α-N-acetylgalactosaminidase in Methamphetamine Psychosis

Methamphetamine use disorder (MUD) is frequently complicated by the emergence of psychotic symptoms, which may range from transient intoxication-related psychosis to persistent methamphetamine-induced psychotic disorder (MP). Although clinical and biological differences between MUD and MP are increasingly being investigated, the role of α-N-acetylgalactosaminidase, a lysosomal enzyme involved in glycoconjugate metabolism and immune regulation, has not been previously examined in this population.

This cross-sectional observational study aimed to compare serum α-N-acetylgalactosaminidase levels among three groups: patients with methamphetamine use disorder (MUD), patients with methamphetamine-induced psychotic disorder (MP), and healthy control (HC) subjects. A secondary objective was to evaluate associations between α-N-acetylgalactosaminidase levels, psychotic symptom severity, and systemic inflammation, and to assess its potential predictive value for MP diagnosis.

Participants were consecutive inpatients diagnosed with MUD or MP according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). All patients were admitted to Elazığ Mental Health and Diseases Hospital between May 1, 2025 and August 31, 2025. The healthy control group consisted of individuals without current or past psychiatric disorders or significant medical illnesses. Adult male participants aged 18-65 years were included.

Venous blood samples were collected at hospital admission prior to initiation of treatment. Samples were centrifuged within 30 minutes and serum was stored at -80°C until analysis. Serum α-N-acetylgalactosaminidase levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. Routine biochemical analyses and urine toxicology screening were also performed. The Aggregate Index of Systemic Inflammation (AISI) was calculated as (neutrophils × monocytes × platelets) / lymphocytes.

Psychotic symptom severity in the MP group was assessed using the Positive and Negative Syndrome Scale (PANSS). Sociodemographic variables and clinical characteristics, including self-mutilation history, drug use onset age, duration of methamphetamine use, and smoking status, were recorded.

The primary outcome measure was the difference in serum α-N-acetylgalactosaminidase levels among MP, MUD, and healthy control groups. Secondary outcomes included correlations between α-N-acetylgalactosaminidase levels and PANSS scores, associations with systemic inflammation indices (AISI), and evaluation of the predictive performance of α-N-acetylgalactosaminidase (alone and in combination with self-mutilation history) for distinguishing MP from MUD using logistic regression and receiver operating characteristic (ROC) analysis.

The study was conducted in accordance with the Declaration of Helsinki and approved by the relevant institutional ethics committee. All participants provided written informed consent prior to participation.

• For Methamphetamine Use Disorder (MUD) Group:

*Inclusion Criteria:

• Diagnosis of MUD according to DSM-5-TR
• Medication-free for at least one month prior to admission
• Age ≥ 18 years and <65 years
• Provided informed consent

For Methamphetamine Use Disorder (MUD) Group:

*Exclusion Criteria:

• Hypertension
• Diabetes mellitus
• Chronic kidney disease
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Cardiac illness
• Severe neurological disorders
• Immunological or systemic illness
• Primary psychiatric disorders other than MUD
• Alcohol use disorder
• For Methamphetamine-Induced Psychotic Disorder (MP) Group:

*Inclusion Criteria:

• Diagnosis of MP according to DSM-5-TR
• Medication-free for at least one month prior to admission
• Age ≥ 18 years and <65 years
• Provided informed consent

For Methamphetamine-Induced Psychotic Disorder (MP) Group:

*Exclusion Criteria:

• Hypertension
• Diabetes mellitus
• Chronic kidney disease
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Cardiac illness
• Severe neurological disorders
• Immunological or systemic illness
• Primary psychiatric disorders other than MP
• Alcohol use disorder
• For Healthy Control Group:

*Inclusion Criteria:

• No psychiatric diagnosis
• No systemic or immunological illness
• Medication-free for at least one month
• Age ≥ 18 years and < 65 years
• Provided informed consent

For Healthy Control Group:

*Exclusion Criteria:

• Hypertension
• Diabetes mellitus
• Chronic kidney disease
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Cardiac illness
• Severe neurological disorders
• Immunological or systemic illness
• Primary psychiatric disorders other than schizophrenia
• Alcohol/drug/substance use