An increased incidence of anxiety, depression and attention deficits in children has been linked to psychological stress during pregnancy. Subjection of a pregnant rat to stress at a time when the foetal limbic and hypothalamic pituitary adrenal (HPA) axes develop results in anxiogenic and depressive behaviour and learning and attention deficits in the offspring, which depend on its gender, intensity and timing of the maternal stress and behaviour being tested. Maternal stress increases corticosterone levels in the foetal brain, decreases foetal testosterone and brain aromatase activity in males, and alters brain catecholamine activity to that in females. Learning deficits, reductions in hippocampal neurogenesis, LTP and dendritic spine density in the prefrontal cortex are more readily seen in prenatally-stressed males, while anxiety, depression and increased response of the HPA axis to stress are more prevalent in females. Genders may differ in the sensitivity of developing brain areas to stress hormones.
Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N-acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited.
People who stop consuming caffeine may have symptoms, but the incidence and severity of caffeine withdrawal are not known. This study was performed to determine the effects in the general population of ending one's dietary intake of caffeine.
We studied 62 normal adults whose intake of caffeine was low to moderate (mean amount, 235 mg--the equivalent of 2.5 cups of coffee--per day). They completed questionnaires about symptoms and tests of their mood and performance when consuming their normal diets (base-line period) and at the end of each of two two-day periods during which they consumed caffeine-free diets and under double-blind conditions received capsules containing placebo (placebo period) or caffeine (caffeine period) in amounts equal to their daily caffeine consumption.
More subjects had abnormally high Beck Depression Inventory scores (11 percent), high scores on the trait scale of the State-Trait Anxiety Inventory (8 percent), low vigor scores (11 percent) and high fatigue scores (8 percent) on the Profile of Mood States, and moderate or severe headache (52 percent) during the placebo period than during either the base-line period (2, 0, 0, 0, and 2 percent, respectively; P less than 0.05) or the caffeine period (3, 2, 2, 0, and 6 percent; P less than 0.05). More subjects reported unauthorized use of medications during the placebo period (13 percent) than during the caffeine period (2 percent, P = 0.017). Performance of a tapping task was slower during the placebo period than during the base-line and caffeine periods (P less than 0.01).
Persons who consume low or moderate amounts of caffeine may have a withdrawal syndrome after their daily consumption of caffeine ceases.
Bidirectional associations between mood disorders and cardiovascular diseases are extensively documented. However, the precise physiological and biochemical mechanisms that underlie such relationships are not well understood. This review focuses on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders. The discussion places an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and the activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction involving the dopamine, norepinephrine and serotonin systems, and (e) behavioral changes including fatigue and physical inactivity. The review also discusses experimental investigations using preclinical disease models to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, (c) a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with an extensive human research literature, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance understanding the association between depression and cardiovascular disease. This will ultimately promote the development of better treatments and interventions for individuals with co-morbid psychological and somatic pathologies.
The authors examined patterns of change in depressive symptoms during smoking cessation treatment in 163 smokers with past major depressive disorder (MDD). Cluster analysis of Beck Depression Inventory (A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) scores identified 5 patterns of change. Although 40% of participants belonged to clusters characterized by increasing depressive symptoms during quitting (rapid increasers, n = 31, and delayed increasers, n = 35), almost 47% were in clusters characterized by decreasing symptoms (delayed decreasers, n = 24, and rapid decreasers, n = 52). Both rapid and delayed increasers had especially poor smoking cessation outcomes. Results suggest that among smokers with an MDD history there is substantial heterogeneity in patterns of depressive symptoms during quitting and that patterns involving increased symptoms are associated with low abstinence rates.
Mental disorders are of major public health significance. It has been claimed that vigorous physical activity has positive effects on mental health in both clinical and nonclinical populations. This paper reviews the evidence for this claim and provides recommendations for future studies. The strongest evidence suggests that physical activity and exercise probably alleviate some symptoms associated with mild to moderate depression. The evidence also suggests that physical activity and exercise might provide a beneficial adjunct for alcoholism and substance abuse programs; improve self-image, social skills, and cognitive functioning; reduce the symptoms of anxiety; and alter aspects of coronary-prone (Type A) behavior and physiological response to stressors. The effects of physical activity and exercise on mental disorders, such as schizophrenia, and other aspects of mental health are not known. Negative psychological effects from exercise have also been reported. Recommendations for further research on the effects of physical activity and exercise on mental health are made.
Health surveys, studies on physical symptom reporting, and medical registration of physical complaints find consistent sex differences in symptom reporting, with women having the higher rates. By and large, this female excess of physical symptoms is independent from the symptom measure, response format and time frame used, and the population under study. As most studies concern healthy individuals, the sex difference can not simply be attributed to a greater physical morbidity in women. In this paper we propose a number of explanations for this phenomenon, based on a biopsychosocial perspective on symptom perception. We discuss a symptom perception model that brings together factors and processes from the extant literature which are thought to affect symptom reporting, such as somatic information, selection of information through attention and distraction, attribution of somatic sensations, and the personality factors somatisation and negative affectivity. Finally, we discuss the explanations for sex differences in physical symptoms that arise from the model.
Pathological gambling has been termed both the 'pure' and the 'hidden' addiction. 'Pure' because it is not associated with the intake of any addicting substance, and 'hidden' because it is an extension of a common, socially accepted behaviour. The Taq A1 variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours. We have sought to determine if there is a similar association with pathological gambling. A total of 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the US participated in the study. Of these 171 donated a sample of blood, 127 filled out several questionnaires, and 102 did both. Of the 171 pathological gamblers 50.9% carried the D2A1 allele versus 25.9% of the 714 known non-Hispanic Caucasian controls screened to exclude drug and alcohol abuse, p < 0.00000001, odds ratio (OR) = 2.96. For the 102 gamblers who filled out the questionnaires, 63.8% of those in the upper half of the Pathological Gambling Score (more severe) carried the D2A1 allele (OR versus controls = 5.03), compared to 40.9% in the lower half (less severe). Of those who had no comorbid substance abuse, 44.1% carried the D2A1 allele, compared to 60.5% of those who had comorbid substance abuse. Forty-eight controls and 102 gamblers completed a shorter version of the Pathological Gambling Score. Of the 45 controls with a score of zero, 17.8% carried the D2A1 allele. Of the 99 gamblers with a score of 5 or more, 52.5% carried the D2A1 allele (chi 2 = 15.36, p = 0.00009). These results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviours.
To determine the association of race with clinical and laboratory outcomes after initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected women in the United States.
Prospective cohort study.
A total of 961 HIV-1-infected women participating in the Women's Interagency HIV Study initiating HAART between July 1, 1995 and September 30, 2003.
Over a median of 5.1 years of follow-up, in univariate Cox regression analyses, white women were more likely than African American women to attain a virologic response (relative hazard [RH]=1.34, P=0.005), less likely to experience viral rebound (RH=0.76, P=0.051), and less likely to die (RH=0.63, P=0.040). There were no significant differences, however, among racial groups in outcomes after adjustment for pre-HAART CD4, HIV-1 RNA, history of AIDS-defining illness, age, antiretroviral therapy use, baseline HIV-1 exposure category, and post-HAART behavioral and clinical variables associated with poorer response (discontinuation of HAART, lower income, smoking, current drug use, and depression). Continuous HAART use and lack of depression differed by race and were the strongest predictors of favorable outcomes.
No significant differences by race were found in virologic, immunologic, or clinical outcomes after adjustment for continued HAART use and depression. These findings suggest that strategies to enhance HAART continuation, including assessing pharmacogenetic influences that may result in greater toxicity and discontinuation rates, and treating depression can improve individual and population-based effects of treatment and potentially mitigate racial disparities in AIDS-related outcomes.
Massage is increasingly applied to relieve symptoms in patients with cancer. This practice is supported by evidence from small randomized trials. No study has examined massage therapy outcome in a large group of patients. At Memorial Sloan-Kettering Cancer Center, patients report symptom severity pre- and post-massage therapy using 0-10 rating scales of pain, fatigue, stress/anxiety, nausea, depression and "other." Changes in symptom scores and the modifying effects of patient status (in- or outpatient) and type of massage were analyzed. Over a three-year period, 1,290 patients were treated. Symptom scores were reduced by approximately 50%, even for patients reporting high baseline scores. Outpatients improved about 10% more than inpatients. Benefits persisted, with outpatients experiencing no return toward baseline scores throughout the duration of 48-hour follow-up. These data indicate that massage therapy is associated with substantive improvement in cancer patients' symptom scores.