Central Nervous System Opportunistic Infections in HIV-1 Infection

Neurologic disease is commonly encountered in the population infected with human immunodeficiency virus type 1 (HIV-1). Although HIV-1 is responsible for many of these neurologic complications, other organisms will affect the nervous system as the immune deficiency state progresses. With the wide use of potent antiretroviral therapy, the mortality from and incidence of opportunistic infections (OIs) among persons with advanced HIV-1 infection has decreased. Nevertheless, these diseases are still seen frequently, especially among those with limited access to new antiretroviral therapies. Therefore, it remains important to recognize the most common OIs of the central nervous system (CNS) as well as primary CNS lymphoma, which will be the focus of this review.     

Psychosocial correlates of immune status and disease progression in HIV-1 infected homosexual men: Review of preliminary findings,and commentary

Abstract

Behavioral factors may have an effect on the course of infection in HIV-1 infected individuals. These effects can be mediated by the immune system of the host, which, based on psychoneuroimmunologic findings, can be affected by some psychosocial factors. We present a short review of some putative psychoneuroimmunologic pathways and their possible implications for HIV-1 infected individuals. We next summarize the findings of recent psychoimmunological work with HIV-1 seropositives and discuss the methodological problems in studying the psychoneuroimmunologic aspects of HIV-1 infection. Psychoneuroimmunologic research in HIV-1 seropositives is a rapidly developing field, yielding contradictory findings so far, but which in the long run could provide important knowledge for psychoimmunologic interventions, targeted at improving or preserving immune status and retarding disease progression, as well as optimizing psychosocial functioning.     

HIV-1 Infection, Neuroendocrine Abnormalities, and Clinical Outcomes

Different lines of evidence suggest that human immunodeficiency virus type 1 (HIV-1) infection is complicated by a variety of adverse effects on neuroendocrine systems. Soon after the discovery of HIV-1, reports began to appear suggesting that a number of neurotransmitter and neuroendocrine activities were negatively impacted by this infection. In 1987 it was observed that fine-needle aspiration of the lung in patients with acquired immunodeficiency syndrome resulted in syncopal reactions. Subsequently, an abnormality in the autonomic nervous system was reported in these patients. However, investigations in this area have remained limited due to the assumption that HIV-1-mediated activation of various endocrine systems was related to the major life stressor of living with a fatal disease. Evidence accumulated over the years has indicated, instead, that there are various other mechanisms in addition to life stressors that also play an important role in negatively impacting the neuroendocrine systems in this infection. This article examines various developments that have taken place in this area in order to provide avenues for future research.     

Stress, peer affiliation, and transforming growth factor-beta1 in differentially reared primates

A bidirectional regulatory interaction between the central nervous system and the immune system is largely provided by cytokines and their specific receptors, which are expressed by cells of both systems. Transforming growth factor-beta1 (TGF-beta1), produced by glial cells and lymphocytes and regulated by steroid hormones, is one such cytokine. In the current study, we examined the relationship between TGF-beta1 and peer affiliation in bonnet macaques (Macaca radiata) either reared normally or exposed as infants to conditions in which their mothers faced fluctuating requirements for food procurement (variable foraging demand [VFD]). Rearing under VFD conditions has been previously shown to produce dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in these animals. Serum levels of TGF-beta1 after exposure to a moderate stressor had no correlation with peer affiliation under baseline conditions (r=.07), but were highly correlated with affiliation after subsequent challenge with a fear stimulus (r=.62). Affiliation after the fear stimulus also was inversely correlated with baseline levels of affiliation (r=-.71). These data suggest that changes in peripheral TGF-beta1 may be reflective of latent behavioral and biochemical propensities possibly related to affect. Further examination of the effects of early adversity will improve our understanding of the relationship between the HPA axis and immune function.     

AIDS: ethics, justice and social policy

ABSTRACT Principles of justice and equality demand that HIV seropositive individuals and those with AIDS should not be discriminated against in any area of social provision. If social policy on AIDS is constructed in terms of reciprocal obligations, that is if obligations to the HIV seropositive individual and obligations of the HIV seropositive individual are given equal weight, the civil rights of HIV seropositive individuals may be secured and this may create a climate in which HIV seropositive individuals will more readily notify partners, and others at risk of infection, of their HIV status. It is conceivable that such a climate could facilitate greater control of the spread of HIV/AIDS.     

Glucocorticoid sensitivity in humans-interindividual differences and acute stress effects

The hypothalamus pituitary adrenal (HPA)- axis is one of the major output systems of the neuroendocrine stress response. Its major end products, glucocorticoids (GCs), have a plethora of effects throughout the organism, most of which are believed to be protective against disturbances of homeostasis. However, negative effects have also been described under specific conditions of hyper- or hypo(re)activity of the HPA axis. Both beneficial and adverse effects of GCs ultimately depend on the target tissue sensitivity to these steroids. Recent findings suggest that GC sensitivity (a) may vary between different target tissues in the same organism, (b) shows large individual differences and (c) can be acutely changed in times of acute stress. In the present review, data are summarized which show differences in GC sensitivities in patients suffering from diverse somatic and psychiatric diseases, as well as chronically stressed individuals. Furthermore, studies are presented that show a rapid modulation of GC sensitivity in response to exercise or psychosocial stress in healthy adults. The response pattern of acute GC sensitivity modulation seems to be influenced by age and sex hormone status of the individual. While the GC signalling cascade may be subject to modulation at several levels, the pathway for acute modulation of GC sensitivity remains to be elucidated.     

Effect of Interleukin-1beta on Pituitary-Adrenal Responses and Body Weight in Neonatal Rats: Interaction with Maternal Deprivation

The hypothalamic-pituitary-adrenal (HPA) axis of the infant rat is normally hyporesponsive during postnatal days (pnd) four to fourteen. This interval is termed the stress hyporesponsive period (SHRP). The HPA axis, however, does respond to selective stimuli, such as interleukin-1beta (IL-1beta) during this period. Furthermore, maternal deprivation has been shown to alter the system so that it is responsive to mild stimuli. The present studies examined the interaction between 24 h of maternal deprivation and intraperitoneal administration of recombinant human (rh) IL-1beta (4 μg/kg) at 3 ages (i.e., pnd 6, 12, 18) during or after the SHRP. The results demonstrate that maternal deprivation modifies the response of the HPA axis induced by IL-1beta in an age-dependent fashion: 1) a greater response at pnd 6; 2) a quicker response at pnd 12; and 3) a suppressed response pattern at pnd 18. Moreover, these responses across ages differ as a function of maternal contact postinjection: 1) deprivation augments the ACTH and CORT response and maternal contact postinjection further augments this response at pnd 6; 2) deprivation increases the ACTH and CORT response to vehicle and the CORT response to IL-1beta in 12 day-old pups and the mother has a modest inhibitory effect; and 3) at pnd 18 deprivation leads to lower ACTH concentrations, but higher overall CORT levels and maternal contact postinjection effectively suppresses both the ACTH and CORT response to IL-1. These differences in the HPA response do not appear to be due to differences in the immune response. Plasma concentrations of endogenous rat IL-1beta determined 1 and 2 h after injection of rhIL-1beta were not modified by deprivation and were reduced at pnd 18 compared to pnd 6 and 12 in NDEP pups. Finally, IL-1beta reduced food intake, as reflected by a decrease in body weight, in deprived pups at all 3 ages. The findings in the present experiments suggest that there are additional pathways through which IL-1beta can act on the CNS to activate the HPA axis besides direct action at the hypothalamus.     

Stress and inflammatory disease: widening roles for serotonin and substance P

Serotonin has been implicated in mediating the hypothalamo-pituitary-adrenal (HPA) axis response to stress and is an important therapeutic target for a number of psychiatric disorders including depression. The neurokinin substance P has been shown to inhibit stress-induced HPA axis activity and we have demonstrated that endogenous substance P is able to reduce the duration of the HPA axis response to stress suggesting an important role in the termination of the stress response. This may be important in controlling the transition from acute to chronic stress and substance P has recently attracted attention as a potential antidepressant.In addition to these central effects, serotonin and substance P are considered to be pro-inflammatory agents. Despite being implicated in mediating inflammation there have been few studies investigating the effects of manipulations of serotonergic or substance P systems on chronic inflammatory disease. Treatment of rats with adjuvant-induced arthritis(AA), a model of chronic inflammatory stress, with a substance P antagonist specific for the NK1 receptor subtype resulted in a reduction in hind paw inflammation suggesting substance P may influence inflammation. We have noted that depletion of whole body serotonin and selective central depletion of serotonin results in a decrease in the severity of inflammation in rats with adjuvant arthritis. Furthermore, treatment with a selective serotonin reuptake inhibitor results in an earlier onset and increased severity of inflammation in adjuvant arthritis, confirming a pro-inflammatory role for serotonin. Serotonin is also present in the immune tissues and concentrations in the spleen fall following the development of inflammation in adjuvant arthritis. Concentrations of serotonin are significantly higher in normal female spleen than in males, and this may underlie the greater predisposition of females to certain autoimmune diseases.There is increasing evidence of a role for transmitters such as serotonin and substance P,both centrally and peripherally, in mediating a wide variety of inflammatory and psychiatric disorders. A better understanding of the mechanisms of action of these transmitters and the development of suitable drugs targeting specific receptor subtypes has great potential to impact on clinical practice in the near future. The purpose of this review is to consider the separate roles of serotonin and substance P in relation to HPA axis stress responses, in the context of a model of chronic inflammatory disease, highlighting novel directions of current research for each of these transmitters.     

The neuroendocrinology of posttraumatic stress disorder: new directions

Studies of the hypothalamic-pituitary-adrenal (HPA) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at gamma-aminobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.     

Programming of the hypothalamo-pituitary-adrenal axis: serotonergic involvement

The ability of the early environment to programme the developing hypothalamo-pituitary-adrenal (HPA) axis has been reported in several animal species. There is considerable evidence that a similar process can occur in the human, and that long-term alterations in HPA function are associated with altered susceptibility to disease in later life. The phenotype of HPA function following early manipulation depends on the timing and intensity of the manipulation as well as the gender of the fetus/neonate. There is considerable interplay between the developing HPA and the reproductive axes and emerging evidence indicates that this interaction is modified by early environmental manipulation. Studies are rapidly unravelling the mechanisms that underlie developmental programming of the HPA axis. In this context, the serotonergic system has been identified as a primary system involved in this process. Understanding the mechanisms involved in neuroendocrine programming will facilitate the development of interventions aimed at reversing or ameliorating the impact of an adverse intrauterine environment.     

The central nucleus of the amygdala; a conduit for modulation of HPA axis responses to an immune challenge?

Physical stressors such as infection, inflammation and tissue injury elicit activation of the hypothalamic-pituitary-adrenal (HPA) axis. This response has significant implications for both immune and central nervous system function. Investigations in rats into the neural substrates responsible for HPA axis activation to an immune challenge have predominantly utilized an experimental paradigm involving the acute administration of the pro-inflammatory cytokine interleukin- 1β (IL-1β). It is well recognized that medial parvocellular corticotrophin-releasing factor cells of the paraventricular nucleus (mPVN CRF) are critical in generating HPA axis responses to an immune challenge but little is known about how peripheral immune signals can activate and/or modulate the mPVN CRF cells. Studies that have examined the afferent control of the mPVN CRF cell response to systemic IL-1β have centred largely on the inputs from brainstem catecholamine cells. However, other regulatory neuronal populations also merit attention and one such region is a component of the limbic system, the central nucleus of the amygdala (CeA). A large number of CeA cells are recruited following systemic IL-lβ administration and there is a significant body of work indicating that the CeA can influence HPA axis function. However, the contribution of the CeA to HPA axis responses to an immune challenge is only just beginning to be addressed. This review examines three aspects of HPA axis control by systemic IL-1β: (i) whether the CeA has a role in generating HPA axis responses to systemic IL-1β, (ii) the identity of the neural connections between the CeA and mPVN CRF cells that might be important to HPA axis responses and(iii) the mechanisms by which systemic IL-Iβ triggers the recruitment of CeA cells.     

The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome

The hypothalamo-pituitary-adrenal (HPA) axis plays a major role in the regulation of responses to stress. Human stress-related disorders such as chronic fatigue syndrome (CFS), fibromyalgia syndrome (FMS), chronic pelvic pain and post-traumatic stress disorder are characterized by alterations in HPA axis activity. However, the role of the HPA axis alterations in these stress-related disorders is not clear. Most studies have shown that the HPA axis is underactive in the stress-related disorders, but contradictory results have also been reported, which may be due to the patients selected for the study, the methods used for the investigation of the HPA axis, the stage of the syndrome when the tests have been done and the interpretation of the results. There is no structural abnormality in the endocrine organs which comprise the HPA axis, thus it seems that hypocortisolemia found in the patients with stress-related disorder is functional. It may be also an adaptive response of the body to chronic stress. In this review, tests used in the assessment of HPA axis function and the HPA axis alterations found in CFS and FMS are discussed in detail.     

背景应激对静息态下大脑自发神经活动的影响

本研究试图探究背景应激对应激相关大脑自发神经活动的影响。使用日常应激水平作为背景应激的量化指标。同时，使用静息态fMRI技术，采集了个体在静息态下的大脑自发神经活动，并使用局部一致性（ReHo）作为指标。结果发现，背景应激越高的个体，右侧海马（扩展到丘脑和脑干）静息态下局部一致性水平越高。结果提示，经历了高背景应激的个体会表现出边缘系统脑区的自发神经活动的持续活跃状态。     

Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA Axis Reactivity During a Psychosocial Stressor

Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without prenatal substance exposure (N = 53; ages 9-12 years) were examined using the Trier Social Stress Test for Children. Area under the curve with respect to increase (AUC(I)) analyses revealed that prenatal substance exposure or physical abuse significantly increased the likelihood of a negative AUC(I) (i.e., little or no HPA reactivity). Among children with prenatal substance exposure and physical abuse, 85% exhibited a negative AUC(I). The results underscore the importance of addressing this combined risk.     

Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1-associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatric functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatric functioning, potential treatment implications will also be discussed.     

神经质人格的神经生理基础

神经质作为一种人格特质, 核心特征是具有负性情绪体验的倾向。高神经质个体表现出更强的情绪反应、更差的情绪感知和应对, 因而体验到更多的负性情绪, 进而容易形成一系列精神障碍和身体疾病。因此, 神经质成为精神病理学中一个重要的风险因素。来自自主神经系统、神经内分泌系统和脑的证据发现, 高神经质个体心血管灵活性降低、HPA轴基线活动增强、EEG活动增大以及负性情绪引起的杏仁核活动增强, 其中杏仁核的自上而下和自下而上通路可能是整合多方面证据的关键。进一步研究应致力于将遗传学、电生理学、生物化学、脑成像技术等相结合, 构建神经质产生、形成的神经生理模型。     

人类应激内分泌轴功能状态的测量

HPA轴(下丘脑?垂体?肾上腺皮质轴, hypothalamic-pituitary-adrenal cortex axis)是人类重要的应激内分泌轴, 静息与应激条件下HPA轴的机能障碍能引发应激相关疾病, 而HPA轴机能障碍的表现和原因并不明确。皮质醇作为HPA轴的终端产物能直接反映HPA轴活动, 唾液皮质醇优于其他生物样本皮质醇的特性使其成为测量HPA轴活动的最优指标, 因此寻找到合适的唾液皮质醇标识来反映静息与应激条件下的HPA轴调节变化, 能促进理解HPA轴机能障碍与疾病间的神经内分泌通路。近来研究常用的是以皮质醇觉醒反应(cortisol -awakening response, CAR)与特里尔社会应激测试(Trier social stress test, TSST)来分别表示静息与应激条件下的HPA轴活动。未来研究将结合应激反应的生理、心理指标, 进一步考察HPA轴调节的脑网络, 为应激反应提供脑-神经内分泌通路的生物基础。     

Lactation and stress: protective effects of breast-feeding in humans

Whilst most research on breast-feeding has been designed to assess its importance for infant health or to find a human nutrient replacement for infant formula, the effects of breast-feeding on maternal health have received little scientific attention. In several animal studies lactation has been shown to be associated with a marked blunting of physiological and behavioral responses to physical and psychological stress. However, the literature on the effects of lactation on stress in humans remains limited. This review focuses primarily on recent findings on the effects of breast-feeding on neuroendocrine and behavioral responses to acute stress exposure in lactating women. The available data suggest that breast-feeding suppresses the hypothalamic-pituitary-adrenal (HPA) axis response to physical and psychosocial stress. However, lactation in women, in contrast to lactating rats, does not seem to result in a general restraint of the endocrine stress response during the whole period of lactation. Recent data strongly suggest that the blunted HPA axis response to stress in women seems to be counterbalanced if the acute stressor, at least when of a psychosocial nature, occurs later than 1 h after suckling. Further elucidation of the underlying psychobiological mechanisms involved in suppressed stress responses during lactation will no doubt lead to new insights into improved health sequelae of breast-feeding in women and to a better understanding of the psychobiology of human stress protection in general.     

Poverty and Single Parenting: Relations with Preschoolers' Cortisol and Effortful Control

Poverty and single parent status, which often co‐occur, have been shown to relate to lower effortful control, and this may be in part due to disruptions in hypothalamic–pituitary–adrenal (HPA) axis activity. Both poverty and single parent status may compromise parenting, which in turn may disrupt HPA axis activity and the development of effortful control. We examined whether parenting and HPA axis activity accounted for the effects of poverty and single parent status on the development of effortful control in preschool children (N = 78). Effortful control was measured at two time points, 6 months apart. Individually, poverty and single parent status were related to blunted HPA axis activity, characterized by low AM and PM cortisol. However, when examined together, the effects were present only for preschoolers whose parents were in poverty. Parental warmth and negativity accounted for the relations between poverty and blunted cortisol. Blunted cortisol was related to lower effortful control at Time 2. These results suggest a pathway through which poverty may impact children's developing effortful control through parenting, which in turn may shape HPA axis activity. Copyright © 2012 John Wiley & Sons, Ltd.