ones