The Psoriasis and Comorbidity Series: ‘Neglected’ Comorbidities, Part 2—Mental Health

Last issue, we discussed the bidirectional relationship of psoriasis and obstructive sleep apnea (OSA) in which psoriasis can both result from and contribute to the development or worsening of OSA. Today, we will identify a similar bidirectional relationship between psoriasis and mental health disorders, specifically anxiety and depression. We look forward to connecting again next issue for the final installment in our comorbidity series on psoriasis and malignancy.

The disease burden of psoriasis extends beyond the physical symptoms experienced by patients. It affects all aspects of quality of life, including physical, psychological, social, sexual, and occupational elements via continuous exposure to stress, feelings of stigmatization, and disapproval of one’s external appearance, along with long-term problems associated with chronic disease.^1,2 Intuitively, skin diseases with visible physical symptoms such as psoriasis can lead to embarrassment and frustration, impacting a patient’s self-image, self-esteem, and sense of well-being. The subsequent self-stigmatization, self-isolation, and loss of social support can lead to loneliness, anxiety, and depression.²

Significance and Prevalence

Psoriasis affects 1% to 3% of the global population.³ In a study of 197 untreated patients with psoriasis, 9.7% “wished they were dead” at the time of the study, whereas 5.5% reported suicidal ideation.² A 2022 meta-analysis of 5 databases found a positive association between psoriasis and unspecified anxiety disorder (odds ratio 1.48 [1.18; 1.85]) and between psoriasis and anxiety symptoms (odds ratio 2.51 [2.02; 3.12]).⁴ Psoriasis has been associated with several mental health adverse effects, including increased risk of anxiety, depression, low self-esteem, alexithymia (difficulty identifying or expressing emotions), stress, self-harm, and suicidality.⁵

Although one might argue mental health is hardly a neglected area of medicine, mental health disorders in this high-risk population are still underrecognized and undertreated.⁶ Recent studies have reported that individuals with psoriasis are 2 to 3 times more likely to develop depression than the general population.⁷Moreover, patients with psoriasis have an elevated risk of suicidal ideation and behavior, including a potentially increased risk of completing suicide.⁶ Patients with psoriasis have a greater mental health comorbidity burden than patients without psoriasis (such as healthy or matched controls), reference populations, and individuals with other dermatologic conditions.⁵

Of note, multiple studies have shown that the psychological impact does not always correlate with the clinical severity of the ongoing skin disease.⁶ In other words, the severity of psoriasis affects quality of life, but not the degree of depression. Data suggest that social stigmatization, high stress levels, physical limitations, depression, employment problems, and other psychosocial comorbidities experienced by patients with psoriasis are not always proportional to, or predicted by, other measurements of disease severity, such as body surface area involvement or plaque severity.¹ Is the relationship of these diseases more complex than the original stigmatization hypothesis?

Shared Pathogenesis

The modern understanding of psoriasis has evolved from a chronic skin condition to a multifactorial systemic disease. Simultaneously, there has been increasing evidence supporting an association between anxiety, depression, and inflammation.⁴ Numerous studies have identified an independent, increased risk of mental health disorders in patients with psoriasis.⁶ Additionally, an increased risk of new-onset psoriasis among individuals with depressive symptoms suggests that the presence of a metal health condition may predispose patients to psoriasis or be the trigger in the psoriasis cycle rather than a result.⁵

Shared mechanisms in the pathogeneses of psoriasis and depression further support their bidirectional relationship. Identified mechanisms include a significant immune-mediated inflammatory overlap, such as an increase in the circulating inflammatory cytokines TNF- , IL-1 , IL-2, INF- , IL-6, IL-17, IL-13, IL-23, IL-10, C-reactive protein, and prostaglandin E2.^2,8,9 Studies of immune chemistry showed increased levels of CD2+, CD4+, and CD8+ T-lymphocytes in both conditions.^2,9 Brain derived neuropathic factor, which plays a role in neuropathic and mental health disorders, is decreased in both depression and psoriasis. Other mechanisms that play a role in the pathogenesis of both diseases include hyperactivity of the HPA-axis, leading to upregulation of the serotonin transporter gene 5-HTT and reduced circulating serotonergic neurotransmitters, low levels of melatonin, and vitamin D3 deficiency through a decrease in circulating regulatory T-cells.^2,4,9

Interventions and Recommendations

Psoriasis and depression amplify each other, which highlights the need to address both physical and psychological symptoms. The negative effect on quality of life paired with the independent, elevated risk of mental health disorders has the potential to create a vicious cycle.⁶ If left untreated, depression in patients with psoriasis or psoriatic arthritis can lead to higher rates of suicidality and self-harm.⁷

Novel therapeutic options for moderate to severe psoriasis include TNF- inhibitors, IL-17 inhibitors, and IL-23 inhibitors.⁷ Studies have shown that biologic treatment of psoriasis decreases symptoms of depression; however, psoriasis treatment does not always equal better odds for the remission of mental health disorders.⁶ Etanercept, adalimumab, infliximab, ustekinumab, and guselkumab can effectively reduce depressive symptoms in patients with psoriasis.⁷

Because of the substantial role that the psychosocial burden of psoriasis plays in patient perception of disease severity, quality of life, and disease course, a measure of psychosocial morbidity should be included when assessing disease severity and treatment efficacy.¹ Dermatologists should be particularly attentive to vulnerable subpopulations, including women; younger patients; patients with early onset of disease; those who self-assess their psoriasis to be severe; and patients with certain comorbid conditions such as psoriatic arthritis because they have been shown to carry an increased risk of mental and behavioral changes, including suicidal ideation.^2,6Additionally, patients who are experiencing depression may be nonadherent to treatment, creating a complexity to patient care.^4,6

Managing all comorbidities associated with psoriasis can constitute a considerable task for the clinician. The use of screening tools may help discover patients in need of referral to psychotherapy and other specialties or further investigation.⁶ Screening for comorbid depression and anxiety should be standardized and systematically implemented in dermatology practices to alleviate the associated psychological burden of psoriasis.

A consensus needs to be reached on specific depression screening tools to optimize the monitoring of changes in psychological symptoms of patients being treated for psoriatic disease across different treatment types.⁴ We recommend the free Patient Health Questionnaire-9 (PHQ-2/PHQ-9) depression assessment tool from the American Psychological Association, which is available in over 30 languages. The PHQ-2, comprising the first 2 items of the PHQ-9, asks the degree to which an individual has experienced a depressed mood and anhedonia in the past 2 weeks. Its purpose is to screen for depression, not to establish a diagnosis or monitor severity. Patients who screen positive should continue with the PHQ-9 questions to determine if they meet the criteria for a diagnosis of depression. For anxiety screening and diagnosis, the Generalized Anxiety Disorder-7 (GAD-2/GAD-7) assessment tool can be used.

A holistic approach to treating patients with psoriatic disease is recommended. A focus on not only skin symptoms but all aspects of the disease, including comorbidities, may improve disease management and prevent long-term mental and physical impairment.