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July 2009

Basic aspects of psychodermatology.

Psychodermatological or psychocutaneous disorders are conditions resulting from the interaction between the mind and the skin. There are three major groups of psychodermatological disorders; psychophysiologic disorders, psychiatric disorders with dermatologic symptoms, and dermatologic disorders with psychiatric symptoms. Along with the standard dermatological treatment, majority of these disorders can be treated with cognitive-bihevioral psychotherapy, psychoterapeutic stress-and-anxiety-management technicques and psychotropic drugs. Therefore, understanding of biopsychosocial approaches and liaison approach involving general practice, psychiatrist, dermatologist and psychologist treatment in this field is essential.

Psychiatr Danub. 2008 Sep;20(3):415-8

Neuroimmunoendocrine circuitry of the ‘brain-skin connection’.

The skin offers an ideally suited, clinically relevant model for studying the crossroads between peripheral and systemic responses to stress. A ‘brain-skin connection’ with local neuroimmunoendocrine circuitry underlies the pathogenesis of allergic and inflammatory skin diseases, triggered or aggravated by stress. In stressed mice, corticotropin-releasing hormone, nerve growth factor, neurotensin, substance P and mast cells are recruited hierarchically to induce neurogenic skin inflammation, which inhibits hair growth. The hair follicle is both a target and a source for immunomodulatory stress mediators, and has an equivalent of the hypothalamus-pituitary-adrenal axis. Thus, the skin and its appendages enable the study of complex neuroimmunoendocrine responses that peripheral tissues launch upon stress exposure, as a basis for identifying new targets for therapeutic stress intervention.

Trends Immunol. 2006 Jan;27(1):32-9

Safety update on commonly used psychotropic medications in dermatology.

It is the experience of dermatologists worldwide that a significant proportion of their patient population has underlying psychological components to their dermatologic complaints. Since these patients are often reluctant to see a mental health professional, the effective management of the underlying psychopathology may require the use of psychotropic medications by the dermatologists. This paper aims to update dermatologists on recent safety information on some of the most commonly prescribed psychotropic medications in psychodermatology. In the process it will also address the implications of these recent safety updates for prescribing clinicians.

J Drugs Dermatol. 2006 Feb;5(2):109-15

Atopic dermatitis and stress? How do emotions come into skin?

It is widely accepted, that stress can induce or exacerbate atopic dermatitis. The physiological mechanisms that mediate this negative influence of stress on atopic dermatitis are not clearly understood. This topic has been actively investigated in recent years focusing on neuroimmunological, psychoendocrinological studies and examination of integrity and function of skin barrier under stress. Different neuropeptides and neurotrophins seem to play an important role in stress-induced neurogenic inflammation and connection of nervous and immune system. Mast cells play a key role in the development of inflammatory reaction to stress. Skin barrier is altered by stress by means of increased cortisol level. Thereby lamellar body secretion is decreased and epidermal expression of antimicrobial peptides (beta-defensin and cathelicidin) is down-regulated. We review recent investigations in this field.

Hautarzt. 2008 Apr;59(4):314-8

The sex steroid precursor DHEA accelerates cutaneous wound healing via the estrogen receptors.

Age-related impaired wound healing states lead to substantial morbidity and cost, with treatment in the USA resulting in an expenditure of over $9 billion per annum. Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with immunomodulatory properties whose levels decline significantly with advanced age in humans. Conversion of DHEA locally to downstream steroid hormones leads to estrogenic and/or androgenic effects which may be important in age-related skin homeostasis, and which would avoid systemic adverse effects related to estrogen. We report that systemic DHEA levels are strongly associated with protection against chronic venous ulceration in humans. DHEA accelerated impaired healing in an impaired healing model (mice rendered hypogonadal) associated with increased matrix deposition and dampens the exaggerated inflammatory response. Such effects were mediated by local conversion of DHEA to estrogen, acting through the estrogen receptor, and vitro studies suggest a direct effect on specific pro-inflammatory cytokine production by macrophages via mitogen activated kinase (MAP) and phosphatidylinositol 3 (PI3) kinase pathways. In addition, we show that local injection of DHEA accelerates impaired healing in an ageing mouse colony. We suggest that exogenous application of DHEA accelerates impaired wound repair, results which may be applicable to the prophylaxis and treatment of human impaired wound healing states.

J Invest Dermatol. 2005 Nov;125(5):1053-62

Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a “young” concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create “supermen/women” (doping).

Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4279-84

Psychological approach to different skin diseases: life events and tendency to complain.

BACKGROUND: For nearly two decades, dermatology has associated with psychology to find a better way to care for dermatology conditions. A scientific trend called psychosomatics is creating a link between dermatology and psychology. OBJECTIVE: The purpose of this article was to examine two concepts closely linked to psychodermatology (life events and tendency to complain) and to emphasize the difference between factors playing a role in the onset of certain skin diseases (psoriasis, alopecia areata, benign tumors, eczema). RESULTS: We found that psoriasis patients have a greater tendency to complain than people with the other disease. This point to the importance of taking emotions into account when studying psoriasis. We also found that life events play a role in the onset of psoriasis and alopecia areata. Moreover, these events were anterior by more than 12 months in alopecia patients. CONCLUSION: We propose exploring emotions in psoriasis patients and life events over the prior year in alopecia areata patients.

Ann Dermatol Venereol. 2001 Jan;128(1):21-4

Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress.

Withania somnifera (WS) Dunal is classified in Ayurveda, the ancient Hindu system of medicine, as a rasayana, a group of plant-derived drugs reputed to promote physical and mental health, augment resistance of the body against disease and diverse adverse environmental factors, revitalise the body in debilitated conditions and increase longevity. These attributes are remarkably similar to the properties ascribed to adaptogens like Panax ginseng (PG) in contemporary medicine. As such, the adaptogenic activity of a standardised extract of WS roots was investigated against a rat model of chronic stress (CS). The stress procedure was mild, unpredictable footshock, administered once daily for 21 days to adult male Wistar rats. CS induced significant hyperglycaemia, glucose intolerance, increase in plasma corticosterone levels, gastric ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and mental depression. These CS induced perturbations were attenuated by WS (25 and 50 mg/kg po) and by PG (100 mg/kg po), administered 1 h before footshock for 21 days. The results indicate that WS, like PG, has significant antistress adaptogenic activity, confirming the clinical use of the plant in Ayurveda.

Pharmacol Biochem Behav. 2003 Jun;75(3):547-55

Central role of Ferrous/Ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts.

Reactive oxygen species (ROS) are important second messengers for the induction of several genes in a variety of physiological and pathological conditions. Ultraviolet B (UVB) irradiation has recently been shown to generate lipid peroxidation products and hydroxyl radicals (HO.) with detrimental long term effects like cancer formation and premature aging of the skin. Here, we addressed the question of whether ferric/ferrous iron via the generation of ROS may mediate the UVB response, finally leading to connective tissue degradation, a hallmark in carcinogenesis and aging. Therefore, we studied the involvement of iron and ROS in the modulation of Jun N-terminal kinase 2 (JNK2) activity, c-jun and c-fos mRNA levels, key signaling steps in the transcriptional control of matrix-degrading metalloprotease (MMP)-1/interstitial collagenase and MMP-3/stromelysin-1 after UVB irradiation of human dermal fibroblasts in vitro. The iron-driven generation of lipid peroxides and hydroxyl radicals were identified as early events in the downstream signaling pathway of the UVB response leading to a 15-fold increase in JNK2 activity, a 3.5-fold increase in c-jun, to a 6-fold increase in MMP-1, and a 3.8-fold increase in MMP-3 mRNA levels, while virtually no alteration of c-fos mRNA levels were observed. Diminished generation of reactive oxygen species resulted in a significant reduction of JNK2 activity, c-jun, MMP-1, and MMP-3 mRNA levels after UVB irradiation compared with UVB-irradiated cells. Collectively, we have identified the iron-driven Fenton reaction and lipid peroxidation as possible central mechanisms underlying signal transduction of the UVB response.

J Biol Chem. 1998 Feb 27;273(9):5279-87

Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture.

Hyaluronan (HA) is produced by keratinocytes in human skin organ culture, and degraded locally in epidermis by an unknown metabolic route. The present work tested whether reactive oxygen species (ROS), spontaneously produced in the tissue, could contribute to HA catabolism in epidermis. Epidermal HA was endogenously labeled with 3H-glucosamine for 24 h, then chased for 24 h in the presence of superoxide dismutase (SOD) and catalase to reduce the concentration of ROS. In control cultures, 35% of labeled HA was degraded during the 24 h chase while the corresponding figures in the presence of SOD and catalase were 19% and 23%, respectively (p < 0.05). Methionine, a quencher of hypochlorous acid, did not significantly inhibit the degradation. In additional experiments, the iron and copper chelator Detapac was even more effective, reducing the degradation to 8-9%, and suggesting that the ROS responsible for the degradation were produced in the Fenton reaction. Dermal HA, and proteoglycans in both epidermis and dermis were not influenced by the treatments, indicating that the inhibition by SOD, catalase and Detapac on epidermal HA catabolism was specific. It is suggested that endogenous ROS is involved in the catabolism human epidermal HA.

Free Radic Biol Med. 1997;23(7):996-1001