MORE PRONOUNCED NEUROAXONAL INTEGRITY DISTURBANCES IN METHAMPHETAMINE-ASSOCIATED PERSISTENT PSYCHOSIS COMPARED TO SCHIZOPHRENIA

Abstract Background Methamphetamine (METH) can cause multiple physical and psychological harms. Psychosis is one of the most serious health consequences from using METH, with this requiring aggressive treatment and being associated neurocognitive impairment and structural brain abnormalities. While the majority of METH-associated psychosis are brief (METH-associated brief psychosis, MBP); the psychosis can become persistent for >1 month in a subset of people (METH-associated persistent psychosis, MPP), with a symptom profile substantially similar to schizophrenia. Blood levels of neurofilament light chain (NFL) have been proposed as a measure of neuroaxonal integrity in several neuropsychiatric disorders. Aims & Objectives We aimed to delineate the neuroaxonal damage linked to METH-associated psychosis, especially its persistent form, and compare it to schizophrenia. Methods We enrolled 135 individuals with METH use disorder (55 with no psychosis [MNP group], 54 with MBP, and 24 with MPP), 78 with schizophrenia, and 85 healthy controls. Blood NFL levels measured by single molecule array (SiMoA) immunoassay. We compared NFL levels between different groups and used regression analyses to identify clinical variables related to NFL levels. Results Individuals with MUD had significantly higher NFL levels compared to controls but comparable to patients with schizophrenia. We found age (p<.01) and duration of METH use (p = 0.01) were positively correlated with NFL levels whereas BMI is negatively correlated with NFL levels. Subsequent group comparisons showed that the NFL levels in MPP group were higher than MBP and MNP group while the levels were comparable between the latter two groups. Interestingly, MPP group had increased NFL levels compared to schizophrenia group. Furthermore, those with a prolonged psychosis associated with METH, i.e. schizophrenia-like, had a even higher NFL levels than all the resting groups. Discussion & Conclusions These results suggest substantial neuroaxonal alterations following METH use, with a longer duration associated with higher injury. In particular, persistent psychosis The pronounced increase of NFL levels in the people with MPP and suffering from persistent psychosis might indicate that dual disruptive effect (from METH use and psychosis) on the neuroaxonal integrity and the pathology could differentiate MPP and schizophrenia.