The role of ASTN2 variants in childhood and adult ADHD, comorbid disorders and associated personality traits.

Previous linkage and genome wide association (GWA) studies in ADHD indicated astrotactin 2 (ASTN2) as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). ASTN2 plays a key role in glial-guided neuronal migration. To investigate whether common variants in ASTN2 contribute to ADHD disorder risk, we tested 63 SNPs spanning ASTN2 for association with ADHD and specific comorbid disorders in two samples: 171 families of children with ADHD and their parents (N = 592), and an adult sample comprising 604 adult ADHD cases and 974 controls.

Expressional profile of the diacylglycerol kinase eta gene DGKH.

Bipolar disorder (BPD) is a genetically complex mental disorder, which is characterized by recurrent depressive and manic episodes, occurring with a typical cyclical course. In a recent study, we were able to identify a risk haplotype for BPD, as well as for unipolar depression and adult attention-deficit/hyperactivity disorder (ADHD), within the DGKH gene. DGKH codes for the eta (η) isoform of diacylglycerol kinase, which is involved in the phosphoinositol pathway.

DGKH genetic risk variant influences gene expression in bipolar affective disorder.

Background: DGKH is a replicated risk gene of bipolar disorder (BD). However, the pathophysiological role of the coded protein, diacylglycerol kinase eta, remains elusive.

Methods: In this proof-of-concept study we isolated mRNA from peripheral blood and fibroblasts of heterozygote DGKH risk variants carriers (risk haplotype rs994856/rs9525580/rs9525584 GAT) with bipolar disorder and non-risk variant carriers with and without bipolar disorder.

Interaction of NOS1AP with the NOS-I PDZ domain: Implications for schizophrenia-related alterations in dendritic morphology.

Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and altered dendritic development. Amongst the most promising candidate molecules for schizophrenia are neuronal nitric oxide (NO) synthase (NOS-I, also known as nNOS) and its adapter protein NOS1AP (previously named CAPON). However, the precise molecular mechanisms by which NOS-I and NOS1AP affect disease pathology remain to be resolved.

On the role of NOS1 ex1f-VNTR in ADHD-allelic, subgroup, and meta-analysis.

Attention deficit/ hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder featuring complex genetics with common and rare variants contributing to disease risk. In a high proportion of cases, ADHD does not remit during adolescence but persists into adulthood. Several studies suggest that NOS1, encoding nitric oxide synthase I, producing the gaseous neurotransmitter NO, is a candidate gene for (adult) ADHD.

A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients.

Objectives: Methylphenidate (MPH) is a commonly used stimulant medication for treating attention-deficit/hyperactivity disorder (ADHD). Besides inhibiting monoamine reuptake there is evidence that MPH also influences gene expression directly.

Methods: We investigated the impact of MPH treatment on gene expression levels of lymphoblastoid cells derived from adult ADHD patients and healthy controls by hypothesis-free, genome-wide microarray analysis.

KCNIP4 as a candidate gene for personality disorders and adult ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder in children with striking persistence into adulthood and a high co-morbidity with other psychiatric disorders, including personality disorders (PD). The 4p15.31 region was shown to be associated with ADHD in several genome wide association studies (GWAS).

PPP2R2C as a candidate gene of a temperament and character trait-based endophenotype of ADHD.

There are several lines of evidence that the 4p16 region is a candidate locus of both attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder. None of the harbored candidate genes of this region were hitherto shown to be associated with ADHD despite promising functionality. One of the most promising candidate genes in this region is protein phosphatase 2, regulatory subunit B, gamma (PPP2R2C), which, however, thus far has not been assessed for a potential association with ADHD.

DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders.

Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls.

Cross-disorder analysis of bipolar risk genes: further evidence of DGKH as a risk gene for bipolar disorder, but also unipolar depression and adult ADHD.

Recently, several genome-wide association studies (GWAS) on bipolar disorder (BPD) suggested novel risk genes. However, only few of them were followed up and further, the specificity of these genes is even more elusive. To address these issues, we genotyped SNPs in ANK3, CACNA1C, CMTM8, DGKH, EGFR, and NPAS3, which were significantly associated with BPD in previous GWAS, in a sample of 380 BPD patients.