A humble fish can experience features of mental health conditions such as schizophrenia and autism, raising the possibility that some of our most complex social behaviours may be more deeply encoded in our DNA than previously thought.
Researchers from Griffith University's Institute for Biomedicine and Glycomics created the world's first complete collection of zebrafish models lacking members of the neurexin gene family, one of the strongest group of genes associated with psychiatric disorders.
Despite no obvious changes in brain development or behaviour during their early development, the fish developed profound, permanent and highly specific behavioural changes emerging in their juvenile stage.
This delayed emergence was one of the central findings of the study and strikingly mimics the human disease trajectories.
Dr Jean Giacomotto said the findings challenged assumptions about the biological complexity required for mental-health-related behaviours.
"These animals function and behave remarkably normally early in life, but as they mature, removing specific neurexin genes led to profound changes in their social behaviour, anxiety and aggression, features also affected in patients with surprisingly comparable timing," Dr Giacomotto said.
"The findings suggest that even highly complex behaviours may arise from deeply conserved biological and genetic programs.
"We often think of social behaviour as being shaped primarily by experience, environment and learning.
"Yet changing a single family of genes was enough to profoundly and permanently reshape how these animals interact with others and respond to their environment."
Zebrafish gave the researchers a unique window into the silent neuronal changes that precede the emergence of mental health conditions.
"Because they mimic the human diseases trajectory, we can now work backwards and identify when brain circuits begin to diverge, what triggers that transition, and whether we can intervene before severe behavioural changes emerge and possibly after to reverse them," Dr Giacomotto said.
"The models also provide a novel and unique platform to search for treatments capable of preventing, delaying or reversing these changes.
"The ultimate goal is to move from genes, to mechanisms, to treatments."
The paper 'Towards modelling mental disorders in zebrafish. Neurexins severely modulate anxiety, affiliative social behaviour and aggression' has been published in Molecular Psychiatry.
