What we do
About our project
Risk factor
The risk of SMI is especially high for offspring of parents affected by schizophrenia, bipolar disorder, and major depressive disorder. They have a 2-to-3 fold increased risk to develop psychotic, mood, anxiety and externalizing disorders, implicating that half of them develop some form of psychopathology before the age of 20.
Neurodevelopment
Over thirty years ago, the neurodevelopmental hypothesis of schizophrenia was proposed, postulating that the combined effects of genes and perinatal brain alterations increase the risk of schizophrenia. Abnormal fetal brain structures may leave traces which only become fully exposed until the critical periods of maturation and neuronal pruning occur in adolescence. During critical periods the affected structures are “called” into operation, resulting in prodromal and, subsequently, diagnostic symptoms of the disorder. Importantly, it has been speculated that neurodevelopmental alterations also underlie bipolar disorder and major depressive disorder.
Procedure
We will include 20 pregnant couples, with one of the biological parents having a diagnosis of SMI before pregnancy, and 20 couples without familial history of SMI (singleton pregnancies only). Parents(-to-be) will be invited around 25–27 weeks and 32–35 weeks gestational age (GA), and 4–6 weeks postnatal. During the first two time points the mother will undergo MRI scanning where we scan the brain of the fetus. At 4–6 weeks postnatal we will scan the neonate. These time points were chosen because a rapid increase in total and regional brain volumes occurs between 25 and 40 weeks of gestation. Information on perceived stress, parent-child bonding, and presence and severity of psychiatric symptoms will be assessed at each time point.
MRI scanning
To make the procedure as comfortable as possible for the mother and newborn, we will use appropriate positioning, and specifically for the newborn, swaddling and timing of feeds, to help optimize effective scanning. We will not use pharmacological sedation or general anesthesia. As soon as the mother or the neonate show signs of discomfort, we will stop the procedure.
The risks for participation in this study are negligible. MRI is generally accepted as safe, both in pregnancy and in neonates, based on extensive experience. Therefore, no special preparation for the participants on top of the Erasmus MC standard procedure is needed.
Our research focus
Relevance
The primary aim of this proposal is to contribute new knowledge to the etiology of SMI and to elucidate how familial high risk for SMI influences perinatal brain development. Ultimately, by identifying alterations in perinatal neurodevelopment with non-invasive imaging techniques, we may provide biomarkers to predict who is vulnerable to SMI later in life. Obviously, we must wait at least 20 years before we can answer this question. However, in the shorter term, our findings may offer targets for early preventative interventions, thereby addressing an important public health issue.
The developing brain has an enormous degree of plasticity, making it highly sensitive to even subtle external influences. Understanding which alterations in neural development occur due to familial susceptibility to SMI will pave the way for public health intervention or monitoring strategies aimed at improving neurodevelopment through cognitive, behavioral, or low-risk biological interventions from early in life onwards. This may significantly improve functional outcomes and help prevent the onset of SMI (e.g. psychological support for parents, stress reduction, or nutritional supplements).
Funds & Grants
- Vrienden van Sophia (Neeltje van Haren)
- Trustfonds (Lisanne van Houtum)
Collaborations
Internal collaborations
- Dept of Radiology & Nuclear Medicine
- Dept of Obstetrics and Gynecology
