Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

Abstract

The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of cytokines and stress-related mediators. Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia. We determined the relationship between cortisol, cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6), and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs. Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients. SCH were randomly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum cortisol and IL-2 levels were assayed by radioimmunometric assay, and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay. Following a 2-week washout period, serum levels of cortisol, IL-2, and IL-6 were increased in patients with schizophrenia compared to HC. Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH. Moreover, elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms. In all, 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms, but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol. The improvement of negative symptoms was related to the change in cortisol. Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms, and is improved with atypical antipsychotic treatment.

Serum Cortisol and DHEA-S Levels in Schizophrenic Patients with Different Response to Antipsychotic Therapy: Association with Psychopathology / Серумски Концентрации На Кортизол И DHEA-S Кал Пациенти Со Шизофренша Со Различен Одговор На Антипсихотичната Терапша Асоци.1Аци.1А Со Психопатологшата

“…Our study showed that plasma cortisol levels were significantly elevated in the group of patients with schizophrenia compared with controls, which is in agreement with the results of most of the studies [2][3][4][5][6][7][8][9]. However there arestudies reporting no significant differences between the schizophrenic patients and healthy controls in terms of cortisol levels [10,29], as well as lower cortisol levels in patients with schizophrenia [11].…”

“…HPA axis abnormalities may cause an increase in the baseline cortisol level [3]. It has been demonstrated that serum baseline cortisol levels are increased in patients with schizophrenia [2][3][4][5][6][7][8][9]. However there are also other studies with contrary findings [10][11].…”

“…In some studies cortisol secretion was primarily associated with more severe positive symptoms [2,5,25], whereas in others it was associated with higher ratings of negative symptoms [7,17,26]. It has been suggested that the relation between cortisol levels and symptoms severity is due to the augmenting effects of cortisol on dopamine activity [27].…”

Brain morphological changes associated with exposure to HSV1 in first-episode schizophrenia

“…Animal studies have shown that circulating glucocorticoids play a permissive role in inducing the host immune response and behavioral changes such as increased locomotion and aggression. 24 Interestingly, several studies have reported elevated cortisol levels, increased production of interleukin-2 (IL-2) and IL-6 45,46 and increased volume of the pituitary gland 47,48 in schizophrenia patients compared to healthy controls. IL6 has been shown to stimulate the hypothalamicpituitary axis 46 thus possibly setting up a vicious circle that may confer vulnerability to brain structural alterations in schizophrenia patients but not in healthy subjects.…”

Technology of Immunocorrection at Mental Disorders

“…В исследованиях X.Y. Zhang et al (2005) после 12-недельного лечения рисперидоном выявлено значительное снижение повышенного до начала терапии уровня кортизола параллельно с редукцией негатив-ной симптоматики и снижение повышенной концентрации IL-2 и IL-6 параллельно с положительной динамикой позитивных симптомов. Подобное влияние на повышение уровня IL-2 и IL-6 и на позитив-ные симптомы установлено после лечения галоперидолом.…”