Psychological and bioclinical CHD risk factors. quantitative differences between obese, normal and thin subjects

The etiological role played in coronary heart disease could be clarified further by taking into account the various components and modes of expression of anxiety or depression, which are specifically associated with different degrees of relative weight. To test this hypothesis, psychological and bioclinical differences are evaluated, before and after age 45, between obese, normal and thin subjects of an occupational sample. All 1,694 male subjects volunteered to a CHD screening test. The variables considered are anxiety and depression self-ratings, response style to the anxiety scale, blood pressure, serum lipids urea and blood glucose.

Results indicate significant differences between sub-groups considered. Obese subjects, both under and over 45, exhibit higher bioclinical risks, but lower anxiety and depression as compared to the normal and thin subjects. They are characterized by suspiciousness and an “intermediate” response style. Thin subjects exhibit comparatively lower risks, but higher psychological ones. They are characterized by anxiety, depression, and either agreeing or disagreeing response style. Their bioclinical and psychological scores are higher for the over-45's as compared to the under-45's. Normal subjects show intermediate bioclinical and psychological scores in all comparisons performed. Their scores are higher over 45 yr-of-age.

It is suggested that anxiety, depression and their style of expression are key elements in the relationship that holds between relative weight and proneness to coronary heart disease.     

Personality aspects of CHD related behavior

The motivation of people in health-related behavior is a determinant of both the application and the efficiency of preventative measures. The present study addresses itself to psychological aspects of both preventative and curative behavior in CHD. The IPAT Anxiety Scale being sensitive to the subject's motivation in a given role situation (e.g. the patient's role), we hypothesized that anxiety levels and/or response styles to the anxiety questionnaire would be differentially associated with these preventative and curative behavior. Healthy volunteers to a CHD screening test, sick volunteers to a curative examination, and healthy control individuals were compared in their self-rated anxiety scores, acquiescence, and extremity of response indices. The hypothesis was partly supported: there were no statistically significant differences in self-rated anxiety scores, but the response style indices differentiated significantly the healthy volunteer, the sick volunteer, and the control individuals. The results contribute to the understanding of CHD related behavior pointing out some of its personality aspects. They have, in addition, methodological consequences in epidemiological studies based on volunteer individuals, which ought to be examined further.     

Preventive behavior and awareness of myocardial infraction: A factorial definition of anxiety

The ways of organizing anxiety are approached as a function of various dimensions of CHD: information about risk factors and certainty of illness (MI patients), information about risks and uncertainty of illness (healthy volunteers for a medical check-up), and lack of actual concern for illness (healthy control individuals). A factor analysis of the Anxiety Scale Questionnaire items and the testing of the factorial solution invariance from sample to sample indicate a lack of congruence among the three ASQ factorial structures. The factorial solutions of the three groups reveal that awareness of myocardial infarction and preventive behavior are differentially associated with distinctive patterns of anxiety and with specific defense mechanisms. This finding contributes to consider “anxiety” not only as a CHD risk factor, but as a motivational factor that could impel individuals to prevent or to deal early with the disease.     

Comparative studies of metabolic and affective anomalies in the lean and obese

(1) The in vivo fat mobilizing capacity of the obese is adequate and exceeds that of the lean at rest and under non-nutritional stimulation. A high correlation exists between body weight, the weight of adipose tissue, body surface area and the magnitude of adipokinesis, as well as total fat, triglyceride levels and VMA excretion. (2) Under usual nutritional stimulation, body surface area and lean body weight appear to be the determining factors of the absolute amounts of FFA production rates, pool sizes, lipid levels and VMA excretion. The often documented failure of the obese to increase FFA levels in starvation or other stimulation is a misleading phenomenon, explainable in kinetic studies by an inadequate restraint of fat mobilization at rest (vs the needs of lean body mass), providing energy even during prolonged fast, without the need to increase FFA production rate. (3) The full exhibition of fat mobilizing capacity of the large adipose tissue of the obese becomes apparent, however, under external stimulation, e.g. epinephrine. This indicates normal metabolic activity of the obese fat tissue. (4) The comparison of affective measures between the lean and obese showed a non-significant increase of anxiety and inward hostility in the obese patients. (5) Analysis of correlation between anxiety, inward/ outward hostility and the numerous biochemical data: (a) FFA production rate and pool size; (b) total fat and triglyceride; (c) VMA excretion both at rest and under stimulation (with epinephrine and starvation) give evidence of no correlation both in the obese and lean. (6) Emotional factors cannot be invoked to explain or contribute to metabolic anomalies of FFA and circulating lipids in the obese. Psychogenic influences are important in the genesis of obesity by overeating. The metabolic anomalies are secondary to an excessive mass of adipose tissue and are not distinguishable according to the specific psychogenic influence that may have contributed to the development of obesity.     

Stress, psychological characteristics, and respiratory variables]

This study compares the respiratory reactions of 40 normal subjects and 40 coronary patients. The respiratory measures are taken under stress and under normal situations. The psychological features of the eighty subjects are known; they are drawn from a test battery implementing the MMPI, the ABV and the DS. The study is meant to identify the interaction between the psychological and bioclinical measures. The bioclinical measures comprise several respiratory parameters: they are taken under mental and physical stress.     

Obesity promotes injury induced femoral artery thrombosis in mice

An FeCl(3) induced femoral arterial thrombosis model was applied to lean (47+/-1.4 g) and obese (64+/-1.7 g) mice (Swiss genetic background) in order to study the relation between obesity and thrombotic risk. As compared to lean mice, obese mice showed a significantly shorter occlusion time (9.9+/-1.0 min versus 13+/-0.5 min; p=0.04) and lower total blood flow (37+/-7.3% versus 69+/-6.7%; p=0.008). A significant negative correlation was observed between body weight and both occlusion time (r=-0.57; p=0.014) and blood flow (r=-0.57; p=0.028). Analysis of the coagulation profile revealed significantly higher levels of plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex, Factor V activity and combined Factors II/VII/X activity, and moderately elevated Factor VIII activity in obese mice. The degree of arterial damage and the thrombus extension were, however, not significantly different. A significant positive correlation was observed between body weight and either PAI-1 (r=0.63; p=0.003), Factors II/VII/X levels (r=0.80; p<0.0001) or Factor V levels (r=0.65; p=0.003). Thus, this injury induced femoral artery thrombosis model in mice establishes experimentally a correlation between obesity and prothrombotic tendency.     

Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke

Obesity is an independent risk factor for stroke and is associated with poorer outcome after stroke. We investigated whether this poorer outcome is related to brain microvascular disruption. Focal cerebral ischaemia was induced in lean or obese (ob/ob) mice by transient middle cerebral artery occlusion. The incidence of haemorrhagic transformation and the volume of ischaemic brain damage were significantly greater in obese mice. Blood–brain barrier permeability and brain microvascular MMP-9 expression were also markedly increased in obese mice. These effects were independent of leptin or glycaemic status, suggesting that obesity potentiates brain microvascular disruption after experimental stroke.     

Anxiety and hypothalamic-pituitary-adrenal axis responses to psychological stress are attenuated in male rats made lean by large litter rearing

An excellent strategy to treat overactive responses to stress is to exploit the body's inherent stress-inhibitory mechanisms. Stress responses are known to differ between individuals depending upon their level and distribution of adiposity and their experiences in early life. For instance, we have recently shown that female rats made obese by overfeeding during the neonatal period have exacerbated responses to psychological stress. The converse may be true for those that are underfed during this period. In this investigation we hypothesized that rats made lean by neonatal underfeeding would have reduced anxiety and attenuated hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress. Our findings show that male (but not female) rats, made smaller by being suckled in a large litter, show reduced anxiety-related behaviour compared with those from normal litters when tested in the elevated plus maze. These smaller males also have attenuated activation of the paraventricular nucleus of the hypothalamus in response to the psychological stress, restraint, and corticosterone responses to restraint that return more quickly to baseline than controls. These findings are exciting from the perspective of understanding and potentially exploiting the body's inherent stress-inhibitory mechanisms to treat overactive responses to stress. They also provide an indication that being lean may be able to ameliorate overactive stress responses. Understanding the mechanisms by which these stress responses are attenuated in lean animals will be important for future strategies to treat diseases associated with overactive HPA axes in humans.     

Parasympathetic response to acute stress is attenuated in young Zucker obese rats

We compared arterial blood pressure (BP) and heart rate (HR) control in 9- to 11-week old obese Zucker rats (n=10; weight=452+/-45 g, average+/-SD) to age-matched, lean Zucker animals (n=13; weight=280+/-46 g). BP was measured by indwelling catheter. Baseline pressure was 113.1+/-7.0 mm Hg in the lean vs. 111.7+/-5.6 in the obese rats (NS). Baseline HR was 413+/-43 in the lean vs. 422+/-22 bpm in the obese animals (NS). Rats were classically conditioned by following a 15-second tone (CS+) with a 0.5-second tail shock. There were no between-group differences in the BP response to CS+. Conversely, heart rate (HR) decreased significantly (p<0.05) more during the last 10 s of the tone in the lean group (-46.0+/-21.5 bpm) vs. the obese (-17.8+/-21.7 bpm). This bradycardia was blocked by atropine. Finally, the change in HR divided by the change in arterial BP (DeltaHR/DeltaBP) following an intravenous bolus of phenylephrine (PE; 5 microg/kg) and following sodium nitroprusside (NP; 5 microg/kg) was determined. The DeltaHR/DeltaBP following PE was smaller in the obese (n=6; -1.36+/-0.60) vs. lean (n=5; -2.80+/-0.92); there was no difference in the response following NP. These data indicate that the BP response to a behavioral challenge did not differ in the obese rat vs. the lean animal, but that the obese subjects had an attenuated parasympathetic response to the stress, probably secondary to alterations in baroreflex function.     

Effects of obesity on neuroendocrine, cardiovascular, and immune cell responses to acute psychosocial stress in premenopausal women

OBJECTIVE: To analyze the neuroendocrine and immune cell responses to acute psychosocial stress in obese compared to non-obese premenopausal women. METHODS: N=15 obese (BMI> or =30) and N=24 (BMI<30) non-obese premenopausal women underwent public speaking stress. State anxiety, ACTH, cortisol, and the redistribution of immune cells were measured before, during, and 10 and 45min after public speaking. Serum hsCRP and serum IL-6 levels were analyzed before, and IL-6 additionally 45min after stress. RESULTS: In response to public speaking stress, both groups showed significant but comparable increases in state anxiety, plasma ACTH, and blood pressure (all p<0.01; time effects). The cortisol stress response was significantly enhanced in obese women (p<0.05; interaction effect). In addition, heart rate and diastolic blood pressure were significantly higher in obese women 10min following stress (p<0.05, t-tests). Public speaking stress led to a significant increase in IL-6 concentrations (p<0.001; time effect), and obese women displayed higher IL-6 levels both pre- and post-stress (p<0.05; group effect; between-group t-tests: pre-stress p<0.05; post-stress p<0.01). Baseline numbers of circulating leukocytes, granulocytes, CD3+ cells and hsCRP concentration were significantly higher in obese women (between-group t-tests: all p<0.05, but the groups did not differ in the stress-induced redistribution of circulating leukocyte subpopulations. CONCLUSIONS: Our data reveal a strong association of obesity with chronic low-grade inflammation in premenopausal women. This pro-inflammatory state, together with altered neuroendocrine and cardiovascular stress responsiveness, may conceivably constitute one of the mechanisms linking psychological stress and the long-term health risks associated with obesity.     

Fatigue, depressive symptoms, and anxiety from adolescence up to young adulthood: a longitudinal study

Fatigue is a common complaint among adolescents. We investigated the course of fatigue in females during the transition from adolescence to young adulthood and examined psychological, immunological, and life style risk factors for development of fatigue and chronic fatigue syndrome (CFS)-related symptoms. Six hundred and thirty-three healthy females (age 14.63 ± 1.37 years) filled out questionnaires measuring fatigue severity, depressive symptoms, anxiety, chronic fatigue syndrome (CFS)-related symptoms, sleep features, and life style characteristics at baseline and 4½ years thereafter. Of 64 participants LPS- and CD2CD28-induced cytokine data at baseline were available. The best predictor of fatigue in young adulthood was previous fatigue severity. In participants who were non-fatigued during adolescence and who experienced a notable increase in fatigue, fatigue development was preceded by emotional problems and CFS-related complaints during adolescence. Increases as well as decreases in fatigue severity were accompanied by respectively increase and decrease in depressive symptoms and anxiety, suggesting that these symptoms cluster and co-vary over time. Higher interferon (IFN)-γ, higher IFN-γ/interleukin (IL)-4 ratio, lower tumor necrosis factor-α and lower IL-10 at baseline were related to fatigue severity at follow up. The rise in total number of CFS-related symptoms at follow up was predicted by anxiety and decreased physical activity during adolescence. Sleep and substance use were associated with fatigue severity and anxiety and depression. In conclusion, vulnerability to develop fatigue and associated symptoms in young adulthood can to a certain extent be identified already years before the manifestation of complaints.     

A Randomised Trial of a Weight Loss Intervention for Overweight and Obese People Diagnosed with Coronary Heart Disease and/or Type 2 Diabetes

Background

Weight reduction limits disease progression in obese people with coronary heart disease (CHD) and/or type 2 diabetes mellitus (T2DM).

Purpose

To test a 16-week group-based weight reduction intervention combining exercise, diet and behaviour change strategies aimed to increase self-efficacy (Healthy Eating and Exercise Lifestyle Program??HEELP) on weight, body mass index (BMI), waist circumference and exercise.

Methods

Participants with CHD and/or T2DM and BMI between 27 to 39?kg/m² were randomised to HEELP (n?=?83) or usual care (n?=?65).

Results

Participants were aged a mean 63.47?years (SD 8.9), male (58?%) and Caucasian (79?%). HEELP participants lost significantly more weight, BMI and waist circumference and exercised more days/week for a longer duration/week than usual care. Clinically significant weight loss (??5?%) was more common in HEELP than usual care.

Conclusion

The HEELP resulted in weight loss and improved exercise behaviour in obese people with CHD and T2DM.     

Nucleus Accumbens D1 Receptor–Expressing Spiny Projection Neurons Control Food Motivation and Obesity

BackgroundObesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. There is growing recognition that food motivation is altered in people with obesity. However, it remains unclear how brain circuits that control food motivation are altered in obese animals.MethodsUsing a novel behavioral assay that quantifies work during food seeking, in vivo and ex vivo cell-specific recordings, and a synaptic blocking technique, we tested the hypothesis that activity of circuits promoting appetitive behavior in the core of the nucleus accumbens (NAc) is enhanced in the obese state, particularly during food seeking.ResultsWe first confirmed that mice made obese with ad libitum exposure to a high fat diet work harder than lean mice to obtain food, consistent with an increase in food motivation in obese mice. We observed greater activation of D₁ receptor–expressing NAc spiny projection neurons (NAc D1^SPNs) during food seeking in obese mice relative to lean mice. This enhanced activity was not observed in D₂ receptor–expressing neurons (D2^SPNs). Consistent with these in vivo findings, both intrinsic excitability and excitatory drive onto D1^SPNs were enhanced in obese mice relative to lean mice, and these measures were selective for D1^SPNs. Finally, blocking synaptic transmission from D1^SPNs, but not D2^SPNs, in the NAc core decreased physical work during food seeking and, critically, attenuated high fat diet–induced weight gain.ConclusionsThese experiments demonstrate the necessity of NAc core D1^SPNs in food motivation and the development of diet-induced obesity, establishing these neurons as a potential therapeutic target for preventing obesity.     

Elevation of calcitonin immunoreactivity in the pituitary and thyroid glands of genetically obese rats (fa/fa)

This paper contains the first demonstration of quantitative changes in the levels of calcitonin-like immunoreactivity in the pituitary. The concentration of calcitonin-like material in lean Zucker rats (?/+) was 0.42 ± 0.09 ng/mg wet weight of pituitary. The pituitaries of obese rats (fa/fa) contained significantly greater levels (1.56 ± 0.56 ng/mg wet weight). This 271% increase represents the first indication that pituitary calcitonin-like material may have a physiological role in genetically obese rats. Thyroidal calcitonin also was elevated in the obese (111%). These large elevations in the calcitonin content of the glands of obese rats were not accompanied by significant elevations of calcitonin in the blood. This suggests that obese rats have problems with mechanisms for the release of calcitonin into the blood and might not be able to combat hypercalcemia as effectively as leans. However, this hypothesis remains to be tested.     

Affect and Cognitions in Obese Binge Eaters and Nonbinge Eaters: The Association Between Depression, Anxiety, and Bulimic Cognitions

Levels of depression, anxiety, and related cognitions; cognitions associated with the bulimia syndrome; and cognitions concerning eating and dieting were compared for 25 obese binge eaters and 27 obese nonbinge eaters at a private weight reduction center. Obese bingers demonstrated higher levels of anxiety, depression, and related cognitions than nonbingers. Obese bingers also reported more dysfunctional cognitions related to the bulimia syndrome generally and to dieting and eating behaviors. Further, maladaptive cognitions related to bulimia and eating and dieting continued to discriminate between obese bingers and nonbingers when levels of depression and anxiety were statistically controlled, whereas differences in dysphoric and anxiety-related cognitions were eliminated under these conditions. The results suggest that cognitions related to bulimia and dysfunctional dieting and eating     

Leptin deficiency per se dictates body composition and insulin action in ob/ob mice

Obese humans are often insulin- and leptin resistant. Since leptin can affect glucose metabolism, it is conceivable that a lack of leptin signal transduction contributes to insulin resistance. It remains unclear whether leptin affects glucose metabolism via peripheral and/or central mechanistic routes. In the present study, we aimed: (i) to determine the relative contributions of lack of leptin signal transduction and adiposity to insulin resistance and (ii) to establish the impact of central leptin action on glucose metabolism. To address the first point, ob/ob mice were subjected to severe calorie restriction, so that their body weight became similar to that of wild-type mice. Insulin sensitivity was measured in obese ob/ob, lean (food restricted) ob/ob and lean, weight-matched wild-type mice. To address the second point, leptin (or vehicle) was i.c.v. infused to the lateral cerebral ventricle of ob/ob mice and insulin sensitivity was determined. Hyperinsulinaemic euglyceamic clamps were used to quantify insulin sensitivity. Food restriction barely affected body composition, although it profoundly curtailed body weight. Insulin suppressed hepatic glucose production (HGP) to a greater extent in lean ob/ob than in obese ob/ob mice, but its impact remained considerably less than in wild-type mice (% suppression: 11.8 +/- 8.9 versus 1.3 +/- 1.1 versus 56.6 +/- 13.0%/nmol, for lean, obese ob/ob and wild-type mice, respectively; P < 0.05). The insulin-mediated glucose disposal (GD) of lean ob/ob mice was also in between that of obese ob/ob and wild-type mice (37.5 +/- 21.4 versus 25.1 +/- 14.6 versus 59.6 +/- 17.3 mumol/min/kg/nmol of insulin, respectively; P < 0.05 wild-type versus obese ob/ob mice). Leptin infusion acutely enhanced both hepatic insulin sensitivity (insulin-induced inhibition of HGP) and insulin-mediated GD (9.1 +/- 2.4 versus 5.0 +/- 2.7%/nmol of insulin, and 25.6 +/- 5.6 versus 13.6 +/- 4.8 mumol/min/kg/nmol of insulin, respectively; P < 0.05 for both comparisons) in ob/ob mice. Both a lack of leptin signals and adiposity may contribute to insulin resistance in obese individuals. Diminution of central leptin signalling can critically affect glucose metabolism in these individuals.     

Attachment style,relationship quality,and psychological distress in patients with psychogenic non-epileptic seizures versus epilepsy

ObjectivesPsychopathology levels are elevated in patients with psychogenic non-epileptic seizures (PNES) and those with epilepsy. However, patients with PNES report higher rates of trauma and neglect, poorer health-related quality of life (HRQoL), and an increased prevalence of insecure attachment. We examined to what extent attachment style and relationship quality with their main informal carer impact on levels of HRQoL, depression, and anxiety in patients with PNES versus those with epilepsy.MethodConsecutive patients with PNES (N = 23) and epilepsy (N = 72) completed questionnaires about attachment style, quality of their relationship with their main informal carer, seizure severity, HRQoL, depression, and anxiety.ResultsPatients with PNES reported higher levels of anxiety and depression and lower HRQoL than those with epilepsy. PNES: No significant correlations were found with HRQoL but depression correlated positively with attachment avoidance, attachment anxiety, and relationship conflict. Anxiety correlated positively with attachment avoidance, attachment anxiety, and relationship conflict, and negatively with relationship depth and support. Epilepsy: HRQoL correlated negatively with seizure severity, depression, anxiety, attachment avoidance, and attachment anxiety. Depression correlated positively with attachment avoidance, attachment anxiety, and relationship conflict. Anxiety correlated positively with seizure severity, attachment avoidance, and attachment anxiety. Correlations between measures of relationship quality and anxiety were stronger in patients with PNES versus those with epilepsy (zs = 2.66 to 2.97, ps < 0.004). Attachment style and relationship quality explained larger amounts of variance in depression (45%) and anxiety (60%) in the patients with PNES than those with epilepsy (16% and 13%).SignificanceLevels of anxiety and depression were higher in patients with PNES than those with epilepsy. Interpersonal problems were much more closely associated with anxiety and depression in patients with PNES than those with epilepsy. The findings support the use of therapeutic interventions for PNES focusing on attachment and relationship issues.     

Anxiety, independent of depressive symptoms, is associated with in-hospital cardiac complications after acute myocardial infarction

Objective

Post-myocardial infarction (MI) anxiety, independent of demographic and medical variables, has been linked to in-hospital cardiac complications in prior studies, but such studies have not included a concomitant assessment of depressive symptoms. The aim of this exploratory study was to determine whether post-MI anxiety was associated with in-hospital cardiac complications, independent of depressive symptoms.

Methods

Subjects within 72 hours of acute MI (n=110) were prospectively assessed for anxiety [using the Beck Anxiety Inventory (BAI)] and depressive symptoms (using the Beck Depression Inventory-II and structured interview diagnoses of major depressive disorder). Individual in-hospital complications and pooled serious cardiac complications (defined as recurrent ischemia, reinfarction, congestive heart failure, and ventricular arrhythmia requiring intervention) were recorded via chart review.

Results

On hierarchical multiple logistic regression analysis that accounted for demographic variables, cardiac illness, and depressive symptoms, post-MI anxiety was significantly associated with pooled serious in-hospital cardiac complications (P=.003). In addition, when the anxiety measure was limited to only the psychological symptoms of anxiety (“BAI-P”), post-MI anxiety remained an independent predictor of cardiac complications (P=.015).

Conclusions

These findings suggest that the association of post-MI anxiety with in-hospital cardiac complications exists above and beyond the effects of depression. Larger studies are needed to confirm these findings, and treatment studies are needed to determine the impact of anxiety treatment on in-hospital cardiac outcomes.     

Food restriction and leptin impact brain reward circuitry in lean and obese Zucker rats

The rewarding effect produced by electrically stimulating certain sites in the lateral hypothalamus (LH) can be potentiated by food restriction and body weight loss in lean rats. Central leptin and insulin administration can suppress the rewarding impact of the stimulation. To determine whether there are additional peripheral signals that mediate the effect of weight loss on brain reward circuitry, we assessed changes in LH-self-stimulation following food restriction in the obese Zucker rat which develops resistance to circulating leptin and insulin. In addition, we examined the impact of acute food deprivation and leptin administration on LH self-stimulation in lean and obese Zucker rats. The number of brain stimulation rewards earned was measured over a range of LH stimulation frequencies that drove reward rates from zero to asymptotic levels. Restriction reduced frequency thresholds in a subset of lean and obese rats, whereas BSR was unaltered by acute food deprivation. Despite impairment in leptin signaling, intraventricular leptin (4 microg) increased thresholds in most lean and obese rats in which the rewarding effect was sensitive to restriction. These results show that brain reward circuitry in the obese Zucker rat is sensitive to weight loss and leptin.