Neurology Central

Four new genes define strands of schizophrenia

New research from NYU Langone Medical Center (NY, USA) has revealed four key genes that define four previously unknown conditions falling within the diagnosis of schizophrenia. The findings, which were published recently in EBioMedicine, highlight potential reasons behind variations in schizophrenia symptoms that have not previously been understood and provide hope for precision treatments for patients affected.

“A common fallacy is that schizophrenia can be treated as a single disease,” explained lead author Dolores Malaspina (NYU Langone Medical Center).

The current study recruited 48 individuals that had been diagnosed with schizophrenia, identifying symptom sets in patients that had rare or unknown changes in the DNA code of the four genes previously identified as of interest by the research team. All of the genes played a role in the disruption of growth or regulation of nerve circuits.

The four analyzed genes included PTPRG, SLC39SA13, ARMS/KIDINS220 and TGM5, all of which resulted in different symptoms, intelligence levels and disease features in patients.

Mutations in PTPRG resulted in earlier onset of severe psychosis and patients possessing the mutation had a history of learning disabilities, they also showed deficits in working memory. SLC39SA13 mutations were associated with widespread cognitive deficits, low educational attainment and the most severe examples of emotional and motivational deficits.

Alterations in the version of ARMS/KIDINS220 exhibited normal to high performing cognitive function but showed consistent cognitive decline following college age. TGM5 has less severe schizophrenia symptoms but had more often been diagnosed with attention deficit disorder during their childhood.

Malaspina commented of the results: “Perhaps as many as 30% of schizophrenic patients may now become candidates for more precise treatment based on the individual characteristics of these four genes. Our approach provides a new framework for finding influential genes across complex genetic diseases associated with paternal age, from schizophrenia to autism.”

The team argue that focus should now be placed on processing speed in TGM5 cases, working memory in PTPRG, zinc augmentation in SLC39A13 and nerve cell protection in patients with ARMS/KIDINS220 mutations, as well as core psychosis symptoms.

“Treatments that do not work for all patients may be highly effective in some,” reinforced first author Thorsten Kranz (NYU Langone Medical Center).

Malaspina concluded: “Our biologically driven study begins to answer longstanding questions in the field about why any two people diagnosed with schizophrenia may have drastically different symptoms. For the first time, we have defined four syndromes mechanistically.”

Source: NYU Langone Medical Center press release