Key result
The subcellular distribution of a nucleus-enriched DISC1 isoform in the orbitofrontal cortex was significantly altered in brains from patients with schizophrenia and major depression.
Observational
An isoform of DISC1 shows altered subcellular distribution in the orbitofrontal cortex of patients with schizophrenia and major depression, suggesting its implication in psychiatric conditions beyond the originally identified Scottish family.
Does not support clinical translation; leaves open DISC1 isoform's mechanistic role in schizophrenia and depression.
Disrupted-In-Schizophrenia 1 (DISC1) was identified as the sole gene whose ORF is truncated and cosegregates with major mental illnesses in a Scottish family. DISC1 has also been suggested, by association and linkage studies, to be a susceptibility gene for schizophrenia (SZ) in independent populations. However, no analysis of DISC1 protein in human brains, especially those of patients with SZ, has yet been conducted. Here we performed a biochemical analysis of DISC1 protein in a well characterized set of autopsied brains, including brains of patients with SZ, bipolar disorder, and major depression (MD), as well as normal control brains. We identified an isoform of DISC1 by using MS and demonstrated that it is enriched in the nucleus of HeLa cells. In the orbitofrontal cortex, the subcellular distribution of this DISC1 isoform, assessed by the nuclear to cytoplasmic ratio in the immunoreactivity of the isoform, is significantly changed in brains from patients with SZ and MD. This altered distribution is also observed in those subjects with substance and alcohol abuse. The changes in MD brains are significantly influenced by substance/alcohol abuse as well as postmortem interval; however, the alteration in SZ brains is free from brain-associated confounding factors, although an interaction with substance/alcohol abuse cannot be completely ruled out. These results suggest that DISC1 may be implicated in psychiatric conditions in other populations than the unique Scottish family.
No takes yet. Share an insight, caveat, or question.
Sawamura et al. (2005) conducted an observational in Schizophrenia, bipolar disorder, major depression. Schizophrenia, major depression, and substance/alcohol abuse vs. Normal control brains was evaluated on Subcellular distribution of DISC1 isoform (nuclear to cytoplasmic ratio) in the orbitofrontal cortex. The subcellular distribution of a nucleus-enriched DISC1 isoform in the orbitofrontal cortex was significantly altered in brains from patients with schizophrenia and major depression.
Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context: