The Assessment of Platelet Indices Levels in Patients with Generalized Anxiety Disorder

Background: The prevalence of anxiety disorders is increasing in the world. Studies revealed that generalized anxiety disorder may lead to change in platelet size, volume and functions. Thus, the changes in platelet indices may increase the future risk of thrombotic diseases in patients with Generalized Anxiety Disorder (GAD). Aim: To evaluate platelet indices (total count of platelet, mean platelet volume, platelet distribution width, plateletcrit) levels in patients with generalized anxiety disorder. Material and Methods: A cross-sectional study was performed in the Department of Physiology, Dhaka Medical College, Dhaka from July 2019 to June 2020. After obtaining ethical clearance, a total of 144 individuals were selected based on inclusion and exclusion criteria with ages ranging from 18 50 years. Group A was the study group selected from Out Patient Department of Psychiatry of Dhaka Medical College Hospital, Dhaka, diagnosed by an experienced psychiatrist. Group B was the control group who were apparently healthy adults selected from different areas of Dhaka city. The subjects were interviewed and detailed history regarding personal, family, medical and drug history were taken. Prior to sample collection, informed written consent was taken from the participants. Platelet indices (total count of platelet, mean platelet volume, platelet distribution width, plateletcrit) were measured in the Department of Laboratory Medicine, Dhaka Medical College Hospital, Dhaka. Statistical Analysis: For statistical analysis, the Unpaired Student’s “t” test was considered using SPSS 25.0 version. Results: Mean platelet volume of generalized anxiety disorder patients was How to cite this paper: Mukta, F.Y., Akhter, Q.S., Azad, A.B., Layla, K.N., Akter, T., Rahman, K.L. and Sarker, S. (2021) The Assessment of Platelet Indices Levels in Patients with Generalized Anxiety Disorder. Journal of Biosciences and Medicines, 9, 116-124. https://doi.org/10.4236/jbm.2021.99010 Received: July 28, 2021 Accepted: September 11, 2021 Published: September 14, 2021 Copyright © 2021 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/


Introduction
Mental disorders are a major public health problem in the world. Mental disorders are increasing in the developed countries and the prevalence rate is about 50%. Among mental disorders, the prevalence of anxiety disorder is common [1]. The prevalence of mental disorders is also high in Bangladesh. So, psychiatric morbidity is a significant public health problem in Bangladesh [2]. Anxiety increases platelet activity and may play an important role in cardiovascular diseases such as myocardial infarction, ischemic heart diseases, congestive heart failure, coronary artery disease, unstable angina, etc [3].
Generalized Anxiety Disorder (GAD) is characterized by persistent and chronic worry that lasts for at least 6 months [4]. It can occur during stressful life circumstances such as family, financial, health, exam, future related problems, etc. It has a harmful effect on health. It aggravates physical diseases especially cardiovascular and cerebrovascular diseases [5].
Platelets are key components of hemostasis. Platelets can quickly adhere and aggregate at the sites of vascular injury. Thus, they form the platelet plug [6]. Platelets can be used as important tools in various psychiatric research. Platelets contain many clotting and growth factors, as well as, serotonin (5-HT), ADP, ATP and calcium at high concentrations. They have α-2, β-2 adrenaline receptors, benzodiazepine receptors and 5-HT receptors on their membrane similar to neurons. So, they can reflect the biochemical changes of the central nervous system [7].
Platelet indices such as total count of platelet, Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) and plateletcrit are the important biomarkers of platelet activation [8]. Platelets with higher mean platelet volume are metabolically and enzymatically more active with increased thrombotic potential [9]. Large platelets aggregate more rapidly than the smaller platelets as they contain a higher level of thromboxane A 2 and procoagulant factors like P-selectin, Glycoprotein-IIb/IIIa, etc [10].
Altered platelet indices act as a risk factor for arterial thrombotic events like myocardial infarction, cerebrovascular thromboembolism transient ischemic attacks, etc [11]. Some studies have shown altered platelet indices levels in anxiety disorder in different populations. In Turkey, a study among 61 generalized anxiety disorder patients reveals that mean platelet volume and platelet distribution width are significantly higher than healthy subjects [12]. Another study among 60 generalized anxiety disorder patients also reveals that mean platelet volume values are significantly increased in generalized anxiety disorder patients than healthy controls [13].
Stressful life and anxiety elevate blood catecholamine levels which are potent stimuli for platelet activation. Increased sympathetic activity causes excess secretion of catecholamines that can stimulate platelets via α-2 adrenoceptors. Then the shape of platelets is changed from discoid to spherical and means platelet volume values are also changed. Active platelets may cause thrombosis and increase the risk of cardiovascular diseases [14]. Vizioli et al. (2009) also performed a study and found that anxiety and stress cause increased sympathetic activity and thus cause higher mean platelet volume values. Thus, anxiety may increase the future risk of thrombotic diseases [15]. So, this study was conducted to assess platelet indices levels in generalized anxiety disorder patients and bring more awareness to prevent thrombotic disease-related morbidity.

Material and Methods
This prospective type of analytical cross-sectional study was carried out the De-  3) Study Duration: July 2019 to June 2020. 4) Sample Size Calculation: The sample size was estimated on the basis of the prevalence rate of generalized anxiety disorder from previous study. We assumed that the level of significance was 5%. The sample size actually obtained for this study was 72 subjects for each group.
• Gender: Male and female. • History of taking antipsychotic drug.
• History of comorbid psychiatric illness like unipolar major depressive disorder, schizophrenia, etc. 9) Procedure Methodology After selection of the subjects, the nature, purpose and benefit of the study were explained to each subject in details. They were encouraged for voluntary participation. They were allowed to withdraw from the study whenever they feel like. Informed written consent was taken from the participants. The research work was carried out after obtaining ethical clearance from concerned departments, Research Review Committee and Ethical Review Committee of Dhaka Medical College, Dhaka. Study subjects and controls who were interested to take part in the study were requested to attend the Department of Physiology, Dhaka Medical College, Dhaka. Before taking blood, detailed personal, family, drug and medical history were taken. Anthropometric measurement of the study subjects and controls was done and blood pressure was measured. All the information's were recorded in a prefixed data collection form. Then both study subjects and controls were brought to the Department of Laboratory Medicine, Dhaka Medical College Hospital, Dhaka. Platelet indices (total count of platelet, mean platelet volume, platelet distribution width, plateletcrit) were estimated in the Department of Laboratory Medicine, Dhaka Medical College Hospital, Dhaka, by using Penta Dx Nexus Automated Haematology Analyzer machine. Subjects who are unable to come to Dhaka Medical College, their blood samples were carried in a cool box to the respective department of Dhaka Medical College Hospital, Dhaka for investigations. 10) Statistical Analysis All the parameters were expressed as mean ± SD (standard deviation). Unpaired Student's "t" test was performed to compare between two groups. The p value < 0.05 was accepted as level of significance. Statistical analyses were performed by using a computer based statistical program SPSS (Statistical package for social science) version 25.0.

Results and Discussions
In the current study, Table 1 and Figure 1 show that the mean total count of platelet of both groups was within normal range but lower than the control group which was not statistically significant. Similarly, Almis and Aksoy (2018)  in panic disorder than healthy control which was not statistically significant. This finding was due to non-linear inverse relation between platelet volume and platelet count [16] [17] [18].
On the contrary, Gul et al. (2014) found higher platelet count in panic disorder than healthy control which was not statistically significant [19]. Ransing et al. (2016), Kokacya et al. (2015) also found higher platelet count in panic disorder than healthy control which was not statistically significant. This disagreement was due to various method of estimation of total count of platelet [12] [20]. Table 1 and Figure 2 show that the mean of Mean Platelet Volume (MPV) was higher in study group than control group which was statistically significant (p < 0.001). Similar type of observations was found by different researchers. Some postulated mechanisms are suggested by various researchers of different countries which may imply the possible mechanism regarding the changes in the present study. Platelets contain α-2, β-2, 5-HT receptors similar to central nervous  and Boro (2020) also found that mean platelet volume levels are significantly higher in anxiety disorder patients group than control group [16] [17] [18].
On the other hand, Gul et al. (2014) showed that mean platelet volume of panic disorder patients was significantly lower than healthy controls. Ransing et al. (2017) also found lower mean platelet volume in panic disorder patients than healthy controls. This disagreement in findings might have occurred due to abnormalities of 5-HT receptor functioning. So, platelet 5-HT (serotonin) uptake and platelet activity decreased. This abnormal function of platelet may be due to different variations in genetic composition of different population. Thus, mean platelet volume was lower in panic disorder [19] [20].
In the current study, Table 1 and Figure 3 also show that mean platelet distribution width of both the study subjects and healthy individuals were within   normal range but mean platelet distribution width of study subjects was higher than control group. The mean differences between the groups were not statistically significant. In generalized anxiety disorder mean platelet volume increases and platelet become more active. So, more platelet aggregation occurred. Then platelet changes their own characteristics. They begin to swell and form pseudopods protruding from their surface. Thus, platelet becomes more variable in volume, size (platelet distribution width) and more reactive than normal [13].
In the present study, Table 1 and Figure 4 also show that the mean plateletcrit of both the study group and control group were within normal range. The mean plateletcrit of study subjects was no significantly higher than controls.

Conclusion
After analyzing the results of the study, it can be concluded that patients with a generalized anxiety disorder may have more future risk of thrombosis due to a 14 significantly higher level of mean platelet volume, a higher level of platelet distribution width and plateletcrit than healthy adults.