An interesting new study has found four specific genetic variants that suggests that schizophrenia may not be a single disease, but rather a group of distinct disorders that have similar outward symptoms.
Researchers discovered the importance of coding variants of these four influential genes that may suggest different schizophrenia subtypes. That is, schizophrenia may be a complex constellation of symptoms that vary based upon the underlying gene variant.
The new research (Kranz et al., 2016) examined 48 people with psychotic symptoms and carried out a certain type of gene sequencing (exome sequencing) targeting four specific genes — PTPRG, SLC39A13, TGM5, and ARMS/KIDINS220. Only fifteen (15) of the 48 subjects in the study (31.25 percent) carried “rare or novel missense coding variants in one or more of these genes.” These four subtypes of schizophrenia appear to differ in important ways:
The subgroups significantly differed in important features, including: specific working memory deficits for PTPRG (n = 5); severe negative symptoms, global cognitive deficits and poor educational attainment, suggesting a developmental disorder, for SLC39A13 (n = 4); slow processing speed, childhood attention deficit disorder and milder symptoms for TGM5 (n = 4); and global cognitive deficits with good educational attainment suggesting neurodegeneration for ARMS/KIDINS220 (n = 5).
The researchers suggest that this could open the door to better understanding more effective treatments for people with schizophrenia who happen to have one of these rare gene coding variants.
In particular, treatment approaches may usefully address processing speed in TGM5 carriers, working memory in PTPRG, zinc augmentation in SLC39A13, and neuroprotection in ARMS/KIDINS220 carriers. Precision approaches can be informed by knowledge of these genotypes to advance treatment for persons with psychoses.
Does This Change Schizophrenia Treatment?
While the new research findings are interesting, it’s unlikely they’ll result in any significant changes to schizophrenia treatment any time soon.
Patients would have to go extensive (and expensive) genetic testing for these four specific gene coding variants. And even then, few of them would be helped by such testing. That’s because fully 70 percent of people in the study did not have any of these coding variants, and so would not be helped by any of these types of treatment efforts.
And the treatment suggestions made by the researchers are largely based on mouse studies — not studies of actual humans. The vast majority of mouse studies do not replicate in human studies. Many human studies would be needed in order to confirm whether the treatment methods proposed would actually benefit those with the specific coding variants.
As with all research in the area of mental illness and genes, this study provides tantalizing clues to the complexity of schizophrenia and its precursors. But it still doesn’t provide much actionable information today for professionals or their patients with schizophrenia.
Kranz, TM et al. (2016). Phenotypically distinct subtypes of psychosis accompany novel or rare variants in four different signaling genes. EBioMedicine.