Brain Mechanism May Help Treat Aggression

A variety of psychiatric disorder present with violence and aggression destructive to the patient and society worldwide; disability, disease, death and some socioeconomic problems often trace back to aggressive behaviors.

Some pharmacological regimens can help aggression, but this common condition is difficult to treat with most treatments failing repeatedly and some types of aggression being considered as intractable. A glance at any news story will show violence persists despite best efforts, policies, and sociocultural factors attempting to address it.

EPFL’S Brain Mind Institute have identified some neurobiological mechanisms that control aggression in a study attempting to identify molecular targets to develop more effective treatments. Special model mice showing symptoms of psychiatric disorders such as autism, bipolar disorder, and schizophrenia were studied as they can involve aggressive behavior, characteristic are that the models lack genes that produce ST8SIA2 enzymes that produce polysialic acid which forms complex groups of sicky proteins on neuron surfaces helping them to migrate and connect in both mice and humans.

Scientists investigated whether absence of  ST8SIA2 enzymes and polysialic acid during early development affects aggressive and violent behavior. Mice are not typically aggressive unless provoked making it easy to observe measure deviation in behavior. Time it took knockout mice to attack harmless opponents, and whether attacks were directed at vulnerable body parts were measured along with other things. Knockout mice were found to show signs of abnormal aggressive behavior.

Two behavioral traits in certain types of aggression were investigated that can be measured reliably in mice: reduced fear processing; and reduced anxiety, both of which are traits known to be of importance in emergence of abnormal aggression. Fear learning deficits are typically found among psychopathy and aggressive patients showing different psychopathologies hypothesized to promote antisocial behaviors as they preclude learning from punishment and from following normative socialization.

Examination of model animal brains showed behavioral alterations are due to problems with neurons of the amygdala; knockout mice neurons of the amygdala were found to be largely unable to form new connections and showed impairments with glutamate neurotransmission that transmits signals related to fear processing. Deficiency of GluN2B containing NMDA neuron receptor in the amygdala was identified as key element for developing aggression which is involved in connectivity of neurons as well as proper formation of fear memories.

Building on these findings scientists activated NMDA receptors in the knockout mice using D-cycloserine, treatment was found to effectively reduce aggressive behavior and associated low fear of the animals, according to the scientists. Findings serve as proof of concept, but open up potential effective pharmaceutical targets and treatment for aggression which can be backed up with this solid biological evidence.