Tim Outhred

Heart rate variability is associated with emotion recognition: direct evidence for a relationship between the autonomic nervous system and social cognition.

It is well established that heart rate variability (HRV) plays an important role in social communication. Polyvagal theory suggests that HRV may provide a sensitive marker of ones ability to respond and recognize social cues. The aim of the present study was to directly test this hypothesis. Resting-state HRV was collected and performance on the Reading the Mind in the Eyes Test was assessed in 65 volunteers. HRV was positively associated with performance on this emotion recognition task confirming our hypothesis and these findings were retained after controlling for a variety of confounding variables known to influence HRV - sex, BMI, smoking habits, physical activity levels, depression, anxiety, and stress. Our data suggests that increased HRV may provide a novel marker of ones ability to recognize emotions in humans. Implications for understanding the biological basis of emotion recognition, and social impairment in humans are discussed.

Matter Over Mind: A Randomised-Controlled Trial of Single-Session Biofeedback Training on Performance Anxiety and Heart Rate Variability in Musicians

Background Musical performance is a skilled activity performed under intense pressure, thus is often a profound source of anxiety. In other contexts, anxiety and its concomitant symptoms of sympathetic nervous system arousal have been successfully ameliorated with HRV biofeedback (HRV BF), a technique involving slow breathing which augments autonomic and emotional regulatory capacity. Objective: This randomised-controlled study explored the impact of a single 30-minute session of HRV BF on anxiety in response to a highly stressful music performance. Methods A total of 46 trained musicians participated in this study and were randomly allocated to a slow breathing with or without biofeedback or no-treatment control group. A 3 Group×2 Time mixed experimental design was employed to compare the effect of group before and after intervention on performance anxiety (STAI-S) and frequency domain measures of HRV. Results Slow breathing groups (n = 30) showed significantly greater improvements in high frequency (HF) and LF/HF ratio measures of HRV relative to control (n = 15) during 5 minute recordings of performance anticipation following the intervention (effect size: η2 = 0.122 and η2 = 0.116, respectively). The addition of biofeedback to a slow breathing protocol did not produce differential results. While intervention groups did not exhibit an overall reduction in self-reported anxiety, participants with high baseline anxiety who received the intervention (n = 15) displayed greater reductions in self-reported state anxiety relative to those in the control condition (n = 7) (r = 0.379). Conclusions These findings indicate that a single session of slow breathing, regardless of biofeedback, is sufficient for controlling physiological arousal in anticipation of psychosocial stress associated with music performance and that slow breathing is particularly helpful for musicians with high levels of anxiety. Future research is needed to further examine the effects of HRV BF as a low-cost, non-pharmacological treatment for music performance anxiety.

Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy

Clinical research has demonstrated differential efficacy of selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which may relate to differential acute effects these medications have on emotional brain processes. Here we present findings from a Multi-Level Kernel Density Analysis meta-analysis that integrates and contrasts activations from disparate fMRI studies in order to examine whether single dose SSRIs and NRIs have different effects on emotion processing tasks in healthy participants. Seven SSRI and four NRI studies were eligible for inclusion. SSRIs decreased amygdala responses, suggesting reduced emotional reactivity to emotional stimuli, whereas NRIs increased frontal and medial activation, suggesting increased emotion regulation. As hypothesised, an interaction of antidepressant and task type was found, such that SSRIs modulated amygdaloid-hippocampal, medial and frontal activity during both the presentation of faces and pictures, whereas NRIs only modulated the activation in medial and frontal regions during the presentation of pictures. Findings are interpreted within a novel model of the differential effects of SSRIs and NRIs on emotion processing.

Mood disorders: neurocognitive models

In recent years, a number of neurocognitive models stemming from psychiatry and psychology schools of thought have conceptualized the pathophysiology of mood disorders in terms of dysfunctional neural mechanisms that underpin and drive neurocognitive processes. Though these models have been useful for advancing our theoretical understanding and facilitating important lines of research, translation of these models and their application within the clinical arena have been limited—partly because of lack of integration and synthesis. Cognitive neuroscience provides a novel perspective for understanding and modeling mood disorders. This selective review of influential neurocognitive models develops an integrative approach that can serve as a template for future research and the development of a clinically meaningful framework for investigating, diagnosing, and treating mood disorders.

The contribution of BDNF and 5-HTT polymorphisms and early life stress to the heterogeneity of major depressive disorder: A preliminary study

Objective: Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor (BNDF) and reuptake by the serotonin transporter (5-HTT) appear to contribute to depression in combination with stressful life events. The aim of the current study was to investigate the contribution of early life stress (ELS), BDNF (Val versus Met alleles) and 5-HTT polymorphisms (L versus S alleles) to melancholic (n = 65) and non-melancholic depression (n = 59). Methods: A mediation approach ((G × G) × E mediation model) was employed to confirm the indirect effects of ELS on the relationship between 5-HTTPLR × BDNF polymorphism combinations and depression subtype. A series of binary logistic regressions were then conducted to determine whether genotype, ELS, and their interaction were able to predict depression subtype. Results: Key findings indicated that BDNF and 5-HTT polymorphisms in combination with ELS contributed to the development of non-melancholic depression. An interaction between BDNF and ELS increased the risk of non-melancholia by 3.327, whereas the interaction between 5-HTT and ELS increased risk by 2.406. Conclusion: The results support a role for genetic factors in the development of non-melancholia. The lack of findings in melancholia indicates that other mechanisms may underlie the subtype. Alternatively, null findings may reflect a Type II error associated with a small sample size. Future studies should consider further examination of differential gene–environment interactions for melancholia versus non-melancholia.

Therapeutic Mechanisms of Lithium in Bipolar Disorder: Recent Advances and Current Understanding

Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium—along with the reuptake of lithium in clinical practice. Recent research has further cemented glycogen synthase kinase 3β (GSK3β) inhibition as a key mechanism, and the inter-associations between GSK3β-mediated neuroprotective, anti-oxidative and neurotransmission mechanisms have been further elucidated. In addition to highly illustrative cellular research, studies examining higher-order biological systems, such as circadian rhythms, as well as employing innovative animal and human models, have increased our understanding of how lithium-induced changes at the cellular level possibly translate to changes at behavioural and clinical levels. Neural circuitry research is yet to identify clear mechanisms of change in bipolar disorder in response to treatment with lithium, but important structural findings have demonstrated links to the modulation of cellular mechanisms, and peripheral marker and pharmacogenetic studies are showing promising findings that will likely inform the exploration for predictors of lithium treatment response. With a deeper understanding of lithium’s therapeutic mechanisms—from the cellular to clinical levels of investigation—comes the opportunity to develop predictive models of lithium treatment response and identify novel drug targets, and recent findings have provided important leads towards these goals.

The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder.

OBJECTIVE The aim of the present study was to characterize the neurocognitive effects of lithium in bipolar disorder to inform clinical and research approaches for further investigation. METHODS Key words pertaining to neurocognition in bipolar disorder and lithium treatment were used to search recognized databases to identify relevant literature. The authors also retrieved gray literature (e.g., book chapters) known to them and examined pertinent articles from bibliographies. RESULTS A limited number of studies have examined the effects of lithium on neurocognition in bipolar disorder and, although in some domains a consistent picture emerges, in many domains the findings are mixed. Lithium administration appears to reshape key components of neurocognition - in particular, psychomotor speed, verbal memory, and verbal fluency. Notably, it has a sophisticated neurocognitive profile, such that while lithium impairs neurocognition across some domains, it seemingly preserves others - possibly those vulnerable to the effects of bipolar disorder. Furthermore, its effects are likely to be direct and indirect (via mood, for example) and cumulative with duration of treatment. Disentangling the components of neurocognition modulated by lithium in the context of a fluctuating and complex illness such as bipolar disorder is a significant challenge but one that therefore demands a stratified and systematic approach, such as that provided by the Lithium Battery. CONCLUSIONS In order to delineate the effects of lithium therapy on neurocognition in bipolar disorder within both research and clinical practice, a greater understanding and measurement of the relatively stable neurocognitive components is needed to examine those that indeed change with lithium treatment. In order to achieve this, we propose a Lithium Battery-Clinical and a Lithium Battery-Research that can be applied to these respective settings.

The functional epistasis of 5‐HTTLPR and BDNF Val66Met on emotion processing: a preliminary study

An epistatic interaction of 5‐HTTLPR and BDNF Val66Met polymorphisms has been implicated in the structure of rostral anterior cingulate cortex (rACC) and amygdala (AMY): key regions associated with emotion processing. However, a functional epistasis of 5‐HTTLPR and BDNF Val66Met on overt emotion processing has yet to be determined. Twenty‐eight healthy, Caucasian female participants provided saliva samples for genotyping and underwent functional magnetic resonance imaging (fMRI) during which an emotion processing protocol were presented. Confirming the validity of this protocol, we observed blood oxygen level–dependent (BOLD) activity consistent with fMRI meta‐analyses on emotion processing. Region‐of‐interest analysis of the rACC and AMY revealed main effects of 5‐HTTLPR and BDNF Val66Met, and an interaction of 5‐HTTLPR and BDNF Val66Met. The effect of the BDNF Met66 allele was dependent on 5‐HTTLPR alleles, such that participants with S and Met alleles had the greatest rACC and AMY activation during the presentation of emotional images relative to other genetic groupings. Increased activity in these regions was interpreted as increased reactivity to emotional stimuli, suggesting that those with S and Met alleles are more reactive to emotional stimuli relative to other groups. Although limited by a small sample, this study contributes novel and preliminary findings relating to a functional epistasis of the 5‐HTTLPR and BDNF Val66Met genes in emotion processing and provides guidance on appropriate methods to determine genetic epistasis in fMRI.

Pregnant mothers with resolved anxiety disorders and their offspring have reduced heart rate variability: implications for the health of children.

Objective Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments. Methods The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children’s fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version. Results HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months. Conclusions Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology.

The impact of escitalopram on vagally mediated cardiovascular function to stress and the moderating effects of vigorous physical activity: a randomized controlled treatment study in healthy participants

Recent concerns over the impact of antidepressant medications, including the selective serotonin reuptake inhibitors (SSRIs), on cardiovascular function highlight the importance of research on the moderating effects of specific lifestyle factors such as physical activity. Studies in affective neuroscience have demonstrated robust acute effects of SSRIs, yet the impact of SSRIs on cardiovascular stress responses and the moderating effects of physical activity remain to be determined. This was the goal of the present study, which involved a double-blind, randomized, placebo-controlled, cross-over trial of a single-dose of escitalopram (20 mg) in 44 healthy females; outcomes were heart rate (HR) and its variability. Participants engaging in at least 30 min of vigorous physical activity at least 3 times per week (regular exercisers) showed a more resilient cardiovascular stress response than irregular vigorous exercisers, a finding associated with a moderate effect size (Cohens d = 0.48). Escitalopram attenuated the cardiovascular stress response in irregular exercisers only (HR decreased: Cohens d = 0.80; HR variability increased: Cohens d = 0.33). HR during stress under escitalopram in the irregular exercisers was similar to that during stress under placebo in regular exercisers. These findings highlight that the effects of regular vigorous exercise during stress are comparable to the effects of an acute dose of escitalopram, highlighting the beneficial effects of this particular antidepressant in irregular exercisers. Given that antidepressant drugs alone do not seem to protect patients from cardiovascular disease (CVD), longitudinal studies are needed to evaluate the impact of exercise on cardiovascular stress responses in patients receiving long-term antidepressant treatment.