Purpose: Systemizer Profile Questionnaire (SPQ), which has not been used before, investigates difficulties in mentalisation, sensory- and/or social sensitivity and social cognition (MSSSC) in subjects with Autism-Spectrum-Disorders (ASD) with and without Attention-Deficit-Hyperactivity-Disorder (ADHD). The aim of this study was to evaluate the reliability and validity of the SPQ domains, and to assess the predictive validity of the SPQ against the Ritvo Autism Asperger Diagnostic Scale (RAADS).
Methods: Three-hundred-fifty-four study subjects with ICD-10 verified ASD confirmed by RAADS and 354 controls matched on age group and gender were recruited and evaluated systematically with SPQ, standardized questions about demographic and clinical data.
Schizotypal personality disorder (SPD) is characterised by thought disorders, experiences of illusions, obsessive ruminations, bizarre or eccentric behaviour, cognitive problems and deficits in social functioning - symptoms that SPD shares with schizophrenia. Efforts have been undertaken to investigate the relationship between these conditions regarding genetics, pathophysiology, and phenomenology. However, treatment of SPD with antipsychotics has received less scientific attention.
View Article and Find Full Text PDFQuetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported in the European Summary of Product Characteristics (SPCs).
View Article and Find Full Text PDFAripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents.
View Article and Find Full Text PDFObjective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
April 2012
Mutation of the neurexin1-gene, NRXN1, interrupting the expression of neurexin1 has been associated with schizophrenia, autism, and intellectual disability. We have identified a family multiply affected with psychiatric, neurological, and somatic disorders along with an intricate co-segregation of NRXN1 mutations. The proband suffered from autism, mental retardation, and epilepsy and on genotyping it was revealed that he carried a compound heterozygous mutation in the NRXN1 consisting of a 451 kb deletion, affecting the promoter and first introns in addition to a point mutation, predicted to be deleterious to NRXN1.
View Article and Find Full Text PDFIn two recent studies 10 copy number variants (CNV) were found to be overrepresented either among patients suffering from affective disorders in an Amish family or in the Wellcome Trust Case-Control Consortium study. Here, we investigate if these variants are associated with affective disorders in a combined analysis of three case-control samples from Denmark, Norway and Iceland. A total of 1897 cases (n=1223 unipolar and n=463 bipolar) and 11 231 controls were analyzed for CNVs at the 10 genomic loci, but we found no combined association between these CNVs and affective disorders.
View Article and Find Full Text PDFBackground: Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication.
Methods: Eleven known risk variants of type II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month.
Objective: Rare copy number variants have been implicated in different neurodevelopmental disorders, with the same copy number variants often increasing risk of more than one of these phenotypes. In a discovery sample of 22 schizophrenia patients with an early onset of illness (10-15 years of age), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q13 duplications in psychotic illness.
View Article and Find Full Text PDFIntroduction: A large proportion of patients admitted to psychological departments and wards suffer from depression. Knowledge is limited about the clinical aspects and treatment of depression at admission and discharge, as well as about the differences between psychiatric hospitals. The purpose of this study was to develop a database for patients admitted to a psychiatric department comprising registration of central clinical parameters.
View Article and Find Full Text PDFObjective: The aim of the present retrospective pilot study was to examine the clinical impact of the cytochrome P450 (CYP) enzyme CYP2D6 poor metabolizer (PM) genotype in patients taking antipsychotic medication. The impaired metabolic capacity of the PM genotype results in higher steady-state plasma concentrations at a given dose, thus increasing the risk of toxic effects from medication.
Methods: We identified 18 PM patients with a schizophrenia spectrum diagnosis from a clinical database covering all patients who have been analyzed in an ongoing standardized CYP2D6 screening program.
Disrupted-in-schizophrenia-1 (DISC1), located on chromosome 1q42.1, is linked to rare familial schizophrenia in a large Scottish family. The chromosomal translocation that segregates with the disease results in a truncated protein that impairs neurite outgrowth and proper development of the cerebral cortex, suggesting that lost DISC1 function may underlie neurodevelopmental dysfunction in schizophrenia.
View Article and Find Full Text PDFReduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays.
View Article and Find Full Text PDFIntroduction: The purinergic receptor gene P2RX(7) is located in a major linkage hotspot for schizophrenia and bipolar disorders, 12q21-33. It has previously been associated with bipolar disorder but has never been analysed in relation to schizophrenia, although it is involved in several neuronal processes associated with schizophrenia.
Methods: Nine functionally characterised variants in P2RX(7) were genotyped in 389 patients diagnosed with schizophrenia, each matched on sex, birth-year and month with two healthy controls.
Background: Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
October 2008
Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin.
View Article and Find Full Text PDFBackground: Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation.
View Article and Find Full Text PDFBackground: Diagnostic stability and illness course of chronic non-organic psychoses are complex phenomena and only few risk factors or predictors are known that can be used reliably. This study investigates the diagnostic stability during the entire course of illness in patients with non-organic psychoses and attempts to identify non-psychopathological risk factors or predictors.
Method: 100 patients with functional psychosis were initially characterised using the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT), medical records and health registers.
Neuregulin 1 has been implicated as a susceptibility gene in schizophrenia. Several research groups have reported association with the 5' end of the gene although no causative variant has been reported. We have investigated whether there is association with the 5' end of the gene in Danish schizophrenia patients.
View Article and Find Full Text PDFConcern has been expressed as to the reliability of clinical ICD-10 diagnosis of schizophrenia. This study was designed to assess the diagnostic reliability of the clinical ICD-10 diagnosis of schizophrenia in a random sample of Danish in- and outpatients with a history of psychosis. A sample of 100 subjects was assessed using the operational criteria OPCRIT checklist for psychotic and affective illness.
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