Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans.

The effect of orally administrated gamma-aminobutyric acid (GABA) on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L-theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.

Drug targets in stress-related disorders.

Nervous and immune systems mutually cooperate via release of mediators of both neurological and immunological derivation. Adrenocorticotropin hormone (ACTH) is a product of the hypothalamus-pituitary adrenal axis (HPAA) which stimulates secretion of corticosteroids from adrenals. In turn, corticosteroids modulate the immune response in virtue of their anti-inflammatory activity. On the other hand, catecholamines, products of the sympathetic nervous system (SNS), regulate immune function by acting on specific beta-adrenergic receptors. Conversely, cytokines released by monocytes/macrophages and lymphocytes, upon antigenic stimulation, are able to cross the blood-brain-barrier, thus modulating nervous functions (e.g., thermoregulation, sleep, and appetite). However, cytokines are locally produced in the brain, especially in the hypothalamus, thus contributing to the development of anorexic, pyrogenic, somnogenic and behavioural effects. Besides pathogens and/or their products, the so-called stressors are able to activate both HPAA and SNS, thus influencing immune responses. In this respect, many studies conducted in medical students taking exams have evidenced an array of stress-induced immune alterations. Phobic disorders and migraine without aura (MWA) represent examples of stress-related disorders in which phagocytic immune deficits, endotoxemia and exaggerated levels of proinflammatory cytokines [Tumor Necrosis Factor-alpha (TNF- alpha), and interleukin- 1 beta] have been detected. Quite interestingly, administration of a thymic hormone could ameliorate clinical symptoms in phobic patients. In MWA patients, a beta-blocker, propranolol, could mitigate migraine, whose cessation coincided with a drop of TNF-alpha serum concentration. In phobic disorders and in MWA, benzodiazepines are very often administered and, in this respect, some of them, such as diazepam, inhibit immune functions, while others, e.g., alprazolam, enhance immune responses. Alprazolam could improve clinical symptoms in MWA patients. Chronic Fatigue Syndrome (CFS) is a disorder whose etiology and pathogenesis are still unknown. In this syndrome both abnormalities of nervous and immune systems have been reported. Despite many immune parameters evaluated in CFS no specific biomarkers of disease have been found. Our own data are in agreement with current literature in that we found decreased levels of serum (IFN)-gamma in these patients, thus indicating a predominance of T helper (h)1 response in CFS. Also leptin, a hormone which regulates food intake, fluctuates within normal ranges in CFS individuals. Quite interestingly, in depressed patients, used as controls, leptinaemia was more elevated than in CFS. Finally, in a series of recent therapeutic trials several immunomodulating agents have been used, such as staphypan Berna, lactic acid bacteria, kuibitang and intravenous immunoglobulin. In conclusion, it seems that major drug targets in stress-related disorders are immune cells in terms of inhibition of proinflammatory cytokines and modulation of Th responses. In particular, according to recent evidences, antidepressants seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing IFN- beta release or augmenting NK activity in depressed patients.

Worry affects the immune response to phobic fear.

Worry, the cognitive enumeration and anticipation of potential future negative events, is associated with autonomic dysregulation, which may in turn have implications for the immune system. People endorsing high (n = 7) and normal levels of trait worry (n = 8) were briefly exposed to a phobic stimulus and the autonomic and immune responses and recovery were assessed. A time-matched control group (n = 6) was not exposed to any stimulus. Both worry groups showed increased heart rate and skin conductance in response to phobic fear. However, only the normal worry group showed a concomitant increase in natural killer cells in peripheral blood. Patterns of change during the follow-up period suggested that phobic fear had disrupted a normal circadian increase in natural killer cells. Adrenergic and hypothalamus-pituitary-adrenal mechanisms may be responsible for the differences between high and normal worry groups in their natural killer cell response to and recovery from phobic fear.

Human brain-immune relationships: a PET study.

To study brain-immune relations, we correlated positron emission tomographic (PET) measures of regional cerebral blood flow (rCBF) with immune measures in 10 female volunteers. The natural killer (NK) activity correlated negatively with activity bilaterally in the secondary sensory cortex, whereas the Concanavalin A (Con A) response correlated positively with rCBF bilaterally in secondary visual, motor, and sensory cortices, the thalamus, the putamen, and the left hippocampus. Although representing preliminary data from a small number of subjects, these observations provide further support for the presence of interactions between the brain and the immune system.

Circulating lymphocyte phenotypic surface markers in anxiety disorder patients and normal volunteers.

BACKGROUND: Although the relationship between stress and immune function is an area of active investigation, there have been few reports studying the relationship between anxiety disorders and the immune system. METHODS: This study employs flow cytometry to measure circulating lymphocyte phenotypic markers in 20 medication-free patients with panic disorder, 33 medication-free patients with generalized social phobia, and 32 healthy controls. RESULTS: Both patients with panic disorder and patients with social phobia had increased CD16 (natural killer) cell numbers. Panic disorder patients also had increased numbers of CD19 cells (B lymphocytes), human leukocyte antigen (HLA)-DR-presenting cells, and more cells with the combination of HLA-DR and CD19 surface markers (B lymphocytes with HLA-DR on their surface). CONCLUSIONS: These preliminary data suggest that subjects with panic disorder may have alterations in circulating lymphocyte profiles.

Serum interleukin-2 and soluble interleukin-2 receptor levels in generalized social phobia.

Alternations in immune function have been described in a variety of psychiatric disorders including schizophrenia and depression; however, we do not know of any research involving social phobia and the immune system. This preliminary study explores the relationship between social phobia and two well-established immune parameters, serum interleukin-2 (IL-2) levels, a potent immune and central nervous system modulator, and soluble interleukin-2 receptors (SIL-2Rs), a well-known marker of T-cell activation. Fifteen subjects with generalized social phobia and 15 healthy volunteers had serum IL-2, and SIL-2Rs measured by enzyme-linked immunoassay. Subjects with social phobia and normal volunteers had similar mean serum IL-2 and SIL-2R levels. The data suggest that, unlike other psychiatric disorders, these immune measures may not be used to differentiate patients with generalized social phobia from normal volunteers.

[AIDS phobia (its clinical picture and typology)]. / SPIDofobiia (klinika, tipologiia).

Clinical, psychological and neurological examinations were performed of 478 subjects (208 males and 270 females) seeking confidential testing for HIV infection in one-on-one counseling facilities. The findings were correlated with serological evidence on HIV-antibodies and somatic status. The psychological response to seronegative, seropositive and false positive results was registered and compared to individual somatic status. Behavioral patterns were established for subjects with neurotic reactions, neurosis, neurosis-bordering condition, psychopathy and schizophrenia.

Role of thymic hormones in neuroimmunomodulation. Their use in patients with phobic disorders.

Many evidences support the existence of a bilateral connection between the thymic gland and the hypothalamic-pituitary-adrenal axis (HPAA). In this respect, neurohormones such as the adrenal corticotropin hormone and glucocorticoids cause thymic involution, while the growth hormone and the prolactin upregulate thymic functions. On the other hand, a thymic hormone, the thymosin fraction 5, activates the HPAA, thus closing-up the regulatory loop between immune system and nervous system. In this review, a clinical trial with two thymic hormones (Timostimolina and Thymopentin) in agoraphobic patients with phagocytic dysfunctions is reported. Results obtained indicate that both substances lead to a partial and temporary immunological recovery, since a further depression of phagocytic activities occurs in coincidence with panic attack. The use of alternative immunomodulators in these patients is discussed.

[Anxiety and immunologic disorder: phobia, generalized anxiety syndrome and panic attacks from the psychoimmunologic viewpoint with the intention of generating hypotheses]. / Angst und immunologische Störung: Phobien, generalisiertes Angstsyndrom und Panikattacken psycho-immunologisch betrachtet in hypothesengenerierender Absicht.

From a behaviour therapist's viewpoint anxiety is perceived in a framework expanded to the psycho-neuro-immunological dimension. After describing phobic anxieties, cognitive mechanisms, and allergic-immunological disturbances, clinical experience won from 34 phobic patients treated with behavior therapy is demonstrated. 31 of these proved to be poly-allergic. A comparison of both physiological fear and allergic symptoms lets a relationship seem obvious between anaphylactic or collapse inclination and psychological fear reaction. Mediated by cognitive variables persons with emphatic perception may develop an association between anxiety and allergic processes with high probability, the reciprocal influence of which can increase with vehemence. Comprehensive psychologic-medical diagnostic and therapeutic measures could improve the effectivity of therapy as well as anxious patients' "compliance" and "coping skills".

Impact of perceived self-efficacy in coping with stressors on components of the immune system.

This experiment examined the impact of experimentally varied perceived self-efficacy in exercising control over stressors on components of the immunological system. Immunological changes while coping with phobic stressors were measured within an intrasubject control design that included a baseline phase, an efficacy-acquisition phase, and a maximal-efficacy phase. In each of these phases, perceived coping self-efficacy, level of autonomic and endocrine activation, and several components of the immunological system were measured. Development of strong perceived self-efficacy to control phobic stressors had an immunoenhancing effect. A slow growth of perceived self-efficacy, heart rate acceleration, and cortisol activation attenuated immunological system status during the efficacy-acquisition phase. Rapid growth of perceived self-efficacy also predicted maintenance of immunoenhancement during the maximal perceived self-efficacy phase.

Administration of thymopentin to patients with phobic disorders improves depressed phagocytic functions.

Seven patients with phobic disorders were administered with a synthetic thymic extract, thymopentin (TP-5), in order to correct depressed polymorphonuclear cell (PMN) and monocyte phagocytosis and killing capacities. Subcutaneous administration (50 mg, three times weekly, for a period of 8 wks) of TP-5 resulted in a significant increase in phagocytic function with no change in the phagocytic capacity of PMN. These data support the concept that immunomodulators can achieve a correction of immune deficiencies associated with phobic disorders.

Immunological response to stress in agoraphobia and panic attacks.

The authors studied in vitro immune function as measured by lymphocytic proliferative response to mitogen stimulation in 36 patients with agoraphobia and panic attacks who were participating in a double-blind placebo-controlled psychopharmacological study of anxiety disorder. No significant difference in immune status was observed between panic patients and healthy controls.