Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder.

BACKGROUND: Proinflammatory cytokines have been reported to be elevated in individuals experiencing chronic stress as well as in those with major depressive disorder. Much less is known about cytokines in anxiety disorders such as posttraumatic stress disorder (PTSD) and panic disorder (PD). We hypothesized that PD and PTSD would be associated with a generalized proinflammatory cytokine signature. METHOD: We utilized Luminex technology to examine 20 cytokines and chemokines in serum from 48 well-characterized individuals with a primary DSM-IV PD or PTSD diagnosis, and 48 age- and gender-matched healthy controls. We conservatively employed a Bonferroni correction for multiple testing (alpha=.05/20=.0025). RESULTS: Individuals with primary PTSD or PD had significantly elevated median peripheral cytokine levels for 18 of 20 different cytokines compared to age- and gender-matched healthy controls (all P<.0025). To assess for the presence of a generalized proinflammatory state, we also examined the proportion of subjects with detectable levels of at least six of nine common proinflammatory cytokines and chemokines (IL-6, IL-1alpha, IL-1beta, IL-8, MCP-1, MIP-1alpha, Eotaxin, GM-CSF, and IFN-alpha). For men and women, 87% of anxiety patients had six or more detectable levels of these proinflammatory cytokines, compared with only 25% of controls (Fisher's Exact Test (FET) P=.000). Confirmatory analysis of the subset of individuals without current psychiatric medication use or comorbid depression was of comparable significance. CONCLUSIONS: These findings suggest that a generalized inflammatory state may be present in individuals with PD or PTSD.

Plasma levels of tumor necrosis factor-alpha in patients with panic disorder: effect of alprazolam therapy.

Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) were measured in 10 outpatients with panic disorder, twice (at a 48-h interval) before and twice on days 30-32 of treatment with alprazolam (2-2.5 mg/day), and twice in 10 age- and sex-matched healthy controls. TNF-alpha concentrations did not differ in patients and control subjects, either before therapy or at days 30-32 of therapy. In five patients before therapy, and in three of them after therapy, TNF-alpha values were higher than the maximal concentrations of the cytokine in controls.

The psychoimmunological association of panic disorder and allergic reaction.

During treatment of out-patients suffering from DSM-III R panic disorder (PD) with and without agoraphobia, our attention was drawn to a high frequency of comorbid allergic reactions. In a controlled study, the prevalence of immediate type I reactions was determined in panic patients. Conversely, the prevalence of psychological disorders was recorded among allergic patients. Altogether, 79 out-patients with PD, 100 type I allergic out-patients and 66 controls underwent structured clinical interviews and tests for allergies. Of the patients suffering from PD, 70 per cent displayed type I immediate reactions (controls = 29 per cent). Vasodilatation (often approaching circulation collapse) is a frequently occurring allergic syndrome which is a very dramatic experience. Fifty per cent of the allergic patients showed mild to severe psychological disturbances (controls = 25 per cent); and 16 per cent had problems requiring treatment (controls = 9 per cent). Ten per cent of the allergic patients revealed PD (controls = 2 per cent). The association between PD and allergic (vasomotor) reactions was found to be highly significant. A functional relationship is hypothesized in terms of conditioning cognitive and vasomotor interactions during autonomic arousal.

[The psychoimmunological network og panic disorders, agoraphobia and allergic reactions]. / Das psychoimmunologische Netzwerk von Panikstörung, Agoraphobie und allergischer Reaktion.

While treating panic and agoraphobia patients with behaviour therapy, a high frequency of allergic reaction of the IgE-mediated type I was observed. Panic disorder, agoraphobia, allergic disorder, and vasomotor reactions are briefly discussed in the framework of psycho-endocrino-immunological research. A pilot study had shown a high correlation between panic disorder with and without agoraphobia and allergic reaction. A controlled study was then planned to test the hypothesized psychoimmunological relationship. 100 allergic patients, 79 panic/agoraphobic patients, and 66 controls underwent psychodiagnostic and allergic screening. 70% of the anxiety patients responded to test allergens with IgE-mediated type-I immediate reactions in comparison to 28% of the control persons. Another 15% of the panic patients reacted to nickle compound with type-IV delayed skin reactions (7% of the controls). Conversely, 10% of the allergic patients suffered from panic disorder (45% had experienced panic attacks) in contrast to 2% of the controls (24% of these reported panic attacks). The relative risk for allergic patients to develop panic disorder with and without agoraphobia is obviously five times as high as for controls. With this assumption of a psychoimmunological preparedness in mind, a behavioural medical diagnostic and therapeutic concept seems more adequate in coping both with panic/agoraphobia and allergic disorder.

[Psychoimmunologic correlation between allergies, panic and agoraphobia]. / Psychoimmunologischer Zusammenhang zwischen Allergien, Panik und Agoraphobie.

The present behavioral medical paper is a contribution to basic research in neuroimmunology. The relationship of panic/agoraphobia and allergy/anaphylaxis (IgE-mediated immediate reaction) is demonstrated and discussed with specific consideration of vasomotor reactions, tachycardia and hyperventilation in panic patients and allergies with anaphylactic reactions. The vegetative symptoms of panic reactions and anaphylaxis showed a high correlative correspondence. 74% of 23 panic and/or agoraphobia patients in a pretest to an epidemiologic study turned out to have an allergic illness that needed treatment; but there were no more anxiety disorders disclosed in 50 allergic patients than in the general population according to expectancies found in epidemiologic publications. If these data are confirmed then panic and agoraphobia cannot be seen as merely a cognitive-emotional event, but also as a further kind of allergic disease with genetic, ecological, psychological and social determinants; they would then have to be diagnosed as psychoimmunological disturbances and treated with behavior medicine (preferably with exposition and immunotherapy or hyposensitization). Anxiety therapies would improve qualitatively and could be cut down in duration.

Psychoimmunoendocrine aspects of panic disorder.

Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.

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.