Association of Serum IL-6, CRP(Q) and Ferritin Levels among Acute Transient Psychotic Disorder, Cannabis-Induced Psychotic Disorder and Healthy Controls: A Cross-Sectional Study

(ATPD) and Cannabis-Induced Psychotic Disorder (CIPD) remain less clearly understood from a biological perspective.

 

ATPD is characterized by the sudden onset of psychotic symptoms including hallucinations, delusions, and disorganized behavior, typically resolving within weeks to months[2]. Unlike schizophrenia, ATPD often follows acute psychosocial stressors and shows a favorable prognosis. CIPD, on the other hand, is precipitated by cannabis use and presents with psychotic features that may resolve after abstinence or progress to chronic psychotic illness in vulnerable individuals.

 

Differentiating transient psychoses from emerging primary psychotic disorders is clinically challenging. Current diagnostic approaches rely heavily on phenomenology and longitudinal follow-up, which may delay targeted interventions. Therefore, identifying objective biological markers that reflect underlying pathophysiology is of paramount importance.

 

In recent years, the role of inflammation in psychiatric disorders has gained increasing attention. Neuroinflammatory processes are believed to influence neurotransmitter systems, synaptic plasticity, neurodevelopment, and blood-brain barrier integrity. Elevated levels of inflammatory cytokines and acute-phase reactants have been consistently reported in schizophrenia and mood disorders with psychotic features [3].

 

Interleukin-6 (IL-6) is a pro-inflammatory cytokine involved in immune regulation and neuroimmune communication. It can cross the blood-brain barrier and influence dopaminergic and glutamatergic neurotransmission. Elevated IL-6 levels have been linked to symptom severity, cognitive deficits, and poor treatment response in psychotic disorders [4].

 

C-reactive protein (CRP) is an acute-phase protein synthesized by the liver in response to systemic inflammation. Increased CRP levels have been associated with psychosis risk, metabolic abnormalities, and cognitive impairment [5]. Ferritin, an iron-storage protein, also acts as an inflammatory marker and reflects oxidative stress and immune activation, both of which are implicated in psychotic pathology[6].

 

Despite growing evidence linking inflammation to psychosis, limited studies have simultaneously examined IL-6, CRP, and ferritin in transient psychotic disorders such as ATPD and CIPD. Understanding inflammatory profiles across these conditions may provide insights into disease mechanisms, prognosis, and potential therapeutic targets.

 

The present study aims to compare serum IL-6, CRP(Q), and ferritin levels among ATPD patients, CIPD patients, and healthy controls in a tertiary care setting, thereby contributing to the emerging field of psycho neuroimmunology.

Study Design and Setting

This cross-sectional observational study was conducted at the Department of Psychiatry, SCB Medical College and Hospital, Cuttack, Odisha, a tertiary care teaching hospital.

 

Study Population

A total of 90 participants were enrolled and divided into three groups:

●       Group A: Acute Transient Psychotic Disorder (ATPD) – 30 patients

●       Group B: Cannabis-Induced Psychotic Disorder (CIPD) – 30 patients

●       Group C: Normal Population (NP) – 30 healthy controls

 

Inclusion Criteria

●       Age between 18 and 60 years

●       Diagnosis of ATPD or CIPD as per ICD-10 criteria

●       For controls: absence of psychiatric illness

●       Written informed consent

 

Exclusion Criteria

●       History of chronic psychotic disorders

●       Acute or chronic inflammatory or autoimmune diseases

●       Current infection or fever

●       Substance use other than cannabis (for CIPD group)

●       Use of anti-inflammatory or immunosuppressive drugs

 

Clinical Assessment

Psychiatric evaluation was performed by qualified psychiatrists. Severity of psychotic symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS). Cannabis use was evaluated using the Cannabis Use Disorder Identification Test-Revised (CUDIT-R).

 

Laboratory Assessment

Venous blood samples were collected under aseptic conditions. Serum IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA). CRP(Q) and ferritin levels were estimated using standardized automated biochemical methods.

 

Statistical Analysis

Data were analyzed using SPSS software. Descriptive statistics were expressed as mean ± standard deviation. Group comparisons were performed using one-way ANOVA followed by post-hoc tests. Correlation analysis was conducted using Pearson’s correlation coefficient. A p-value < 0.05 was considered statistically significant.

Table-1. Sociodemographic profile of the study participants

 

Figure1 Age distribution of the study participant

 

Table 2. Comparison of socio-demographic profile of the study participants

 

Table 3. Comparison of socio-economic characteristics between three groups 

 

Table 4. Comparison of clinical presentation among three groups

 

Table 5. Comparison of IL6 levels among the three groups

 

Mean serum IL-6 levels were significantly higher in the ATPD and CIPD groups compared to the healthy control group (p < 0.001). CIPD patients showed higher IL-6 levels than ATPD patients, though the difference did not reach statistical significance.

 

Figure2

 

Table 6. Comparison of CRP(Q) levels among the three groups

 

CRP(Q) levels followed a similar pattern, with significantly elevated values in both psychotic groups compared to controls (p < 0.001). CIPD patients demonstrated the highest mean CRP levels.

 

Figure3

 

Table 7. Comparison of Serum Ferritin levels among the three groups

 

Ferritin levels were also significantly increased in ATPD and CIPD groups compared to the normal population (p < 0.001). The CIPD group showed relatively higher ferritin levels, suggesting greater inflammatory and oxidative stress burden.

 

Figure 4

The present study demonstrates that patients with ATPD and CIPD exhibit significantly elevated serum IL-6, CRP(Q), and ferritin levels compared to healthy individuals, supporting the hypothesis that systemic inflammation plays a role in transient psychotic disorders.

 

Elevated IL-6 levels observed in both psychotic groups align with previous studies in first-episode psychosis and schizophrenia. IL-6-mediated neuroinflammation may influence dopamine dysregulation and glutamatergic dysfunction, contributing to psychotic symptomatology.

 

Higher inflammatory marker levels in CIPD patients may reflect the immunomodulatory effects of cannabis. Chronic cannabis use has been shown to alter cytokine balance, activate microglia, and increase oxidative stress, potentially exacerbating inflammatory responses in vulnerable individuals.

 

Ferritin elevation suggests dysregulated iron metabolism and increased oxidative stress, which may contribute to neurotoxicity and symptom severity. The observed correlations between inflammatory markers and symptom severity further reinforce the clinical relevance of immune activation in psychosis.

 

These findings highlight the potential utility of inflammatory biomarkers in differentiating transient psychoses and identifying individuals at risk for progression to chronic psychotic disorders.

This study provides evidence that ATPD and CIPD are associated with increased systemic inflammation, as reflected by elevated serum IL-6, CRP(Q), and ferritin levels. The findings support the role of immune dysregulation in the pathophysiology of transient psychotic disorders and suggest that inflammatory biomarkers may serve as valuable adjuncts in diagnosis, prognosis, and treatment planning.

 

Clinical Implications and Future Directions

Routine assessment of inflammatory markers may enhance early identification of high-risk psychotic states. Future longitudinal studies are needed to determine whether these biomarkers predict conversion to chronic psychosis and to explore the role of anti-inflammatory interventions in improving outcomes.

 

Strengths and Limitations

The study’s strengths include a well-defined sample and simultaneous evaluation of multiple inflammatory markers. Limitations include its cross-sectional design, modest sample size, and lack of longitudinal follow-up.

 

Conflict of interest: Nil

Financial Support: Nil

 

IEC Regd.No.ECR/84/Inst/OR/2013/RR-20,SCB Medical college, Cuttack, odisha, India

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