Influence of Acute Multispecies and Multistrain Probiotic Supplementation on Cardiovascular Function and Reactivity to Psychological Stress in Young Adults: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: The potential influence of probiotic supplementation on cardiovascular health and stress responsivity remains largely unexplored. Some evidence suggests the possibility that probiotics may influence blood pressure. A separate body of research suggests that exaggerated cardiovascular reactions to acute psychological stress in the laboratory predict cardiovascular morbidity and mortality. The current investigation explored the effect of acute probiotic use on (1) resting cardiovascular measures in healthy young adults and (2) cardiovascular and psychological reactions to an acute psychological stressor in the laboratory. METHOD: Participants (N = 105, M [SD] age = 20.17 [1.26], 84.8% white) completed a 2-week, double-blind, and placebo-controlled trial of a multispecies and multistrain probiotic. Exclusion criteria included previous probiotic use, diagnosed gastrointestinal disorder, and/or current antibiotic use. At visits 1 and 2, participants completed the Paced Auditory Serial Addition Test, a widely used psychological stress task. Participants were randomly assigned to a probiotic blend or matched placebo. RESULTS: Compared with placebo, 2-week probiotic supplementation did not affect resting measures of cardiovascular function, cardiovascular responses during or recovery from stress, or psychological reactions to acute psychological stress. CONCLUSIONS: Contrary to expectations, short-term use of a probiotic supplement in healthy participants did not influence measures of cardiovascular function or responsivity to psychological stress. Future research is needed to determine species- and strain-specific effects of probiotics in healthy participants with various degrees of stress responsiveness, as well as in diseased populations.

Concurrent physical activity modifies the association between n3 long-chain fatty acids and cardiometabolic risk in midlife adults.

Greater consumption of n3 (ω3) polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce risk for cardiovascular disease events, yet their effects on metabolic risk factors and diabetes remain unclear. This cross-sectional study used a community volunteer sample to test whether the associations between n3 fatty acids and cardiometabolic risk vary as a function of physical activity. Participants were 344 generally healthy adults, 30-54 y of age, not taking fish oil supplements or confounding medications. Serum phospholipid EPA and DHA were used together (EPA+DHA) as a biomarker of n3 fatty acid exposure. Cardiometabolic risk was calculated as a continuous measure based on standardized distributions of blood pressure, waist circumference, HDL cholesterol, triglycerides, glucose, and a simple count of risk factors. Insulin resistance was estimated from the homeostatic model assessment. Physical activity was found to predict cardiometabolic risk (P ≤ 0.02) and insulin resistance (P ≤ 0.02) and to moderate the association between EPA+DHA and both cardiometabolic risk (P-interaction ≤ 0.02) and insulin resistance (P-interaction ≤ 0.02). Specifically, higher EPA+DHA was associated with lower cardiometabolic risk and insulin resistance in persons engaged in regular physical activity but not in relatively inactive individuals. These findings were noted in several components of cardiometabolic risk, in men and women separately, and in models adjusted for overall diet quality. In midlife adults, habitual physical activity may be necessary to unmask the salutary effects of n3 fatty acids on cardiometabolic risk and insulin resistance.

Daytime sleep accelerates cardiovascular recovery after psychological stress.

BACKGROUND: Sleep restriction and poor sleep quality is linked with cardiovascular morbidity. PURPOSE: The present study aimed to explore the influence of daytime sleep supplementation on cardiovascular reactivity. METHOD: Participants (N = 85) were generally healthy young adults and were randomized to a 60-min polysomnographically-monitored sleep condition or to a no-sleep condition. Participants then completed a standard three-phase mental stress reactivity task. RESULTS: Significantly lower mean arterial pressure means were found in the recovery phase of the stress reactivity task among participants that accrued more than 45 min of daytime sleep. CONCLUSION: These findings suggest daytime sleep may offer cardiovascular benefit in the form of greater cardiovascular recovery from psychological stress. Further research should assess daytime sleep characteristics (time of day, length, and architecture) on cardiovascular response, in an effort to better understand its role as a possible recuperative agent against suboptimal nocturnal sleep patterns.

Serum phospholipid docosahexaenonic acid is associated with cognitive functioning during middle adulthood.

Existing evidence links greater dietary intake of fish and (n-3) PUFA to better early brain development and lowered risk of cognitive disorders in late life. The mechanisms for these associations remain unclear and may be related to specific (n-3) fatty acids and may concern cognitive function generally rather than only early brain development and age-related cognitive dysfunction. In this investigation, we tested potential associations between (n-3) fatty acids in serum phospholipids and major dimensions of cognitive functioning in mid-life adults. Participants were 280 community volunteers between 35 and 54 y of age, free of major neuropsychiatric disorders, and not taking fish oil supplements. Dietary biomarkers were alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenonic acid (DHA) in serum phospholipids measured using GC. Five major dimensions of cognitive functioning were assessed with a 75-min battery of neuropsychological tests. In covariate adjusted regression models, higher DHA (mol %) was related to better performance on tests of nonverbal reasoning and mental flexibility, working memory, and vocabulary (P

Acute intake of B. longum probiotic does not reduce stress, anxiety, or depression in young adults: A pilot study.

BACKGROUND: The gut microbiome communicates bidirectionally with the brain, linking the gut to psychological phenomena such as stress, depression, and anxiety. Probiotics, or ingestible supplements containing billions of mutualistic bacteria, have demonstrated the mechanistic potential to influence mood; however, few studies have experimentally examined the acute effects of these compounds on individuals not recruited for psychopathology or gut dysfunction. The present study hypothesized reductions in stress, anxiety and depression symptoms following an acute, one week dosing period of B. longum intake. METHODS: The efficacy of a one-week period of orally administered B. longum was tested utilizing a double-blind experimental design. Participants were randomly assigned to either placebo or probiotic capsules under double blinded conditions and completed the Perceived Stress Scale (PSS), the Center for Epidemiological Studies Depression scale (CES-D), and the State-Trait Anxiety Inventory (STAI Y2 form) to assess for differences before and after one-week intervention. RESULTS: No significant reduction in symptoms between groups over the one-week period was found. CONCLUSIONS: These findings suggest that 7-days of B. longum does not reduce stress, depressive symptoms, or anxiety in generally healthy young adults.

Premeditated aggression is associated with serum cholesterol in abstinent drug and alcohol dependent men.

Relationships between aggressive subtypes and lipids were explored in 18 adult males undergoing treatment for substance dependence. A positive association was observed between a measure of premeditated aggression and total cholesterol. This was in contrast to an inverse association between lower cholesterol and higher impulsivity and anxiety.

High omega-6 and low omega-3 fatty acids are associated with depressive symptoms and neuroticism.

OBJECTIVE: To examine the concentrations of omega-3 and omega-6 polyunsaturated fatty acids in serum obtained from nonpatient community volunteers not selected for hypercholesterolemia. Previously we reported that the relative concentrations of omega-3 and omega-6 polyunsaturated fatty acids in serum covary with depressive symptomatology and neuroticism in hypercholesterolemic adults. METHODS: A total of 116 adults without current Axis I psychopathology completed the Beck Depression Inventory (BDI) and the NEO Personality Inventory--Revised (NEO-PI-R). Fasting serum phospholipid eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic acid (AA) were determined (% of total pool). RESULTS: Higher AA and AA:EPA ratio, adjusted for age, gender, and race, were associated with greater depressive symptomatology (BDI score of >or=10). Lower EPA, and higher AA, AA:EPA ratio and AA:DHA ratio were associated with greater NEO-PI-R Neuroticism. The six Neuroticism subscales were each associated with two or more fatty acid measurements. CONCLUSIONS: In conjunction with other reports, these findings suggest that the omega-3 and omega-6 fatty acids are related to negative affect at both the symptom and trait levels.

Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults.

BACKGROUND: In animals, dendritic arborization and levels of brain derived neurotrophic factor are positively associated with intake of the omega-3 fatty acids. Here, we test whether omega-3 fatty acid intake in humans varies with individual differences in gray matter volume, an in vivo, systems-level index of neuronal integrity. METHODS: Fifty-five healthy adults completed two 24h dietary recall interviews. Intake of long-chain omega-3 fatty acids was categorized by tertiles. Regional gray matter volumes in a putative emotional brain circuitry comprised of the anterior cingulate cortex (ACC), amygdala and hippocampus were calculated using optimized voxel-based morphometry on high-resolution structural magnetic resonance images. RESULTS: Region of interest analyses revealed positive associations between reported dietary omega-3 intake and gray matter volume in the subgenual ACC, the right hippocampus and the right amygdala, adjusted for total gray matter volume of brain. Unconstrained whole-brain analyses confirmed that higher intake of omega-3 fatty acids was selectively associated with increased greater gray matter volume in these and not other regions. CONCLUSIONS: Higher reported consumption of the long-chain omega-3 fatty acids is associated with greater gray matter volume in nodes of a corticolimbic circuitry supporting emotional arousal and regulation. Such associations may mediate previously observed effects of omega-3 fatty acids on memory, mood and affect regulation.

Serum omega-3 fatty acids are associated with variation in mood, personality and behavior in hypercholesterolemic community volunteers.

Low dietary intake of omega-3 polyunsaturated fatty acids has been linked to several features of psychiatric symptomatology, including depression, disorders of impulse control, and hostility. Preliminary intervention trials of omega-3 fatty acid supplementation for clinical depression and other disorders have reported benefit. However, few studies have investigated the relationships between these fatty acids and normative variability in mood, behavior and personality. Participants were 105 hypercholesterolemic, but otherwise healthy, non-smoking adults. Fasting serum alpha-linolenic (alpha-LNA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) were assayed with gas chromatography. Participants completed the Beck Depression Inventory (BDI), the NEO Five Factor Personality Inventory (NEO-FFI) and the Barratt Impulsiveness Scale (BIS). In multivariate analyses, higher levels of the long chain omega-3 PUFAs, EPA and DHA, were associated with significantly reduced odds of scoring >or=10 on the BDI. Similarly, DHA and EPA covaried inversely with NEO-Neuroticism scores, whereas DHA was positively associated with NEO-Agreeableness. On the BIS, DHA was inversely related to cognitive impulsivity and alpha-LNA was inversely related to motor and total impulsivity. These findings suggest that omega-3 fatty acid status is associated with variability in affect regulation, personality and impulse control.

Cardiovascular reactions to psychological stress and abuse history: the role of occurrence, frequency, and type of abuse.

BACKGROUND AND OBJECTIVES: Extreme cardiovascular reactions to psychological stress have been associated with traumatic life experiences. Previous studies have focused on the occurrence or frequency of abuse rather than type of abuse. We examined how occurrence, frequency, and the type of abuse history are related to cardiovascular reactivity (CVR) to acute psychological stress. DESIGN: The study consisted of between group and continuous analyses to examine the association between occurrence, type, and frequency of abuse with cardiovascular reactions to acute psychological stress. METHODS: Data from 64 participants were collected. Heart rate, systolic blood pressure, and diastolic blood pressure were measured at baseline and during a standard mental arithmetic stress task. RESULTS: Individuals who experienced abuse showed diminished CVR to acute psychological stress; this was driven specifically by the history of sexual abuse. Frequency of abuse did not relate to stress reactions. CONCLUSIONS: These findings accord with previous work suggesting a relationship between traumatic life experience and hypoarousal in physiological reactivity and extend previous findings by suggesting the relationship may be driven by sexual abuse.

A comparison of anticonvulsants in the treatment of impulsive aggression.

This study compared the behavioral effects of 3 anticonvulsants in impulsive aggressive men. In a double-blind, placebo-controlled, parallel groups design, participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n = 7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy measure was the average aggression score, a global severity index from the Overt Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a significant reduction in impulsive aggression during all 3 anticonvulsant conditions compared with placebo. However, the treatment effect during carbamazepine administration was slightly delayed compared with phenytoin and valproate. These findings suggest that increased use of anticonvulsants could make a significant impact in the control of impulsive aggression in both mental health and criminal justice settings.

Short-term supplementation of acute long-chain omega-3 polyunsaturated fatty acids may alter depression status and decrease symptomology among young adults with depression: A preliminary randomized and placebo controlled trial.

The current study examined the psychological effects of acute and low-dose long-chain omega-3 polyunsaturated fatty acids (LCPUFAs) supplementation on young adults with depressive symptoms. Participants (N=23, M age (SD)=20.2 (1.25), 78% female), with a Beck Depression Inventory (BDI) score of greater than 10, were randomly assigned to a placebo (corn oil) or LCPUFAs group (1.4g of eicosapentaenoic and docosahexaeonic acids) and were instructed to consume the assigned capsules daily for 21-days. BDI was completed prior to supplementation and at day 21. Group differences in depression status on day 21 were analyzed using chi-square tests. After 21-days of supplementation, there was a significant difference in depression status between groups. 67% of the LCPUFAs no longer met criteria for being depressed, while only 20% in the placebo group were no longer depressed. A mixed ANOVA revealed a significant group x time interaction for BDI scores. Post-hoc analyses revealed the LCPFUAs group had a significant reduction in BDI scores over time, while the placebo group's scores did not significantly change. These findings suggest that LCPUFAs may alter depression and depressive symptomology in young adults in a relatively short amount of time.

Characterizing aggressive behavior.

In the research literature, aggressive behavior has traditionally been classified into two distinct subtypes, impulsive or premeditated. Impulsive aggression is defined as a hair-trigger aggressive response to provocation with loss of behavioral control. Premeditated aggression is defined as a planned or conscious aggressive act, not spontaneous or related to an agitated state. The present study outlines the development of a clinically useful self-report instrument, the Impulsive/Premeditated Aggression Scales (IPAS), designed to characterize aggressive behavior as predominately impulsive or predominately premeditated in nature. The IPAS showed strong reliability and validity. Analysis of the IPASscores demonstrated thepresence of two types of aggressive behavior, impulsive and premeditated, in men referred for anger problems. The aggression of most individuals in the present sample was characterized as predominately impulsive in nature (90%).

Long-chain omega-3 fatty acids and optimization of cognitive performance.

Low consumption of the omega-3 fatty acids, eicosapentaenoic and docosahexaenonic acids, is linked to delayed brain development and, in late life, increased risk for Alzheimer's disease. The current review focuses on cognitive functioning during midlife and summarizes available scientific evidence relevant to the hypothesis that adequate dietary consumption of the long-chain omega-3 fatty acids is necessary for optimal cognitive performance. Taken together, the findings suggest that raising the currently low consumption among healthy adults may improve some aspects of cognitive performance. Nonetheless, evidence from randomized clinical trials is comparatively sparse and leaves unclear: (a) whether such effects are clinically significant, (b) whether effects of eicosapentaenoic acid and DHA differ, (c) which dimensions of cognitive function are affected, (d) the dose-response relationships, or (e) the time course of the response. Clarification of these issues through both laboratory and clinical investigations is a priority given the broad implications for public health, as well as for military personnel and other positions of high performance demand and responsibility.

Is the association between depression and blunted cardiovascular stress reactions mediated by perceptions of stress?

Symptoms of depression are related to blunted cardiovascular reactions to acute stress tasks. However, it is unclear what factors might mediate this association and whether blunted responses are specific to mental stress tasks or are also evident with other forms of stress. The present study assessed cardiovascular reactivity to both mental and postural stress and the role of background stress exposure and stress perception. Undergraduate students (N=119, 81 females) were screened for depressive symptoms using the Beck Depression Inventory. Twenty-six participants with probable depression and 26 non-depressed controls underwent cardiovascular stress testing. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were measured at rest and in response to a 5min orthostatic challenge and an 8min mental arithmetic task. Stress exposure was measured using the Undergraduate Stress Questionnaire. Perceptions of general life stress were assessed using the Perceived Stress Scale (PSS) and perceptions of the stress task impact were measured using Threat Appraisal (TA). Symptoms of depression were associated with blunted HR, F(2,98)=5.26, p=.010, η(2)=.097, and SBP, F(2,98)=6.47, p=.008, η(2)=.117, reactions to the mental stress but not to postural challenge. HR reactions were mediated by PSS score, while both PSS score and TA emerged independently as mediators of SBP reactions. These results confirm a negative relationship between depressive symptoms and cardiovascular reactions to acute stress, suggest that this association may be stress task-specific, and may be mediated by perceptions of stress.

Long-chain, n-3 fatty acids and physical activity--independent and interactive associations with cardiac autonomic control.

BACKGROUND/OBJECTIVES: Intake of the marine-based, n-3 fatty acids and engagement in physical activity are inversely related to cardiac morbidity and mortality. Among putative mechanisms, both n-3 fatty acids and physical activity may act through modulation of autonomic control of the cardiovascular system. This investigation examined the independent and interactive associations of n-3 fatty acids (eicosapentaenoic and docosahexanenoic acid; EPA, DHA) and physical activity with heart rate variability (HRV). METHODS: Subjects were 259 healthy 30-54 year-old adults. Serum phospholipid fatty acid composition was employed as a biomarker of dietary n-3 fatty acid exposure. Physical activity based on the Paffenbarger questionnaire was coded as < or ≥ 2000 kcal/week. Standard time-domain (standard deviation of normal-to-normal intervals and root-mean squared of successive differences; SDNN, RMSSD) and frequency domain (high frequency and low frequency power) measures of HRV were derived from resting electrocardiographic recordings. RESULTS: In linear regression models with covariate adjustment for age, gender and race, greater n-3 fatty acid exposure was associated with greater SDNN and RMSSD, and high physical activity was associated with greater RMSSD. n-3 fatty acid exposure also predicted variation in SDNN, RMSSD, and high-frequency power in interaction with physical activity. Specifically, n-3 fatty acid exposure covaried positively with these three HRV indices only among participants expending 2000 kcal per week or more in physical activity. These latter findings were noted for DHA but not EPA. CONCLUSIONS: These results suggest that the cardiovascular benefits of n-3 fatty acid consumption may be mediated, in part, by effects on cardiac autonomic control and may be dependent upon concomitant habitual exercise.

Preliminary evidence that acute long-chain omega-3 supplementation reduces cardiovascular reactivity to mental stress: a randomized and placebo controlled trial.

OBJECTIVE: Exaggerated cardiovascular reactivity predicts cardiovascular morbidity and mortality. Some evidence suggests that omega-3 fatty acids improve cardiovascular function. The objective of this study was to examine the influence of an acute low dose of long-chain omega-3 fatty acids on young, healthy individuals. METHODS: Participants (n=34) were randomly assigned to either 21-days of omega-3 fatty acids (1.4 g EPA and DHA) or matched placebo. Cardiovascular measurements were obtained in the laboratory during baseline and during a standard mental arithmetic task, where participants were instructed to engage in serial subtractions by 17s from a four-digit number and cardiovascular reactivity to the task was calculated. RESULTS: Mean arterial pressure reactivity was significantly reduced by supplementation (F(1,32)=5. 12, p=.03, η(2)=.144) but not by placebo. CONCLUSION: Supplementation of omega-3 fatty acids may reduce cardiovascular reactivity to stress.

High perceived stress in relation to life events is associated with blunted cardiac reactivity.

The current study examined whether the perception of life stress related to cardiovascular reactivity. Participants (n = 100) completed the Perceived Stress Scale, the Undergraduate Stress Questionnaire, and undertook a standard mental arithmetic stress task. Blood pressure and pulse rate were measured at baseline, during, and following stress task exposure. Reactivity was the difference between stress and baseline cardiovascular activity. A perceived stress difference score (PSDS) was calculated by subtracting the Undergraduate Stress Questionnaire scores from the Perceived Stress Scale scores. Two groups were created: high PSDS (n = 15; PSDS at least 1SD above the mean) and low PSDS (n = 15; PSDS at least 1SD below the mean). There was a significant difference between groups in pulse rate reactivity, F(1,28) = 8.73, p = .006, η² = .24. High PSDS scores were associated with significantly lower pulse rate reactions to stress. Those who perceived their lives as more stressful than their actual stress exposures justified would appear to be characterised by blunted cardiac reactivity.

Long-chain omega-3 fatty acids and blood pressure.

BACKGROUND: High dose fish oil supplementation reduces blood pressure (BP) in hypertensive patients. The current study examines how modest variations in omega-3 fatty acid intake may affect BP in a healthy community sample. METHODS: Study participants included 265 Pittsburgh-area adults 30-54 years of age (11% black, 51% female) not taking omega-3 fatty acid supplements or antihypertensive medications. Standardized assessments of clinic and 24-h ambulatory BP, and pulse rate were obtained. Docosahexanenoic acid (DHA) and eicosapentaenoic acid (EPA) in fasting serum phospholipids were measured by capillary gas chromatography. Regression analyses controlled for age, gender, race, body mass index (BMI), self-reported sodium intake, and physical activity. RESULTS: Participants included 181(68%) normotensives, 66 (25%) prehypertensives, and 18 (7%) persons with untreated hypertension. DHA was inversely associated with clinic diastolic (ß = -0.121, P = 0.03), awake ambulatory diastolic BP (ß = -0.164, P = 0.004), and 24-h diastolic BP (ß = -0.135, P = 0.02). A two standard deviation greater DHA was associated with 2.1 mm Hg lower clinic and 2.3 mm Hg lower awake ambulatory diastolic BP. In addition, DHA was inversely associated with pulse rate measured at rest in the clinic. EPA was related to clinic pulse rate but not clinic or ambulatory BP. CONCLUSION: In this sample of American adults not on antihypertensive medications, a modest, inverse association was found between DHA exposure and both clinic and ambulatory diastolic BP. Therefore, increasing DHA consumption through diet modification rather than large dose supplementation represents a candidate strategy for future studies of hypertension prevention.

Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder.

Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression. Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n=12), and in a control group without lifetime history of psychiatric diagnosis (n=14). Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the ratio of 20:4(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n-3) was found in patients, but not in controls. Taken together, decreases in 22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n-3), which is derived from 20:4(n-3) through a Delta5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for depression. Future research should further investigate these relationships.