Major depressive disorder is a serious mental disorder that profoundly affects an individual's quality of life. Although the aetiologies underlying this disorder remain unclear, an increasing attention has been focused on the influence imposed by psychological stress over depression. Despite limited animal models of psychological stress, significant progress has been made as to be explicated in this review to elucidate the physiopathology underlying depression and to treat depressive symptoms. Therefore, we will review classical models along with new methods that will enrich our knowledge of this disorder.

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The Effects of Psychological Stress on Depression

For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.

Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?

Rosacea is a chronic cutaneous inflammatory disease that affects the facial skin. Clinically, rosacea can be categorized into papulopustular, erythematotelangiectatic, ocular, and phymatous rosacea. However, the phenotypic presentations of rosacea are more heterogeneous. Although the pathophysiology of rosacea remains to be elucidated, immunologic alterations and neurovascular dysregulation are thought to have important roles in initiating and strengthening the clinical manifestations of rosacea. In this article, we present the possible molecular mechanisms of rosacea based on recent laboratory and clinical studies. We describe the genetic predisposition for rosacea along with its associated diseases, triggering factors, and suggested management options in detail based on the underlying molecular biology. Understanding the molecular pathomechanisms of rosacea will likely aid toward better comprehending its complex pathogenesis.

https://www.mdpi.com/1422-0067/17/9/1562/pdf/1

Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition

Psoriasis and anxiety are chronic conditions with significant morbidity and there is evidence that they may exacerbate one another. There is little data on the prevalence of anxiety in psoriasis and the effect of psoriasis treatment on comorbid anxiety. The objective of this study was to perform a systematic review of the literature to describe the prevalence and severity of clinical anxiety disorders or anxiety symptoms among adult patients with psoriasis and characterize the effect of anti-psoriatic interventions on clinical anxiety disorders or anxiety symptoms. We searched PubMed, EMBASE, and the Cochrane Database using search terms 'psoriasis' and 'anxiety'. Results were tabulated and verified by two independent reviewers. Meta-analyses were not performed due to heterogeneity of data. Of 213 publications identified, 938 194 patients from 15 papers were included. The mean age ranged from 31.9-59.4 years old, with a mean PASI score of 7.65-22.8 (reported by nine studies) and a body surface area involvement of 25.9-39.8% (reported by two studies). The prevalence of anxiety in patients with psoriasis was 7-48%, which was significantly higher than healthy controls in two of three studies (HR 1.29-1.31, P = 0.001 and OR 2.91 [95% CI, 2.01-4.21], P < 0.001). Four of five studies (n = 2029) demonstrated an improvement in anxiety symptoms with psoriasis treatment. This review demonstrates a high prevalence of anxiety of adult patients with psoriasis suggesting that patients would benefit from systematic screening. Although the data suggest that anxiety may be improved through various psoriasis treatments, larger prospective randomized trials are needed to confirm this effect.

The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials.

Psychodermatology is an evolving area of science that focuses on the interaction between the mind, skin and body. It is known that various neuroendocrine mediators - including adrenocorticotropin, β-endorphin, catecholamines and cortisol - are produced in response to stress. The resulting increase in endogenous glucocorticoids can disrupt the skin's barrier function, leaving it vulnerable to inflammatory disorders like atopic dermatitis (AD). In turn, AD is associated with high levels of stigmatization, social withdrawal, anxiety and depression among patients and their carers. It is well known that the stress caused by AD can make the symptoms of the disease worse. Therefore, the goal of psychodermatological treatment is not only to improve the condition of the skin, but also to teach patients/carers how to cope with the disease. This requires a multifaceted approach, and time and patience, to ascertain the needs of individual patients. A multidisciplinary team that includes a dermatologist, psychiatrist and psychologist will be necessary to deliver high-quality, tailored care to patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjd.13084

Psychodermatological aspects of atopic dermatitis.

Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

/pdf/psychological-stress-and-the-cutaneous-immune-response-roles-1yfndue61s.pdf

Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis.

Psychotic, sleepless, and depressed, Mr. F decides to make a new start in another country. When his travel plans are interrupted, his psychosis worsens. What could be exacerbating his symptoms? CASE Psychotic and sleepless Mr. F, age 30, is referred to our psychiatric outpatient clinic for follow-up care after hospitalization to treat a psychotic episode. His psychotic symptoms started 2 years ago without an identifiable trigger. Mr. F complains of episodic mood symptoms, such as depression, irritability, and angry outbursts; persistent auditory hallucinations (voices calling him names); and persecutory delusions. While in the hospital he was diagnosed with psychotic disorder not otherwise specified and started on olanzapine titrated to 30 mg/d. During evaluation, Mr. F is depressed and exhibits motor retardation, slow speech, bland affect, impaired short-term memory, and auditory hallucinations. He describes social anxiety and has ideas of reference and problems interpreting facial expressions. He is guarded and suspicious. Although auditory hallucinations and depression affect Mr. F's daily activities, he is attempting to find a job. Mr. F has used alcohol since age 16 to escape social difficulties. He says he last used alcohol 1 year ago, but refuses to provide details about how much alcohol he typically consumed. Sporadic cannabis use also started when Mr. F was in his teens. Mr. F's symptoms improve with olanzapine, but he complains of weight gain and sedation, so we switch him to aripiprazole, 10 mg/d. Two weeks later he reports feeling jittery and anxious, so we discontinue aripiprazole and start loxapine, 25 mg/d at night, and propranolol, 60 mg/d, for residual akathisia. Despite limited clinical improvement, Mr. F irrationally says he wants to join the Navy. After a week, his psychotic symptoms improve but anxiety persists, so we start clonazepam, 1 mg/d, and oxcarbazepine, 600 mg/d. After 2 weeks he says he feels calmer, but has gained 20 lbs and is constantly tired. Against our advice, Mr. F decides to discontinue loxapine and propranolol, but continues clonazepam and oxcarbazepine. At his next visit 4 weeks later, Mr. F is in good spirits. He says he is looking for a job as a dental assistant, and shows no apparent signs of psychosis. Mr. F misses his next appointment but returns 3 months later with evident deterioration in his general appearance. He says he is having difficulty sleeping and is depressed, stating "I just lay in bed; I don't want to deal with life." He is withdrawn and unwilling to elaborate on his personal problems but asks for a refill of clonazepam and oxcarbazepine, which we provide. What is the significance of Mr. F's sleep disturbance? a) sleep disturbance is a core feature of schizophrenia b) sleep disturbance can indicate exacerbation of schizophrenia c) sleep disturbance is secondary to psychotropic medications d) all of the above The authors' observations Sleep disturbances, including poor sleep efficiency, increased sleep-onset latency, decreased rapid eye movement (REM) sleep latency, and decreased stage 4 of non-REM sleep, occur in 16% to 30% of patients with schizophrenia and are associated with reduced quality of life and poor coping skills. (1) Sleep-onset and sleep maintenance problems and sleep-wake reversal generally persist despite antipsychotic treatment. (2), (3) Slow-wave sleep deficiency can lead to negative symptoms and memory deficits in patients with schizophrenia because (4): * declarative and procedural memory consolidation are associated with slow-wave and stage 2 sleep, respectively * procedural learning and visual spatial memory are correlated with delta power in slow-wave sleep. (3), (8) Acute psychosis exacerbations are associated with restless, agitated sleep. Insomnia often is an early warning sign of clinical relapse. …

Diana I. Mummert

Papers

Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis.

Descent after a Missed Flight