Autoantibodies against acetylcholine receptors are increased in archived serum samples from patients with schizophrenia.

Previous studies have demonstrated that the levels of IgG against neurotransmitter receptors are increased in patients with schizophrenia. Genome-wide association (GWA) studies of schizophrenia confirmed that 108 loci harbouring over 300 genes were associated with schizophrenia. Although the functional implications of genetic variants are unclear, theoretical functional alterations of these genes could be replicated by the presence of autoantibodies. This study examined the levels of plasma IgG antibodies against four neurotransmitter receptors, CHRM4, GRM3, CHRNA4 and CHRNA5, using an in-house ELISA in 247 patients with schizophrenia and 344 non-psychiatric controls. Four peptides were designed based on in silico analysis with computational prediction of HLA-DRB1 restricted and B-cell epitopes. The relationship between plasma IgG levels and psychiatric symptoms, as defined by the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT), were examined. The results showed that the levels of plasma IgG against peptides derived from CHRM4 and CHRNA4 were significantly increased in patients with schizophrenia compared with control subjects, but there was no significant association of plasma IgG levels with any symptom domain or any specific symptoms. These preliminary results suggest that CHRM4 and CHRNA4 may be novel targets for autoantibody responses in schizophrenia, although the pathogenic relationship between increased serum autoantibody levels and schizophrenia symptoms remains unclear.

An examination of plasma autoantibodies against voltage gated calcium channels in schizophrenia.

Autoantibodies targeting the central nervous system have been shown to induce psychiatric symptoms resembling schizophrenia. Concurrently, genetic studies have characterised a number of risk variants associated with schizophrenia although their functional implications are largely unknown. Any biological effects of functional variants on protein function may potentially be replicated by the presence of autoantibodies against such proteins. Recent research has demonstrated that the R1346H variant in the CACNA1I gene coding for the Cav 3.3 protein results in a synaptic reduction of Cav3.3 voltage gated calcium channels and, consequently, sleep spindles, which have been shown to correlate with several symptom domains in patients with schizophrenia. The present study measured plasma levels of IgG against two peptides derived from CACNA1I and CACNA1C, respectively, in patients with schizophrenia and healthy controls. The results demonstrated that increased anti-CACNA1I IgG levels were associated with schizophrenia but not associated with any symptom domain related to the reduction of sleep spindles. In contrast to previously published work indicating that inflammation may be a marker for a depressive phenotype, plasma levels of IgG against either CACNA1I or CACNA1C peptides were not associated with depressive symptoms, suggesting that anti-Cav3.3 autoantibodies may function independently of pro-inflammatory processes.

An evaluation of mental health clinical pharmacist independent prescribers within general practice in remote and rural Scotland.

Background A 12-month pilot was implemented in two general practices in remote and rural Scotland, with patients referred by general practitioners to specialist mental health pharmacist independent prescribers. Objective The objective was to evaluate the pilot service from the perspectives of the patients and the care team. Methods The pharmacists routinely recorded patient-specific data of all clinical issues and their actions at the time of each consultation. Further datasets comprised baseline and follow-up Patient Health Questionnaire (PHQ-9) and/or Generalised Anxiety Disorder (GAD-7) rating scales, a patient survey and interviews with members of the care team. Results Of the 75 patients, two-thirds (n = 47, 62.7%) were referred with a diagnosis of mixed depression and anxiety. There were 324 consultations (median 3, IQR 2-5, range 1-14) and 181 prescribing actions. At pilot completion, 34 patients (45.3%) had PHQ-9 and/or GAD-7 scores reduced by 50%. Patient questionnaires and staff interviews generated positive responses. Conclusion This pilot has provided evidence that specialist mental health pharmacist independent prescribers delivered quality care to patients with diagnoses of moderate to severe depression and/or anxiety. Whilst accepting study limitations, there is potential to translate the pilot model of care to sustained services throughout general practice.