Effects of D-Aspartic Acid on Schizophrenia

Normally, an organism will display a set of reflex behaviors such as the startle response in order to prepare itself to react to certain stimulus. However, certain mental health conditions like schizophrenia can reduce one’s reactivity to moderately intense stimuli. Interestingly, mice studies show that D-aspartic acid supplementation may help reduce schizophrenia-like behaviors through certain mechanisms.

Errico et al. investigated the effects of D-aspartic acid in mice with schizophrenia.[5] In order to induce schizophrenia-like behaviors, all the mice were injected with amphetamine and were kept in a cage. After a few days, the mice displayed impaired startle response when exposed to background noise. A group of mice was then treated with D-aspartic acid mixed in drinking water and another group was fed with regular food and water ad libitum. Both groups were then subjected to undergo a behavioral test known as acoustic startle response . Researchers observed that mice treated with D-aspartic acid were more likely to exhibit startle response as evidenced by rapid contraction of the facial and skeletal muscles when exposed to loud noise. Of note, this effect was not observed in mice fed with regular food and water. This result suggests that D-aspartic acid supplementation in mice may help alleviate schizophrenia-like behaviors induced by amphetamine.

The N-methyl-D-aspartate receptor (NMDAR) is a group of proteins that help regulate the transmission of signals from one nerve cell to another. This receptor is believed to play a major role in learning and memory formation. Studies show that dysregulation in NMDAR is strongly linked with the development of schizophrenia.[6] Interestingly, Krashia et al. reported that higher levels of D-aspartic acid are associated with improved NMDAR activity in mice.[7] The researchers examined the brains of mice treated with D-aspartic acid and found higher levels of this compound compared to untreated mice. It was found that high D-aspartic levels increase NMDAR numbers, which in turn cause dopamine neurons to build a protective uptake mechanism. This mechanism may help reduce schizophrenia-like symptoms and prevent its development.

Another study by Errico et al. investigated the effects of D-aspartic acid supplementation on schizophrenia-like behaviors in mice.[8] In order to induce schizophrenia-like behaviors, the mice were injected with phencyclidine (PCP). An increase in locomotor activity and inhibition of the startle response were observed after PCP injection. After producing PCP-induced schizophrenia-like behaviors, the mice were grouped into two:

D-aspartic acid-treated mice H 2 O-treated mice (control)

Both groups were then observed and subjected to undergo magnetic resonance imaging (MRI). Interestingly, while D-aspartic acid failed to produce statistically significant effects on schizophrenia-like behaviors, MRI results showed that the brains of mice treated with D-aspartic acid have increased cortico–hippocampal connectivity (which is usually reduced in schizophrenia patients) compared to control. These results suggest that D-aspartic acid supplementation may help improve impaired cortico–hippocampal brain network organization in mice with schizophrenia-like behaviors induced by PCP.