European Journal of Cardiovascular Medicine

The FEP (first episode psychoses) are diagnosed when a subject has a sign of psychosis in clinical scenario for the first time and had never presented any symptom before. FEP can present as Schizophrenia, Schizophreniform Disorder, and/or Brief psychotic disorder based on affective psychosis and duration based on the presence of mood symptoms. Brief psychotic disorder is considered when psychotic disorder is of minimum one day and <1 month with complete premorbid functioning level return. In schizophrenic disorder, psychotic symptoms are 1-6 months. For schizophrenia, psychotic symptom duration is minimum 6 months. One of the core features of schizophrenia is poor cognition affecting various cognitive domains with highest effect on social cognition, processing speed problem‑solving, working memory, attention, and/or memory. These neurocognitive effects are related to poor functional outcomes as difficulties securing and maintaining a job, lower success rates in psychosocial rehabilitation programs, difficulties interacting with the community, and challenges with instrumental and problem‑solving skills.¹

These disorders have been linked to inflammation marked by increase in levels of various inflammatory mediators including CRP (C‑reactive protein) that affect tight junction, enters brain and inflamed the microglia to release IL-6 and transforming growth factor (TGF). Normal CRP levels are <3mg/dl. Raised CRP levels are associated with psychosis symptom and cognitive impairment directly causing NMDA receptor pathway hypofunction vital for schizophrenia and cognition. Another inflammatory mediator is ESR (Erythrocyte Sedimentation Rate) that is seen in relapse and remission of schizophrenia in subjects with no physical illness. NLR (Neutrophil to Lymphocyte Ratio) depicts adaptive and innate immunity causing activation of other immunomodulatory and pro‑inflammatory cytokines in any SIRS (systemic inflammatory response).²

These cause increased neutrophil‑mediated killing of other cells, and neutrophil apoptosis inhibition leading to decrease in lymphocytes and increase in neutrophils.  Microglial activation release anti-inflammatory and proinflammatory cytokines leading to neuronal death and neurotoxicity further causing poor cognition contributing to pathogenesis of schizophrenia. Anti-inflammatory and proinflammatory cytokines levels can be assessed from complete blood count test which is an inexpensive test. In FEP, NLR values are considerably higher.³

Despite raised levels of ESR, NLR, and CRP are seen in different inflammatory conditions are not pathognomonic of any special disease, existing literature data has reported that there is increased levels of various inflammatory markers and poor cognition is seen in subjects with psychosis, however, the relationship between these is not established clearly. Also, the previous literature data is scarce in this context. Hence, it is vital to assess the mechanisms that affect the cognition beyond cytokine‑induced neurodegeneration and cognitive impairment.⁴ Considering these factors, the present study was aimed to assess the levels of serum inflammatory markers and severity of cognitive impairment in subjects with first-episode psychoses and to identify any potential association in cognitive decline and inflammatory markers.

The present cross-sectional study was aimed to assess the levels of serum inflammatory markers and severity of cognitive impairment in subjects with first-episode psychoses and to identify any potential association in cognitive decline and inflammatory markers. The study was done at Department of Psychiatry of the Institute. Verbal and written informed consent were taken from all the subjects before study participation.

The study assessed 100 drug‑naïve subjects that visited the Department of Psychiatry of the Institute within the defined study period. All subjects were assessed using semi-structured proforma and DSM-5. The inclusion criteria for the study were subjects aged 18 to 60 years, had confirmed diagnosis of FEP, psychosis secondary to general medical conditions, those diagnosed with any other major psychiatric illnesses, with known medical or surgical conditions requiring analgesics or corticosteroids, did not suffer from or have any current major inflammatory or infectious diseases, and drug‑naïve subjects. The exclusion criteria for the study were subjects with concurrent use of substances or affective psychosis.

Data from the study subjects were gathered by interviewing both the subjects and their guardians using a detailed semi-structured proforma containing information concerning demographics, psychiatric, medical, and clinical history. Psychotic symptoms were assessed using PANSS (Positive and Negative Syndrome Scale) and BPRS (Brief Psychiatric Rating Scale). Cognitive assessment was done using MoCA (Montreal Cognitive Assessment) and MMSE (Mini‑Mental Status Examination) scales.

The inflammatory marker levels were measured in venous blood which was collected after adequate history recording followed by assessment on MoCA, MMSE, PANSS, and BPRS scales. Blood collection was done on the same day as enrolment and scales were applied within the next two days. Blood tests were aimed to find inflammatory markers in drug-naïve subjects and the association with cognition before pharmacotherapy was initiated.

To assess CRP levels, plasma was collected and incubated at room temperature for 30 minutes to allow clotting and after clotting, serum was collected by centrifugation and Integrated Chemistry System was used to measure CRP. For ESR, EDTA‑anticoagulated blood was collected in glass pipette and was placed vertically in a stand for an hour followed by assessment of sedimentation rate by measuring serum column at tube top in mm per hour. For NLR, it was determined by division of absolute neutrophil count by the absolute lymphocyte count obtained from a complete blood count with a differential.

Statistical analysis of the collected data were done using the chi-square test, Fisher’s exact test, Mann Whitney U test, and SPSS (Statistical Package for the Social Sciences) software version 24.0 (IBM Corp., Armonk. NY, USA) using ANOVA, chi-square test, and student's t-test. The significance level was considered at a p-value of <0.05.

The present cross-sectional study was aimed to assess the levels of serum inflammatory markers and severity of cognitive impairment in subjects with first-episode psychoses and to identify any potential association in cognitive decline and inflammatory markers. The study assessed 100 drug‑naïve subjects that visited the Department of Psychiatry of the Institute within the defined study period. All subjects were assessed using semi-structured proforma and DSM-5. Cognitive defects were assessed using MMSE (Mini‑Mental Status Examination) and MoCA (Montreal Cognitive Assessment) scale. NLR, ESR, and CRP levels were also assessed.

It was seen that for demographic data in study subjects with FEP, mean age of the subjects was 30.4±2.6 years. Majority of study subjects were aged <40 years with 82% (n=82) subjects and 18% (n=18) subjects from 40-60 years. There were 52% (n=52) females and 48% (n=48) male subjects in the study. There were 56% (n=56) single and 44% (n=44) married subjects in the study with 16%, 18%, and 66% being urban, semi-urban, and rural residents. Occupation was unemployed, unskilled, semiskilled, and skilled in 60%, 18%, 18%, and 4% subjects respectively. Educational status was primary, secondary, higher secondary, graduation, and post-graduation in 12%, 30%, 34%, 18%, and 6% subjects respectively (Table 1).

Table 1: Demographic data in study subjects with FEP

The study results showed that for subscales in MOCA scale in study subjects, total scores for orientation, delayed recall, abstraction. Language, attention, naming, and visuospatial were 6, 3, 2, 5, 6, 3, and 5 respectively. The mean scores for these subscales were 4.46±0.488, 3.04±0.583, 1.14±0.789, 2.4±0.636, 3.84±0.847, 2.64±0.517, and 3.44±0.674 respectively. The maximum and minimum scores were 3 and 5, 1 and 4, 1 and 2, 1 and 3, 1 and 4, 2 and 3, and 1 and 4 for orientation, delayed recall, abstraction. Language, attention, naming, and visuospatial domains respectively (Table 2).

Table 2: Subscales in MOCA scale in study subjects

Concerning the MMSE subscale scores in study subjects, the total scores for copying, language, recall, attention, registration, and orientation were 1, 8, 3, 5, 3, and 10 respectively. The mean score for these domains was 0.5±0.460, 6.36±1.104, 2.16±0.386, 3.5±0.503, 2.8±0.0, and 7.16±0.726 respectively. The maximum and minimum scores were 0 and 1, 3 and 8, 2 and 3, 3 and 5, 3 and 3, and 7 and 9 respectively for copying, language, recall, attention, registration, and orientation domain (Table 3).

Table 3: MMSE subscale scores in study subjects

The present study assessed 100 drug‑naïve subjects that visited the Department of Psychiatry of the Institute within the defined study period. All subjects were assessed using semi-structured proforma and DSM-5. Cognitive defects were assessed using MMSE (Mini‑Mental Status Examination) and MoCA (Montreal Cognitive Assessment) scale. NLR, ESR, and CRP levels were also assessed. The study design was similar to the study design adopted by the previous studies of Beydoun MA et al⁵ in 2018 and Kulaksizoglu B et al⁶ in 2016 where study design similar to the present study was also reported by the authors in their studies.

The study results showed that for demographic data in study subjects with FEP, mean age of the subjects was 30.4±2.6 years. Majority of study subjects were aged <40 years with 82% (n=82) subjects and 18% (n=18) subjects from 40-60 years. There were 52% (n=52) females and 48% (n=48) male subjects in the study. There were 56% (n=56) single and 44% (n=44) married subjects in the study with 16%, 18%, and 66% being urban, semi-urban, and rural residents. Occupation was unemployed, unskilled, semiskilled, and skilled in 60%, 18%, 18%, and 4% subjects respectively. Educational status was primary, secondary, higher secondary, graduation, and post-graduation in 12%, 30%, 34%, 18%, and 6% subjects respectively. These results were consistent with the findings of Kuyumcu ME et al⁷ in 2012 and Fathian F et al⁸ in 2019 where authors assessed subjects with demographic data comparable to present study in their studies with FEP.

It was seen that for subscales in MOCA scale in study subjects, total scores for orientation, delayed recall, abstraction. Language, attention, naming, and visuospatial were 6, 3, 2, 5, 6, 3, and 5 respectively. The mean scores for these subscales were 4.46±0.488, 3.04±0.583, 1.14±0.789, 2.4±0.636, 3.84±0.847, 2.64±0.517, and 3.44±0.674 respectively. The maximum and minimum scores were 3 and 5, 1 and 4, 1 and 2, 1 and 3, 1 and 4, 2 and 3, and 1 and 4 for orientation, delayed recall, abstraction. Language, attention, naming, and visuospatial domains respectively. These findings were in agreement with the results of Chang CH et al⁹ in 2019 and Baek SH et al¹⁰ in 2022 where results for subscales in MOCA scale reported by the authors in their studies were comparable to the results of the present study.

On assessing the MMSE subscale scores in study subjects, the total scores for copying, language, recall, attention, registration, and orientation were 1, 8, 3, 5, 3, and 10 respectively. The mean score for these domains was 0.5±0.460, 6.36±1.104, 2.16±0.386, 3.5±0.503, 2.8±0.0, and 7.16±0.726 respectively. The maximum and minimum scores were 0 and 1, 3 and 8, 2 and 3, 3 and 5, 3 and 3, and 7 and 9 respectively for copying, language, recall, attention, registration, and orientation domain. These results were in line with the findings of Mazza MG et al¹¹ in 2020 and Ermakov EA et al¹² in 2022 where MMSE subscale scores comparable to the present study were also reported by the authors in their studies.

The present study, considering its limitations, concludes that subjects that have first episode psychosis have increased levels of inflammatory markers including neutrophil‑lymphocyte ratio and C‑reactive protein which can be attributed to neuroinflammation leading to psychosis development. Cognitive deficits in the first episode of psychosis is poorly related with the inflammatory markers.

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