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Immune system abnormalities exist across a range of psychiatric disorders. Autoimmunity, characterized by the production of antibodies against the body’s own antigens, is a feature of immune system dysfunction and could play a role in mental disorder pathophysiology. Better understanding of the associations of auto-immunoglobulin G (IgG) repertoires with clinical features of mental illness could yield novel models of psychosis pathophysiology and markers for biological patient stratification.
To undertake global screening for auto-IgG expression in a large cohort of people with psychotic disorders; to determine whether associations exist between autoantibody expression and clinical features.
Cross-sectional quantification of auto-IgGs in blood plasma of 461 people with established psychotic disorder diagnoses. For global screening, pooled samples of phenotypically representative patient groups were exposed to planar protein microarrays containing 42,000 human antigens. For targeted profiling, expression levels of 380 autoantibodies were quantified by suspension bead array (SBA) in each patient’s plasma.
We identified highly individual autoantibody profiles with no evidence for co-expression patterns. We found 6 autoantibodies robustly associated with specific psychopathology: anti-AP3B2, detected in 5% of the cohort of whom 100% had persecutory delusions; anti-TDO2 (5% of the cohort, 100% hallucinations); anti-CRYGN (4%, 86% initial insomnia); anti-APMAP (3%, 86% poor appetite); anti-OLFM1 (2.5%, 100% above median cognitive function); and anti-WHAMMP3 (2%, 90% anhedonia and dysphoria). Examination of the auto-IgG binding site on the TDO2 protein revealed a putative pathophysiological mechanism involving the kynurenine pathway.
We identified 6 frequently occurring autoantibodies that were associated with specific clinical features in people with psychotic disorders.
We aimed to assess the incidence of obstructive sleep apnoea (OSA) in people with schizophrenia, to explore clinical associates with OSA and how well OSA screening tools perform in this population.
All patients registered in a community outpatient Clozapine clinic, between January 2014 and March 2016, were consecutively approached to participate. Participants were screened for OSA using at home multichannel polysomnography (PSG) and were diagnosed with OSA if the apnoea-hypopnoea index (AHI) was >10 events/hr. Univariate comparison of participants to determine whether AHI > 10 events/hr was associated with demographic factors, anthropometric measures and psychiatric symptoms and cognition was performed. The sensitivity, specificity, positive predictive value and negative predictive value of the commonly used sleep symptoms scales and OSA screening tools were also determined.
Thirty participants were recruited, 24 men and 6 women. Mean age was 38.8 (range: 25–60), and mean body mass index (BMI) was 35.7 (range 19.9–62.1). The proportion of participants with OSA (AHI > 10 events/hr) was 40%, 18 (60%) had no OSA, 4 (13%) had mild OSA (AHI 10.1–20), zero participants had moderate OSA (AHI 20.1–30) and 8 (27%) had severe OSA (AHI > 30). Diagnosis of OSA was significantly associated with increased weight, BMI, neck circumference and systolic blood pressure. Diagnosis of OSA was not significantly associated with Positive and Negative Symptoms Scale, Montgomery Asperger’s Depression Rating Scale, Personal and Social Performance scale or Brief Assessment of Cognition for Schizophrenia scores. All OSA screening tools demonstrated poor sensitivity and specificity for a diagnosis of OSA.
OSA was highly prevalent in this cohort of people with schizophrenia and was associated with traditional anthropometric OSA risk factors.
Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes.
Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes.
Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82).
Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.
Clozapine is the most effective medication for treatment refractory schizophrenia. However, descriptions of the mental health and comorbidity profile and care experiences of people on clozapine in routine clinical settings are scarce. Using data from the 2010 Australian Survey of High Impact Psychosis, we aimed to examine the proportion of people using clozapine, and to compare clozapine users with other antipsychotic users on demographic, mental health, adverse drug reaction, polypharmacy and treatment satisfaction variables.
Data describing 1049 people with a diagnosis of schizophrenia or schizoaffective disorder, who reported taking any antipsychotic medication in the previous 4 weeks, were drawn from a representative Australian survey of people with psychotic disorders in contact with mental health services in the previous 12 months. We compared participants taking clozapine (n = 257, 22.4%) with those taking other antipsychotic medications, on a range of demographic, clinical and treatment-related indicators.
One quarter of participants were on clozapine. Of participants with a chronic course of illness, only one third were on clozapine. After adjusting for diagnosis and illness chronicity, participants taking clozapine had significantly lower odds of current alcohol, cannabis and other drug use despite similar lifetime odds. Metabolic syndrome and diabetes were more common among people taking clozapine; chronic pain was less common. Psychotropic polypharmacy did not differ between groups.
Consistent with international evidence of clozapine underutilisation, a large number of participants with chronic illness and high symptom burden were not taking clozapine. The lower probabilities of current substance use and chronic pain among clozapine users warrant further study.
Rates of the metabolic syndrome in people with psychotic illness are high. Emerging evidence suggests that cannabis use may have a positive impact on cardiometabolic risk factors in the general population, but little is known about its impact for people with psychotic illness. Our aim was to investigate whether the rate of the metabolic syndrome in people with psychotic illness was associated with frequency of cannabis use.
The 2010 Australian psychosis survey used a two-phase design to randomly select a nationally representative sample of 1825 adults with psychotic illness for interview and physical assessment. This study is based on 1813 participants who provided data on cannabis use. Multiple logistic regression was used to model the influence of frequency of cannabis use on the metabolic syndrome, adjusting for potential covariates including antipsychotic medication use, smoking, alcohol use and cognitive function.
One-third (33.0%) of participants had used cannabis in the past year. The proportion of non-users, occasional users and frequent users with the metabolic syndrome was 63.0, 51.7 and 43.5%, respectively (p < 0.001). In unadjusted analyses, both occasional use and frequent cannabis use were associated with significantly lower odds of the metabolic syndrome. In the adjusted analyses, the association between the metabolic syndrome and frequent cannabis use remained significant [odds ratio = 0.56, 95% confidence interval (CI) 0.39–0.80], but not the association with occasional use (odds ratio = 0.75, 95% CI 0.49–1.13).
While cannabis use may be detrimental for mental health, these data suggest that it may also have a cardiometabolic protective effect. Further investigation is required to understand the mechanism underlying this paradoxical finding.
There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.
The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.
The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.
Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.
Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression. However, there has been little research to determine optimal parameters for treatment.
This study compared two rTMS treatment regimes for the treatment of major depression. Seventy-seven participants were randomized to either spaced or daily treatment. Spaced rTMS was given 3 days/week for 6 weeks (18 treatments in total) and daily rTMS was given 5 days/week for 4 weeks (20 treatments in total). All participants were assessed at baseline and after 4 weeks of treatment. Participants in the spaced treatment group were also assessed after 6 weeks of treatment. All participants were treated at 110% of the resting motor threshold with high-frequency rTMS (10 Hz) to the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency rTMS to the right DLPFC.
Participants in the daily treatment group showed more improvement by week 4 than those in the spaced treatment group; however, both groups had similar improvement by treatment completion. There was significant improvement in both groups in ratings of depression and anxiety, with no significant differences between groups.
Our study indicates that the efficacy of rTMS is related to the number of treatments given and that spacing the treatments neither improves nor reduces efficacy.
In 48 conscious resting subjects we examined the temporal coupling of heart beat timing and the onset of inspiration (cardioventilatory coupling), and the relationship between coupling and spectral indices of autonomic function. Using the proportional Shannon entropy (SHα) of the RI-1 interval (interval between inspiration and the preceding ECG R wave) as a measure of coupling we detected statistically significant coupling in 32 of the 48 subjects. This was confirmed by visual inspection of time series plots of RI intervals, in which coupling was evident as horizontal banding. Coupling resulted in a significant preference for whole number heart rate/respiratory frequency ratios. The strongest coupling was associated with low ventilatory frequency and high heart rate variability in the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency ranges, but was not related to blood pressure variability, or to a spectral measure of baroreflex sensitivity (α-index, low frequency range). There was no difference in coupling strength between males and females. We have previously described cardioventilatory coupling in spontaneously breathing anaesthetised subjects. The current study extends those observations by demonstrating that the qualitative features of coupling seen during anaesthesia are also observed in the conscious state. We conclude that the role of coupling in normal physiological respiratory control needs to be more widely explored. Experimental Physiology (2003) 88.6, 775-782.
The effects of propofol on mean arterial pressure, heart rate and Aδ and C somatosympathetic reflexes, recorded in renal nerves, evoked by repeated individual supramaximal electrical stimuli applied to radial nerves, were observed in anaesthetized, paralysed and artificially ventilated dogs. Propofol was infused at rates from 0.4 to 2.0 mg kg−1min−1. Mean C and Aδ reflexes were abolished at plasma concentrations (mean, SEM) of 24.3 (3.3) and 29.2 (2.6) μg mL−1 (P < 0.05), respectively, when mean arterial pressure and mean heart rate were reduced by approximately 55% (P < 0.01) and 26% (P > 0.05), respectively. Recovery of Aδ and C reflexes occurred at plasma concentrations of 13.1 (2.3) and 9.9 (1.3) μg mL−1 (P > 0.05), respectively. There was a logarithmically linearly related fall in mean arterial pressure by 70% up to a plasma concentration ≈97 μg mL−1 (r2=0.7) with a 28% reduction in heart rate which was uncorrelated with the plasma concentrations (r2=0.12). In conclusion, propofol abolished Aδ and C responses at comparable plasma concentrations and caused a major reduction in both mean arterial pressure and heart rate which is consistent with resetting of the baroreflexes. The reduction in mean arterial pressure was logarithmically, linearly correlated with a progressive increase in plasma concentrations without evidence of a ceiling effect.