New insights into the mechanisms underlying hippocampal atrophy in individuals at risk for psychosis

Dysregulation of the dopamine neurotransmitter system has long been associated with schizophrenia and other psychoses, but recently researchers have begun investigating the glutamate and GABA systems as well. Studies have shown that the excitatory-inhibitory imbalance begins with improperly functioning NMDA-type glutamate receptors (NMDARs) in the temporal regions of the brain, but much of the evidence is in psychotic brains. and it remains questionable whether the disequilibrium is caused by or precedes psychotic symptoms.

A new study in people with copy variant number 22q11.2 deletion syndrome (22q11DS) now explores the excitatory inhibitory neurotransmitter system prior to the onset of psychosis. Deletion carriers are more prone to psychiatric disorders, such as anxiety and mood disorders, and have a 30% lifetime risk of developing a psychiatric disorder, such as schizophrenia, by adulthood. These carriers provide a unique opportunity for longitudinal studies on neuropsychiatric disorders, as they can be studied and followed up before and after neuropsychiatric disorders.

This research biological Psychiatrypublished by Elsevier.

Researchers led by Dr. Valentina Mancini of the University of Geneva School of Medicine used magnetic resonance imaging (MRI) combined with proton magnetic resonance spectroscopy (MRS) to detect the excitatory neurotransmitters glutamate and glutamine (Glx), and Inhibitory neurotransmitter levels were estimated. The neurotransmitter GABA in the brains of her 60 individuals with 22q11DS and 45 healthy controls. They focused on her three brain regions implicated in the pathophysiology of schizophrenia: the anterior cingulate cortex (ACC), superior cortex (STC), and hippocampus.

Deletion carriers had higher levels of Glx in hippocampus and STC, but not in ACC, compared to controls. Carriers also had significantly lower hippocampal GABA levels, but lower levels of ACC and STC. Importantly, those with psychosis among 22q11DS carriers also had higher hippocampal Glx levels, suggesting that hippocampal alterations may drive downstream pathology.

Hippocampal atrophy has also been observed in the brains of people with schizophrenia. In the current study, Glx concentrations were associated with greater atrophy, possibly indicating increased hippocampal vulnerability.

Our results highlight a gradual change in the ratio of excitatory and inhibitory neurotransmitter concentrations in the temporal limbic region, particularly in the hippocampus. They also found that people with higher levels of excitatory neurotransmitters had a greater decrease in hippocampal volume over time. These people also began experiencing psychotic symptoms such as hallucinations and delusions. Our study provides new insights into the potential mechanisms underlying hippocampal atrophy in individuals at risk for psychosis and links these neurological abnormalities with the emergence of psychotic symptoms. ”

Dr. Valentina Mancini, Faculty of Medicine, University of Geneva

John Crystal, MD, Editor biological psychiatry, “This study of 22q.11 deletion syndrome, a syndrome with increased risk of schizophrenia, builds on previous findings that link excessive glutamate release and decreased cortical volume, suggesting atrophy,” he said of the study. “This form of atrophy may contribute to cognition and cognition.” Dysfunction. ”

Dr. Mancini added that the study could have clinical implications. “This finding may inform new therapeutic strategies aimed at early glutamatergic dysfunction in individuals at risk for psychosis. Given the critical role of the hippocampus in memory processes, excitatory and inhibitory By preventing gender imbalance and volume loss, we may be able to mitigate the cognitive decline typically observed in psychotic patients.” ”