A glimpse into the genetic basis of schizophrenia

For schizophrenia, biomarkers or supportive diagnostic tests are scarce and for many patients the efficacy of pharmacological treatment is limited. The PGC-SZ (Psychiatric Genomics Consortium – Schizophrenia), including scientists from the Max Planck Institute of Psychiatry in Munich, has now identified more than 100 genetic loci related to schizophrenia.

The results point to molecules that are currently the most promising targets for therapeutics also aligning well with recent theories about factors causing schizophrenia. The novel findings provide a relevant foundation for mechanistic and treatment development studies.

Schizophrenia is known to be a heritable disorder, highlighting inherited genetic variants to be a key causative for this disease. Due to the scarcity of biomarkers or supportive diagnostic tests, diagnosis is almost exclusively clinician-based. Furthermore, although pharmacological treatments are available for schizophrenia, their efficacy is limited for many patients.

The PGC-SZ, including Bertram Müller-Myhsok, Research Group Leader at the Max Planck Institute of Psychiatry in Munich, has now performed a genome-wide association study and identified more than 100 genomic loci that are significantly related to schizophrenia.

“Our findings include molecules that are currently the most promising targets for therapeutics and point to molecular systems aligning with the predominant theories on factors causing schizophrenia,” states Bertram Müller-Myhsok. “This might suggest that the many novel findings we report also provide a relevant foundation for treatment development studies.”

Particularly variations in genes related to altered glutamatergic synaptic and calcium channel function might serve as a panel of biomarkers for future diagnosis of schizophrenia or might allow better understanding of the molecular mechanisms underlying the disease.

Such associations with genes playing a role in the central nervous system are most relevant for the development of treatment strategies. The results of the study verified genetic associations with the gene coding for the type 2 dopaminergic receptor (DRD2).

“All available antipsychotic drugs are thought to exert their main therapeutic effects through blockade of DRD2,” explains Bertram Müller-Myhsok. “Since the discovery of this mechanism over 60 years ago, no new antipsychotic drug of proven efficacy has been developed based on other target molecules.” Thus, therapeutic stasis is in large part a consequence of the fact that the disease-causing mechanisms are still unknown. Identifying the causes of schizophrenia is therefore a critical step towards improving treatment and outcome for patients suffering from this disorder.

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