DISC1 (Disrupted in schizophrenia-1) plays essential roles in neuronal proliferation, neuronal migration and axon guidance and has been implicated in schizophrenia and related psychiatric disorders.
Substantial genetic and biological research on DISC1 has been reported in the intervening 10 years: DISC1 is now recognized as a genetic risk factor for a spectrum of psychiatric disorders and DISC1 impacts on many aspects of central nervous system (CNS) function, including neurodevelopment, neurosignaling, and synaptic functioning.
Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia.
Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders.
We show levels of Disrupted-in-schizophrenia-1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ-treated cultured cells.
In the present review, we will focus on the emerging roles of TRAX and its interacting proteins (including DISC1 and GSK3β) in psychiatric disorders and the potential implications for developing therapeutic interventions.
The Disrupted-in-Schizophrenia 1 (DISC1) locus on human chromosome 1 was identified as a consequence of its involvement in a balanced translocation (1;11)(q42.1;q14.3) segregating with major psychiatric disorders in a Scottish family.
Although DISC1 is not a risk gene for sporadic cases of specific psychiatric disorders defined by categorical diagnostic criteria (e.g., schizophrenia and major depressive disorder), DISC1 is now regarded as an important molecular lead to decipher molecular pathology for specific dimensions relevant to major mental illnesses.
To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1.
Adult male and female mice with lifelong expression of mutant DISC1 exhibit behavioral abnormalities consistent with hypofunction of NMDA neurotransmission.
In this study, we investigated the brain anatomical networks of 278 healthy volunteers with different genotypes in the common missense variant (Ser704Cys) of the Disrupted-in-Schizophrenia-1 (DISC1) gene, which is one of the main susceptibility genes of schizophrenia and other psychiatric disorders.
Recently several potential susceptibility genes for major psychiatric disorders (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1), dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been reported.
The hypothesis that genetic variation in Disrupted in Schizophrenia 1 (DISC1) influences risk of schizophrenia and other major psychiatric disorders is supported by a growing body of genetic association data and plausible functional biology.
However, subsequent studies have shown association of DISC1 variants with a range of different neurocognitive phenotypes and psychiatric disorders, including bipolar disorder (BPD), and major depression.
These effects of DISC1 polymorphisms on brain morphology provide further support for an involvement of DISC1 in the neurobiology of major psychiatric disorders such as schizophrenia.
As disrupted-in-schizophrenia 1 (DISC1) is a genetic risk factor across a spectrum of psychiatric disorders, we focus on the results of studies using mice with various mutations of DISC1.
DN-DISC1 mice also display several behavioral abnormalities, including hyperactivity, disturbance in sensorimotor gating and olfactory-associated behavior, and an anhedonia/depression-like deficit.