Isolation rearing significantly perturbs brain metabolism in the thalamus and hippocampus.

Psychosocial neglect during childhood severely impairs both behavioral and physical health. The isolation rearing model in rodents has been employed by our group and others to study this clinical problem at a basic level. We previously showed that immediate early gene (IEG) expression in the hippocampus and medial prefrontal cortex (mPFC) is decreased in isolation-reared (IR) compared to group-reared (GR) rats. In the current study, we sought to evaluate: (1) whether these changes in IEG expression would be detected by the measurement of brain glucose metabolism using positron emission tomography (PET) with fluorodeoxyglucose (FDG) and (2) whether PET FDG could illuminate other brain regions with different glucose metabolism in IR compared to GR rats. We found that there were significant differences in FDG uptake in the hippocampus that were consistent with our findings for IEG expression (decreased mean FDG uptake in IR rats). In contrast, in the mPFC, the FDG uptake between IR and GR rats did not differ. Finally, we found decreased mean FDG uptake in the thalamus of the IR rats, a region we had not previously examined. The results suggest that PET FDG has the potential to be utilized as a biomarker of molecular changes in the hippocampus. Further, the differences found in thalamic brain FDG uptake suggest that further investigation of this region at the molecular and cellular levels may provide an important insight into the neurobiological basis of the adverse clinical outcomes found in children exposed to psychosocial deprivation.

The placebo effect and relaxation response: neural processes and their coupling to constitutive nitric oxide.

The placebo effect appears to be a real phenomenon as is the scientifically demonstrated and examined relaxation response. Given this, we attempt to understand how these phenomena work in light of our current understanding of central and peripheral nervous system mechanisms. Central to our hypothesis is the significance of norepinephrine, nitric oxide and opioid signaling both in the central and peripheral nervous system. In this regard, we find that nitric oxide controls norepinephrine processes on many levels, including synthesis, release and actions. In closing, we conclude that enough scientific information exists to support these phenomena as actual physical processes that can be harnessed to provide better patient care.

Functional brain mapping of the relaxation response and meditation.

Meditation is a conscious mental process that induces a set of integrated physiologic changes termed the relaxation response. Functional magnetic resonance imaging (fMRI) was used to identify and characterize the brain regions that are active during a simple form of meditation. Significant (p<10(-7)) signal increases were observed in the group-averaged data in the dorsolateral prefrontal and parietal cortices, hippocampus/parahippocampus, temporal lobe, pregenual anterior cingulate cortex, striatum, and pre- and post-central gyri during meditation. Global fMRI signal decreases were also noted, although these were probably secondary to cardiorespiratory changes that often accompany meditation. The results indicate that the practice of meditation activates neural structures involved in attention and control of the autonomic nervous system.

Neuroimmunologic implications in coronary artery disease.

In this review, the role of the macrophage in the pathophysiology of coronary artery disease (CAD) is examined. The central interaction of macrophage, endothelial cell and smooth muscle cell in the context of hyperlipidemia is considered. The macrophage appears to be at the beginning of a chain of events that starts with elevated low density lipoprotein (LDL). Stress, particularly in those with a core hostility, may be associated not only with higher catecholamine levels but also with higher serum lipid levels. These lipids will in turn be processed to oxidized LDL by macrophage and endothelial cells. Oxidized LDL molecules will contribute to atherosclerotic plaquing. A side effect of such plaque formation may be a diminished vasodilatory response to the nitric oxide (NO) produced by macrophages and endothelium. Indeed, paradoxical vasoconstriction occurs in atherosclerosis in response to neurotransmitters such as serotonin and acetylcholine, which under normal circumstances cause vasodilation. There also is evidence that both macrophages and endothelial cells can regulate NO production through a specific mu 3 morphine receptor, an effect that can be blocked by naloxone. The clinical effectiveness of morphine and nitroglycerin in CAD patients may relate to these mechanisms. More research will be needed to elucidate the neuroimmunologic basis for atherosclerosis with prospects for better treatment and management in future.

Neuroleptic catatonia and its relationship to psychogenic catatonia.

Neuroleptics are among those pharmacological agents that can cause a nonpsychogenic catatonic state. Neuroleptic malignant syndrome (NMS) is marked by a change in state of consciousness, ranging from withdrawal through stupor to coma. In addition, it is characterized by autonomic dysfunction, hyperthermia, mutism, and rigidity. It is included in the differential diagnosis of the catatonic syndrome. Evidence is reviewed to suggest that agents responsible for improving NMS act on the dopamine (DA) gamma aminobutyric acid (GABA) connections in the mesostriatal and mesolimbic systems and also in the hypothalamus. In addition, based on symptomatology, pathophysiology, and therapeutic mechanisms, the relationship between nonpsychogenic neuroleptic-induced catatonia and psychogenic catatonia is examined.