α-N-acetylgalactosaminidase in Methamphetamine Psychosis

Could α-N-acetylgalactosaminidase Levels Be Associated With the Presence of Psychotic Symptoms in Methamphetamine Use Disorder? A Cross-Sectional Observational Study

This cross-sectional observational cohort study examined serum α-N-acetylgalactosaminidase levels in methamphetamine use disorder (MUD), methamphetamine-induced psychotic disorder (MP), and healthy control (HC) groups. The study aimed to determine whether decreased α-N-acetylgalactosaminidase levels are associated with psychotic symptoms in methamphetamine users.

Study Overview

• Status: Completed
• Conditions: Methamphetamine Use Disorder; Methamphetamine-induced Psychosis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 93

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Elâzığ
    • Elâzığ, Elâzığ, Turkey (Türkiye), 23200
      • Elazığ Mental Health and Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consisted of adult male inpatients aged 18-49 years who were admitted to Elazığ Mental Health and Diseases Hospital between May 1, 2025 and August 31, 2025.

The MP group included consecutive inpatients diagnosed with methamphetamine-induced psychotic disorder and the MUD group included consecutive inpatients diagnosed with methamphetamine use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR).

Both patient groups consisted of active methamphetamine users and were hospitalized for clinical management at the time of assessment. Urine toxicology screening was performed at admission to confirm substance use status.

The Healthy Control (HC) group consisted of adult male individuals without current or past psychiatric disorders and without substance use disorders, matched to patient groups in terms of age and body mass index. HCs had no significant medical illnesses.

Description

1. 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

2. 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

3. 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Methamphetamine Use Disorder; Adult participants (18-65 years) diagnosed with Methamphetamine Use Disorder according to DSM-5-TR criteria. Participants were evaluated at hospital admission (baseline). No intervention was assigned by the study protocol. Blood samples were collected for measurement of serum α-N-acetylgalactosaminidase levels and complete blood count parameters. No psychometric scales were administered to this group. Sociodemographic and clinical data were recorded for all participants.
Methamphetamine-Induced Psychotic Disorder; Adult participants (18-65 years) diagnosed with Methamphetamine-Induced Psychotic Disorder according to DSM-5-TR criteria. Participants were evaluated at hospital admission (baseline). No intervention was assigned by the study protocol. Blood samples were collected for measurement of serum α-N-acetylgalactosaminidase levels and complete blood count parameters. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). Sociodemographic and clinical data were recorded for all participants.
Healthy Control; Healthy control adult participants (18-65 years) without any current or past psychiatric disorder. No intervention was administered as part of the research protocol. Participants underwent a baseline clinical evaluation and provided a single blood sample for measurement of serum α-N-acetylgalactosaminidase levels and complete blood count inflammatory markers. Sociodemographic and clinical data were recorded for all participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
α-N-acetylgalactosaminidase	Serum α-N-acetylgalactosaminidase levels measured by ELISA (ng/mL).	At hospital admission (baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aggregate Index of Systemic Inflammation (AISI)	Aggregate Index of Systemic Inflammation (AISI) is calculated using the following formula: (neutrophils × monocytes × platelets) / (lymphocytes). All the parameters mentioned here are complete blood count parameters.	At hospital admission (baseline)
Positive and Negative Syndrome Scale (PANSS) Score	Positive and Negative Syndrome Scale (PANSS) was developed to assess positive and negative symptoms and general psychopathology in patients with schizophrenia-spectrum disorder, and to measure the level of these symptoms. It is administered via a semi-structured interview, taking into account the last week. Information can also be obtained from the patient's relatives and healthcare staff. It consists of a total of 30 items: 7 items addressing positive symptoms, 7 addressing negative symptoms, and 16 addressing general psychopathology symptoms. Each item is scored from 1 to 7, and the scores are summed for the final score. This scale was only administered to the methamphetamine-induced psychotic disorder group.	At hospital admission (baseline)

Collaborators and Investigators

• Sponsor: Elazığ Mental Health and Diseases Hospital
• Investigators: Principal Investigator: Mehmet Hamdi ÖRÜM, MD, Associate Professor, Elazığ Mental Health and Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Actual): August 31, 2025
• Study Completion (Actual): August 31, 2025

Study Registration Dates

• First Submitted: February 20, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Methamphetamine; Psychotic Disorder; Psychostimulants; α-N-acetylgalactosaminidase; Methamphetamine Psychosis
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Psychotic Disorders
• Other Study ID Numbers: EMHDH-2025-METH-NAGALASE-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Deidentified individual participant data (IPD) underlying the results reported in this study (including demographic variables, serum α-N-acetylgalactosaminidase levels, complete blood count parameters, and Positive and Negative Syndrome Scale (PANSS)) will be made available to qualified researchers upon reasonable request for academic purposes.

Data will be shared after removal of all direct identifiers and in accordance with applicable ethical approvals and data protection regulations. Access to the data will require a methodologically sound research proposal and a data use agreement. Requests should be directed to the corresponding author.

• IPD Sharing Time Frame: Data will be available beginning 6 months after publication and will remain available for 5 years.
• IPD Sharing Access Criteria: Access will be granted to researchers who provide a methodologically sound proposal. Requests must be approved by the principal investigator and may require a data use agreement in accordance with institutional and ethical regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No