Weaning and depression: a closer look.

The association of weaning with depression has long been recognized. However, interest in the study of post-weaning depression has waned over the last few decades partly due to changes in the nosology of perinatal psychiatric disorders. In this paper, we review the relevant literature and conclude that post-weaning depression is a rare but severe complication of breastfeeding cessation. Given that post-weaning depression is an understudied and often undiagnosed clinical condition, research is needed to address this important unmet need.

Occurrence of postpartum manic or mixed episodes in women with bipolar I disorder: A systematic review and meta-analysis.

OBJECTIVE: Accurate information on the frequency and prevalence of manic or mixed episodes is important for therapeutic, prognostic, and safety concerns. We aimed to estimate the risk of relapse of manic and mixed episodes after delivery in women with bipolar I disorder or schizoaffective disorder-bipolar type. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search in PubMed, PsycINFO, Embase, and Cochrane databases was carried out on November 17, 2022, using the terms ((bipolar disorder) OR (manic depressive illness)) AND (mania)) AND (postpartum)) AND (recurrence)) AND (relapse). The search was updated on March 29, 2023. Case studies and qualitative analyses were excluded. Twelve studies reporting on 3595 deliveries in 2183 women were included in the quantitative analysis. RESULTS: The overall pooled estimate of postpartum relapse risk was 39% (95% CI = 29, 49; Q(11) = 211.08, p < 0.001; I2 = 96.31%). Among those who had a relapse, the pooled estimate of risk for manic and mixed episodes was 38% (95% CI = 28, 50; Q(11) = 101.17, p < 0.001; I2 = 91.06%). Using data from the nine studies that reported the percentage of medication use during pregnancy, we estimated a meta-regression model with the percent medication use as a continuous explanatory variable. The estimated prevalence of relapse was 58.1% (95% CI, 9.6 to 39.3 to 76.8) for studies with no medication use and 25.9% (95% CI, 10.5-41.3) for studies with 100% medication use. The difference between the two prevalence estimates was statistically significant, z = -2.099, p = 0.0359. CONCLUSIONS: Our findings suggest an overall pooled estimate of postpartum relapse risk of 39%, while the pooled estimate of risk for manic and mixed episodes was 38%. These findings highlight the need to educate patients with bipolar I disorder, and their healthcare professionals about the high risk of relapse of manic or mixed episodes after delivery.

The impact of 6 months of exercise-based cardiac rehabilitation on sympathetic neural recruitment during apneic stress.

The current study evaluated the hypothesis that 6 mo of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in 11 patients with IHD (1 female; 61 ± 9 yr) pre (pre-CR) and post (post-CR) 6 mo of aerobic and resistance training-based CR. Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1 min of baseline and the second half of apneas. At baseline, overall sympathetic activity was less post-CR (all P < 0.01). During EI-APN, AP recruitment was not observed pre-CR (all P > 0.05), but increases in both within-burst AP firing frequency (Δpre-CR: 2 ± 3 AP spikes/burst vs. Δpost-CR: 4 ± 3 AP spikes/burst; P = 0.02) and AP cluster recruitment (Δpre-CR: -1 ± 2 vs. Δpost-CR: 2 ± 2; P < 0.01) were observed in post-CR tests. In contrast, during EE-APN, AP firing frequency was not different post-CR compared with pre-CR tests (Δpre-CR: 269 ± 202 spikes/min vs. Δpost-CR: 232 ± 225 spikes/min; P = 0.54), and CR did not modify the recruitment of new AP clusters (Δpre-CR: -1 ± 3 vs. Δpost-CR: 0 ± 1; P = 0.39), or within-burst firing frequency (Δpre-CR: 3 ± 3 AP spikes/burst vs. Δpost-CR: 2 ± 2 AP spikes/burst; P = 0.21). These data indicate that CR improves some of the sympathetic nervous system dysregulation associated with cardiovascular disease, primarily via a reduction in resting sympathetic activation. However, the benefits of CR on sympathetic neural recruitment may depend upon the magnitude of initial impairment.

Inflight leg cuff test does not identify the risk for orthostatic hypotension after long-duration spaceflight.

Landing day symptoms from orthostatic hypotension after prolonged spaceflight can be debilitating, but severity of these symptoms can be unpredictable and highly individual. We tested the hypothesis that an impaired baroreflex response to an inflight leg cuff test could predict orthostatic intolerance on return to Earth. Eight male astronauts (44 ± 7 years of age (mean ± SD); mean mission length: 167 ± 12 days) participated in a standardized supine-to-sit-to-stand test (5 min-30s-3 min) pre- and postflight, and a 3 min thigh cuff occlusion test pre- and inflight with continuous monitoring of heart rate and arterial blood pressure. The arterial baroreflex was not changed inflight as shown by similar reductions in mean arterial pressure (MAP) response to leg cuff deflation (preflight -19 ± 2 mmHg vs. inflight -18 ± 5 mmHg). With the sit/stand test, the nadir of MAP was lower postflight (-17 ± 9 mmHg) than preflight (-11 ± 6 mmHg, p < 0.05). A greater increase in heart rate (25 ± 7; 16 ± 3 bpm) and decrease in stroke volume (-24 ± 11; -6 ± 4 mL) occurred with sit/stand postflight than leg cuffs inflight (p < 0.001). Inflight testing was influenced by elevated cardiac output resulting in a smaller drop in total peripheral resistance. Two of eight subjects exhibited orthostatic hypotension during the postflight stand test; their responses were not predicted by the inflight leg cuff deflation test. These results suggest that the baroreflex response examined by inflight leg cuff deflation was not a reliable indicator of postflight stand responses.

Interrelationships between pulse arrival time and arterial blood pressure during postural transitions before and after spaceflight.

We tested the hypothesis that acute changes in arterial blood pressure (BP) when astronauts moved between supine and standing posture before and after spaceflight can be tracked by beat-to-beat changes in pulse arrival time (PAT). Nine male crewmembers (45 ± 7 yr of age; mean mission length: 165 ± 13 days) participated in a standardized supine-to-sit-to-stand test (5 min-30 s-3 min) before flight and 1 day following return to Earth with continuous monitoring of ECG and finger arterial BP. PAT was determined from the R-wave of the ECG to the foot of the BP waveform. On average, modest cardiovascular deconditioning was detected by ~10 beats/min increase in heart rate in supine and standing posture after spaceflight (P < 0.05). When looking across the full data collection period, the r2 values between inverse of PAT (1/PAT) and systolic (SBP) and diastolic BP (DBP) varied considerably between individuals (SBP preflight 0.142 ± 0.186, postflight 0.262 ± 0.243). Individual variability was consistent during periods of transition (SBP preflight 0.284 ± 0.324, postflight 0.297 ± 0.269); however, when SBP dropped >20 mmHg, r2 was significant in 5 of 5 preflight tests and 5 of 7 postflight tests. The standard error of the estimate based on a simple linear model during both pre- and postflight testing was 9-11 mmHg for SBP and 6-7 mmHg for DBP. Overall, the results support the hypothesis that PAT tracked dynamic changes in BP. PAT as a noninvasive, nonintrusive surrogate for changes in BP could be developed as an indicator of risk for syncope on return from spaceflight or other Earth-based applications.NEW & NOTEWORTHY Astronauts returning to Earth's gravity are at increased risk of low blood pressure on standing. Arterial pulse arrival time tracked the decrease in arterial blood pressure on moving from supine to upright posture. Nonintrusive technology providing indicators sensitive to acute changes in blood pressure could act as an early warning system to identify risk for hypotension that place astronauts, or people on Earth, at risk of impaired cognitive performance, fainting, and falls.

Effects of 6 Months of Exercise-Based Cardiac Rehabilitation on Autonomic Function and Neuro-Cardiovascular Stress Reactivity in Coronary Artery Disease Patients.

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro-cardiovascular reactivity during short-duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P<0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P<0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P<0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P<0.01). Heart rate variability (all P>0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre-CR from CTRL (all P>0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P<0.05); yet, responses were reduced following CR (all P<0.05) to levels observed in CTRL. Conclusions Six months of exercise-based CR was associated with marked improvement in baseline autonomic function and neuro-cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training.

Regional cerebral cortical thickness correlates with autonomic outflow.

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known. This study tested the hypothesis that inter-individual differences in autonomic outflow across the adult age-span are related to cerebral cortex thickness. A total of 55 healthy, active individuals participated in this study (21-73years; 18 female). Physical fitness was treated as a possible covariate (VO2peak: 26-81mL/kg/min). Cardiovagal baroreflex sensitivity, heart rate variability, and muscle sympathetic nerve activity (MSNA) were assessed during a laboratory session. T1-weighted images acquired at 3T facilitated measures of cortical thickness (Brain Voyager 2.8.4). A priori cortical regions of interest included the medial prefrontal cortex (MPFC) and insula cortex. Cortical thickness at the MPFC correlated strongly with markers of autonomic outflow including heart rate variability (ln-high frequency power (slope: -16, r2=0.65), SDNN (slope: 22, r2=0.22), total power (slope: 2872, r2=0.24)), and MSNA variables (burst frequency (slope: 1, r2=0.16), burst incidence (slope: -26, r2=0.62) and total MSNA (slope: -847, r2=0.56)). Further associations with burst incidence were observed within the left insula (p<0.05). Importantly, the strength of the relationship between autonomic variables and cortical thickness was determined by age, and was not altered following adjustments for cardiorespiratory fitness. The current results implicate cortical atrophy in the frontal lobe as a contributor to both the sympathetic and parasympathetic changes that occur with age.

High cardiorespiratory fitness in early to late middle age preserves the cortical circuitry associated with brain-heart integration during volitional exercise.

This study tested the hypothesis that high cardiorespiratory fitness (peak oxygen uptake) preserves the cortical circuitry associated with cardiac arousal during exercise in middle- to older-aged individuals. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 52 healthy, active individuals (45-73 yr; 16 women, 36 men) across a range of fitness (26-66 ml·kg-1·min-1). Seven repeated bouts of isometric handgrip (IHG) at 40% maximal voluntary contraction force were performed with functional magnetic resonance imaging at 3 T, with each contraction lasting 20 s and separated by 40 s of rest. HR responses to IHG showed high variability across individuals. Linear regression revealed that cardiorespiratory fitness was not a strong predictor of the HR response (r2 = 0.09). In a region-of-interest analysis both the IHG task and the HR time course correlated with increased cortical activation in the bilateral insula and decreased activation relative to baseline in the anterior and posterior cingulate and medial prefrontal cortex (MPFC). t-Test results revealed greater deactivation at the MPFC with higher fitness levels beyond that of guideline-based activity. Therefore, whereas high cardiorespiratory fitness failed to affect absolute HR responses to IHG in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal.NEW & NOTEWORTHY Our first observation suggests that fitness does not strongly predict the heart rate (HR) response to a volitional handgrip task in middle- to older-aged adults. Second, the BOLD response associated with the handgrip task, and with the HR time course, was associated with response patterns in the cortical autonomic network. Finally, whereas high cardiorespiratory fitness failed to affect absolute HR responses to isometric handgrip in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal, beyond that achieved through healthy active living.

Impact of Long-Term Endurance Training vs. Guideline-Based Physical Activity on Brain Structure in Healthy Aging.

Brain structure is a fundamental determinant of brain function, both of which decline with age in the adult. Whereas short-term exercise improves brain size in older adults, the impact of endurance training on brain structure when initiated early and sustained throughout life, remains unknown. We tested the hypothesis that long-term competitive aerobic training enhances cortical and subcortical mass compared to middle to older-aged healthy adults who adhere to the minimum physical activity guidelines. Observations were made in 16 masters athletes (MA; 53 ± 6 years, VO2max = 55 ± 10 ml/kg/min, training > 15 years), and 16 active, healthy, and cognitively intact subjects (HA; 58 ± 9 years, VO2max = 38 ± 7 ml/kg/min). T1-weighted structural acquisition at 3T enabled quantification of cortical thickness and subcortical gray and white matter volumes. Cardiorespiratory fitness correlated strongly with whole-brain cortical thickness. Subcortical volumetric mass at the lateral ventricles, R hippocampus, R amygdala, and anterior cingulate cortex, correlated with age but not fitness. In a region-of-interest (ROI) group-based analysis, MA expressed greater cortical thickness in the medial prefrontal cortex, pre and postcentral gyri, and insula. There was no effect of group on the rate of age-related cortical or subcortical decline. The current data suggest that lifelong endurance training that produces high levels of cardiorespiratory fitness, builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span. This reserve likely has important implications for neurological health later in life.