A randomised controlled trial evaluating the Guide Cymru mental health literacy intervention programme in year 9 (age 13-14) school pupils in Wales.

BACKGROUND: Adolescent mental health has become a public health concern as 10-20% of adolescents have experiences with mental health problems. Improving mental health education is critical to reducing stigma and improving access to appropriate care when needed. Here we examine the impact of a mental health literacy programme (Guide Cymru) in young adolescents in the UK. A randomised controlled trial assessed the effectiveness of the Guide Cymru intervention. METHOD: A total of 1,926 pupils (860 males and 1066 females) aged 13-14 (year 9) took part in the study. The secondary schools were randomised into the active and control arms of the study. Teachers in the active arm of the study were trained on the Guide Cymru and then delivered the intervention to their pupils. Pupils in the active groups received six modules of mental health literacy (the Guide Cymru), and control schools received teaching as usual. Mental health literacy across several domains (e.g., knowledge, stigma, help-seeking intentions) were assessed both before and after the intervention. Data collection for the randomised controlled trial ran from September 2019 to March 2020. Multi-level modelling analysis was conducted to account for the clustered nature of the design. RESULTS: All aspects of mental health literacy, including mental health knowledge (g = 0.32), good mental health behaviours (g = 0.22), mental health stigmas (g = 0.16), intentions to seek help (g = 0.15), and avoidant coping (g = 0.14) improved after completing the Guide Cymru programme (ps < .001). DISCUSSION: The current study presents evidence for the Guide Cymru's effectiveness in improving secondary school pupils' mental health literacy. We demonstrate that providing teachers with appropriate resources and training to deliver the Guide Cymru programme within their classrooms can improve the mental health literacy of pupils. These findings have important implications for the beneficial impacts the secondary school system can have on reducing the burden of mental health problems at a critical point in a young person's life. TRIAL REGISTRATION: ISRCTN15462041. Registered 03/10/2019.

Evaluating the performance of wearable devices for contact tracing in care home environments.

COVID-19 has had a devastating impact worldwide, including in care homes where there have been substantial numbers of cases among a very vulnerable population. A key mechanism for managing exposure to the virus and targeting interventions is contact tracing. Unfortunately, environments such as care homes that were most catastrophically impacted by COVID-19 are also those least amenable to traditional contact tracing. A promising alternative to recall and smartphone-based contact tracing approaches is the use of discrete wearable devices that exploit Bluetooth Low Energy (BLE) and Long-Range Wide Area Network (LoRaWAN) technologies. However, the real-world performance of these devices in the context of contact tracing is uncertain. A series of experiments were conducted to evaluate the performance of a wearables system that is based on BLE and LoRaWAN technologies. In each experiment, the number of successful contacts was recorded and the physical distance between two contacts was compared to a calculated distance using the Received Signal Strength Indication (RSSI) to determine the precision, error rate, and duration of proximity. The overall average system contact detection success rate was measured as 75.5%; when wearables were used as per the manufacturer's guidelines the contact detection success rate increased to 81.5%, but when obstructed by everyday objects such as clothing or inside a bag the contact detection success rate was only 64.2%. The calculated distance using RSSI was close to the physical distance in the absence of obstacles. However, in the presence of typical obstacles found in care home settings, the reliability of detection decreased, and the calculated distance usually appeared far from the actual contact point. The results suggest that under real-world conditions there may be a large proportion of contacts that are underestimated or undetected.

Use of Multiple Low Cost Carbon Dioxide Sensors to Measure Exhaled Breath Distribution with Face Mask Type and Wearing Behaviour.

The use of cloth face coverings and face masks has become widespread in light of the COVID-19 pandemic. This paper presents a method of using low cost wirelessly connected carbon dioxide (CO2) sensors to measure the effects of properly and improperly worn face masks on the concentration distribution of exhaled breath around the face. Four types of face masks are used in two indoor environment scenarios. CO2 as a proxy for exhaled breath is being measured with the Sensirion SCD30 CO2 sensor, and data are being transferred wirelessly to a base station. The exhaled CO2 is measured in four directions at various distances from the head of the subject, and interpolated to create spatial heat maps of CO2 concentration. Statistical analysis using the Friedman's analysis of variance (ANOVA) test is carried out to determine the validity of the null hypotheses (i.e., distribution of the CO2 is same) between different experiment conditions. Results suggest CO2 concentrations vary little with the type of mask used; however, improper use of the face mask results in statistically different CO2 spatial distribution of concentration. The use of low cost sensors with a visual interpolation tool could provide an effective method of demonstrating the importance of proper mask wearing to the public.

Researcher engagement in policy deemed societally beneficial yet unrewarded.

Maintaining the continued flow of benefits from science, as well as societal support for science, requires sustained engagement between the research community and the general public. On the basis of data from an international survey of 1092 participants (634 established researchers and 458 students) in 55 countries and 315 research institutions, we found that institutional recognition of engagement activities is perceived to be undervalued relative to the societal benefit of those activities. Many researchers report that their institutions do not reward engagement activities despite institutions' mission statements promoting such engagement. Furthermore, institutions that actually measure engagement activities do so only to a limited extent. Most researchers are strongly motivated to engage with the public for selfless reasons, which suggests that incentives focused on monetary benefits or career progress may not align with researchers' values. If institutions encourage researchers' engagement activities in a more appropriate way - by moving beyond incentives - they might better achieve their institutional missions and bolster the crucial contributions of researchers to society.

Altered neural signatures of interoception in multiple sclerosis.

Multiple sclerosis (MS) patients present several alterations related to sensing of bodily signals. However, no specific neurocognitive impairment has yet been proposed as a core deficit underlying such symptoms. We aimed to determine whether MS patients present changes in interoception-that is, the monitoring of autonomic bodily information-a process that might be related to various bodily dysfunctions. We performed two studies in 34 relapsing-remitting, early-stage MS patients and 46 controls matched for gender, age, and education. In Study 1, we evaluated the heartbeat-evoked potential (HEP), a cortical signature of interoception, via a 128-channel EEG system during a heartbeat detection task including an exteroceptive and an interoceptive condition. Then, we obtained whole-brain MRI recordings. In Study 2, participants underwent fMRI recordings during two resting-state conditions: mind wandering and interoception. In Study 1, controls exhibited greater HEP modulation during the interoceptive condition than the exteroceptive one, but no systematic differences between conditions emerged in MS patients. Patients presented atrophy in the left insula, the posterior part of the right insula, and the right anterior cingulate cortex, with abnormal associations between neurophysiological and neuroanatomical patterns. In Study 2, controls showed higher functional connectivity and degree for the interoceptive state compared with mind wandering; however, this pattern was absent in patients, who nonetheless presented greater connectivity and degree than controls during mind wandering. MS patients were characterized by atypical multimodal brain signatures of interoception. This finding opens a new agenda to examine the role of inner-signal monitoring in the body symptomatology of MS.

Race and Resting-State Heart Rate Variability in Brazilian Civil Servants and the Mediating Effects of Discrimination: An ELSA-Brasil Cohort Study.

OBJECTIVES: African Americans are characterized by higher heart rate variability (HRV), a finding ostensibly associated with beneficial health outcomes. However, these findings are at odds with other evidence that blacks have worse cardiovascular outcomes. Here, we examine associations in a large cohort from the ELSA-Brasil study and determined whether these effects are mediated by discrimination. METHODS: Three groups were compared on the basis of self-declared race: "black" (n = 2,020), "brown" (n = 3,502), and "white" (n = 6,467). Perceived discrimination was measured using a modified version of the Everyday Discrimination Scale. Resting-state HRV was extracted from 10-minute resting-state electrocardiograms. Racial differences in HRV were determined by regression analyses weighted by propensity scores, which controlled for potentially confounding variables including age, sex, education, and other health-related information. Nonlinear mediation analysis quantified the average total effect, comprising direct (race-HRV) and indirect (race-discrimination-HRV) pathways. RESULTS: Black participants displayed higher HRV relative to brown (Cohen's d = 0.20) and white participants (Cohen's d = 0.31). Brown relative to white participants also displayed a small but significantly higher HRV (Cohen's d = 0.14). Discrimination indirectly contributed to the effects of race on HRV. CONCLUSIONS: This large cohort from the Brazilian population shows that HRV is greatest in black, followed by brown, relative to white participants. The presence of higher HRV in these groups may reflect a sustained compensatory psychophysiological response to the adverse effects of discrimination. Additional research is needed to determine the health consequences of these differences in HRV across racial and ethnic groups.

Differential Associations of Specific Selective Serotonin Reuptake Inhibitors With Resting-State Heart Rate and Heart Rate Variability: Implications for Health and Well-Being.

OBJECTIVE: Debate has focused on the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants on heart rate (HR) and HR variability (HRV), both of which are predictors of adverse cardiovascular events. Here, we examine the associations between specific SSRI antidepressants and resting state HR (and HRV) after accounting for a host of potential confounding factors using propensity score techniques. METHODS: Participants included 10,466 not taking antidepressants, 46 participants taking escitalopram, 86 taking citalopram, 66 taking fluoxetine, 103 taking paroxetine, and 139 taking sertraline. HR and HRV (root mean square of successive squared differences, high frequency) were extracted from 10-minute resting-state ECGs. Analyses including propensity score weighting and matching were conducted using R-statistics to control for potentially confounding variables. RESULTS: Major findings indicated that users of all SSRI medications-except fluoxetine-displayed lower HRV relative to nonusers. Users of paroxetine also displayed significantly lower HRV relative to users of citalopram (Cohen's d = 0.42), fluoxetine (Cohen's d = 0.54), and sertraline (Cohen's d = 0.35), but not escitalopram. Although associations were also observed for HR, these were less robust than those for HRV. CONCLUSIONS: Although paroxetine is associated with decreases in HRV relative to nonusers, as well as users of other SSRI medications, fluoxetine was the only medication not to display significant alterations in HR or HRV. These conclusions are limited by the cross-sectional design and nonrandomized nature of medication prescriptions. Findings highlight the importance of focusing on specific medications, rather than more heterogeneous groupings according to antidepressant action, and may have implications for health and well-being for the longer term.

Vagally mediated heart rate variability in headache patients--a systematic review and meta-analysis.

OBJECTIVE: Vagal nerve activity-indexed by heart rate variability (HRV)-has been linked to altered pain processing and inflammation, both of which may underpin headache disorders and lead to cardiovascular disease (CVD). Here we examined the evidence for differences in parasympathetic (vagal) activity indexed by time- and frequency-domain measures of HRV in patients with headache disorders compared to healthy controls (HCs). METHODS: A systematic review and meta-analysis was conducted on studies investigating group differences in vagally mediated HRV (vmHRV) including time- (root-mean-square of successive R-R-interval differences (RMSSD)) and frequency- (high-frequency HRV) domain measures. Studies eligible for inclusion were identified by a systematic search of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Seven studies reporting a total of 10 comparisons of patients with headache disorders (HF-HRV n = 67, RMSSD n = 122) and HCs (HF-HRV n = 64, RMSSD n = 125) were eligible for inclusion. Random-effects meta-analysis revealed a significant main effect on RMSSD (Z = 2.03, p = 0.04; Hedges' g = -0.63; 95% CI (-1.24, -0.02); k = 6) and similar pooled effect size estimates for HF-HRV when breathing was controlled (g = -0.30; 95% CI (-0.69; 0.10)) but not when breathing was not controlled (g = 0.02; 95% CI (-0.69; 0.74)). Controlling for breathing had no effect on RMSSD. CONCLUSION: vmHRV is reduced in patients with headache disorders, findings associated with a medium effect size. Suggestions for future research in this area are provided, emphasizing a need to investigate the impact of headache disorders and commonly comorbid conditions-including mental disorders-as well as the investigation of the risk for CVD in migraine in particular. We further emphasize the need for large-scale studies to investigate HRV as a mechanism mediating the association of migraine and CVD.

Heart rate variability and the relationship between trauma exposure age, and psychopathology in a post-conflict setting.

BACKGROUND: Cumulative exposure to potentially traumatic events (PTEs) increases risk for mental distress in conflict-affected settings, but the psychophysiological mechanisms that mediate this dose-response relationship are unknown. We investigated diminished heart rate variability (HRV) - an index of vagus nerve function and a robust predictor of emotion regulation capacity - as a vulnerability marker that potentially mediates the association between PTE exposure, age and symptoms of posttraumatic stress disorder (PTSD), psychological distress and aggressive behavior, in a community sample from Timor-Leste - a post-conflict country with a history of mass violence. METHOD: Resting state heart rate data was recorded from 45 cases of PTSD, depression and intermittent explosive disorder (IED); and 29 non-case controls. RESULTS: Resting HRV was significantly reduced in the combined case group compared with non-cases (p = .021; Cohen's d = 0.5). A significant mediation effect was also observed, whereby a sequence of increased age, reduced HRV and elevated PTSD symptoms mediated the association between PTE exposure and distress (B = .06, SE = .05, 95% CI = [.00-.217]) and aggression (B = .02, SE = .02, 95% CI = [.0003-.069])). CONCLUSION: The findings demonstrate an association between diminished resting HRV and psychopathology. Moreover, age-related HRV reductions emerged as a potential psychophysiological mechanism that underlies enhanced vulnerability to distress and aggression following cumulative PTE exposure.

Localisation of Sensor Nodes with Hybrid Measurements in Wireless Sensor Networks.

Localisation in wireless networks faces challenges such as high levels of signal attenuation and unknown path-loss exponents, especially in urban environments. In response to these challenges, this paper proposes solutions to localisation problems in noisy environments. A new observation model for localisation of static nodes is developed based on hybrid measurements, namely angle of arrival and received signal strength data. An approach for localisation of sensor nodes is proposed as a weighted linear least squares algorithm. The unknown path-loss exponent associated with the received signal strength is estimated jointly with the coordinates of the sensor nodes via the generalised pattern search method. The algorithm's performance validation is conducted both theoretically and by simulation. A theoretical mean square error expression is derived, followed by the derivation of the linear Cramer-Rao bound which serves as a benchmark for the proposed location estimators. Accurate results are demonstrated with 25%-30% improvement in estimation accuracy with a weighted linear least squares algorithm as compared to linear least squares solution.

Differential improvement in depressive symptoms for tDCS alone and combined with pharmacotherapy: an exploratory analysis from the Sertraline vs. Electrical Current Therapy for Treating Depression Clinical Study.

Transcranial direct current stimulation (tDCS) is a promising therapy for major depression treatment, although little is known of its effects in ameliorating distinct symptoms of depression. Thus, it is important, not only to increase knowledge of its antidepressant mechanisms, but also to guide its potential use in clinical practice. Using data from a recent factorial, double-blinded, placebo-controlled trial applying tDCS-alone and combined with sertraline to treat 120 depressed outpatients over 6 wk (Brunoni et al., 2013), we investigated the pattern of improvement in symptoms of depression from the Montgomery-Asberg depression scale (MADRS). First, we performed one multivariate analysis of variance with the score improvement of the 10 MADRS items as dependent variables. Significant (p < 0.05) results were further explored with follow-up analyses of variance. TDCS (alone and combined with sertraline) improved concentration difficulties and pessimistic and suicidal thoughts. The combined treatment also improved apparent and reported sadness, lassitude and inability to feel. Indeed, tDCS/sertraline significantly ameliorated all but the 'vegetative' depression symptoms (inner tension, sleep and appetite items). We further discuss whether bifrontal tDCS over the dorsolateral prefrontal cortex could be associated with improvement in cognitive (concentration) and affective (pessimistic/suicidal thoughts) processing, while the combined treatment might have a more widespread antidepressant effect by simultaneously acting on different depression pathways. We also identified patterns of antidepressant improvement for tDCS that might aid in tailoring specific interventions for different subtypes of depressed patients, e.g. particularly those with suicidal ideation.

Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women.

BACKGROUND: Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI. METHODS: Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period. RESULTS: We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing). In contrast, escitalopram was associated with decreased left amygdala and increased right IFG activity during presentation of negative pictures (attenuation of negative emotion processing). In addition, escitalopram decreased right IFG activity during the processing of neutral stimuli, akin to the effects on positive stimuli (decrease in negative appraisal). LIMITATIONS: Although we used a women-only sample to reduce heterogeneity, our results may not generalize to men. Potential unblinding, which was related to the subjective occurrence of side effects, occurred in the study; however, manipulation check analyses demonstrated that results were not impacted. CONCLUSION: These novel findings demonstrate that a single dose of the commonly prescribed escitalopram facilitates a positive information processing bias. These findings provide an important lead for better understanding effects of antidepressant medication.

The impact of 5-HTTLPR on acute serotonin transporter blockade by escitalopram on emotion processing: preliminary findings from a randomised, crossover fMRI study.

OBJECTIVE: Benefit from antidepressant treatment such as selective serotonin reuptake inhibitors (SSRIs) may depend on individual differences in acute effects on neural emotion processing. The short ('S') allele of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) is associated with both negative emotion processing biases and poorer treatment outcomes. Therefore, the aim of the present study was to explore the effects of 5-HTTLPR on the impact of the SSRI escitalopram during processing of positive and negative emotional images, as well as neutral stimuli. METHODS: The study employed a double-blind, randomised, placebo-controlled crossover design on 36 healthy Caucasian female participants who underwent functional magnetic resonance imaging (fMRI) scanning following placebo or escitalopram treatment, separated by a 7-day washout period. RESULTS: Changes in the left amygdala signal with escitalopram treatment during processing of emotional stimuli were linearly related to the 5-HTTLPR 'S' allele load such that the signal to positive stimuli decreased and the signal to negative stimuli increased with an increasing number of low-expressing 'S' alleles. While 5-HTTLPR subgroups were small in size, individual subject changes with treatment and task condition increase confidence in the findings. CONCLUSIONS: While preliminary, our findings comprise the first pharmacogenetic study demonstrating an effect of the 5-HTTLPR 'S' allele load on escitalopram-induced changes in amygdala activity during emotional processing, consistent with a 5-HTT expression dosage model. The present findings have implications for the impact of this polymorphism on antidepressant efficacy in patients with mood and anxiety disorders.

Mixed-methods feasibility outcomes for a novel ACT-based video game 'ACTing Minds' to support mental health.

OBJECTIVES: To determine the feasibility and acceptability of 'ACTing Minds', a novel single-player adventure video game based on acceptance and commitment therapy (ACT). DESIGN: A single-arm, mixed-methods repeated measures feasibility study. SETTING: Intervention and questionnaires were completed at home by participants. Semistructured interviews were also conducted at home via the Zoom platform. PARTICIPANTS: Thirty-six participants were recruited into the study, 29 completed all phases of the feasibility design. Eligibility criteria required participants to be over the age of 18 and self-reporting experiencing ongoing depression, anxiety or stress. INTERVENTION: Participants completed a single session of the 'ACTing Minds' video game, lasting approximately 1 hour, designed to educate users on key principles from ACT. PRIMARY OUTCOME MEASURES: Participant recruitment and retention, questionnaire completion, long-term intervention adherence and acceptability of the intervention. Reflexive thematic analysis was conducted on semistructured interviews run immediately postintervention and 3 weeks later. SECONDARY OUTCOME MEASURES: Measures of depression, anxiety, stress, psychological flexibility, social connectedness and well-being were assessed at baseline, immediately following intervention completion, and after a 3-week follow-up period. We used a standardised battery of questionnaires. PRIMARY RESULTS: Twenty-nine participants completed the study. A reflexive thematic analysis indicated that participants responded positively to the intervention and the study at all stages. Themes reflect participants' desire for an engaging therapeutic experience, use of game for exploring emotions, as well as their perspectives on how they had applied their learning to the real world. SECONDARY RESULTS: Quantitative results indicated small to large effect sizes associated with decreases in depression (ηp2 = 0.011), anxiety (ηp2 = 0.096) and stress (ηp2 = 0.108), and increases in psychological flexibility (ηp2 = 0.060), social connectedness (ηp2 = 0.021), well-being (ηp2 = 0.011) and participation in usual activities (ηp2 = .307). CONCLUSIONS: Implementation of the 'ACTing Minds' intervention is warranted, based on both qualitative and quantitative outcomes. TRIAL REGISTRATION NUMBER: NCT04566042 ClinicalTrials.gov.

Group-based positive psychotherapy for people living with acquired brain injury: a protocol for a feasibility study.

BACKGROUND: Acquired brain injury (ABI) and other chronic conditions are placing unprecedented pressure on healthcare systems. In the UK, 1.3 million people live with the effects of brain injury, costing the UK economy approximately £15 billion per year. As a result, there is an urgent need to adapt existing healthcare delivery to meet increasing current and future demands. A focus on wellbeing may provide an innovative opportunity to reduce the pressure on healthcare services while also supporting patients to live more meaningful lives. The overarching aims of the study are as follows: (1) evaluate the feasibility of conducting a positive psychotherapy intervention for individuals with ABI and (2) ascertain under what conditions such an intervention would merit a fully powered randomised controlled trial (RCT) compared to a standard control group (TAU). METHODS AND ANALYSIS: A randomised, two-arm feasibility trial involving allocation of patients to either a treatment group (positive psychotherapy) or control group (treatment as usual) group, according to a 1:1 ratio. A total of 60 participants at three sites will be recruited including 20 participants at each site. Assessments will be conducted at baseline, on completion of the 8-week intervention and 3 months following completion. These will include a range of questionnaire-based measures, psychophysiology and qualitative outcomes focusing on feasibility outcomes and participant experience. This study has been approved by the Wales Research Ethics Committee (IRAS project ID: 271,251, REC reference: 19/WA/0336). DISCUSSION: This study will be the first to examine the feasibility of an innovative, holistic positive psychotherapy intervention for people living with ABI, focused on individual, collective and planetary wellbeing, and will enable us to determine whether to proceed to a full randomised controlled trial. TRIAL REGISTRATION: ISRCTN12690685 , registered 11th November 2020.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study.

Decreased heart rate variability (HRV) is a cardiovascular predictor of mortality. Recent debate has focused on whether reductions in HRV in major depressive disorder (MDD) are a consequence of the disorder or a consequence of pharmacotherapy. Here we report on the impact of transcranial direct current stimulation (tDCS), a non-pharmacological intervention, vs. sertraline to further investigate this issue. The employed design was a double-blind, randomized, factorial, placebo-controlled trial. One hundred and eighteen moderate-to-severe, medication-free, low-cardiovascular risk depressed patients were recruited for this study and allocated to either active/sham tDCS (10 consecutive sessions plus two extra sessions every other week) or placebo/sertraline (50 mg/d) for 6 wk. Patients were age and gender-matched to healthy controls from a concurrent cohort study [the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)]. The impact of disorder, treatment and clinical response on HRV (root mean square of successive differences and high frequency) was examined. Our findings confirmed that patients displayed decreased HRV relative to controls. Furthermore, HRV scores did not change following treatment with either a non-pharmacological (tDCS) or pharmacological (sertraline) intervention, nor did HRV increase with clinical response to treatment. Based on these findings, we discuss whether reduced HRV is a trait-marker for MDD, which may predispose patients to a host of conditions and disease even after response to treatment. Our findings have important implications for our understanding of depression pathophysiology and the relationship between MDD, cardiovascular disorders and mortality.

A meta-analysis on the impact of alcohol dependence on short-term resting-state heart rate variability: implications for cardiovascular risk.

BACKGROUND: Alcohol dependence is associated with an increased likelihood of cardiac events. Reductions in heart rate variability (HRV) may be one mechanism linking dependence with these events. HRV may also be related to poor social functioning and the lack of impulse control commonly observed in alcohol-dependent individuals. However, prior studies on the impact of alcohol dependence on HRV have reported contradictory findings highlighting the need for a meta-analysis. METHODS: Studies comparing short-term HRV in alcohol-dependent populations and healthy controls who were nondependent were considered for meta-analysis. Only studies reporting findings from participants without cardiovascular disease were included in the analysis. RESULTS: Meta-analyses were based on 6 articles that fulfilled inclusion criteria, comprising a total of 177 alcohol-dependent participants and 216 nondependent participants. Alcohol-dependent participants displayed reduced HRV (Hedges' g = -0.6, p > 0.001) in comparison with nondependent participants. No differences were observed between the summary effect sizes obtained from different HRV domains (Q = 1.19, p = 0.55). CONCLUSIONS: Alcohol dependence is associated with reduced HRV, an effect associated with a medium effect size. Findings highlight the importance of monitoring alcohol-dependent patients for cardiac disease and emphasize the need for cardiovascular risk reduction strategies in these patients.

The impact of depression heterogeneity on inhibitory control.

OBJECTIVE: Major depressive disorder (MDD) is associated with deficits in executive cognitive function, including inhibitory control. However, inconsistencies have been found across studies. Depression is a heterogeneous disorder and these inconsistencies may therefore relate to heterogeneity in relatively small samples. METHOD: Here we sought to examine event-related potentials (ERPs) during a cognitive Go/No-Go task in melancholic (n = 60) and non-melancholic depressed patients (n = 54) relative to controls (n = 114). RESULTS: Behavioural responses indicate that inhibitory control processes are differentially affected by subtypes of depression such that melancholic patients exhibit a greater number of commission errors and more variable response rates in comparison to non-melancholic patients and controls respectively. However, ERPs do not differ during a cognitive Go/No-Go task when ERPs associated with correct responses are examined. CONCLUSIONS: These findings indicate that while patients with melancholia differ from patients without melancholia and controls, no neurophysiological differences are observed when controlling for observable behavioural impairment.

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.