Towards an understanding of depression and suicidality in psoriasis and psoriatic arthritis

Abstract

Although the high depressive burden of psoriasis is well-established, its underlying neurobiology and clinical, systemic inflammation-related correlates, in particular the role of psoriatic arthritis (PsA), are less understood. The thesis aims to address key current knowledge gaps in the comorbidity of psoriasis with depression and suicidality, primarily from a psychoimmunological angle and in the Covid-19 pandemic context, and investigate: (i) associations of PsA with affective burden in psoriasis; (ii) brain structure, connectivity and blood inflammatory substrates of comorbid psoriasis and depression; (iii) pandemic effects on depression, suicidality and illness perceptions in psoriasis. To address aim (i), a tertiary patient survey (single-centre) was conducted using validated psychometric questionnaires; replicability was tested in BADBIR (British Association of Dermatologists Biologic and Immunomodulators Register). PsA was associated with increased overall depressive burden and anxiety, but not suicidality, in psoriasis. The association of PsA with moderate-to-severe depression was not robust. However, one in three patients with PsA showed a depressive syndrome, and half of all tertiary patients with psoriasis experienced lifetime suicidality; depression was undiagnosed in 24-50% of cases. For aim (ii), UK Biobank magnetic resonance imaging (MRI) and blood biomarker data were used. In a cross-sectional analysis of over 5,000 UK Biobank participants with psoriasis, both lifetime and current depression contributed to neutrophil count increases among women. Neurostructurally, in a matched sample of 1,048 patients with psoriasis and controls, the psoriasis-depression comorbidity was marked by increased precuneus cortical thickness. Although psoriasis did not affect brain volume and structural connectivity, there was a depression-independent reduction in resting-state functional fronto-occipital connectivity in psoriasis, accentuated by PsA. These brain changes were not associated with increased neutrophil or C-reactive protein levels. Finally, regarding aim (iii), a longitudinal survey design of tertiary patients with psoriasis found deteriorating mood and 12-month suicidality as the pandemic progressed, without overall depressive symptom change. Furthermore, in a cross-sectional analysis, depression did not additionally aggravate, and may have attenuated, the worsening observed in patients' psoriasis treatment perceptions during the pandemic compared to pre-pandemic. These findings highlight the need for routine depression screening in psoriasis, in particular when PsA co-exists, and suicidality monitoring, in particular in the post-pandemic era. This thesis also provides some evidence that supports neutrophil-associated substrates of the psoriasis-depression link in female patients, and suggests a distinct neurostructural signature of depression in psoriasis. Overall, these findings are expected to help improve the detection and management of depression and suicidality comorbidity in psoriasis and inform future research in the translationally important field of depression in chronic systemic inflammatory disease.

Date of Award	1 Aug 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Hector Chinoy (Supervisor), Elise Kleyn MBChB, FRCP, MMedSci, PhD (Supervisor), Richard Warren (Supervisor), Peter Talbot (Supervisor) & Martyn Mcfarquhar (Supervisor)