High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy

<p>Abstract</p> <p>Background</p> <p>Many copy number variants (CNVs) are documented to be associated with neuropsychiatric disorders, including intellectual disability, autism, epilepsy, schizophrenia, and bipolar disorder. Chromosomal deletions of 1q21.1, 3q29, 15q13.3, 22q11.2, and <it>NRXN1 </it>and duplications of 15q11-q13 (maternal), 16p11, and 16p13.3 have the strongest association with schizophrenia. We hypothesized that cases with both schizophrenia and epilepsy would have a higher frequency of disease-associated CNVs and would represent an enriched sample for detection of other mutations associated with schizophrenia.</p> <p>Methods</p> <p>We used array comparative genomic hybridization (CGH) to analyze 235 individuals with both schizophrenia and epilepsy, 80 with bipolar disorder and epilepsy, and 191 controls.</p> <p>Results</p> <p>We detected 10 schizophrenia plus epilepsy cases in 235 (4.3%) with the above mentioned CNVs compared to 0 in 191 controls (p = 0.003). Other likely pathological findings in schizophrenia plus epilepsy cases included 1 deletion 16p13 and 1 duplication 7q11.23 for a total of 12/235 (5.1%) while a possibly pathogenic duplication of 22q11.2 was found in one control for a total of 1 in 191 (0.5%) controls (p = 0.008). The rate of abnormality in the schizophrenia plus epilepsy of 10/235 for the more definite CNVs compares to a rate of 75/7336 for these same CNVs in a series of unselected schizophrenia cases (p = 0.0004).</p> <p>Conclusion</p> <p>We found a statistically significant increase in the frequency of CNVs known or likely to be associated with schizophrenia in individuals with both schizophrenia and epilepsy compared to controls. We found an overall 5.1% detection rate of likely pathological findings which is the highest frequency of such findings in a series of schizophrenia patients to date. This evidence suggests that the frequency of disease-associated CNVs in patients with both schizophrenia and epilepsy is significantly higher than for unselected schizophrenia.</p

A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology

BACKGROUND: Understanding variations in the incidence of schizophrenia is a crucial step in unravelling the aetiology of this group of disorders. The aims of this review are to systematically identify studies related to the incidence of schizophrenia, to describe the key features of these studies, and to explore the distribution of rates derived from these studies. METHODS: Studies with original data related to the incidence of schizophrenia (published 1965–2001) were identified via searching electronic databases, reviewing citations and writing to authors. These studies were divided into core studies, migrant studies, cohort studies and studies based on Other Special Groups. Between- and within-study filters were applied in order to identify discrete rates. Cumulative plots of these rates were made and these distributions were compared when the underlying rates were sorted according to sex, urbanicity, migrant status and various methodological features. RESULTS: We identified 100 core studies, 24 migrant studies, 23 cohort studies and 14 studies based on Other Special Groups. These studies, which were drawn from 33 countries, generated a total of 1,458 rates. Based on discrete core data for persons (55 studies and 170 rates), the distribution of rates was asymmetric and had a median value (10%–90% quantile) of 15.2 (7.7–43.0) per 100,000. The distribution of rates was significantly higher in males compared to females; the male/female rate ratio median (10%–90% quantile) was 1.40 (0.9–2.4). Those studies conducted in urban versus mixed urban-rural catchment areas generated significantly higher rate distributions. The distribution of rates in migrants was significantly higher compared to native-born; the migrant/native-born rate ratio median (10%–90% quantile) was 4.6 (1.0–12.8). Apart from the finding that older studies reported higher rates, other study features were not associated with significantly different rate distributions (e.g. overall quality, methods related to case finding, diagnostic confirmation and criteria, the use of age-standardization and age range). CONCLUSIONS: There is a wealth of data available on the incidence of schizophrenia. The width and skew of the rate distribution, and the significant impact of sex, urbanicity and migrant status on these distributions, indicate substantial variations in the incidence of schizophrenia

Medical Comorbidity in Women and Men with Schizophrenia: A Population-Based Controlled Study

BACKGROUND: Persons with persistent mental illness are at risk for failure to receive medical services. In order to deliver appropriate preventive and primary care for this population, it is important to determine which chronic medical conditions are most common. OBJECTIVE: We examined chronic medical comorbidity in persons with schizophrenia using validated methodologies. DESIGN: Retrospective analysis of longitudinal administrative claims data from Wellmark Blue Cross/Blue Shield of Iowa. PARTICIPANTS: Subjects with schizophrenia or schizoaffective disorder (N = 1,074), and controls (N = 726,262) who filed at least 1 claim for medical services, 1996 to 2001. MEASUREMENTS: Case subjects had schizophrenia as the most clinically predominant psychotic disorder, based on psychiatric hospitalization, psychiatrist diagnoses, and outpatient care. Controls had no claims for any psychiatric comorbidity. Using a modified version of the Elixhauser Comorbidity Index, inpatient and outpatient claims were used to determine the prevalence of 46 common medical conditions. Odds ratios (ORs) were adjusted for age, gender, residence, and nonmental health care utilization using logistic regression. RESULTS: Subjects with schizophrenia were significantly more likely to have 1 or more chronic conditions compared with controls. Adjusted OR (95% confidence interval [CI]) were 2.62 (2.09 to 3.28) for hypothyroidism, 1.88 (1.51 to 2.32) for chronic obstructive pulmonary disease, 2.11 (1.36 to 3.28) for diabetes with complications, 7.54 (3.55 to 15.99) for hepatitis C, 4.21 (3.25 to 5.44) for fluid/electrolyte disorders, and 2.77 (2.23 to 3.44) for nicotine abuse/dependence. CONCLUSIONS: Schizophrenia is associated with substantial chronic medical burden. Familiarity with conditions affecting persons with schizophrenia may assist programs aimed at providing medical care for the mentally ill

Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome in people with severe mental illnesses: Systematic review and metaanalysis

<p>Abstract</p> <p>Background</p> <p>Severe mental illnesses (SMI) may be independently associated with cardiovascular risk factors and the metabolic syndrome. We aimed to systematically assess studies that compared diabetes, dyslipidaemia, hypertension and metabolic syndrome in people with and without SMI.</p> <p>Methods</p> <p>We systematically searched MEDLINE, EMBASE, CINAHL & PsycINFO. We hand searched reference lists of key articles. We employed three search main themes: SMI, cardiovascular disease, and each cardiovascular risk factor. We selected cross-sectional, case control, cohort or intervention studies comparing one or more risk factor in both SMI and a reference group. We excluded studies without any reference group. We extracted data on: study design, cardiovascular risk factor(s) and their measurement, diagnosis of SMI, study setting, sampling method, nature of comparison group and data on key risk factors.</p> <p>Results</p> <p>Of 14592 citations, 134 papers met criteria and 36 were finally included. 26 reported on diabetes, 12 hypertension, 11 dyslipidaemia, and 4 metabolic syndrome. Most studies were cross sectional, small and several lacked comparison data suitable for extraction. Meta-analysis was possible for diabetes, cholesterol and hypertension; revealing a pooled risk ratio of 1.70 (1.21 to 2.37) for diabetes and 1.11 (0.91 to 1.35) of hypertension. Restricting SMI to schizophreniform illnesses yielded a pooled risk ratio for diabetes of 1.87 (1.68 to 2.09). Total cholesterol was not higher in people with SMI (Standardized Mean Difference -0.10 (-0.55 to 0.36)) and there were inconsistent data on HDL, LDL and triglycerides with some, but not all, reporting lower levels of HDL cholesterol and raised triglyceride levels. Metabolic syndrome appeared more common in SMI.</p> <p>Conclusion</p> <p>Diabetes (but not hypertension) is more common in SMI. Data on other risk factors were limited by poor quality or inconsistent research findings, but a small number of studies show greater prevalence of the metabolic syndrome in SMI.</p

Validation study of the early onset schizophrenia diagnosis in the Danish Psychiatric Central Research Register

The objective of this study is to assess (1) the concordance and validity of schizophrenia register diagnoses among children and adolescents (early onset schizophrenia = EOS) in the Danish Psychiatric Central Research Register (DPCRR), and (2) the validity of clinical record schizophrenia diagnoses. Psychiatric records from 200 patients with a first-time diagnosis of schizophrenia (F20.x) at age  0.78–0.83 depending on classification. Compared to diagnoses made in outpatient settings, EOS diagnoses during hospitalizations were more likely to be valid and had fewer registration errors. Diagnosed in inpatient settings, EOS diagnoses are reliable and valid for register-based research. Schizophrenia diagnosed in children and adolescents in outpatient settings were found to have a high number of false-positives, both due to registration errors and diagnostic practice. Utilizing this knowledge, it is possible to reduce the number of false-positives in register-based research of EOS