Digging deeper in the differential effects of inflammatory and psychosocial stressors in remitted depression: Effects on cognitive functioning

Abstract

Background: Major Depressive Disorder (MDD) covers a wide spectrum of symptoms, including cognitive dysfunction, which can persist during remission. Both inflammatory states and psychosocial stress play a role in MDD pathogenesis.

Methods: The effects of inflammatory (i.e., Salmonella typhi vaccine) and psychosocial stressor (i.e., Trier Social Stress Test), as well as their combination were investigated on cognition in women (aged 25-45 years, n = 21) with (partially) remitted MDD and healthy controls (n = 18) in a single-blind placebo-controlled study. In a crossover design, patients received on the first day one of the aforementioned interventions and on the other day a placebo, or vice versa, with a washout period of 7-14 days. Short-term and verbal memory, working memory, attention, verbal fluency, information processing speed, psychomotor function, and measures of attentional bias to emotions were measured. Exploratory analyses were performed to assess the correlation between biomarkers of inflammation and the Hypothalamic-Pituitary-Adrenal axis and cognitive functioning.

Results: In patients, inflammatory stress decreased information processing speed and verbal memory, and increased working memory; after psychosocial stress, there was an increase in attention. There was also an increased negative attentional bias in patients after inflammatory stress. Neither stressor had any effect in controls.

Limitiations: Limitations are the relatively small sample size and antidepressant use by a part of the participants. The effects of the stressors were also measured a relatively short period after administration.

Conculsion: Patients were sensitive to the cognitive effects of inflammation and psychosocial stress on cognition, while controls were not.

Trial registration: ClinicalTrials.gov NCT01533285.

Keywords: ACTH; AUC; Acetylcholine Esterase; AchE; Area Under the Curve; BMI; COWAT; CPT; CRH; CTQ; Childhood Trauma Questionnaire; Cognition; Continuous Performance Test; Controlled Oral Word Association Test; Corticotropin Releasing Hormone; Depression; HPA axis; HVLT; Hopkins Verbal Learning Test; Hypothalamic-Pituitary-Adrenal axis; IFN-α; IFN-γ; IL-6; Inflammation; Interferon-gamma; Interleukin-6; KYN; KYNA; LCT; Line Copying Test; MADRS; MDD; Major Depressive Disorder; Montgomery–Åsberg Depression Rating Scale; N-methyl-D-aspartate; NMDA; Psychosocial stress; QUIN; SDST; Symbol Digit Substition Test; TNF-α; TSST; Trier Social Stress Test; Tumor Necrosis Factor-Alpha; Typhoid vaccine; adrenocorticotropic hormone; body mass index; kynurenic acid; kynurenine; quinolinic acid; α-7 nicotinic acetylcholine receptor; α7nAchR.