Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

Abstract

ObjectiveThe present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders.MethodsOne hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the χ2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy.ResultsThe rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects.ConclusionOur findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations.

Tyrosine hydroxylase down-regulation after loss of Abelson helper integration site 1 (AHI1) promotes depression via the circadian clock pathway in mice

“…6). In 8 conclusion, the present study demonstrates that the mood-related protein AHI1 links the molecular circadian clock pathway to regulate TH expression.…”

“…Mutations in AHI1 are identified as a frequent factor of an autosomal recessive Joubert syndrome that is characterized by abnormal neurodevelopment and mental disturbance (1)(2)(3). Moreover, many lines of evidence indicate the linkage between AHI1 and neuropsychiatric disorders, including schizophrenia (SCZ) (4-7), depression (8), and autism (9). In animal model, Ahi1 knockout (KO) mice exhibit typical depressive behaviors, sharing common neurological characters in human psychiatric disorders, accompanied by decreases of neurotransmitters such as dopamine (DA) and serotonin (5-HT) in various brain regions (10)(11)(12).…”

Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice

“…Increasing evidences have shown that Abelson helper integrationsite-1 (Ahi1) mutation is associated with a series of psychiatric diseases [29,30]. In addition, our previous studies also demonstrated that Ahi1 KO causes depression-like behaviors in mice [31,21], suggesting Ahi1 can be effectively targeted to develop a depression model.…”

Effect of chronic unpredictable stress on mice with developmental under-expression of the Ahi1 gene: behavioral manifestations and neurobiological correlates

“…Studying Ahi1 expression levels in lymphoblasts from schizophrenia patients, we found reduced expression in patients with early onset of the disorder 13 , leading us to suggest that reduced Ahi1 levels may be associated with susceptibility to schizophrenia. Association of Ahi1 with autism 14 , 15 and bipolar disorder 16 has also been reported.…”