MedicalResearch.com Interview with:
Hannah J. Jones, PhD
Centre for Academic Mental Health, School of Social and Community Medicine,
Medical Research Council (MRC) Integrative Epidemiology Unit
University of Bristol, Bristol, England
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Jones: Schizophrenia is a highly heritable condition characterised by relatively diverse symptoms and frequent comorbid disorders. However, at present we don’t know how genetic risk for schizophrenia is expressed in children/adolescents in the general population.
To investigate this, we studied data from individuals within the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort which consists of approximately 14,000 children born to women living in the former Avon Health Authority area in England with an expected delivery date from April 1, 1991, to December 31, 1992.
We used genetic data from approximately 5,000 ALSPAC children and measures from adolescence relating to psychopathology to determine whether genetic risk for schizophrenia is associated with variation in psychotic experiences (e.g. delusions, hallucinations), negative symptoms (e.g. apathy, withdrawal), depressive disorder and anxiety disorder during this developmental period.
We derived a score of genetic risk for schizophrenia in each individual within our study. This score is normally distributed such that most people have some genetic risk and a few people have very high or very low genetic risk.
We found very weak evidence of an association between genetic risk for schizophrenia and psychotic experiences in adolescence and no evidence of an association with depressive disorder. However, we found strong evidence of association between genetic risk for schizophrenia and negative symptoms and anxiety disorder.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Jones: Our results suggest that during adolescence psychotic experiences are not reflecting a genetic component of schizophrenia as much as they are reflecting other causes of delusions and hallucinations, such as having a history of traumatic experiences as a child or cannabis use. The association between schizophrenia genetic risk and psychotic experiences might therefore get stronger with increasing age which is something we aim to investigate in the future. Our findings also suggest that negative symptoms and anxiety disorder are the main ways in which genetic risk for schizophrenia is expressed during adolescence.
Our findings have potentially important implications for clinical studies of individuals identified as having high risk for psychosis, where current approaches for informing prediction of transition to illness rely heavily on the presence of psychotic experiences rather than negative symptoms or anxiety. Our results are also consistent with an evolving literature describing anxiety as a common symptom during the prodromal stage of psychosis.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Jones: Future studies using population based samples are needed to determine whether these findings are robust. Within our study we conducted sensitivity analyses to ensure our findings were consistent across risk scores generated using genetic variants with weak to strong associations with schizophrenia and different measures of psychopathology. Although results were relatively consistent, there are a number of questions that aren’t resolved.
For instance, it is not clear whether the lack of association between schizophrenia genetic risk and psychotic experiences is because psychotic experiences are measured with more error in comparison to our other measures. It is also possible that findings from the genome-wide association study used to generate our risk scores reflect more strongly other characteristics of schizophrenia, such as negative symptoms or comorbid conditions such as anxiety, rather that delusion and hallucinations. This could be further investigated if genetics consortia acquired more detailed data on the specific symptom dimensions of schizophrenia.
If our findings are robust, future research in population samples should focus on factors that may mediate the associations between genetic risk and psychopathology. Specifically, how does having a greater genetic risk for schizophrenia lead to people developing anxiety symptoms or psychosis?
MedicalResearch: Is there anything else you would like to add?
Dr. Jones: Our study does not involve clinical samples but is aimed at helping identify individuals who are at greater risk within the general population. We know that the majority of people with anxiety disorder or negative symptoms will not go on to develop schizophrenia but nevertheless, understanding how genetic risk is expressed in adolescence is the first step in understanding more about the aetiology of schizophrenia and developing targeted interventions.
Jones HJ, Stergiakouli E, Tansey KE, et al. Phenotypic Manifestation of Genetic Risk for Schizophrenia During Adolescence in the General Population. JAMA Psychiatry.Published online January 27, 2016. doi:10.1001/jamapsychiatry.2015.3058.
Dr. Hannah Jones (2016). Study Links Schizophrenia Genetics with Expression During Adolescence