[Show abstract][Hide abstract] ABSTRACT: Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls.
We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α. These immune parameters were compared in schizophrenia with childhood trauma, schizophrenia without childhood trauma and healthy controls.
Patients with childhood trauma had higher levels of IL-6 and TNF-α than patients without trauma and healthy controls, and TNF-α levels correlated with the extent of the trauma. Patients with no trauma had similar immune profiles to controls.
Childhood trauma drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.
Psychological Medicine 02/2012; 42(9):1865-71. · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Toll-like receptors (TLRs) are pattern recognition receptors that play an important role as mediators of innate immunity. Human studies have shown changes in endometrial TLR expression during the menstrual cycle and during pregnancy. Our objective was to measure peripheral TLR activity over the course of the menstrual cycle.
We recruited 11 healthy females, and using ELISA we measured sex hormone levels and IL-1β, IL-6, IL-8 and TNF-α following stimulation of whole blood with different TLR agonists during follicular, and early and late luteal phases of the menstrual cycle.
During the follicular phase, we observed lower levels of IL-6 and TNF-α following stimulation with the TLR2 agonist HKLM when compared with the early luteal phase; lower levels of IL-1β, IL-6 and TNF-α following stimulation with the TLR4 agonist LPS, and lower levels of IL-1β and TNF-α following stimulation with the TLR5 agonist flagellin. Decreased IL-6 levels in the late compared to the early luteal phase were also observed following stimulation with the TLR5 agonist flagellin. Compared with the follicular phase, the late luteal phase of the cycle resulted in decreased levels of IL-1β and TNF-α following stimulation with the TLR1/TLR2 agonist Pam3CSK and the TLR6/TLR2 agonist FSL1, as well as decreased levels of TNF-α following stimulation with the TLR8 agonist ssRNA40. There were no differences in cytokine release across the menstrual cycle following stimulation with the TLR3 agonist polyriboinosinic polyribocytidylic acid, or the TLR7 agonist Imiquimod.
This study is the first to demonstrate that TLR responsivity in peripheral blood fluctuates throughout the menstrual cycle.
[Show abstract][Hide abstract] ABSTRACT: Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders.
[Show abstract][Hide abstract] ABSTRACT: Lithium is a commonly prescribed pharmacological treatment for mood disorders. It is associated with a number of side effects and potentially serious toxicity. To date, there is little data from Irish samples on the subject of Lithium toxicity.
To examine the incidence and clinical correlates of lithium toxicity in Cork, Ireland.
Our study identified 130 cases of biochemical lithium toxicity over 5 years, with an incidence rate of approximately 5.4 cases per 100,000 per year. Mean toxic lithium level was 2.16 mmol/L ±SD 0.87 mmol/L. Of these, 36% cases were reviewed medically in the general hospital at the time of toxicity. A number of issues in relation to lithium toxicity were identified. Neurological symptoms were common, including tremor, confusion, ataxia, drowsiness. However, only 4.2% patients were reviewed by a neurologist while in hospital. Medications that interact with lithium were found in 50% cases, with significant polypharmacy in 15%. The psychiatric services were involved in patient care in 76% cases, and 85% patients presenting with toxicity were reviewed by a psychiatrist. Rates of admission to hospital and haemodialysis were 70 and 11%, respectively.
Improvements in the standards of care in relation to lithium prescribing are required.
Irish Journal of Medical Science 04/2011; 180(3):661-5. · 0.51 Impact Factor