The association of depression and anxiety with cardiac autonomic activity:The role of confounding effects of antidepressants

Background: Depression and anxiety may unfavorably impact on cardiac autonomic dysregulation. However, it is unclear whether this relationship results from a causal effect or may be attributable to confounding factors. We tested the relationship between depression and anxiety with heart rate (HR) and heart rate variability (HRV) across a 9-year follow-up (FU) period and investigated possible confounding by antidepressant use and genetic pleiotropy. Methods: Data (no. of observations = 6,994, 65% female) were obtained from the longitudinal Netherlands Study of Depression and Anxiety, with repeated waves of data collection of HR, HRV, depression, anxiety, and antidepressant use. Summary statistics from meta-analyses of genome-wide association studies were used to derive polygenic risk scores of depression, HR, and HRV. Results: Across the 9-year FU, generalized estimating equations analyses showed that the relationship between cardiac autonomic dysregulation and depression/anxiety rendered nonsignificant after adjusting for antidepressant use. A robust association was found between antidepressant use (especially tricyclic antidepressants, selective serotonin, and noradrenalin reuptake inhibitors) and unfavorable cardiac autonomic activity across all waves. However, no evidence was found for a genetic correlation of depression with HR and HRV, indicating that confounding by genetic pleiotropy is minimal. Conclusions: Our results indicate that the association between depression/anxiety and cardiac autonomic dysregulation does not result from a causal pathway or genetic pleiotropy, and these traits might therefore not be inevitably linked. Previously reported associations were likely confounded by the use of certain classes of antidepressants

ATPase Subdomain IA Is a Mediator of Interdomain Allostery in Hsp70 Molecular Chaperones

The versatile functions of the heat shock protein 70 (Hsp70) family of molecular chaperones rely on allosteric interactions between their nucleotide-binding and substrate-binding domains, NBD and SBD. Understanding the mechanism of interdomain allostery is essential to rational design of Hsp70 modulators. Yet, despite significant progress in recent years, how the two Hsp70 domains regulate each other's activity remains elusive. Covariance data from experiments and computations emerged in recent years as valuable sources of information towards gaining insights into the molecular events that mediate allostery. In the present study, conservation and covariance properties derived from both sequence and structural dynamics data are integrated with results from Perturbation Response Scanning and in vivo functional assays, so as to establish the dynamical basis of interdomain signal transduction in Hsp70s. Our study highlights the critical roles of SBD residues D481 and T417 in mediating the coupled motions of the two domains, as well as that of G506 in enabling the movements of the α-helical lid with respect to the β-sandwich. It also draws attention to the distinctive role of the NBD subdomains: Subdomain IA acts as a key mediator of signal transduction between the ATP- and substrate-binding sites, this function being achieved by a cascade of interactions predominantly involving conserved residues such as V139, D148, R167 and K155. Subdomain IIA, on the other hand, is distinguished by strong coevolutionary signals (with the SBD) exhibited by a series of residues (D211, E217, L219, T383) implicated in DnaJ recognition. The occurrence of coevolving residues at the DnaJ recognition region parallels the behavior recently observed at the nucleotide-exchange-factor recognition region of subdomain IIB. These findings suggest that Hsp70 tends to adapt to co-chaperone recognition and activity via coevolving residues, whereas interdomain allostery, critical to chaperoning, is robustly enabled by conserved interactions. © 2014 General et al

Psychometric properties of the Mandarin version of the Childhood Autism Spectrum Test (CAST):an exploratory study

Limited studies have investigated the latent autistic traits in the mainland Chinese population for autism spectrum conditions (ASC). This study explored the psychometric properties of a Mandarin Chinese version of the CAST in a sample consisting of 737 children in mainstream schools and 50 autistic cases. A combination of categorical data factor analysis and item response theory suggested a good-fit model of a two-factor solution for 28 items on the Mandarin CAST including social and communication, and inflexible/stereotyped language and behaviours (Goodness-of-fit indices: RMSEA = 0.029, CFI = 0.957, TLI = 0.950, SRMR = 0.064). The correlation between the two factors was moderate (GFC = 0.425). This study provided evidence for the CAST as a multidimensional measure for ASC screening in a Chinese population and also showed that the symptom manifestation of ASC in Chinese children shares similarity with western populations. © 2014 Springer Science+Business Media

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Cortical thickness and resting-state cardiac function across the lifespan: a cross-sectional pooled mega analysis

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS – or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between cortical thickness and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research

Association between depression, anxiety, and antidepressant use with T-Wave amplitude and QT-interval

Objectives: Cardiac repolarization may be affected by psychiatric disorders and/or antidepressant use, but evidence for this is inconclusive. This study examined the relationship between depressive and anxiety disorder and use of antidepressants with T-wave amplitude (TWA) and QT-interval. Methods: Data was obtained from the Netherlands Study of Depression and Anxiety (n = 1,383). Depression/anxiety was diagnosed with the DSM-IV based Composite International Diagnostic Interview. The use of tricyclic antidepressants (TCAs), selective serotonin and noradrenalin reuptake inhibitors (SNRIs), and selective serotonin reuptake inhibitors (SSRIs) was established. T-wave amplitude and QT-interval corrected for heart rate (QTc) were obtained from an ECG measured in a type II axis configuration. Results: Compared to controls, persons with depression or anxiety disorders did not show a significantly different TWA (p = 0.58; Cohen's d = 0.046) or QTc (p = 0.48; Cohen's d = -0.057). In spite of known sympathomimetic effects, TCA use (p = 0.26; Cohen's d = -0.162) and SNRI use (p = 0.70; Cohen's d = -0.055) were not significantly associated with a lower TWA. TCA use (p = 0.12; Cohen's d = 0.225) and SNRI use (p = 0.11; Cohen's d = 0.227) were also not significantly associated with a prolonged QTc. Conclusion: We did not find evidence that either depressive/anxiety disorder or antidepressant use is associated with abnormalities in TWA or QTc. Earlier found sympathomimetic effects of TCAs and SNRIs are not evident in these measures of cardiac repolarization

Differential Autonomic Nervous System Reactivity in Depression and Anxiety During Stress Depending on Type of Stressor

Objectives It remains unclear whether depressive and anxiety disorders are associated with hyporeactivity or hyperreactivity of the autonomic nervous system (ANS) and whether deviant reactivity occurs in all types of stressors. This study compared ANS reactivity in people with current or remitted depression/anxiety with reactivity in healthy controls during two stress conditions. Methods From the Netherlands Study of Depression and Anxiety, data of 804 individuals with current depression/anxiety, 913 individuals with remitted depression/anxiety, and 466 healthy controls (mean age = 44.1 years; 66.4% female) were available. Two conditions were used to evoke stress: a) an n-back task, a cognitively challenging stressor, and 2) a psychiatric interview, evoking personal-emotional stress related to the occurrence of symptoms of depression/anxiety. Indicators of ANS activity were heart rate (HR), root mean square of differences between successive interbeat intervals (RMSSD), respiratory sinus arrhythmia (RSA), and preejection period. Results As compared with controls, participants with psychopathology had significant hyporeactivity of HR (controls = 4.1 ± 4.2 beats/min; remitted = 3.5 ± 3.5 beats/min; current psychopathology = 3.1 ± 3.4 beats/min), RMSSD (controls = −6.2 ± 14.5 milliseconds; remitted = −5.4 ± 17.8 milliseconds; current psychopathology = −3.5 ± 15.4 milliseconds), and RSA (controls = −9.3 ± 17.0 milliseconds; remitted = −7.4 ± 16.5 milliseconds; current psychopathology = −6.9 ± 15.0 milliseconds) during the n-back task. In contrast, during the psychiatric interview, they showed significant hyperreactivity of HR (controls = 2.7 ± 3.4 beats/min; remitted = 3.5 ± 3.4 beats/min; current psychopathology = 4.0 ± 3.3 beats/min), RMSSD (controls = −3.4 ± 12.2 milliseconds; remitted = −4.1 ± 12.1 milliseconds; current psychopathology = −5.6 ± 11.8 milliseconds), and RSA (controls = −3.8 ± 8.1 milliseconds; remitted = −4.3 ± 7.9 milliseconds; current psychopathology = −5.0 ± 7.9 milliseconds). The lack of group differences in preejection period reactivity suggests that the found effects were driven by altered cardiac vagal reactivity in depression/anxiety. Conclusions The direction of altered ANS reactivity in depressed/anxious patients is dependent on the type of stressor, and only the more ecologically valid stressors may evoke hyperreactivity in these patients

Basal autonomic activity, stress reactivity, and increases in metabolic syndrome components over time

Context Basal autonomic nervous system (ANS) functioning has been linked to the metabolic syndrome (MetS), but the role of ANS reactivity in response to stress remains unclear. Objective To examine cross-sectionally and longitudinally to what extent ANS basal level and stress reactivity are related to MetS. Design 2-year and 6-year data from a prospective cohort: the Netherlands Study of Depression and Anxiety. Setting Participants were recruited from the general community, primary care, and mental health care organizations. Participants 1922 respondents (mean age = 43.7 years). Main outcome measures Indicators of ANS functioning were heart rate (HR), respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP). ANS stress reactivity was measured during a cognitively challenging stressor and a personal-emotional stressor. MetS components included triglycerides, high-density lipoprotein cholesterol, blood pressure, glucose and waist circumference. Results Cross-sectional analyses indicated that higher basal HR, lower basal values of RSA and PEP, and higher RSA reactivity during cognitive challenge were related to less favorable values of almost all individual MetS components. Longitudinal analyses showed that higher basal HR and shorter basal PEP predicted 4-year increase in many MetS abnormalities. Higher RSA stress reactivity during cognitive challenge predicted 4-year increase in number of MetS components. Conclusion Higher basal sympathetic, lower basal parasympathetic activity, and increased parasympathetic withdrawal during stress are associated with multiple MetS components, and higher basal sympathetic activity predicts an increase in metabolic abnormalities over time. These findings support a role for ANS dysregulation in the risk for MetS and, consequently, the development of cardiovascular disease

Exercise interventions for the prevention of depression: a systematic review of meta-analyses

BACKGROUND: Exercise may be a promising target for depression interventions. However, evidence for a beneficial effect of exercise interventions on the prevention of depression differs substantially across different studies. METHODS: A systematic search was performed up to July 2018 using PubMed, Embase, PsycINFO, and Cochrane. Articles were included if a meta-analysis of randomized controlled trials was performed that examined the effect of exercise interventions on the onset of depression or depressive symptoms in the general population. Meta-analyses focusing on treatment of diagnosed depression were excluded. Two authors independently screened the articles and graded the quality of included meta-analyses using AMSTAR 2. RESULTS: Eight meta-analyses were included that showed little overlap in 134 included studies. All meta-analyses reported on depressive symptoms rather than onset of depression. Five of these were rated as moderate quality and three of low quality. Six meta-analyses found significant effects, and two found non-significant effects of exercise interventions in reducing depressive symptoms in children, adolescents, adults and the elderly (effect sizes ranging from - 0.10 to - 0.81). Scarce evidence did not allow to draw conclusions about the role of sex and characteristics of exercise on depression. However, some findings suggest that low intensity exercise was as effective as high intensity exercise. Heterogeneity among primary studies was high, likely caused by differences in study quality and exercise characteristics. CONCLUSIONS: The evidence from this study suggests that exercise interventions have a beneficial effect on depressive symptoms in the general population across a wide age-range