Executive function moderates the relationship between depressive symptoms and resting heart rate variability in heart failure

Heart failure (HF) is associated with high rates of depression. In turn, depression is associated with reduced heart rate variability (HRV), a marker of parasympathetic dysfunction and poorer cardiac outcomes. Cognitive impairment—especially executive dysfunction—is also highly prevalent in HF, but it is unknown whether executive function (EF) impacts the depression-HRV relationship. The primary objective of this paper is to examine whether EF moderates the relationship between depression and HRV in HF. Participants were 109 HF patients. Depressive symptoms were measured using the Beck Depression Inventory-II. EF was assessed using a composite of age-adjusted T scores on the Frontal Assessment Battery, Trail Making Test B, and Stroop Color Word subtest. Parasympathetic function was assessed using resting high frequency HRV (HF-HRV). Multiple hierarchical regression was used to conduct BDI × EF moderation analyses. BDI scores were associated with reduced resting HF-HRV (p < .05). No main effects were detected between EF and resting HF-HRV (p > .05). However, EF moderated the relationship between BDI scores and resting HF-HRV (β = 0.59, p < .01). Simple slope analyses revealed that among participants with poorer EF, higher BDI scores were associated with lower resting HF-HRV (p < .001). Structural brain changes common in HF may contribute to lower EF, increased depression, and poorer autonomic functioning. Alternatively, the results may indicate that individuals with intact EF engage in self-care strategies that negate the detrimental impact of depression on autonomic function. Additional work is needed to clarify these possibilities and the potential benefits of treating depression in HF patients with different cognitive abilities.     

Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine

Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for assessing farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency domain analyses may provide a sensitive and reliable measure of affective states and stress-mediated changes in sympathetic and parasympathetic tones. The aim of this research was to define low (LF) and high frequency (HF) power spectral ranges using pharmacological autonomic blockade, and to examine HRV and BPV parameter changes in response to atropine and propranolol in swine. Ten, 13-week old, barrows (n = 6) and gilts (n = 4) underwent surgery to place an intra-cardiac electrode and a blood pressure catheter attached to a biotelemetric transmitter; pigs had a 3-week recovery period prior to data collection. Each pig was subjected to administration of 4 intravenous (i.v.) drug treatments: a control treatment, 3 mL of saline, and 3 blockade treatments; 0.1 mg/kg of atropine, 1.0 mg/kg of propranolol, and .1 mg/kg of atropine together with 1.0 mg/kg of propranolol. All treatments were delivered by injection in the jugular vein with a minimum of 48 h between individual treatments. Behavior, ECG and blood pressure data were recorded continuously for a total of 1 h, from 30 min pre-injection to 30 min post-injection. For data analyses, two 512-beat intervals were selected for each treatment while the pig was lying and inactive. The first interval was selected from the pre-injection period (baseline), and the second was selected between 10 and 30 min post-injection. Time and frequency domain (power spectral density) analyses were performed on each data interval. Subsequent, LF and HF bands from the power spectral densities were defined based on general linear and regression analyses. The HRV and BPV were computed with a covariate (baseline) factorial analysis of treatment by sex interaction, and day of injection, with mixed models and Tukey's post-hoc tests. The best-fit range for LF was 0.0-0.09 Hz, and HF was 0.09-2.0 Hz (r²: 0.41 and 0.43, respectively). Propranolol and saline injections led to a greater overall total power and overall higher inter-beat interval, HF and LF power. Atropine led to a dominant sympathovagal balance of the cardiac activity in pigs. In addition, atropine led to an increase in LF power of both systolic and diastolic blood pressures in gilts suggesting vagal tone mediation of BPV. The understanding of autonomic regulation of HRV and BPV in domestic swine facilitates our ability to detect and quantify stress responses, and broadens its application in assessing farm animal welfare.     

Sympathetic overactivity and plasma leptin levels in Rett syndrome

Rett syndrome (RTT) is a severe developmental–neurological disorder, characterized by profound and progressive loss of intellectual functioning, occurring after a period (of at least 6 months) of normal development with classic stereotype hand movements, gait ataxia, jerky truncal ataxia, deceleration of brain and body organ growth and cardiac dysautonomia. Pathogenesis of sympathetic overactivity in RTT is unknown, but a previous study observed increased plasma leptin levels in Rett girls and it is well known the role of leptin in the regulation of sympathetic nervous system activity. Aim of our study is to evaluate a relationship between plasma leptin levels and sympathetic activity in RTT. Thirty-two female patients (12.1 ± 6.3 years), affected by RTT were enrolled in the study. In all the subjects, we analyzed heart rate variability, QT corrected interval and plasma leptin levels. A significant correlation was found between plasma leptin levels and LF/HF (expression of sympatho-vagal balance) (Spearman r = 0.44, p = 0.001). There is also a significant negative correlation between HF component (expression of vagal activity) and plasma leptin levels (Spearman r = −0.037, p = 0.03) and a positive correlation between LF component and plasma leptin levels (Spearman r = 0.047, p = 0.01). These results show that in RTT higher plasma leptin levels appear to be associated with sympathetic overactivity, suggesting a role for leptin in cardiac dysautonomia.     

Anterior genu corpus callosum and impulsivity in suicidal patients with bipolar disorder

Suicidality is a life-threatening symptom in patients with bipolar disorder (BD). Impulsivity and mood instability are associated with suicidality in mood disorders. Evidence suggests that gray and white matter abnormalities are linked with impulsivity in mood disorders, but little is known about the association between corpus callosum (CC) and impulsivity in BD. We examined the relationship between CC areas, impulsivity and suicidality in BD patients. We studied 10 female BD patients with a history of suicide attempt (mean ± SD age 36.2 ± 10.1 years), 10 female BD patients without suicide attempt history (44.2 ± 12.5 years) and 27 female healthy subjects (36.9 ± 13.8 years). Impulsivity was evaluated by the Barratt Impulsivity Scale (BIS). We traced MR images to measure the areas of the CC genu, anterior body, posterior body, isthmus and splenium. The genu was divided into anterior, middle and posterior regions. The suicidal and non-suicidal BD patients had significantly higher BIS total, attention and non-planning scores than the healthy subjects (ps < 0.01), and the suicidal BD patients had significantly higher BIS motor scores than the non-suicidal BD and healthy subjects (ps < 0.01). There were no significant differences among the three groups on any regional CC areas, although the suicidal BD patients had the smallest areas. The suicidal BD patients showed a significant inverse correlation between anterior genu area and the BIS total (r = −0.75, p = 0.04), motor (r = −0.79, p = 0.02) and non-planning scores (r = −0.79, p = 0.02). These correlations were not found in the non-suicidal BD patients or healthy subjects. The results suggest that the anterior medial frontal region may be involved in the pathophysiology of impulsive and suicidal behaviors in BD.     

Association of GPR50, an X-linked orphan G protein-coupled receptor,and affective disorder in an independent sample of the Scottish population

A recent report detected association between GPR50, an orphan G protein-coupled receptor, and bipolar disorder (BD) in the Scottish population [29]. We sought to replicate this study in a second sample from the same population, consisting of 338 patients with BD, 359 patients with major depressive disorder (MDD) and 913 control individuals. In addition, the effect of GPR50 genotype on clinical phenotype and treatment response was assessed in a subset of 56 patients with early onset MDD (eoMDD). We identified an association with BD in women with an intronic SNP, rs1202874, that withstood correction for multiple testing (p = 0.0035, permuted p = 0.037, OR = 1.9, 95%CI 1.2–3.0). However, we failed to find an association with the previously associated Δ502-505 polymorphism (p = 0.2). Combined analysis of this and the original samples did detect association between the deletion and susceptibility to BD in females, but with a reduced effect size (p = 0.0006, permuted p = 0.0024, OR = 1.41, 95%CI 1.16–1.71). In the highly phenotyped eoMDD subgroup, we found an association between the Δ502-505 deletion polymorphism and age of onset (p = 0.049), number of episodes (p = 0.044), hypomanic symptoms (p = 0.019), and initial thinking time (p = 0.027), in women; and in family history of depression in men (p = 0.038), uncorrected for multiple testing. No association was seen between Δ502-505 genotype and treatment response at 3 months. To our knowledge this is the first association of rs1202874 with BD and is the second positive association at the GPR50 locus.     

Frontal EEG and emotion regulation: Electrocortical activity in response to emotional film clips is associated with reduced mood induction and attention interference effects

Frontal EEG activity is thought to reflect affective dispositions, but may also reflect the emotional demands of a specific context combined with the capability to regulate emotions in that context. The present study examined this hypothesis by testing whether frontal EEG activity during mood inductions versus a resting baseline predicted emotion regulation. EEG was recorded while participants (N = 66, 40 females) received a fearful, sad, or neutral mood induction. Emotion regulation was measured following the mood inductions as self-reported change in negative mood and as attention interference in a task with mood-congruent emotional distracters. Greater frontal EEG activity during the mood inductions versus baseline was associated with more effective emotion regulation: less post-induction sadness and anxiety and reduced mood-congruent attention interference effects. Effects did not differ between the left and right hemispheres. Results support the hypothesis that frontal EEG activity reflects both emotional context and emotion-regulatory capabilities.     

Early changes of microRNAs expression in the dorsal root ganglia following rat sciatic nerve transection

Abnormal baseline brain functional connectivity in attention-deficit/hyperactivity disorder (ADHD) has been revealed in a number of studies by using resting-state functional MRI (rfMRI). The aim of this study was to investigate the spontaneous frontal activities in medication-naïve ADHD boys using the rfMRI derived index, amplitude of low-frequency fluctuation (ALFF). In total 17 ADHD boys and 17 matched controls were recruited to undergo rfMRI scan on a 3.0 T MRI system. For each subject, six oblique slices covering the frontal areas were acquired with a rapid sampling rate (TR = 400 ms). Functional images were processed in AFNI for calculation of ALFF and then group comparison was performed using voxel-based t-test. With a corrected threshold of p < 0.05 determined by AlphaSim, we found that in comparison with controls, ADHD patients demonstrated higher ALFF values in the left superior frontal gyrus and sensorimotor cortex (SMC), and lower ALFF values in the bilateral anterior, middle cingulate and the right middle frontal gyrus (MFG). Significant correlations were found between patients’ WSCT measures and the peak ALFF located in the right MFG (r = 0.69, p = 0.02), and the left SMC (r = 0.65, p = 0.03). Our results revealed abnormal frontal activities at resting state associated with underlying physiopathology of ADHD, and suggested the ALFF analysis to be a potential approach in further exploration of this disorder.     

Children's heart rate variability as stress indicator: Association with reported stress and cortisol

Stress is a complex phenomenon coordinated by two main neural systems: the hypothalamic–pituitary–adrenal system with cortisol as classical stress biomarker and the autonomic nervous system with heart rate variability (HRV) as recently suggested stress marker. To test low HRV (5 minute measurements) as stress indicator in young children (5-10y), associations with self-reported chronic stress aspects (events, emotions and problems) (N = 334) and salivary cortisol (N = 293) were performed. Peer problems, anger, anxiety and sadness were associated with lower root mean square of successive differences (RMSSD) and high frequency power (i.e. lower parasympathetic activity). Anxiety and anger were also related to a higher low frequency to high frequency ratio. Using multilevel modelling, higher cortisol levels, a larger cortisol awakening response and steeper diurnal decline were also associated with these HRV patterns of lower parasympathetic activity. Conclusion: Low HRV (lower parasympathetic activity) might serve as stress indicator in children.     

Transcranial direct current stimulation influences the cardiac autonomic nervous control

To investigate whether the manipulation of brain excitability by transcranial direct current stimulation (tDCS) modulates the heart rate variability (HRV), the effect of tDCS applied at rest on the left temporal lobe in athletes (AG) and non-athletes (NAG) was evaluated. The HRV parameters (natural logarithms of LF, HF, and LF/HF) was assessed in 20 healthy men before, and immediately after tDCS and sham stimulation. After anodal tDCS in AG the parasympathetic activity (HF_log) increased (P < 0.01) and the sympathetic activity (LF_log) and sympatho-vagal balance (LF/HF_log) decreased (P < 0.01), whereas no significant effects were detected in NAG (P > 0.05). No significant changes in HRV indexes were provoked by sham stimulation in both AG and NAG (P > 0.05). In conclusion, tDCS applied on the left temporal lobe significantly increased the overall HRV in AG, enhancing the parasympathetic and decreasing the sympathetic modulation of heart rate. Consequently the sympatho-vagal balance decreased at rest in AG but not in NAG. Releasing a weak electric current to stimulate selected brain areas may induce favorable effects on the autonomic control to the heart in highly fit subjects.     

Quantitative analysis of the 4977-bp common deletion of mitochondrial DNA in postmortem frontal cortex from patients with bipolar disorder and schizophrenia

Several reports have suggested a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder and schizophrenia. We have focused on the relationship between deleted mitochondrial DNA (mtDNA) and bipolar disorder. To investigate this relationship, we developed a methodology for quantification of the common 4977-bp deletion of mtDNA based on real-time polymerase chain reaction with SYBR Green. In this study, we assessed accumulation of the common deletion in postmortem frontal cortex from 147 individuals (48 controls, 49 patients with bipolar disorder, 50 patients with schizophrenia). We demonstrated age-dependent accumulation of the common deletion of mtDNA (p = 1.09E−10). Females showed significantly higher accumulation of the deletion than did males (p = 0.002). There was no significant association between accumulation and the two studied major mental disorders in the frontal cortex (p > 0.2). However, there was no statistically significant correlation between the common deletion and aging in female patients with bipolar disorder (p = 0.133), and no significant sex difference in patients with bipolar disorder (p = 0.509). These results indicate that aging and sex have effect on accumulation of the common deletion of mtDNA in the prefrontal cortex depending on the diagnosis.     

As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD) = −0.32, 95% CI −0.63 to −0.01, p = 0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry = 0.01, 95% CI −0.34 to 0.36, p = 0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.     

Race and sex-based differences in cytokine immune responses to smallpox vaccine in healthy individuals

We assessed the effects of sex, race and ethnicity on smallpox vaccine-induced immune responses in 1071 armed forces members after primary Dryvax® smallpox vaccination, including 790 males and 281 females; 580 Caucasians, 217 African–Americans, and 217 Hispanics. Analysis of vaccinia-specific cytokine responses revealed that Caucasians had higher total IFNγ ELISPOT responses (median 57 spot-forming units/SFUs per 200,000 cells, p = 0.01) and CD8⁺IFNγ ELISPOT responses (12 SFUs, p < 0.001) than African–Americans (51 and 4 SFUs, respectively) and Hispanics (47 and 8 SFUs, respectively). Similarly, Caucasians secreted higher levels of vaccinia-specific IL-2 (p = 0.003) and IFNα (p < 0.001) compared to other racial/ethnic groups. Males had higher total IFNγ ELISPOT responses (median 55 SFUs) compared to females (41 SFUs, p < 0.001). We observed statistically significant sex-related differences in the secretion of IL-2 (p < 0.001), IL-1β (p < 0.001) and IL-10 (p = 0.017). These data suggest that vaccinia-specific cytokine responses following primary smallpox vaccination are significantly influenced by race and sex of vaccinees.     

Comparison of the larynx-associated lymphoid tissue in the false vocal cords and subglottis in pediatric autopsies

The aim this work was to compare the distribution of cellular phenotypes of the LF in the FVC to the ones in the subglottic region in pediatric autopsy, relating this distribution to age and different causes of death. We analyzed 60 larynges of newborns and children autopsied in the period from 1993 to 2003. The fragments were prepared in order to perform histochemical and immunohistochemical techniques. The morphological analysis showed cases that presented LF only in FVC (35%), LF only in the subglottic region (20%), lack of LF in FVC (30%) and lymphoid aggregates, which did not characterize an LF (15%). The cases of LF in the subglottic region were significantly younger compared to the ones that presented LF in the FVC (p = 0.017). The LF in the subglottic region was bigger than the LF in the FVC (p = 0.020). There was no significant difference between the cause of death and cellular phenotype for both FVC and the subglottic region. In conclusion, the cells that make up the LF in the FVC in newborns and children younger than one year have functional characteristics similar to LF cells in the subglottic region, suggesting that there are similarities with LALT.     

Relationships between pulse wave velocity and heart rate variability in healthy men with a range of moderate-to-vigorous physical activity levels

Pulse wave velocity (PWV) is associated with heart rate variability (HRV) in 24–39-year-old men. This study of 40–65-year-old men ranging in moderate-to-vigorous physical activity levels investigated whether (a) PWV is related to spectral HRV, (b) using normalised units for HRV influences that relationship, and (c) HRV predicts PWV when other factors, including age and blood pressure, are accounted for. Subjects were healthy men (N = 115), mean (SD) age 50.8 (7.1) years. Carotid-femoral PWV was measured using Complior. HRV was derived from a 5 min ECG for total, high-frequency, and low-frequency power (TP, HF, and LF, respectively), the LF/HF ratio, and normalised units for HF (HFnu) and LF (LFnu). Non-parametric data were natural log-transformed. PWV was 8.5 (1.4) m s⁻¹. TP, HF, LF, LF/HF, HFnu and LFnu were 1908 (2195) m s², 577 (1034) m s², 457 (514) m s², 1.5 (1.3), 46.8 (17.9), and 49.4 (19.4), respectively. PWV was inversely associated with TP (R ² = 0.061, p = 0.008), HF (R ² = 0.095, p = 0.001), LF (R ² = 0.086, p = 0.002) and HFnu (R ² = 0.040, p = 0.031), but was not associated with LF/HF (R ² = 0.020, p = 0.136) or LFnu (R ² = 0.028 p = 0.076). Only age and systolic blood pressure (adjusted R ² = 0.306, p < 0.001) predicted PWV in multivariate analysis. This study has shown that PWV was weakly associated with TP and HF. The use of normalised units only influenced the relationship between PWV and LF. Finally, relationships between PWV and HRV are mediated through age and systolic blood pressure in this population of men ranging in moderate-to-vigorous physical activity level.     

Olanzapine plus fluoxetine treatment increases Nt-3 protein levels in the rat prefrontal cortex

Evidence is emerging for a role for neurotrophins in the treatment of mood disorders. In this study, we evaluated the effects of chronic administration of fluoxetine, olanzapine and the combination of fluoxetine/olanzapine on the brain-derived-neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the rat brain. Wistar rats received daily injections of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25 mg/kg) for 28 days, and we evaluated for BDNF, NGF and NT-3 protein levels in the prefrontal cortex, hippocampus and amygdala. Our results showed that treatment with fluoxetine and olanzapine alone or in combination did not alter BDNF in the prefrontal cortex (p = 0.37), hippocampus (p = 0.98) and amygdala (p = 0.57) or NGF protein levels in the prefrontal cortex (p = 0.72), hippocampus (p = 0.23) and amygdala (p = 0.64), but NT-3 protein levels were increased by olanzapine 6 mg/kg/fluoxetine 25 mg/kg combination in the prefrontal cortex (p = 0.03), in the hippocampus (p = 0.83) and amygdala (p = 0.88) NT-3 protein levels did not alter. Finally, these findings further support the hypothesis that NT-3 could be involved in the effect of treatment with antipsychotic and antidepressant combination in mood disorders.     

Association between C-reactive protein and depressive symptoms in women with rheumatoid arthritis

Converging lines of evidence support an association between systemic inflammation and depressive symptoms. Neuroimmune pathways may account for the high prevalence of depression in individuals with inflammatory conditions such as rheumatoid arthritis (RA). However, this relationship is complicated by factors linked to both inflammatory disease activity and mood, such as pain and physical disability. The goal of this cross-sectional study was to examine the relationship between C-reactive protein (CRP) and depressive symptoms among 173 women with RA. Somatic symptoms of depression and circulating CRP were significantly associated in regression analyses adjusted for body mass index (β = .19, p < .05), but this relationship was attenuated when pain and disability were included as covariates (β = .09, p = .24). CRP was not significantly associated with negative mood symptoms of depression. Findings suggest that depression in the context of RA may result from the overlap of somatic depressive and RA symptoms rather than neuroimmune pathways.     

Can interactive skills-based seminars with standardized patients enhance clinicians’ prevention skills? Measuring the impact of a CME program

Objective

Communication skills are crucial for high-risk behavior screening and counseling. Practicing physicians have limited opportunities to improve these skills. This paper assesses the impact of a continuing medical education (CME) program for Student Health Center clinicians that targeted communication skills, screening practices and patient satisfaction.

Methods

Program evaluation included pre- and post-objective structured clinical examinations (OSCE's), chart review, and provider and patient satisfaction surveys. Data were analyzed using paired t-tests and ranked sum tests.

Results

OSCE scores (n = 15) revealed significant improvements in communication skills overall (p = 0.004) and within specific domains (data gathering: p = 0.003; rapport building: p = 0.01; patient education: p = 0.02), but no change in case-specific knowledge (p = 0.1). Participants (n = 14) reported high satisfaction with program methods (mean = 4.6/5) and content (mean = 4.7/5), 70% planning to alter their clinical practice. Chart audits (pre = 96, post = 103) showed increased screening for smoking (RR 1.65, p = 0.03), depressed mood (RR 1.40, p = 0.04), anhedonia (RR 1.47, p = 0.01), sexual activity (RR 1.73, p = 0.002) and drinking (RR 1.77, p = 0.04). Sampling of satisfaction among participants’ patients (pre n = 689, post n = 383) detected no increase in already high baseline satisfaction.

Conclusion

This curriculum improved clinicians’ relevant skills and screening behavior.

Practice implications

Skills-oriented CME can improve clinicians’ communication skills and screening and counseling practices.     

Combined effect of depressive symptoms and hostility on autonomic nervous system function

Depression and hostility have been separately related to indicators of sympathetic hyperactivation and parasympathetic hypoactivation. We examined the associations of depressive symptoms, hostility, and their interaction with pre-ejection period (PEP) and high frequency heart rate variability (HRV), specific indices of sympathetic and parasympathetic cardiac control, respectively. Healthy, young adults (N = 120) completed questionnaires assessing depressive symptoms and hostility and underwent autonomic testing. Although main effects were not observed, a depressive symptoms × hostility interaction was detected for PEP (β = .25, p = .01). Simple slope analyses revealed that hostility was negatively related to PEP among individuals with low depressive symptoms but was not associated with PEP among those with mild-to-moderate depressive symptoms. No interaction effect was detected for high frequency HRV. Our findings suggest that depressive symptoms may moderate the link between hostility and sympathetic activation such that hostility is accompanied by sympathetic hyperactivation only when depressive symptoms are minimal.     

Significant IgG subclass heterogeneity in HLA-specific antibodies: Implications for pathogenicity,prognosis, and the rejection response

IgG subclasses differ in their ability to fix complement and bind Fc receptors. This study describes a detailed analysis of the distribution of HLA-specific IgG subclasses in order to define how this varies in sensitised waiting-list patients. We found significant variation in the level, presence and combinations of each HLA-specific IgG subclass between and within individuals and this is influenced by the type of sensitising event. Graft failure in particular provokes higher levels of IgG1 (vs transfusion, p = 0.071 and pregnancy, p = 0.042), IgG2 (vs transfusion, p = 0.001 and pregnancy, p = 0.016), and IgG4 (vs transfusion, p = 0.052). Both graft failure and pregnancy tend to stimulate multiple IgG subclass responses against HLA, whereas transfusion stimulated antibodies are dominated by responses limited to IgG1 (p = 0.033) and have a low incidence of IgG4 (p = 0.046). In marked contrast, IgG4 characterised nearly all HLA DQ-specific antibodies stimulated by graft rejection (p = 0.006). Such widely varying IgG subclass heterogeneity is likely to be due to underlying immunological processes dependent on the route of sensitisation. This diversity, which implies functional variation, may help explain why HLA-specific antibodies are an obstacle to transplantation in some circumstances but not others. The subclass association with rejection has potential as a biomarker for chronic rejection.     

Heart rate variability and treatment outcome in major depression: A pilot study

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N = 26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N = 16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R² > .43 and p < 0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker.