Current treatment strategies largely fail to ameliorate cognitive deficits associated with schizophrenia. To gain a better understanding of the genetic risk of schizophrenia, and to develop more efficient treatment strategies, researchers from Norway looked for the genetic loci associated with both schizophrenia risk and the severity of these cognitive deficits.
Schizophrenia is a chronic psychiatric illness affecting approximately 1% of the population. There are environmental factors and a genetic risk of schizophrenia that contribute to the risk of developing the illness. Typically, symptoms begin around or just after puberty and can lead to a lifetime of impairment and disability. These symptoms are characterized as:
- Positive Symptoms – those not normally seen in healthy individuals, such as auditory hallucinations and delusions,
- Negative Symptoms – those normally present in healthy individuals but significantly reduced or absent in patients resulting in increased social isolation, apathy, and lack of pleasure, and
- Cognitive Symptoms – impaired attention, verbal and visual learning ability, emotion regulation, executive function, and memory.
Positive symptoms generally respond well to conventional antipsychotic medications. For example, patients with this disorder show sensitivity to drugs that enhance dopamine neurotransmission and gain relief from drugs that block dopamine receptors in the brain. Yet, current treatment strategies largely fail to ameliorate negative symptoms or cognitive impairments. To develop more efficient treatment strategies for patients with schizophrenia, a better understanding of the pathogenesis underlying these cognitive deficits is needed.
In a recent study published in JAMA Psychiatry, researchers from Norway looked to identify genomic regions jointly influencing schizophrenia risk and the cognitive domains of reaction time and verbal-numerical reasoning, and general cognitive function. They were specifically looking for shared loci (a locus is a position or location on a gene) between schizophrenia and cognitive dysfunction.
Between July 24, 2014, to January 17, 2017, they combined and analyzed four extensive genome-wide data sets: the Psychiatric Genomics Consortium cohort (n = 79,757); the UK Biobank cohort (n=36,035); Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n=53,949); and Cognitive Genomics Consortium (COGENT) (n=27,888).In total, they analyzed genetic data from more than 250,000 participants.
They identified 21 loci jointly influencing schizophrenia and cognitive traits:
- 2 loci shared between schizophrenia and verbal-numerical reasoning,
- 6 loci shared between schizophrenia and reaction time, and
- 14 loci shared between schizophrenia and general cognitive function.
One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.3). For 18 of these genetic variants, schizophrenia risk was associated with poorer cognitive performance.
This type of research provides insight into the genetic risk of schizophrenia, furthering our understanding of this debilitating condition. This study supports previous research evidence for a common genetic basis between cognitive dysfunction and schizophrenia risk and identifies specific gene variants that can be used to guide further efforts to develop effective treatments targeted to minimize cognitive dysfunction.
Written by Debra A. Kellen, PhD
Citation: Smeland, O. B., Frei, O., Kauppi, K., Hill, W. D., Li, W., Wang, Y., … Andreassen, O. A. (2017). Identification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive function. JAMA Psychiatry, E1-E11. DOI: 10.1001/jamapsychiatry.2017.1986