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. Replicated SNPs were then followed up in patients suffering from unipolar depression (UPD; n=387) or adult attention-deficit/hyperactivity disorder (aADHD; n=535). While we could not confirm an association of ANK3, CACNA1C, and EGFR with BPD, 10 SNPs in DGKH, CMTM8, and NPAS3 were nominally associated with disease, with two DGKH markers surviving correction for multiple testing. When these were followed up in UPD and aADHD, seven DGKH SNPs were also associated with UPD, while one SNP each in NPAS3 and CMTM8 and four in DGKH were linked to aADHD. Furthermore, a DGKH haplotype consisting of rs994856/rs9525580/rs9525584 GAT was associated with all disorders tested, while the complementary AGC haplotype was protective. The corresponding haploblock spans a 27-kb region covering exons coding for amino acids 65-243, and thus might include functional variants yet to be identified. We demonstrate an association of DGKH with BPD, UPD, and aADHD by applying a two-stage design. These disorders share the feature of mood instability, so that this phenotype might be associated with genetic variation in DGKH.

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Background: Relatively little is known about the long-term psychopathological and psychosocial outcome of early-onset schizophrenia. The existing literature describes more severe courses of illness in these patients compared with adult-onset schizophrenia. This article reports preliminary data of a study exploring the outcome of early-onset schizophrenia 13.4 years (mean) after first admission. Predictors for interindividual outcomes were investigated.

Objective: Olfactory processing depends on dopamine metabolism and orbitofrontal cortex functioning, both known to be disturbed in attention-deficit/hyperactivity disorder (ADHD). Some investigations suggested alterations in olfactory processing (identification and sensitivity) in childhood and adult ADHD. Methods: In the present study we investigated olfactory function (Sniffin’ Sticks) of 29 adult patients with ADHD (17 combined, 11 inattentive, and 1 hyperactive/impulsive subtype) and 29 controls matched for sex, handedness, age, intelligence, and education. Additionally, we measured frontal, temporal, and somatosensory cortical activity during olfactory perception. This was performed with functional near-infrared spectroscopy (fNIRS) during presentation of 2-phenylethanol (olfactory stimulant) and linalool (mixed olfactory/trigeminal stimulant) in two concentrations each. Results: Adult patients with ADHD and controls did not differ in sensitivity for and discrimination and identification of olfactory stimuli. Functional brain imaging measures with fNIRS generally revealed diminished activation in olfaction-associated brain regions in patients with ADHD. Only for a high concentration of linalool, oxygenated haemoglobin (O₂Hb) concentrations in patients were similar to controls (significant increase in the temporal, somatosensory, and inferior-frontal cortex). O₂Hb concentrations in active brain regions positively correlated with ADHD symptoms during childhood and trait impulsivity. These effects were carried for the subgroup with combined subtype. Conclusions: Although we could not replicate altered clinical performance in ADHD, our fNIRS findings suggest an association of cortical olfactory processing with hyperactivity and impulsivity in adult ADHD.