Associations of perceived adverse lifetime experiences with brain structure in UK Biobank participants.

BACKGROUND: Adversity experiences (AEs) are major risk factors for psychiatric illness, and ample evidence suggests that adversity-related changes in brain structure enhance this vulnerability. To achieve greater understanding of the underlying biological pathways, increased convergence among findings is needed. Suggested future directions may benefit from the use of large population samples which may contribute to achieving this goal. We addressed mechanistic pathways by investigating the associations between multiple brain phenotypes and retrospectively reported AEs in early life (child adversity) and adulthood (partner abuse) in a large population sample, using a cross-sectional approach. METHODS: The UK Biobank resource was used to access imaging-derived phenotypes (IDPs) from 6,751 participants (aged: M = 62.1, SD = 7.2, range = 45-80), together with selected reports of childhood AEs and adult partner abuse. Principal component analysis was used to reduce the dimensionality of the data prior to multivariate tests. RESULTS: The data showed that participants who reported experiences of childhood emotional abuse ('felt hated by family member as a child') had smaller cerebellar and ventral striatum volumes. This result was also depicted in a random subset of participants; however, we note small effect sizes ( ηp2  < .01), suggestive of modest biological changes. CONCLUSIONS: Using a large population cohort, this study demonstrates the value of big datasets in the study of adversity and using automatically preprocessed neuroimaging phenotypes. While retrospective and cross-sectional characteristics limit interpretation, this study demonstrates that self-perceived adversity reports, however nonspecific, may still expose neural consequences, identifiable with increased statistical power.

Investigating the effects of cerebellar transcranial direct current stimulation on saccadic adaptation and cortisol response.

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) over the prefrontal cortex has been shown to modulate subjective, neuronal and neuroendocrine responses, particularly in the context of stress processing. However, it is currently unknown whether tDCS stimulation over other brain regions, such as the cerebellum, can similarly affect the stress response. Despite increasing evidence linking the cerebellum to stress-related processing, no studies have investigated the hormonal and behavioural effects of cerebellar tDCS. METHODS: This study tested the hypothesis of a cerebellar tDCS effect on mood, behaviour and cortisol. To do this we employed a single-blind, sham-controlled design to measure performance on a cerebellar-dependent saccadic adaptation task, together with changes in cortisol output and mood, during online anodal and cathodal stimulation. Forty-five participants were included in the analysis. Stimulation groups were matched on demographic variables, potential confounding factors known to affect cortisol levels, mood and a number of personality characteristics. RESULTS: Results showed that tDCS polarity did not affect cortisol levels or subjective mood, but did affect behaviour. Participants receiving anodal stimulation showed an 8.4% increase in saccadic adaptation, which was significantly larger compared to the cathodal group (1.6%). CONCLUSION: The stimulation effect on saccadic adaptation contributes to the current body of literature examining the mechanisms of cerebellar stimulation on associated function. We conclude that further studies are needed to understand whether and how cerebellar tDCS may module stress reactivity under challenge conditions.

Psychiatric comorbid disorders of cognition: a machine learning approach using 1175 UK Biobank participants.

BACKGROUND: Conceptualising comorbidity is complex and the term is used variously. Here, it is the coexistence of two or more diagnoses which might be defined as 'chronic' and, although they may be pathologically related, they may also act independently. Of interest here is the comorbidity of common psychiatric disorders and impaired cognition. OBJECTIVES: To examine whether anxiety and/or depression are/is important longitudinal predictors of cognitive change. METHODS: UK Biobank participants used at three time points (n=502 664): baseline, first follow-up (n=20 257) and first imaging study (n=40 199). Participants with no missing data were 1175 participants aged 40-70 years, 41% women. Machine learning was applied and the main outcome measure of reaction time intraindividual variability (cognition) was used. FINDINGS: Using the area under the receiver operating characteristic curve, the anxiety model achieves the best performance with an area under the curve (AUC) of 0.68, followed by the depression model with an AUC of 0.63. The cardiovascular and diabetes model, and the covariates model have weaker performance in predicting cognition, with an AUC of 0.60 and 0.56, respectively. CONCLUSIONS: Outcomes suggest that psychiatric disorders are more important comorbidities of long-term cognitive change than diabetes and cardiovascular disease, and demographic factors. Findings suggest that psychiatric disorders (anxiety and depression) may have a deleterious effect on long-term cognition and should be considered as an important comorbid disorder of cognitive decline. CLINICAL IMPLICATIONS: Important predictive effects of poor mental health on longitudinal cognitive decline should be considered in secondary and also primary care.

Psychosocial stress affects the acquisition of cerebellar-dependent sensorimotor adaptation.

Despite being overlooked in theoretical models of stress-related disorders, differences in cerebellar structure and function are consistently reported in studies of individuals exposed to current and early-life stressors. However, the mediating processes through which stress impacts upon cerebellar function are currently unknown. The aim of the current experiment was to test the effects of experimentally-induced acute stress on cerebellar functioning, using a classic, forward saccadic adaptation paradigm in healthy, young men and women. Stress induction was achieved by employing the Montreal Imaging Stress Task (MIST), a task employing mental arithmetic and negative social feedback to generate significant physiological and endocrine stress responses. Saccadic adaptation was elicited using the double-step target paradigm. In the experiment, 48 participants matched for gender and age were exposed to either a stress (n = 25) or a control (n = 23) condition. Saliva for cortisol analysis was collected before, immediately after, and 10, and 30 min after the MIST. Saccadic adaptation was assessed approximately 10 min after stress induction, when cortisol levels peaked. Participants in the stress group reported significantly more stress symptoms and exhibited greater total cortisol output compared to controls. The stress manipulation was associated with slower learning rates in the stress group, while control participants acquired adaptation faster. Learning rates were negatively associated with cortisol output and mood disturbance. Results suggest that experimentally-induced stress slowed acquisition of cerebellar-dependent saccadic adaptation, related to increases in cortisol output. These 'proof-of-principle' data demonstrate that stress modulates cerebellar-related functions.