Depression is a comorbidity of psoriasis. Suppression of neurotrophins has been proposed to cause depression. Peripheral brain‐derived neurotrophic factor (BDNF) and its precursor, pro‐BDNF have been shown to be altered in depression. To compare serum pro‐BDNF and BDNF levels, depression, anxiety, and quality of life (QoL) in psoriasis patients, diseased, and healthy controls, to assess impact of 12‐week antipsoriatic treatment on abovementioned markers. At baseline, all groups completed Beck Depression Inventory (BDI), Spielberger State‐Trait Anxiety Inventory‐II (STAI‐II) and DLQI; serum BDNF, proBDNF levels were measured. These were repeated after 3‐months of treatment in psoriasis patients. Depression and anxiety were significantly higher, QoL was poorer in psoriasis. ProBDNF and proBDNF/BDNF ratios were not different among groups at baseline but significantly decreased after treatment in psoriasis. Depression and QoL improved significantly, BDNF and anxiety scores did not change. Altered pro‐BDNF and proBDNF/BDNF ratios may have a role in depression pathogenesis in psoriasis. Antipsoriatic treatment causes improvement in depression, QoL, and reduction of proBDNF and proBDNF/BDNF ratios. Effective disease control may reverse dysregulated neurotrophin pathways and its consequences like depression.