Neelam Mehta1, Itishri Jena2*, Subhashree Ray2, Sudeshna Behera2, Surjeet Sahoo3
1Department of Pathology, TATA Main Hospital, Jamshedpur, 831001, Jharkhand, India.
2Department of Biochemistry, IMS and SUM Hospital, Bhubaneswar, 751003, Odisha, India.
3Department of Psychiatry, IMS and SUM Hospital, Bhubaneswar, 751003, Odisha, India.
*Corresponding Author E-mail: dritishrijena82@gmail.com
ABSTRACT:
The underlying etiopathogenesis of long-term psychiatric disorder schizophrenia is not clear. Hyperhomocystenemia is known to play important role in ethiopathogenesis and development of many cognitive disorder including schizophrenia. The present study was undertaken to find out the association between plasma homocysteine with Positive And Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) of newly detected schizophrenic patients. PANSS and BPRS are commonly used symptoms rating scale of schizophrenia. Assessment of plasma homocysteine, PANSS and BPRS were done in 30 schizophrenic patients and compared with 50 gender and age matched healthy individuals. The plasma homocysteine, BPRS score and PANSS score of schizophrenic patients were 15.48±2.71 μmol/L, 84.2±1.72, 149.01±1.72 respectively, which were significantly high in comparison to controls. This raised value of homocysteine is also positively and significantly correlated with BPRS and PANSS of study population. This study suggests the role of high homocysteine level in development and progression of schizophrenia.
KEYWORDS: Psychiatric disorder, Schizophrenia, Hyperhomocysteinemia, PANSS, BPRS.
INTRODUCTION:
Schizophrenia is a long-term psychiatric disorder with very poor consequences. It is associated with both positive symptoms like hallucinations, delusion and negative symptoms like lack of motivation, social disconnection etc.1,2,3. This disastrous mental disease affects approximately 24 million people worldwide and according to survey done recently the prevalence in India is 0.3% approximately2,4,5. This gives considerable amount of burden to care giver, both physically and mentally6. This is also a troublesome disease to the clinician. The clinician really face many challenges while diagnosing and treating the disease. There are few scoring system which are apparently helpful while treating the disease.
The Brief Psychiatric Rating Scale (BPRS) and Positive And Negative Syndrome Scale (PANSS) are routinely used to assess the symptoms7. BPRS is one the oldest rating scale to assess the psychiatric symptoms of schizophrenia. It was first came to attention in the year 19628. PANSS was developed by Kay et al9 in 1987, which solved some issues related to BPRS7.
The underlying pathophysiology of schizophrenia is unclear. Both genetic predisposition and environmental factors contribute to etiopathogenesis of this disorder10,11. Research done many years ago postulated that abnormality in amino acids involved in methylation reaction may play a role in development of the disease12,13. Methionine and homocysteine are important amino acids involved in methylation reactions. Homocysteine is a sulfur containing amino acid formed during metabolism of methionine. This molecule now recognized widely due to its important role in many cellular functions. Two metabolic pathways are important in regulating plasma homocysteine level. One is transsulfuration to cysteine and the other one is remethylation to methionine. Starting from genetic factors to environmental factors like life style, diet and several medications influence homocysteine level in blood14,15.
Hyperhomocysteinemia is associated with pathophysiology of many conditions like inflammation, ischaemic injury, endothelial dysfunction, hypertension, osteoporosis, age-related disorders, cardiovascular disorders etc., thus plays important role in development of chronic renal failure, hypothyroidism, myocardial infarction14,15,16,17,18,19. Many studies have proved the association between hyperhomocysteinemia with many major psychiatric disorders like major depression20, bipolar disorder21,22 and schizophrenia2,23,24.
Keeping in view the above findings this study was undertaken to find out the association between plasma homocysteine with PANSS and BPRS of newly detected schizophrenic patients.
MATERIALS AND METHODS:
The present research took place in department of Biochemistry in cooperation with Psychiatric department of IMS and SUM hospital, one of the well-known hospital of eastern India. The research was done according to the protocol approved by the Institutional Ethical Committee (IMS SH/IEC/2014/65). Total 80 subjects were enrolled to this hospital based corss-sectional case control study, out of which 30 were schizophrenic cases and 50 were control. 20-40 years aged people who visited the out-patient psychiatric department or admitted as in-patient to the same department and were diagnosed to be as schizophrenic for the first time were enrolled as cases. Gender and age matched other wise healthy human being attending the similar hospital were considered as controls. Subjects with history of head injury, alteration of sensorium, epilepsy, memory loss, delirium, focal neurological deficiency, recent history high fever, any variety of deficiency of sensory parameters, mental retardation, ECT in recent past, lactating and pregnant women, any substance abuse, alcohol intake, drug intake that affect blood homocysteine level, therapy with multivitamin, chronic medical conditions like hypertension, diabetes mellitus, chronic renal disorder, coronary artery disease were excluded from this study. Schizophrenia diagnosis was made through use of the International Classification of Diseases- 10, Diagnostic Criteria for Research (ICD-10 DCR) Guidelines.
Study was done with informed consent taken from all subjects. BPRS was done according to Overall JE et al. 8 For this 24 signs and symptoms (anxiety, depression, somatic concern, hostility, guilt, suicidality, suspiciousness, elated mood, grandiosity, bizzare behavior, unusual thought content, hallucinations, self neglect, disorientation, blunted affect, conceptual disorganization, tension, emotional withdrawal, uncooperativeness, motor retardation, motor hyperactivity, excitement, mannerism and posturing, distractability) of schizophrenia were taken into considerations. 14 items were rated according to individual’s self report and 10 items were according to speech and observed behavior, for 3 items both observed behaviors and self report were also taken into consideration.
PANSS was done according to Kay et al.9. It consists of a seven point rating on 30 symptoms, for which each item and each level of symptom severity are defined. The ratings provide summary scores on a seven items of positive scale, a seven items for negative scale and a sixteen items for general psychopathology scale. The seven items of the positive scale comprise five realms of functioning and include delusions, hallucinatory behavior, excitement, grandiosity, conceptual disorganization, hostility and suspiciousness-persecution. The seven negative items are characteristic of a primary deficit syndrome and comprise emotional withdrawal, blunted affect, poor rapport, difficulty in abstract thinking, passive or apathetic social withdrawal, lack of spontaneity and flow of conversation and stereotyped thinking. The general psychopathology items are anxiety, guilt feelings, depression, tension, somatic concern, mannerisms and posturing, motor retardation, uncooperativeness, lack of judgment and insight, poor attention, unusual thought content, disorientation, disturbance of volition, poor impulse control, preoccupation and social avoidance. Measurements were derived from behavioural reports with a 30 – 45minute clinical interview.
Plasma homocysteine estimation of was done in Cobas integra 400 plus, using the principle of enzymatic assay with EDTA plasma collected after overnight fasting. Data analysis were done using SPSS version 22.0. Student’s unpaired t‑test was utilized to find out any differences between variables and for any associations between the variables, Pearson’s correlation coefficient was used. P value <0.05 was considered as significant statistically.
RESULT:
Age and gender distributions are shown in table 1. It shows that maximum percentage belongs to age group 25-29 years both in cases and controls. More over it shows cases and controls are age and gender matched. Table 2 shows the presence of family history in more than 13% of schizophrenic patients where as in controls only 2% of cases show presence of family history. Table 3 shows notable rise in plasma homocysteine in schizophrenic patients (15.48±2.71μmol/L) when compared to control group (9.09±0.82μmol/L), which is also statistically significant (p < 0.001). There is also notable rise in BPRS (84.2±1.72) and PANSS (149.01±1.72) scores in schizophrenic patients when compared to control group, which are also statistically significant (p<0.001). These raised scores (BPRS and PANSS) are also positively and significantly correlated with plasma homocysteine (table 4, figures 1 and 2).
Table 1: Age and gender distribution of group studied.
Age groups |
Healthy Controls (n=50) |
Schizophrenic Patients (n=30) |
||||
Male |
Female |
Total (%) |
Male |
Female |
Total (%) |
|
20-24 |
15 |
09 |
48 |
05 |
04 |
30 |
25-29 |
08 |
14 |
44 |
06 |
12 |
60 |
30-34 |
03 |
01 |
08 |
01 |
02 |
10 |
Total |
26 |
24 |
100 |
12 |
18 |
100 |
Table 2: Family history of schizophrenia of group studied.
Family History |
Healthy Controls (n=50) |
Schizophrenic Patients (n=30) |
Total (n=80) |
Positive |
01 (2%) |
04 (13.3%) |
05(6.2%) |
Negative |
49(98%) |
26(86.7%) |
75(93.8%) |
Table 3: Homocysteine, BPRS and PANSS in group studied.
Parameters |
Healthy Controls (n=50) |
Schizophrenic Patients (n=30) |
p-value |
Homocysteine (μmol/L) |
9.09±0.82 |
15.48±2.71 |
<0.001 |
BPRS |
60.02±0.84 |
84.2±1.72 |
<0.001 |
PANSS |
111.93±1.85 |
149.01±1.72 |
<0.001 |
Table 4: Correlation between plasma homocysteine with BPRS and PANSS in group studied.
Parameters |
Homocysteine |
|
r-value |
p-value |
|
BPRS |
0.76 |
<0.001 |
PANSS |
0.72 |
<0.001 |
Figure 1: Correlation between homocysteine and BPRS in group studied (r-0.76, p-<0.001).
Figure 2: Correlation between homocysteine and PANSS in group studied (r-0.72, p-<0.001).
DISCUSSION:
This study documented a rise in plasma homocysteine level in schizophrenic patients when compared with healthy controls. This raised value is also significant statistically. Increase in plasma homocysteine also showed a significant positive correlation with BPRS and PANSS, which are commonly used scales to rate symptoms of schizophrenia. This suggests altered homocysteine plays an important role in development and progression of schizophrenia.
Hyperhomocysteinemia is associated with many neurological disorders like alzheimers disease, parkinsonism, stroke, epilepsy, multiple sclerosis, peripheral neuritis, amytropic lateral sclerosis 25. Increase in blood homocysteine is also has significant association with schizophrenia 2, 26, 27. Accumulation of homocysteine is associated with methionine deficiency. Deficiency of methionine in nervous system causes decrease in methylation of arginine residue of myelin basic protein leading to irreversible degeneration of spinal cord 28. Rise in homocysteine challenges integrity of blood brain barrier and there is parallel increase in homocysteine in cerebro spinal fluid (CSF). Increase in homocysteine in CSF leads to damage of white matter, neurofibrillary tangles of brain, leading to cognitive impairment, dementia and many other neurological features 25,29.
Auto-oxidation of homocysteine may lead to generation of free radicals, that results in inflammation of neurons25. More over hyperhomocysteinemia resulting in defective methylation, along with oxidative and endoplasmic reticulum stress initiating release of inflammatory cytokines result in neuroinflammation and neurotoxicity14,25. All these mechanisms together play important role in development of schizophrenia in risk individuals.
CONCLUSION:
Derangement of homocysteine metabolism plays role in development of many neurological disorders, particularly in many cognitive disorders. Our study also documented a significant relationship between increase in homocysteine with commonly used symptoms rating scales used for schizophrenia. However more studies with increased sample size is necessary to further corroborate this relationship.
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Received on 06.09.2023 Modified on 16.12.2023
Accepted on 22.02.2024 © RJPT All right reserved
Research J. Pharm. and Tech 2024; 17(7):3009-3012.
DOI: 10.52711/0974-360X.2024.00470