Causes of death in clozapine-treated patients in a catchment area: a 10-year retrospective case-control study.

Uncertainty regarding the excess of mortality in patients treated with clozapine persists. A decrease in all-cause mortality, and perhaps also in suicide, after clozapine initiation has been reported, but there are no studies in which preventable causes were ascertained in those taking medication in the long term. Here, we aimed to assess a decade of causes of deaths in a catchment area in patients with schizophrenia chronically treated with clozapine and compared them to a clozapine-treated control cohort. Causes of deaths were classified as suicide, expected (e.g. cancer), and unexpected deaths (encompassing causes of death potentially due to clozapine side effects, and unexplained sudden death). We used descriptive statistics for comparing socio-demographic and clinical factors between the three groups. Logistic regression models were used to examine risk factors associated with unexpected death compared to the control group. We found that the overall mortality was similar to that in previous studies (at 0.8% yearly on average) with unexpected deaths accounting for 52% of total deaths. The unexpected deaths group was on average treated with higher clozapine doses (mean 460 mg/day). A small but significant peak of unexpected deaths was found during the 2018 summer heat wave, which might have exacerbated dose-dependent side effects of clozapine. We suggest increased monitoring for those on higher doses of clozapine as one potential intervention to decrease mortality in this population.

Mortality in Schizophrenia and Other Psychoses: Data from the South Korea National Health Insurance Cohort, 2002-2013.

Individuals with psychoses show excess mortality, which is a major public health concern. This study examined all-cause and suicide mortality rates in Korean patients diagnosed with schizophrenia, mood disorder, or mental and behavioral disorder due to psychoactive substance use and to compare this with that of the general population. Data were from the National Health Insurance cohort, 2002 to 2013. A total of 107,190 cases aged 15 years or over were included. Mortality rates per 100,000 person years (PY) were obtained. Poisson regression modelling was conducted to quantify the effect of baseline characteristics on all-cause and suicide mortality risks. Standardized mortality ratios (SMRs) were also calculated. All-cause mortality was the highest among mental and behavioral disorder patients (1,051.0 per 100,000 PY), followed by schizophrenia (949.1 per 100,000 PY) and mood disorder patients (559.5 per 100,000 PY). Highest suicide mortality was found in schizophrenia (177.2 per 100,000 PY), mental and behavioral disorder (143.7 per 100,000 PY), and mood disorder patients (59.7 per 100,000 PY). The rate ratios (RRs) for all-cause and suicide mortality were reduced for younger populations and women. Psychoses patients had higher all-cause (schizophrenia, SMR 2.4; 95% confidence interval [CI] 2.2-2.5; mood disorder, SMR 1.4; 95% CI 1.3-1.5; mental and behavioral disorder, SMR 2.6; 95% CI 2.5-2.8) and suicide (schizophrenia, SMR 8.4; 95% CI 7.2-9.6; mood disorder, SMR 2.8; 95% CI 2.1-3.5; mental and behavioral disorder, SMR 6.8; 95% CI 5.7-7.9) mortality rates than the general population. These findings infer that efforts should be made to reduce excess mortality in psychoses.

Neuropsychological performance and auditory event related potentials in schizophrenia patients and their siblings: a family study.

BACKGROUND: Various neuropsychological domains, and P300 auditory event-related potentials (ERP) and mismatch negativity (MMN) exhibit abnormalities in schizophrenia patients and their first-degree relatives. The aims of this study were to compare cognitive and P300/MMN measurements in schizophrenia patients, their siblings, and controls, and to identify the degree of familial influence on each measure. METHODS: Thirty patients diagnosed with schizophrenia according to DSM-IV, 20 unaffected siblings and 25 healthy controls were able to complete all neuropsyhological and neurophysiological assessments. All participants were administered SCID-I and the patients were also evaluated regarding symptom severity and functioning. Neuropsychological battery testing results and P300/MMN measurements were obtained for all the participants. RESULTS: Both schizophrenia patients and their siblings had lower working memory, as measured by the Auditory Consonant Trigram Test (ACT), and lower MMN amplitude scores than the controls. In addition, the patients had lower attention, verbal memory, executive function, visuomotor speed, and figural memory scores than both the siblings and controls, and lower verbal fluency scores than controls. MMN and P300 amplitudes were lower and P300 latency longer in the schizophrenia patients, as compared to controls. P300 latency was also longer in the schizophrenia patients as compared to siblings and, MMN amplitudes were significantly lower in the siblings compared to controls. Working memory performance measured by ACT significantly predicted inclusion in both the patient and sibling groups and showed significant familial influence. MMN amplitude significantly predicted inclusion only to the patient group and did not show significant familial influence. CONCLUSION: The schizophrenia patients exhibited impairment in various cognitive domains and P300/MMN measurements, versus impairment only in working memory and MMN amplitude in their siblings. Working memory seems to have a relatively strong familial influence among all the neuropsychological and neurophysiological parameters evaluated.

Development of a health screening clinic.

Medical morbidity and mortality levels remain elevated in people with schizophrenia compared with the general population. Despite the increasing recognition of an excess of physical health problems in this population, health screening remains limited. Medical risk in this population can be related to a variety of sources. The disease process itself as well as poor diet and sedentary lifestyle contribute to the overall physical health problems. In addition antipsychotic medication can contribute to the risk of cardiovascular and metabolic problems. The Dundee Health Screening Clinic was developed to address the needs of this population by monitoring physical health and providing follow-up to ensure that patients received the necessary care. The Clinic demonstrates how a coordinated approach can be used to take simple steps to improve the overall well-being of these patients. It was set up by adapting the manpower resources and procedures of the community mental health team and local resource centre, without specific additional funding. Simple clinical measurements and tests were conducted in the Clinic and patients clearly demonstrated on a satisfaction questionnaire that they considered the health checks important. This Clinic is an example of how a holistic approach can impact on both the physical and mental well-being of patients and offer them improved care and therefore a better quality of life.

Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia.

OBJECTIVE: Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. METHOD: Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. RESULTS: Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the alpha 1 and delta subunits of GABA(A) receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. CONCLUSIONS: Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.