Correlation between vaspin and PANSS scores in schizophrenia patients with obesity

Abstract

Objective

Metabolic abnormalities such as diabetes, dyslipidemia, abdominal obesity, metabolic syndrome, and abnormal levels of plasma adipokines have been observed in patients with schizophrenia. This study aimed to investigate the differences and correlations of plasma vaspin levels with metabolic parameters in patients with schizophrenia and to compare with healthy controls.

Method

We measured plasma levels of vaspin and metabolic parameters of 100 patients with schizophrenia and 95 healthy controls. Patients with schizophrenia were evaluated with the Positive and Negative Syndrome Scale (PANSS) and The Global Assessment of Functioning.

Results

Mean levels of body mass index, waist circumference, triglyceride, and low-density lipoprotein cholesterol of the patients were statistically higher than those of the healthy controls (p = 0.002, p < 0.001, p = 0.03, and p = 0.002, respectively). Plasma levels of vaspin were 0.96 ± 0.73 ng/ml in patients with schizophrenia and 0.29 ± 0.15 ng/ml in the healthy controls (p < 0.001). Plasma vaspin levels were statistically higher in patients with schizophrenia than healthy controls both in groups with and without metabolic syndrome and obesity (p < 0.001). Plasma vaspin levels showed a positive correlation with triglyceride in patients with schizophrenia (r = 0.26, p = 0.007). There were positive correlations between vaspin and PANSS scores in schizophrenia patients with obesity (PANSS Positive: r = 0.42, p = 0.01; PANSS Negative: r = 0.42, p = 0.01; PANSS General: r = 0.43, p = 0.01; PANSS Total: r = 0.47, p = 0.006).

Conclusions

Our study showed a significant relationship and positive correlation between vaspin and PANSS scores in schizophrenia patients with obesity. Vaspin may play an important role in the metabolic processes of patients with schizophrenia.

Keywords

adipokines schizophrenia obesity metabolic syndrome vaspin insulin resistance

Introduction

It has been shown that metabolic abnormalities such as diabetes, dyslipidemia, abdominal obesity, and metabolic syndrome (MS) are more common in patients with schizophrenia than in the general population.¹ Unhealthy dietary habits, smoking, excessive alcohol intake, and lack of exercise contribute to the development of metabolic abnormalities in people with schizophrenia.² On the other hand, there are also arguments that people with schizophrenia may have a speciﬁc susceptibility to metabolic abnormalities.² In addition, the treatment of patients with schizophrenia with second-generation antipsychotics, particularly clozapine and olanzapine, are suspected of contributing to the emergence of metabolic disorders.³

Exact mechanisms behind the metabolic abnormalities in schizophrenia are not yet clearly understood. Recent reports claimed that biologically active cytokines named adipokines, secreted by the adipose tissue, may lead to the development of metabolic abnormalities by affecting energy and vascular homeostasis, as well as the immune response.⁴ Vaspin (visceral adipose tissue-derived serpin; serpin A12), which has been originally identified as an adipokine, is mainly produced by the visceral adipose tissue in the Otsuka Long-Evans Tokushima fatty (OLETF) rat animal model of obesity and type 2 diabetes. Obesity, insulin resistance (IR), and type 2 diabetes in humans have been related to higher serum concentrations of vaspin and increased vaspin messenger RNA expression in the human adipose tissue.⁵ Increased levels of vaspin were associated with the body weight and IR of OLETF rats. However, the secretion of vaspin began to decrease as diabetes progressed. According to these data, the increase in vaspin may be a compensatory mechanism to IR and obesity to reduce the associated metabolic stress.⁶ Studies have shown an increase of vaspin in obese individuals and higher vaspin levels were related to waist circumference (WC) and body mass index (BMI).⁷

The vaspin-like-adipokines leptin and adiponectin have a crucial role in the development of MS and are the most studied adipokines in schizophrenia. Leptin’s role in schizophrenia has been associated mainly with its relation to weight gain and obesity.⁸ Studies have shown an increase in the leptin levels after antipsychotic treatment, especially in those taking second-generation antipsychotics. However, it has been suggested that the increase in plasma leptin may be associated with the weight gain during antipsychotic treatment.⁹ Lower plasma adiponectin levels are associated with MS and obesity.¹⁰ Schizophrenia patients with MS had lower adiponectin levels than those without MS. In addition, abnormal adipokine levels and metabolic abnormalities are associated with schizophrenia.¹¹

Uncontrolled diabetes and weight reduction reduce vaspin expression. In contrast, insulin sensitizers normalize vaspin expression and serum concentration.⁶ Recombinant vaspin administration significantly improves glucose tolerance and insulin sensitivity in mice. This effect changes the expression of genes involved in the normalization of plasma glucose levels and in the pathogenesis of IR. Accordingly, vaspin has been proposed to compensate for white adipose tissue that reduces insulin sensitivity by its anti-inflammatory and insulin-sensitizing properties.⁶ Thus, vaspin production is thought to antagonize the effects of a number of proteases that disrupt the insulin effect.¹² This suggests that vaspin may have an important role in the etiology of obesity, IR, and other metabolic diseases.

To the best of our knowledge, the associations of plasma vaspin levels with obesity, IR, metabolic parameters, MS, and psychopathology in patients with schizophrenia have not been determined in the literature. The main hypothesis of this study is that the plasma vaspin levels of patients with schizophrenia will be higher than the healthy control (HC) group. We hypothesized that especially plasma vaspin levels of patients with schizophrenia with obesity will be higher than those without obesity. The primary aim of this study was to compare vaspin plasma levels with metabolic parameters in patients with schizophrenia and age, and gender-matched mentally healthy persons. We also aimed to compare schizophrenia patients with and without obesity according to plasma vaspin levels, metabolic parameters, and Positive and Negative Syndrome Scale (PANSS) scores.

Method

Subjects

This is a prospective cross-sectional study performed at the psychiatry clinics of a hospital in Turkey. Each participant signed an informed consent form per the Declaration of Helsinki. A total of 100 patient with schizophrenia and 95 HCs were enrolled in this study. All participants were adults over 18 years of age. Subjects were selected from the outpatient unit of psychiatry clinics. The diagnosis of schizophrenia was made by staff psychiatrists according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

The study included schizophrenia patients who had no acute psychotic episodes, had no indication for hospitalization, and were followed up in the outpatient clinic. Patients with exclusion criteria were not included in the study. Ninety-eight patients were under treatment with antipsychotics; two patients were recently diagnosed.

HCs were selected among the visitors of the inpatients in other units of the hospital. They were approached while they were in the hospital garden or waiting rooms. The physicians conducting the study performed physical examination and psychiatric examination of HCs. HCs who had exclusion criteria and who had a history of psychiatric disorder or diagnosed with a psychiatric disorder during the examination excluded from the study.

The exclusion criteria included having a neurological condition, diabetes mellitus, hyperlipidemia, cardiovascular diseases, a degree of mental retardation that would hinder the understanding of the tests and the conducting of interviews for all participants.

A sociodemographic data form and the Turkish version of PANSS were administered to assess the general psychopathology of patients with schizophrenia.¹³ The Global Assessment of Functioning (GAF) score was used to evaluate the general functions of patients.¹⁴

The following National Cholesterol Education Program Adult Treatment Panel III modified criteria were used to diagnose MS: (1) WC ≥88 cm in women and ≥102 cm in men, (2) plasma triglyceride (TG) over 150 mg/dl or taking medication due to a high TG, (3) low high-density lipoprotein (HDL) cholesterol or taking medication due to low HDL (less than 50 mg/dl in women and 40 mg/dl in men), (4) fasting blood glucose (FG) over 100 mg/dl or taking medication for high blood glucose, and (5) blood pressure exceeding 130/85 mmHg.

Obesity was determined as a BMI of ≥30 mg/m².

Sample collection and analysis

After a 12-h fasting period, peripheral venous blood samples were collected, centrifuged at 4000 r/min for 10 min, and stored at –80°C. All samples were thawed only once before analyzing serum FG, total cholesterol, TG, HDL cholesterol, low-density lipoprotein cholesterol (LDL), and insulin. Glucose and lipid levels were analyzed in a Roche Cobas c501 auto-analyzer with the original reagents (Roche Diagnostics, Mannheim, Germany). The insulin levels were measured by the electrochemiluminescent-based method in a Roche Cobas e601 analyzer with reagents from the manufacturer (Roche Diagnostics). Serum vaspin levels were determined quantitatively by enzyme linked immunosorbent assay (ELISA) with an ELISA microplate strip washer (ELX50; BioTek Instruments, Winooski, VT) and ELISA microplate reader (ELX808; BioTek Instruments). Vaspin was studied using a commercially available kit from My BioSource Inc. (San Diego, CA). In this assay system, the intra-assay and inter-assay coefficients of variation were always under 10%.

Statistical analyses

The SPSS statistics for Windows ver. 22.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. The independent samples t-test was used for quantitative variables, while the Chi-square test was used for categorical variables. Associations between various parameters were determined by Pearson’s correlation. Multiple linear regression analyses were performed to determine the factors associated with vaspin. We checked the normality of data by skewness. A p value of <0.05 was considered statistically significant.

Results

Sociodemographic features and sample characteristics

This study consisted of 100 patients with schizophrenia and 95 HC subjects. The mean age of patients with schizophrenia was 39.53 ± 10.61 years, while the mean age of patients with HC was 37.48 ± 13.9 years. There was no statistically significant difference concerning gender and age between the groups. Of the patients, 59.4% were single, 45.9% were smoking, and 3% were using alcohol. In addition, 41.4% of the patients had a psychiatric disorder history in their family (Table 1).

Table 1.

Demographic characteristics and metabolic parameters of schizophrenia patients and healthy controls.

	Schizophrenian (%)	Healthy controln (%)	p	χ²/t
Gender
Female	59 (59)	58 (61.1)	0.88^a
Male	41 (41)	37 (38.9)
Age	39.53 ± 10.61	37.48 ± 13.90	0.24	–1.15
Marital status
Single	57 (59.4)	39 (41.1)	<0.001	18.84
Married	26 (27.1)	53 (55.8)
Widow	13 (13.5)	3 (3.2)
Education
Illiterate	6 ( 6.1)	3 (3.2)	<0.001	33.75
Primary school	60 (60.6)	27 (29.5)
Secondary school	21 (21.2)	14 (17.9)
University	12 (12.1)	46 (49.5)
Smoking
Yes	45 (45.9)	29 (32.2)	0.07 ^a
No	53 (54.1)	61 (67.8)	0.07 ^a
Family history
Yes	41 (41.4)	17 (17.9)	<0.001 ^a
No	58 (58.6)	74 (82.1)	<0.001 ^a
WC (cm)	97.22 ± 14.06	84.52 ± 14.49	<0.001	–6.16
BMI (kg/m²)	28.69 ± 6.67	25.83 ± 5.71	0.002	–3.17
FG (mg/dl)	88.54 ± 17.06	86.68 ± 16.91	0.44	–0.76
Insulin	11.26 ± 10.92	14.18 ± 22.73	0.25	1.15
HOMA-IR	2.53 ± 2.43	3.51 ± 8.34	0.26	1.11
TG (mg/dl)	160.82 ± 105.62	133.29 ± 68.94	0.03	–2.13
HDL (mg/dl)	45.91 ± 12.99	44.42 ± 12.04	0.41	–0.82
LDL (mg/dl)	123.38 ± 40.36	106.05 ± 34.53	0.002	–3.19
Total cholesterol (mg/dl)	200.62 ± 46.49	184.56 ± 37.37	0.09	–2.64
MS
Yes	30 (30)	23 (24.2)	0.42^a
No	70 (70)	72 (75.8)	0.42^a
Obesity
Yes	32 (32.7)	19 (20.2)	0.07^a
No	66 (67.3)	75 (79.8)	0.07^a
IR
Yes	37 (37)	28 (29.5)	0.29^a
No	63 (63)	67 (70.5)	0.29^a
Subjects have positive MS components
WC (cm)	72 (72)	42 (44.2)	<0.001 ^a
FG (mg/dl)	21 (21)	9 (9.5)	0.03 ^a
Triglyceride (mg/dl)	41 (41)	31 (32.6)	0.23^a
HDL (mg/dl)	57 (57)	52 (54.7)	0.77^a
BP (mmHg)	1 (1)	6 (6.3)	0.06^a
Vaspin (ng/ml)	0.96 ± 0.73	0.29 ± 0.15	<0.001	–8.68
Vaspin in MS (+) (ng/ml)	1.18 ± 0.98	0.26 ± 0.14	<0.001	–4.44
Vaspin in MS (–) (ng/ml)	0.86 ± 0.58	0.30 ± 0.15	<0.001	–7.93
Vaspin in obesity (+) (ng/ml)	1.17 ± 0.96	0.13 ± 0.17	<0.001	–3.85
Vaspin in obesity (–) (ng/ml)	0.85 ± 0.57	0.29 ± 0.14	<0.001	–8.19
Vaspin in IR (+)	0.99 ± 0.84	0.28 ± 0.16	<0.001	–4.95
Vaspin in IR (–)	0.94 ± 0.66	0.29 ± 0.14	<0.001	–7.51
Correlations of vaspin
TG (mg/dl)
p	0.007	0.835
r	0.26	–0.02

Note: Significant results (i.e., p < 0.05) are in bold. WC: waist circumference; BMI: body mass index; FG: fasting glucose; HOMA-IR: homeostatic model assessment-insulin resistance; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triglyceride; BP: blood pressure; MS: metabolic syndrome; Obesity: BMI ≥ 30 mg/m²; IR: insulin resistance.

^aFisher exact test.

Of the schizophrenia patients, 98 were being treated with antipsychotics, 45% (n = 45) were taking clozapine, while 44% (n = 44) were treated with depot antipsychotics, and 28% (n = 28) of the patients were treated with more than one antipsychotic. Also, 20% (n = 20) of the patients were taking antidepressant drugs. The mean scores for PANSS positive, PANSS negative, PANSS general, and PANSS total were 13.69 ± 4.88, 15.21 ± 5.12, 29.90 ± 0.91, and 59.17 ± 16.71, respectively. The mean GAF score was 6.31 ± 1.39.

Metabolic parameters and vaspin levels in patients with schizophrenia and healthy controls

The mean BMI, WC, TG, and LDL levels of patients were statistically higher than those of HCs (p < 0.001, p < 0.001, p = 0.03, and p = 0.002, respectively). The mean plasma level of vaspin was 0.96 ± 0.73 ng/ml in patients with schizophrenia, while it was 0.29 ± 0.15 in the HC group (p < 0.001; Table 1). There were no statistically significant differences between the groups according to MS, obesity, and IR (p > 0.05). Plasma vaspin levels were statistically higher in patients with schizophrenia compared to the HC’s both in groups with and without MS, obesity, and IR (Table 1).

In the schizophrenia group, there were positive correlations between vaspin and TG. There were no significant correlations between vaspin and metabolic parameters in the HC’s (Table 1).

Comparisons in schizophrenia patients

There were positive correlations only between vaspin and PANSS scores in patients with obesity. However, there were no significant correlations between vaspin and metabolic parameters in patients with and without obesity (Table 2).

Table 2.

Comparisons of schizophrenia patients with and without obesity.

	Schizophrenia
	Obesity (+)		Obesity (–)			p	t/χ²
Gender
Female	27 (84.4)		31 (47)			<0.001	12.482
Male	5 (15.6)		35 (53)			<0.001	12.482
Age	42.50 ± 10.40		38.06 ± 10.60			0.05	–1.95
WC (cm)	111.38 ± 10.84		90.36 ± 9.63			<0.001	–9.71
BMI (kg/m²)	36.68 ± 4.88		24.82 ± 2.92			<0.001	–4.26
FG (mg/dl)	98.87 ± 19.52		83.56 ± 1213.40			<0.001	–4.54
Insulin	14.98 ± 7.35		9.33 ± 12.03			0.01	–2.43
HOMA-IR	3.70 ± 2.09		1.95 ± 2.42			0.001	–3.49
TG (mg/dl)	203.13 ± 123.13		139.03 ± 91.31			0.005	–2.89
LDL (mg/dl)	126.53 ± 43.65		120.97 ± 38.33			0.52	–0.64
Total cholesterol	216.25 ± 49.54		192.08 ± 41.47			0.01	–2.53
IR
Yes	24 (75)		11 (16.7)			<0.001 ^a
No	8 (32)		55 (83.3)
PANSS
Positive	12.35 ± 3.17		14.35 ± 5.43			0.03	2.23
Negative	14.81 ± 4.00		15.41 ± 5.61			0.59	0.53
General	27.90 ± 5.52		30.89 ± 8.73			0.047	2.01
Total	54.50 ± 11.59		61.18 ± 18.51			0.03	2.17
GAF score	6.50 ± 1.41		6.20 ± 1.39			0.32	0.99
Vaspin	1.17 ± 0.96		0.85 ± 0.57			0.09	1.73
Clozapine						0.76^a
Yes (n = 15)	4 (12.5)		11 (16.7)
No (n = 83)	28 (87.5)		55 (83.3)
Clozapine + OA						0.01 ^a
Yes (n = 44)	20 (62.5)		24 (36.4)
No (n = 54)	12 (37.5)		42 (63.6)
DA						0.62^a
Yes (n = 24)	9 (28.1)		15 (22.7)
No (n = 74)	23 (71.9)		51 (77.3)
DA+OA						0.13^a
Yes (n = 44)	18 (56.3)		26 (39.4)
No (n = 54)	14 (43.8)		40 (60.6)
Polypharmacy						0.63^a
Yes (n = 27)	10 (31.3)		17 (25.8)
No (n = 72)	22 (68.8)		49 (74.2)
Antidepressant						0.19^a
Yes (n = 20)	9 (28.1)		11 (16.7)
No (n = 80)	23 (71.9)		55 (83.3)

	Obesity (+)			Obesity (–)
	r	p		r	p
Correlations of vaspin
PANSS
Positive	0.42	0.01		0.111	0.286
Negative	0.42	0.01		0.220	0.033
General	0.43	0.01		0.160	0.123
Total	0.47	0.006		0.150	0.138

Note: Significant results (i.e., p < 0.05) are in bold. WC: waist circumference; BMI: body mass index; FG: fasting glucose; HOMA-IR: homeostatic model assessment-insulin resistance; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triglyceride; BP: blood pressure; MS: metabolic syndrome. PANSS: Positive and Negative Syndrome Scale GAF: global assessment Functioning. DA: depot antipsychotics; OA: other antipsychotics. IR: insulin resistance.

^aFisher’s exact test.

Obesity and using clozapine were related to the vaspin levels in patients with schizophrenia (t = –2.05, p = 0.04 and t = –2.02, p = 0.04, respectively). The mean vaspin levels in schizophrenia patients with MS was 1.18 ± 0.98, while it was 0.86 ± 0.58 in the schizophrenia patients without MS (t = –1.97, p = 0.05). The use of depot antipsychotics, polypharmacy, and antidepressants was not related to the vaspin levels in patients with schizophrenia (p = 0.19, p = 0.23, and p = 0.18, respectively; Table 3).

Table 3.

Distribution of vaspin levels between the groups.

	Schizophrenia patients			Healthy controls
	Vaspin (ng/ml)	p	t	Vaspin (ng/ml)	p	t
MS
Yes (n = 30)	1.18 ± 0.98	0.051	–1.97	0.26 ± 0.14	0.24	1.18
No (n = 70)	0.87 ± 0.58	0.051	–1.97	0.30 ± 0.15	0.24	1.18
Obesity
Yes (n = 32)	1.18 ± 0.97	0.04	–2.05	0.31 ± 0.17	0.58	–0.55
No (n = 66)	0.86 ± 0.58	0.04	–2.05	0.29 ± 0.14	0.58	–0.55
IR
Yes	0.99 ± 0.84	0.75	–0.30	0.28 ± 0.16	0.79	0.25
No	0.94 ± 0.84	0.75	–0.30	0.29 ± 0.14	0.79	0.25
Clozapine
Yes (n = 15)	1.37 ± 0.96	0.01	–2.38
No (n = 85)	0.89 ± 0.66	0.01	–2.38
Clozapine + OA
Yes (n = 45)	1.12 ± 0.86	0.04	–2.02
No (n = 55)	0.83 ± 0.58	0.04	–2.02
DA
Yes (n = 24)	0.91 ± 0.84	0.73	0.45
No (n = 76)	0.97 ± 0.70	0.73	0.45
DA+OA
Yes (n = 44)	0.85 ± 0.66	0.19	1.29
No (n = 56)	1.04 ± 0.78	0.19	1.29
Polypharmacy
Yes (n = 27)	0.82 ± 0.59	0.23	1.20
No (n = 72)	1.01 ± 0.78	0.23	1.20
Antidepressant
Yes (n = 20)	0.92 ± 0.65	0.18	0.23
No (n = 80)	0.97 ± 0.75	0.18	0.23

MS: metabolic syndrome; DA: depot antipsychotics; OA: other antipsychotics; IR: insulin resistance.

Significant results (i.e., p < 0.05) are in bold.

Regression analysis

We conducted multivariate regression analysis to investigate the effects of possible confounders on revealed correlations. The variables of total cholesterol, LDL, PANSS negative score, and patients using clozapine predicted vaspin in schizophrenia patients and schizophrenia patients with obesity (Tables 4 and 5). Although the same prediction not observed in HCs and schizophrenia patients without obesity (p = 0.669, p = 0.203, respectively).

Table 4.

Summary of multiple linear regression model for variables predicting vaspin in schizophrenia patients.

Model	Unstandardized coefficients		Standardized coefficients	t	Sig.	95.0% Confidence interval for B
Model	B	Std. error	Beta	t	Sig.	Lower bound	Upper bound	Adjusted R²	F	Sig.
Constant	–413.406	394.901		–1.047	0.298	–1198.066	371.253	0.200	6.821^a	<0.001
Total cholesterol	11.772	2.835	0.728	4.152	<0.001	6.139	17.406
LDL	–11.911	3.200	–0.650	–3.722	<0.001	–18.270	–5.552
Clozapine only	466.216	192.960	0.229	2.416	0.018	82.809	849.623
PANSS negative	27.561	13.802	0.189	1.997	0.049	0.136	54.985

Note: Significant results (i.e., p < 0.05) are in bold. PANSS: Positive and Negative Syndrome Scale; LDL: low-density lipoprotein; Std: standard; Sig: significance.

^aMultiple linear regression.

Table 5.

Summary of multiple linear regression model for variables predicting vaspin in schizophrenia patients with obesity.

Model	Unstandardized coefficients		Standardized coefficients	t	Sig.	95.0% confidence interval for B
Model	B	Std. error	Beta	t	Sig.	Lower bound	Upper bound	Adjusted R²	F	Sig.
Constant	–1634.653	866.885		–1.886	0.071	–3416.560	147.255	0.445	7.022^a	<0.001
Total cholesterol	14.539	4.652	0.738	3.125	0.004	4.976	24.102
LDL	–18.570	5.143	–0.838	–3.611	0.001	–29.143	–7.998
Clozapine only	1050.711	398.471	0.365	2.637	0.014	231.642	1869.780
PANSS negative	67.670	24.439	0.381	2.769	0.010	17.434	117.906

Note: Significant results (i.e., p < 0.05) are in bold. PANSS: Positive and Negative Syndrome Scale; LDL: low-density lipoprotein; Std: standard; Sig: significance.

^aMultiple linear regression.

Discussion

In this study, the plasma levels of vaspin in schizophrenia patients were higher than HC’s regardless of obesity, MS, and IR. Our findings indicate that schizophrenics have higher values of BMI, WC, TG, and LDL, which are the precursors of metabolic disorders consistent with many studies. The most significant parameter in patients with schizophrenia was WC; it was associated with obesity and MS in schizophrenia.¹⁵ In addition, our findings of MS in schizophrenia were similar to other studies. The prevalence of MS in patients with schizophrenia was reported as 21%¹⁶ in Turkey, 27.5% in Japan,¹⁷ and 38.6% in Spain.¹⁸ Although the rate of obesity in schizophrenia patients is higher than the general population, varying results were reported. The prevalence of obesity in schizophrenia was as 45% to 55% in western countries,^19–21 while it was 20.9 according to a Chinese study.²² We found the prevalence of obesity in schizophrenia as 32.7%. It is obvious that obesity is a common health problem among people with schizophrenia. On the other hand, the diversity in the frequencies can be explained with methodological differences, antipsychotics used in the treatment, ethnic differences, and associated genetic factors.

In this study, we found that obese schizophrenia patients had higher FG, insulin, homeostatic model assessment insulin resistance (HOMA-IR), TG, total cholesterol, and IR compared to nonobese schizophrenia patients. In addition, clozapine use was higher in obese patients. Our study showed that schizophrenia patients with obesity are at risk for diabetes as in many previous studies and that the use of clozapine may increase obesity and related risk factors in patients with schizophrenia.^21,23–26

To our best knowledge, this is the first study investigating plasma vaspin levels in patients with schizophrenia. Adipokines contribute to the regulation of adipogenesis, immune cell migration, adipocyte metabolism, TG storage, and others. Obesity and hyperlipidemia can influence metabolic parameters by changing the production of adipokines.²⁷ Elevated serum vaspin concentrations are associated with obesity as well as impaired insulin sensitivity.²⁸ We determined higher plasma vaspin levels in patients with schizophrenia compared to HC’s independent from obesity, IR, and MS. In addition, schizophrenia patients with obesity had higher vaspin levels than patients without obesity. The association of higher plasma leptin and lower adiponectin levels with MS and metabolic parameters was shown repeatedly in patients with schizophrenia.^29,30 Besides, Chen et al. demonstrated that leptin/adiponectin ratio might be a preferential marker of MS in patients with schizophrenia.³¹ Considering the effects of vaspin on adipogenesis, obesity, and hyperlipidemia, higher obesity and metabolic abnormalities in schizophrenia patients may be related to abnormal vaspin and other adipokine levels.

Previous studies have shown the association of abnormal leptin and adiponectin levels with weight gain after clozapine use in patients with schizophrenia. In our study, we found that the levels of vaspin were higher in patients using clozapine. Weight gain is one of the most important side effects of clozapine.³² This result suggests that clozapine may impair adipogenesis due to adverse effects on adipokine metabolism and may cause weight gain. Nevertheless, the relationships between metabolic abnormalities, the role of adipokines, second-generation antipsychotics treatment, and dysregulated hormonal pathways need further investigations.

Atmaca et al. reported a positive correlation between serum leptin level and improved overall psychopathology.³³ On the other hand, Takayanagi et al. suggest a significant role of leptin in schizophrenia with positive symptoms.¹⁰ In this study, we found a strong correlation between plasma vaspin levels and PANSS scores in schizophrenia patients with obesity, which was not evident in nonobese schizophrenia patients. Numerous studies have shown that obesity worsens prognosis in schizophrenia patients.^34–37 Our study showed a significant relationship among vaspin, PANSS scores, and obesity in schizophrenia patients. This result and previous studies about other adipokines suggest that vaspin may be an important mediator determining the psychopathology in schizophrenia patients with obesity.

Finally, patients with schizophrenia are known to smoke more than general population.³⁸ But in this study, there was no difference between schizophrenia patients and HCs in terms of smoking. The prevalence of smoking reported that 31.2% in adult population of Turkey.³⁹ We found a similar smoking rate in controls in this study. The smoking rates of patients were higher from controls. The fact that no statistical difference was found between the two groups may be due to the relatively low number of patients and controls. In addition, in a previous study we conducted in this region, smoking rate was lower in schizophrenia patients than in many other studies.⁴⁰

Several limitations in this study deserve attention. First, most of the patients in this study were taking medication, and schizophrenia patients with a first episode were not included in the study. In addition, it may be considered as a limitation that other adipokines were not determined together with vaspin. In addition, despite that the body fat distribution may be an important factor associated with the secretion of vaspin, body fat ratio of the subjects was not evaluated in this study.

Conclusion

Recent studies have shown that adipokines secreted from adipose tissue have an important role in the etiology of many diseases. In our study, important findings were found that vaspin, which is one of the new adipokines, is higher in schizophrenia patients than HCs, and that vaspin is associated with PANSS scores indicating disease severity. Vaspin may be a mediator that can be used to predict future metabolic diseases in schizophrenia patients, especially considering the properties of vaspin on secretion of other adipokines. It may also be a guiding mediator for new drugs that may be developed to treat conditions such as obesity and IR in these patients. Further investigations using the longitudinal design and larger sample sizes are needed to elucidate the effects of vaspin and other adipokines in the pathogenesis of metabolic abnormalities in schizophrenia.

Supplemental Material

IJP905463 Supplemental Material1 - Supplemental material for Correlation between vaspin and PANSS scores in schizophrenia patients with obesity

Supplemental material, IJP905463 Supplemental Material1 for Correlation between vaspin and PANSS scores in schizophrenia patients with obesity by Hülya Ertekin, Sema Uysal, Memduha Aydın, Bilge İlhan and Yusuf Haydar Ertekin in The International Journal of Psychiatry in Medicine

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Approval

Ethical approval was obtained by local clinical research ethical committee (Date 25/12/2014, No 25–17).

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was carried out with the support of Çanakkale Onsekiz Mart University Scientific Research Projects Coordination Unit with the project number TSA-2015–561.

ORCID iD

Hülya Ertekin

Supplemental Material

Supplemental material for this article is available online.

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