Sarah M. Conklin

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 <or= 0.05). These associations were generally linear. Associations between DHA and nonverbal reasoning and working memory persisted with additional adjustment for participant education and vocabulary scores (P <or= 0.05). Neither EPA nor ALA was notably related to any of the 5 tested dimensions of cognitive performance. Among the 3 key (n-3) PUFA, only DHA is associated with major aspects of cognitive performance in nonpatient adults <55 y old. These findings suggest that DHA is related to brain health throughout the lifespan and may have implications for clinical trials of neuropsychiatric disorders.

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.

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 (β = -0.121, P = 0.03), awake ambulatory diastolic BP (β = -0.164, P = 0.004), and 24-h diastolic BP (β = -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.

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.

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.

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.

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 Alzheimers 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.

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.

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.

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

ABSTRACT 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.