Serum cholesterol and Suicide in first episode psychosis: A preliminary study.

BACKGROUND: Low levels of cholesterol have been described in suicide behavior including among those individuals who have an increased tendency for impulsivity. Violent suicide attempters show significantly lower cholesterol levels than nonviolent suicide attempters. The suicide rate is particularly high in the prodromal and early phase of schizophrenia. It is unclear if there is a psychopathological relationship between early psychosis, suicide, and cholesterol levels. The present study examines levels of cholesterol and suicide behavior in a cohort of early psychosis.
METHODOLOGY: Sixty admitted patients with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of nonaffective schizophrenia spectrum disorder (early psychosis) were assessed in a naturalistic cross-sectional, cohort study. Psychopathology was assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS), Hamilton Depression Rating Scale, and Scale for Impact of Suicidality-Management, Assessment and Planning of Care (SIS-MAP). Serum levels of cholesterol were estimated in the cohort as well. The findings were analyzed for a clinical correlation of cholesterol levels, suicidal attempters, and psychopathology.
RESULTS: Out of 60 patients, 13 patients had a suicide attempt in the recent past. No serum cholesterol abnormality (3.7 ± 1.2 mmol/L) was observed in patients as a group and those with low suicidality (SIS-MAP <17, serum cholesterol: 4.1 ± 1.3 mmol/L). However, low levels of cholesterol were observed in a subgroup with severe suicidality (SIS-MAP >33; serum cholesterol: 3.5 ± 1.4 mmol/L). Females with moderate suicidality showed statistically significant lower cholesterol levels than males (P = 0.047).
CONCLUSIONS: The study suggests lower levels of cholesterol in patients of psychosis with severe suicidal thoughts and depression in early psychosis. More research is required in this field to determine the neurochemistry of suicide behavior in psychosis and its significance in the prediction of suicidal behavior.

INTRODUCTION

The rate of suicide has been reported to be three times higher in individuals with first-episode psychosis when compared to the general population, and suicide rates are known to high throughout the course of schizophrenia.[1] Suicide rates in patients with psychosis have been documented to be 8.6% before their first visit to a hospital and 5.3% during the 1st year of treatment.[2] Suicidal behavior has been linked to a familial tendency coupled with low frustration tolerance, impulsivity, and poor coping with low social support.[3] Research as early as 35 years ago has linked low serum total cholesterol to 27 suicides in a population of 11,554 as reported by a Canadian study.[4] Epidemiologically, it has been reported that violent suicidal attempts are found to have significantly lower cholesterol levels and higher cortisol levels attributed to probable depressive symptoms and malnutrition.[5] Suicide attempters are not a homogeneous group, and there is a huge intergroup variation in their phenomenology, neurobiology, neurochemistry, and risk factor profile.[6]

Low cholesterol and increased risk of suicide have also been reported in criminal violence, impulsive aggressive behavior, mood disorders, substance abuse, psychosis, and personality disorders.[7] Violent suicide completers also show significantly lower cholesterol and platelet serotonin in the first episode of psychosis in comparison to nonviolent and healthy controls.[8] The neurobiology of suicidal behavior in relation to cholesterol has not been studied sufficiently though a number of studies suggest abnormality in leptin and lipid metabolism linked to suicidal behavior.[9] It remains unclear how low cholesterol in the peripheral system might be related to the brain functions mediating suicidal behavior.[10] A study revealed that patients who had abnormal dexamethasone suppression tests (DST) and lower serum cholesterol were significantly more likely to commit suicide during follow-up. Serum cholesterol concentrations did not differ by DST result, and low cholesterol values were found associated with subsequent suicide.[11] Postmortem brain studies have indicated that violent suicides were found to have lower gray-matter cholesterol content when compared to nonviolent suicides, specifically in the frontal cortex.[12] Data available in this area are confounding while attempts have been made to predict suicidality related to low cholesterol though the complex relationship remains unclear. Low cholesterol also has low specificity for predicting future suicide or completed suicide.[13]

Our study attempted to examine serum cholesterol levels in a cohort of hospitalized patients in the early phase of schizophrenia patients with a suicide attempt in the past with the objectives of determining the level of cholesterol and examining its association with the severity of suicidality among patients of early psychosis and the relationship of cholesterol with clinical parameters and level of suicidality.

METHODOLOGY

The present study is a cross-sectional, naturalistic cohort study carried out at a tertiary general psychiatric center. The Institutional Ethics Committee approval for the study was obtained. The participants were patients with schizophrenia between the age group of 18 and 30 years and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnostic criteria for schizophrenia.[14] All patients were inpatients in the first episode of the illness and consent was obtained from either patients or their legally acceptable representatives. Patients with organic psychiatric conditions, other major psychiatric disorders, substance abuse (excluding nicotine dependence), and major medical or surgical illnesses that would affect the outcome of the study were excluded from the study.

All patients were assessed during the 1st week of admission using the following scales:

Positive and Negative Symptoms Scale for Schizophrenia (PANSS) – This is a scale that has been widely used in the study of patients with schizophrenia and has thirty items with three subscales, namely, a positive symptom scale, a negative symptom scale, and a general psychopathology subscale[15]

Hamilton Depression Rating Scale (HDRS) also abbreviated to HAM-D – This is a multiple item questionnaire used to provide an indication of depression and as a guide to evaluate recovery[16]

Scale for Impact of Suicidality – Management, Assessment and Planning of Care (SIS-MAP) – This is a scale that looks at not only the severity of suicidal behavior but also suggests the level of management and care needed for the patient[17]

Serum cholesterol levels – Venous blood was drawn for routine blood investigation including lipid profile. The data on level of serum cholesterol were retrieved from the biochemistry database of the facility.

The cohort group was further divided into “low suicidality” (SIS-MAP <17), “moderate suicidality” (SIS-MAP: 18–30), and “high suicidality” (SIS-MAP >30). Serum cholesterol level was compared between these three groups. The group was also divided into patients with a suicide attempt in the recent past before admission, and no attempt and serum cholesterol were compared. Serum cholesterol was also correlated with clinical and psychopathological parameters. Data were analyzed statistically using computerized statistical software.

RESULTS

Basic preliminary data

The total sample of study comprised of 60 patients (41 males and 19 females). The mean age of the sample was 26.5 ± 4.6 years (range: 18–39 years). The total PANSS scores of the sample were 81.7 ± 16.3. The sample was further divided into 2 groups on the basis of the presence of a suicide attempt into no suicide attempt (n = 47) and patients with a suicide attempt in the recent past (n = 13). The descriptive data showed no significant differences between patients with and without a suicide attempt across various parameters including serum cholesterol [Table 1].

Table 1

General baseline data of the sample

Correlation between scores on various scales and serum cholesterol

No significant correlations between scores on HDRS, PANSS and its subscales, and SIS-MAP scores were noted in respect to serum cholesterol levels [Table 2].

Table 2

Correlation between serum cholesterol and various scales used

Serum cholesterol in relation to suicidal behavior

When serum cholesterol levels were compared between patients in the cohort based on scores that indicated low, moderate, or high suicidality based on SIS-MAP scores, no statistically significant intergroup differences were noted, but it is worthwhile mentioning that the severe suicidality group showed lower cholesterol levels compared to the other groups [Table 3]. When a gender-based comparison was made between serum cholesterol across the three groups, it was noted that female patients with moderate suicidality showed statistically significant lower cholesterol levels than the other two groups (P = 0.047) [Table 3].

Table 3

Differences in serum cholesterol on various subgroups of the Scale for Impact of Suicidality–Management, Assessment and Planning of Care

DISCUSSION

General assessment of the cohort

There was no difference in the severity of psychopathology between suicide attempters and nonattempters in schizophrenia as per the scores on the PANSS. This is indicative that apart from suicidal behavior, there are many other factors that may increase the severity of psychopathology such as social factors, delusions and hallucinations, and cognitive symptoms.[18] The scores on the SIS-MAP were similar between both groups which was indicative that suicidal thoughts may have been high even in the nonsuicide attempt group. Suicidality is generally on the higher suicide and has been reported in 25%–35% of patients with schizophrenia.[19]

Suicidal behavior and cholesterol

High suicide rates in early psychosis have been consistently reported in studies. Twenty-six patients (43.3%) show high suicidality scores on the SIS-MAP scale. The reasons for the same could be as the data were collected from inpatients, and in cases of severe psychopathology with schizophrenia, suicidal behavior is the most common reason for admission. The patients with higher suicidality had lower serum cholesterol levels when compared to the high suicidality group. Our results show that cholesterol may have an important role in distinguishing suicidal from nonsuicidal patients, which, if confirmed on a higher number of patients and in more studies, may be of considerable clinical significance.

Previous studies have shown an association between low concentrations of serum cholesterol, in suicidal behavior.[20] The observation of lower serum cholesterol levels associated with suicide attempts has also been proven with respect to schizophrenia in a study which showed that patients with a violent suicidal attempt showed significantly lower cholesterol levels than patients with nonviolent attempts and controls. It has also been demonstrated that lower cholesterol levels are associated with fewer lifetime suicide attempts.[21]

Studies with contrary findings have also been published. In a retrospective study with 213 psychiatric inpatients, the researchers found no differences in the serum cholesterol levels between patients who had and had not made a suicide attempt.[22] In a study on patients with major depression, there were no significant differences in serum lipid profiles between depressed patients with or without suicide attempts.[23]

Gender differences in serum cholesterol with respect to suicidal behavior

Our study showed that women with moderate scores on the SIS-MAP had lower cholesterol level. This is in contrast to a study where authors have reported that low cholesterol level was not associated with increased suicide risk but with a decreased risk in men in a study of over 1100 patients.[24] Studies suggest an interesting relationship between cholesterol levels and suicidality, but the exact relationship between cholesterol and the pathophysiology of suicide is still elusive in the light of both genders and even from an overall neurobiological perspective.[25]

The present had a small sample of 60 patients and various confounding factors such as differences in socioeconomic status, metabolic profiles, and dietary differences that would affect serum cholesterol levels were not considered. This was a cross-sectional study, and there is a need for longitudinal follow-up studies where the effect of psychopathology and suicide over time pre- and posttreatment with respect to serum cholesterol is studied.

CONCLUSIONS

Cholesterol has wide-ranging implications in neurobiology for the central nervous system. It plays a crucial role in neuronal protection, membrane stabilization, and lipid metabolism in neurons and as a part of the second messenger system. It has also been indirectly linked to norepinephrine and serotonin levels in the brain.[26] There is need to study cholesterol from the viewpoint of a biomarker and predictor of suicidal behavior in schizophrenia and other psychiatric disorders. Further longitudinal studies in larger samples shall enable us to shed more light in this arena.

Declaration

The authors wish to declare that the data from the same cohort have been studied in a previous study where serum thyroid-stimulating hormone (TSH) levels from the sample were compared and correlated with respect to psychopathology and suicidal severity. That paper has been published as under Shrivastava A, Jadhav V, Karia S, Shah N, De Sousa A. Serum TSH levels and suicidality in patients with first-episode schizophrenia: an exploratory study. Thyroid Research and Practice 2016;13(2):63-6.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.