Introducing the hypothome: a way to integrate predicted proteins in interactomes.

An interactome is defined as a network of protein-protein interactions built from experimentally verified interactions. Basic science as well as application-based research of potential new drugs can be promoted by including proteins that are only predicted into interactomes. The disadvantage of doing so is the risk of devaluing the definition of interactomes.

Mechanical restraint in psychiatry: preventive factors in theory and practice. A Danish-Norwegian association study.

Purpose: To examine how potential mechanical restraint preventive factors in hospitals are associated with the frequency of mechanical restraint episodes.

Design And Methods: This study employed a retrospective association design, and linear regression was used to assess the associations.

Findings: Three mechanical restraint preventive factors were significantly associated with low rates of mechanical restraint use: mandatory review (exp[B] = .

CNVs conferring risk of autism or schizophrenia affect cognition in controls.

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease.

A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar disorder.

Background: Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.

Methods: Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests.

Sequence analysis of 17 NRXN1 deletions.

Background: Genome instability plays fundamental roles in human evolution and phenotypic variation within our population. This instability leads to genomic rearrangements that are involved in a wide variety of human disorders, including congenital and neurodevelopmental disorders, and cancers. Insight into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes.

In vitro drug metabolism by human carboxylesterase 1: focus on angiotensin-converting enzyme inhibitors.

Carboxylesterase 1 (CES1) is the major hydrolase in human liver. The enzyme is involved in the metabolism of several important therapeutic agents, drugs of abuse, and endogenous compounds. However, no studies have described the role of human CES1 in the activation of two commonly prescribed angiotensin-converting enzyme inhibitors: enalapril and ramipril.

A mouse model that recapitulates cardinal features of the 15q13.3 microdeletion syndrome including schizophrenia- and epilepsy-related alterations.

Background: Genome-wide scans have uncovered rare copy number variants conferring high risk of psychiatric disorders. The 15q13.3 microdeletion is associated with a considerably increased risk of idiopathic generalized epilepsy, intellectual disability, and schizophrenia.

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls).

Genome-wide identification of structural variants in genes encoding drug targets: possible implications for individualized drug therapy.

Objective: The objective of the present study was to identify structural variants of drug target-encoding genes on a genome-wide scale. We also aimed at identifying drugs that are potentially amenable for individualization of treatments based on knowledge about structural variation in the genes encoding their targets.

Methods: Information about human drug targets of all therapeutic drugs and nutraceuticals approved by the Food and Drug Administration and with an Anatomical Therapeutic Chemical (ATC) code, namely, 876, was obtained from the DrugBank and applied to interrogate the Database of Genomic Variants.

Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.

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.

Novel variant of CYP2D6*6 is undetected by a commonly used genotyping procedure.

We report the identification of a novel and defective variant of the gene encoding cytochrome P450 2D6 (CYP2D6). This novel variant is a subtype of CYP2D6*6 that was undetected by a commercially available 5' exonuclease-based assay. Because the novel variant was found in only one of 609 individuals, it represents a rare subtype of CYP2D6*6 that may be restricted to a single family or a subpopulation.

Coercion within Danish psychiatry compared with 10 other European countries.

Background: In 2008, the European Committee for the Prevention of Torture and Inhuman or Degrading Treatment or Punishment (CPT) criticized the use of mechanical restraint in Denmark and referred to it as ill-treatment. What do other European countries do better? To answer this question, we compared the use of coercive measures regarding psychiatric inpatients in Denmark and comparable European countries.

Aims: Comparing coercive measures from Denmark, Sweden, Norway, Finland, Iceland, Belgium, The Netherlands, United Kingdom, Ireland, France and Italy.

Mechanical restraint--which interventions prevent episodes of mechanical restraint?- a systematic review.

Purpose: To identify interventions preventing mechanical restraints.

Design And Methods: Systematic review of international research papers dealing with mechanical restraint. The review combines qualitative and quantitative research in a new way, describing the quality of evidence and the effect of intervention.

Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events.

Background: Depression is accompanied by an inflammatory reaction and activation of cell mediated immunity (CMI) and stressors may induce the cytokine network in humans. The proinflammatory cytokine interleukin-18 (IL-18) is less investigated in depression but highly relevant since it is produced by activated macrophages and expressed in the brain.

Methods: The distribution of six polymorphisms in IL10, IL18 and NF was compared between patients with a single episode of depression either preceded by a stressful life event (n=182), or occurring without a prior stressful life event (n=106) and a group of healthy control individuals (n=335).

The impact of substance use disorders on the course of schizophrenia--a 15-year follow-up study: dual diagnosis over 15 years.

Background: This follow-up study compared patients with schizophrenia with co-occurring substance use disorder to patients with schizophrenia and no substance use disorder.

Aims: To investigate the prognostic significance of the effects of substance use disorders on the course of schizophrenia.

Method: Patients with schizophrenia and co-occurring substance use disorder (n=107), and patients with schizophrenia only (n=119) were followed over a 15-year period through the use of national hospitalization registers, data for time and cause of death, and data for homelessness or institutionalization.

Copy number variations in affective disorders and meta-analysis.

In 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.

At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia.

Background: 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.

The importance of early anti-social behaviour among men with a schizophrenia spectrum disorder in a specialist forensic psychiatry hospital unit in Denmark.

Background: People with a major mental disorder are at increased risk of committing crimes, especially violent crimes, compared with the general population. Sub-groups have been identified based on age of onset of anti-social or violent behaviour. Mentally disordered offenders with early onset anti-social behaviour tend to have a lifelong pattern of it, but in a clinical setting, are they easily identifiable as a distinct sub-group?

Aims: Our main aim was to establish whether distinct groups of early and later onset offenders can be identified from the standard clinical record of men with schizophrenia spectrum disorders selected for hospital treatment after conviction for a serious crime, and to test the hypothesis that even in such a clinically selected group, early onset offending would be associated with subsequent persistent and versatile offending.

Variation in the purinergic P2RX(7) receptor gene and schizophrenia.

Introduction: 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.