Abstract
Introduction:
The aim of the study was to examine the peripheral inflammatory parameters in patients with Antisocial Personality Disorder (APD) including white blood cell levels, red cell distribution width (RDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR) by comparing with those of healthy controls.
Methods:
48 patients diagnosed with APD and a matched healthy control group of 52 individuals were included in our study. Venous blood samples were taken from the participants in the fasting state and at approximately the same time of the day. Socio-demographic data sheet, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), Buss-Durkee Hostility Inventory (BDHI) were applied to all of the participants.
Results:
RDW and basophil cell levels were found significantly higher in the patients than the controls (p=0.005, p=0.038 respectively). BLR was found significantly higher in the participants with alcohol use than those without alcohol use (p=0.016). No significant difference in other laboratory parameters was found between the patient group and the control group. Scores of BDI, BAI, BIS-11, motor impulsivity subscale and physical aggression, anger, hostility and verbal aggression subscales of BDHI, and the total score of BDHI were significantly higher in patients than controls (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.003, p=0.001, p<0.001 respectively). A positive correlation was determined between the scale scores and the RDW, basophil, monocyte, lymphocyte levels among the laboratory parameters, and a negative correlation was determined between the MPV levels and the depression and impulsivity levels.
Conclusion:
The results of our study suggested that inflammation might play a role in the etiopathogenesis of APD. Furthermore, a significant relationship was found between the severity of symptoms and some inflammatory parameter levels such as RDW and basophil in APD patients.
Keywords: Antisocial Personality Disorder, inflammatory markers, basophil, RDW
INTRODUCTION
Antisocial Personality Disorder is a personality disorder pattern characterized by unlawful and unethical behaviors, self-centeredness, indifference to others, hardness of heart, irresponsibility, impulsivity, aggression, fraudulence, being manipulative and/or taking risks (1). Aggressive behavior that can be seen in many psychiatric disorders is a general behavior pattern in patients with APD (1, 2). Recent studies found that patients with serious mental illness conditions such as schizophrenia, bipolar disorder (BD), substance abuse, and personality disorders have higher rates of violent behavior (3). It has been shown that violent behavior increases three to four times in anxiety disorder, dysthymia, major depressive disorder (MDD), and eight times in BD, drug or alcohol use disorder (4). Due to the complexity of APD, many genetic, environmental, biological, psychodynamic, cognitive, and psychosocial factors are emphasized in the etiology of the disease (5). Although it is suggested that the disease might result from the interaction of these factors, the etiopathogenesis of APD is not fully understood.
Inflammatory parameters are one of the most emphasized fields in recent studies on the etiology of psychiatric diseases (6–9). It has been reported that stressful life experiences are associated with elevated pro-inflammatory cytokines in childhood, which also plays an important role in mental disorders in adulthood (10). Elevated cytokine levels in the central nervous system have been suggested to strongly influence dopaminergic, noradrenergic, and serotonergic neurotransmission, as well as reported to play a role in mental disorders (11). The effect of inflammatory processes has been observed in many mental disorders including impulsivity and aggression, such as schizophrenia, BD, MDD, anxiety disorder, attention deficit and hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and heroin addiction (6, 12, 13). However, no study was conducted to investigate the correlation between aggression, impulsivity, and inflammation parameters in APD patients. Therefore, the aim of our study was to examine the inflammatory parameters in patients with APD by comparing them with those of healthy controls.
Highlights
Peripheral inflammatory parameters were investigated in patients with Antisocial Personality Disorder (APD).
The study included 48 patients with APD and a healthy control group of 52 people.
Red cell distribution width (RDW) and basophil levels were found to be significantly higher in patients .
Basophil-to-lymphocyte ratio was found to be significantly higher in alcohol users compared to non-alcoholics.
Finally, it has been suggested that inflammation is effective in the etiopathogenesis of APD.
METHOD
For this study, approval was obtained from the Clinical Research Ethics Committee of Firat University on 11.04.2019. Forty-eight patients diagnosed with APD according to DSM-5 diagnostic criteria who have undergone outpatient or inpatient treatment in the Elaziğ Mental Health and Diseases Hospital and the psychiatric department of Elaziğ Fethi Sekin City Hospital and who met the study criteria, and 52 age- and gender-matched controls did not have any psychiatric, neurological and metabolic disease in their past and present history were included in the study. The detailed history of all the participants was taken. Since APD is often accompanied by anxiety and depression symptoms, only the patients with mild anxiety and depression symptoms were included in the study. Those who were diagnosed with mental disorder other than APD, those who were with another personality disorder, those with a physical illness which may affect the psychiatric symptoms, those with a blood disease, those who were illiterate, and those who were not willing to participate in the study were excluded from the study.
Socio-demographic and clinical data sheet, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), Buss-Durkee Hostility Inventory (BDHI) were administered to both the patient group and the healthy control group.
Data Collection Instruments
Socio-demographic and Clinical Data Form: The socio-demographic and clinical data form which we have prepared based on our clinical experience and the information obtained from the reviewed resources taking into account the objectives of the study was used to evaluate the cases. This form was a semi-structured form containing socio-demographic information such as age, gender, marital status, educational status, profession, economic situation as well as clinical data such as smoking, alcohol use, drug use, and medications.
Beck Depression Inventory (BDI): It was developed by Beck in 1961 to measure the risk of depression, and the level and severity of depressive symptoms in adults (14). It is a Likert-type self-report scale with 21 items, each rated on a scale of 0–3, and a cut-off score of 17. The total score ranged from 0 to 63. A score between 0–9 indicates no depressive symptoms, 10–16 mild depressive symptoms, 17–24 moderate depressive symptoms and, 25 and higher severe depressive symptoms. The Turkish validity and reliability studies were conducted in 1989 by Hisli (15).
Beck Anxiety Inventory (BAI): It was developed by Beck et al. (16). It is a 21-item self-report scale used to determine the frequency and severity of anxiety symptoms experienced by individuals. Each item is ranked between 0 and 3, higher scores indicate higher anxiety level. Validity and reliability tests of the Turkish version of the scale were conducted by Ulusoy (17).
Barratt Impulsiveness Scale (BIS-11): Impulsivity is one of the important clinical characteristics of several mental disorders. The BIS-11 was developed by Patton et al. (18), and was translated into Turkish by Güleç et al. (19).
Buss-Durkee Hostility Inventory (BDHI): It was developed to measure the aggressive potential of individuals. It is a Likert-type self-report scale consisting of 34 items, each rated on a scale of 1–5. It has physical aggression, verbal aggression, anger, hostility, indirect aggression sub-scales. Furthermore, the overall aggression is calculated based on the total score, and the higher scores indicate a higher aggressive tendency (20). Validity and reliability tests of the Turkish version of the scale were conducted by Can (21).
Hematological Analysis
3 ml venous blood samples were taken from the individuals in the patient and control groups after 8–12 hours of fasting. The samples were taken from all the participants at approximately the same time of day. On the same day, the samples were centrifuged within 30 minutes using “CELL-DYN 3700 SL analyzer (Abbott Diagnostics, Chicago, USA)” in the biochemistry laboratory of the Elazığ Fethi Sekin City Hospital.
Statistical Analysis
A statistical software package, SPSS 22 for Windows (Statistical Package for Social Sciences for Windows 22), was used to evaluate the data obtained from the participants. Descriptive analyses, including frequency, percentage distribution, mean ± standard deviation calculations, were made to give information about the general characteristics of the participants. The continuous variable data were given as mean ± standard deviation, and the categorical variable data were given as n (%). The qualitative variables in the study were demographical data such as gender, age, educational status, socioeconomic situation as well as smoking, alcohol use, drug use, and accompanying medical conditions. Cross-tabs and chi-square tests were used to evaluate whether there is an association between the qualitative variables. The quantitative variables were the scores from the scales administered to the participants as well as the blood parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). Independent samples t-test and Pearson Correlation analysis were used to evaluate whether there is an association between the quantitative variables. The p values calculated below 0.05 were regarded as statistically significant.
RESULTS
100 participants were included in the study. Fourty eight individuals diagnosed with APD based on the DSM-5 criteria, and 52 healthy controls were included. The mean age of the participants in the study was 29.31±6.1 (years) for the patient group and 29.52±6.4 (year) for the control group (p=0.871). All the participants were male. There was no significant difference in accompanying medical condition and non-psychiatric medication use rates between the groups (p>0.05). The majority of the patients were primary school graduates (n=22, 45.8%) in the patient group, while the majority of the controls were high-school graduates (n=21, 40.3%) and university graduates (n=23, 44.2%) (p<0.001). The majority of the patients had tattoos and scars (n=43, 89.5%). The socio-demographic data of the participants were given in Table 1.
Table 1.
Sociodemographic characteristics of the participants
| Patient group (n=48) | Control group (n=52) | P | |
|---|---|---|---|
| n (%) | n (%) | ||
| Age (mean ± SD) | 29.3±6.1 | 29.5±6.5 | 0.871 |
| Gender (Male/Female) | 48/0 | 52/0 | |
| Marital status | |||
| Single | 32 (66.6%) | 18 (34.6%) | <0.001 |
| Married | 10 (20.8%) | 33 (63.4%) | |
| Divorced | 6 (12.5%) | 1 (1.9%) | |
| Occupation | |||
| Employee | 13 (27.1%) | 51 (98.1%) | <0.001 |
| Unemployed | 35 (72.9%) | 1 (1.9%) | |
| Alcohol use | 18/17/13 | 3/47/2 | <0.001 |
| (yes/no/left) | (37.5/35.4/27.1%) | (5.8/90.3/3.8%) | |
| Substance use | 12/19/17 | 0/52/0 | <0.001 |
| (yes/no/left) | (25/39.5/35.4%) | (0/100/0%) | |
| Smoking | 44/3/1 | 33/16/3 | 0.003 |
| (yes/no/left) | (91.6/6.2/2.1%) | (63.4/30.7/5.8%) | |
| Medical illness | 02/46 | 0/52 | 0.137 |
| (yes/no) | (4.1/95.8%) | (0/100%) | |
mean ± SD, mean ± standard deviation. Chi square test was used in calculations.
P<0.05 was considered statistically significant.
The scores of the BAI and BDI scales used for the evaluation of depression and anxiety were found higher in the patients than the healthy controls (p<0.001, p<0.001, respectively). The scores of the physical aggression, anger, hostility, verbal aggression sub-scales of the BDHI and the overall scale score were higher in the patient group than the control group (p<0.001, p<0.001, p=0.003, p=0.001, p<0.001, respectively). No significant difference was found in the BDHI indirect aggression sub-scale scores (p=0.092). The BIS-11 motor impulsivity sub-scale score was significantly higher in the patient group (p<0.001). No significant difference was found in the BIS-11’s other sub-scale scores (p>0.05) (Table 2).
Table 2.
Comparison of patient and control group scale scores
| Patient group (n=48) (mean ± SD) | Control group (n=52) (mean ± SD) | P | |
|---|---|---|---|
| BAI | 24.04±15.5 | 7.09±6.9 | <0.001 |
| BDI | 27.1±16.6 | 5.8±6.5 | <0.001 |
| BIS-11 | |||
| Attention-related impulsivity | 31.0±4.05 | 31.1±5.19 | 0.911 |
| Motor impulsivity | 15.2±4.7 | 11.4±2.3 | <0.001 |
| Premeditated impulsivity | 19.5±2.8 | 18.6±3.5 | 0.197 |
| BDHI | |||
| Physical aggression | 5.0±1.96 | 2.74±1.52 | <0.001 |
| Anger | 3.75±1.42 | 3.2±1.30 | 0.092 |
| Hostility | 5.2±1.89 | 3.42±2.37 | <0.001 |
| Indirect aggression | 3.58±1.28 | 2.6±1.59 | 0.03 |
| Verbal aggression | 10.06±2.67 | 7.8±3.2 | 0.001 |
| Total aggression | 24.1±6.3 | 17.3±6.27 | <0.001 |
BAI, Beck anxiety inventory; BDI, Beck’ depression inventory; BIS-11, Barratt impulsiveness scale; BDHI, Buss-Durkee hostility inventory. Independent samples t test was used in calculations. P<0.05 was considered statistically significant.
When the laboratory parameters of the participants were examined, no significant difference was found in white blood cell (WBC), red blood cell (RBC), mean corpuscular volume (MCV), mean platelet volume (MPV), hemoglobin, hematocrit, lymphocyte, neutrophil, eosinophil levels between the patient group and the control group (p>0.05), while the basophil and red cell distribution width (RDW) levels were significantly higher in the patient group (p=0.03, p=0.005, respectively). There was no significant difference in the NLR, PLR, MLR levels (p=0.559, p=0.854, p=0.556, respectively). The basophil-to-lymphocyte ratio levels were significantly higher in the participants with alcohol use than those without alcohol use (p=0.016) (Table 3).
Table 3.
Analysis of laboratory parameters of the participants
| Patient group (n=48) (mean ± SD) | Control group (n=52) (mean ± SD) | P | |
|---|---|---|---|
| WBC (103/uL) | 8.52±2.12 | 7.86±1.61 | 0.083 |
| RBC (106/uL) | 5.30±0.39 | 5.38±0.33 | 0.258 |
| Hemoglobin (g/dL) | 15.68±1.43 | 15.91±0.72 | 0.303 |
| Hematocrit (%) | 45.55±3.18 | 45.96±2.16 | 0.444 |
| MCV (fL) | 86.16±6.37 | 85.8±3.49 | 0.735 |
| MPV (fL) | 9.23±1.39 | 9.08±1.21 | 0.555 |
| Platelets (103/uL) | 270.18±74.96 | 244.96±59.3 | 0.064 |
| Lymphocytes (103/uL) | 2.56±0.77 | 2.31±0.6 | 0.075 |
| Monocytes (103/uL) | 0.66±0.22 | 0.63±0.24 | 0.581 |
| Neutrophils (106/uL) | 5.11±1.90 | 4.64±1.34 | 0.154 |
| Eosinophils (103/uL) | 0.19±0.15 | 0.18±0.13 | 0.742 |
| Basophils (103/uL) | 0.45±0.22 | 0.36±0.20 | 0.038* |
| RDW (%) | 41.07±2.84 | 39.6±2.16 | 0.005* |
| PLR | 111.54±35.1 | 110.29±32.2 | 0.854 |
| NLR | 2.21±1.28 | 2.09±0.71 | 0.559 |
| MLR | 0.27±0.096 | 0.28±0.11 | 0.556 |
WBC, white blood (leucocyte) cell; RBC, red blood (erythrocyte) cell; MCV, mean corpuscular volume; MPV, mean platelet volume; RDW, red cell distribution width; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; mean ± SD, mean ± standard deviation.
Independent samples t-test was used.
When p<0.05, the result was considered to be statistically significant.
The correlation analysis showed a positive correlation between the scale scores and the RDW, basophil, monocyte, lymphocyte levels among the laboratory parameters, and a negative correlation between the MPV levels and the depression and impulsivity scale scores (Table 4).
Table 4.
Pearson correlation analysis of the laboratory parameters and scale scores of the patients
| MPV | RDW | Basophils | Platelets | Lymphocytes | Monocytes | Neutrophils | ||
|---|---|---|---|---|---|---|---|---|
| BAI | r | -0.151 | 0.222 | 0.322* | 0.140 | 0.259 | 0.326* | -0.045 |
| p | 0.307 | 0.129 | 0.026 | 0.343 | 0.076 | 0.024 | 0.760 | |
| BDI | r | -0.309* | 0.270 | 0.222 | 0.056 | 0.228 | 0.130 | -0.160 |
| p | 0.033 | 0.064 | 0.130 | 0.704 | 0.120 | 0.379 | 0.277 | |
| BIS-11 | ||||||||
| Attention-related impulsivity | r | -0.032 | -0.143 | -0.056 | 0.153 | 0.317* | 0.153 | -0.064 |
| p | 0.830 | 0.333 | 0.707 | 0.300 | 0.028 | 0.299 | 0.665 | |
| Motor impulsivity | r | -0.377** | 0.329* | 0.009 | 0.238 | 0.245 | -0.001 | 0.038 |
| p | 0.008 | 0.023 | 0.954 | 0.103 | 0.093 | 0.995 | 0.798 | |
| Premeditated impulsivity | r | -0.305* | 0.153 | 0.015 | -0.017 | 0.035 | 0.182 | 0.082 |
| p | 0.035 | 0.299 | 0.920 | 0.909 | 0.811 | 0.216 | 0.578 | |
| BDHI | ||||||||
| Physical aggression | r | -0.284 | -0.076 | 0.029 | 0.175 | 0.119 | -0.087 | 0.007 |
| p | 0.050 | 0.605 | 0.846 | 0.235 | 0.419 | 0.555 | 0.960 | |
| Indirect aggression | r | -0.064 | 0.317* | 0.253 | 0.144 | 0.243 | -0.067 | 0.096 |
| p | 0.664 | 0.028 | 0.082 | 0.329 | 0.096 | 0.651 | 0.518 | |
| Anger | r | -0.277 | 0.242 | 0.059 | 0.143 | 0.321* | -0.045 | -0.011 |
| p | 0.056 | 0.098 | 0.692 | 0.331 | 0.026 | 0.760 | 0.940 | |
| Hostility | r | -0.077 | -0.007 | -0.056 | -0.043 | -0.011 | 0.256 | 0.242 |
| p | 0.603 | 0.961 | 0.708 | 0.770 | 0.943 | 0.079 | 0.097 | |
| Verbal aggression | r | 0.042 | 0.149 | 0.033 | 0.017 | -0.006 | 0.202 | 0.205 |
| p | 0.774 | 0.313 | 0.823 | 0.910 | 0.968 | 0.168 | 0.162 | |
| Total aggression | r | -0.170 | 0.190 | 0.101 | 0.122 | 0.173 | 0.006 | 0.089 |
| p | 0.247 | 0.197 | 0.495 | 0.411 | 0.239 | 0.967 | 0.546 |
BAI, Beck anxiety inventory; BDI, Beck’ depression inventory; BIS-11, Barratt impulsiveness scale; BDHI, Buss-Durkee hostility inventory.
Pearson correlation coefficient was used in the calculations.
The values given in the table are ‘r’ and ‘p’ values.
When
p<0.05,
p<0.001, the result was considered to be statistically significant.
The correlation analysis showed that there was a positive correlation between the BAI, BDI scale scores, the BIS-11 motor impulsivity sub-scale scores, the BDHI physical aggression, indirect aggression, and anger sub-scale scores, and the overall sum score in the patient groups (Table 5).
Table 5.
Pearson correlation analysis between the scores of the Buss-Durke Hostility Inventory and the other scales of the patients
| Physical aggression | Indirect aggression | Anger | Hostility | Verbal aggression | Total aggression | ||
|---|---|---|---|---|---|---|---|
| BAI | r | 0.468** | 0.438** | 0.484** | 0.198 | 0.254 | 0.482** |
| p | 0.001 | 0.002 | 0.000 | 0.176 | 0.082 | 0.001 | |
| BDI | r | 0.412** | 0.438** | 0.512** | 0.190 | 0.226 | 0.463** |
| p | 0.004 | 0.002 | <0.001 | 0.195 | 0.122 | 0.122 | |
| BIS-11 | |||||||
| Attention-related impulsivity | r | 0.027 | -0.096 | -0.006 | -0.053 | -0.186 | -0.103 |
| p | 0.857 | 0.517 | 0.970 | 0.720 | 0.205 | 0.488 | |
| Motor impulsivity | r | 0.333* | 0.412** | 0.448** | 0.262 | 0.289* | 0.430** |
| p | 0.021 | 0.004 | 0.001 | 0.072 | 0.046 | 0.002 | |
| Premeditated impulsivity | r | 0.031 | -0.198 | 0.018 | 0.221 | -0.052 | -0.053 |
| p | 0.837 | 0.176 | 0.902 | 0.130 | 0.130 | 0.723 |
BAI, Beck anxiety inventory; BDI, Beck’s depression inventory; BIS-11, Barratt inventory scale
Pearson correlation coefficient was used in the calculations.
The values given in the table are ‘r’ and ‘p’ values.
When When
p<0.05,
p<0.001, the result was considered to be statistically significant.
DISCUSSION
In our study, representing the first study to investigate the role of inflammation in APD pathophysiology, WBC levels, RDW, MPV, NLR, PLR, MLR, BLR values and anxiety, depression, aggression, and impulsivity levels were compared between the APD patients and the healthy controls. In our study, the RDW and basophil levels were found significantly higher in the APD group. The BLR values were found significantly higher in the participants with alcohol use than those without alcohol use. No significant difference was found in other laboratory parameters and NLR, PLR, and MLR values between the patient group and the control group. The anxiety, depression, aggression, and motor impulsivity levels were found significantly higher in the patient group than the control group. We found positive correlations between the RDW, basophil, monocyte, lymphocyte levels and the anxiety, depression, impulsivity, and aggression levels. There were negative correlations between the MPV values and the depression, and impulsivity levels.
In the literature, there is a limited number of studies to investigate the RDW values in mental disorders. It was demonstrated that RDW is used for differential diagnosis of anemia as well as serves as a mortality marker for the general population and those with various diseases such as acute or chronic heart failure, pulmonary embolism, acute myocardial infarction, peripheral artery disease, and acute kidney failure (22). Many publications reported that inflammation and oxidative stress affect RDW (23). It was also demonstrated that RDW reflects an increase in the levels of circulating hepcidin, IL-6, TNF-alpha, and other cytokines (24). In a study investigating the RDW levels in panic disorder as an anxiety disorder, no significant difference was found between the control group and the patient group (25), while another study concluded that they were significantly higher in the patient group (26). In a study investigating the RDW levels in depression patients, no significant difference was found between the control group and the patient group (27), while another study concluded that they were significantly higher in the patient group. The authors suggested that an elevated RDW level is the result of the early release of reticulocytes into the circulation during inflammatory and infectious pathologies (28). This study supports the RDW results of our study.
In our study, the basophil, a type of WBC counts, were found higher in the patient group than the control group. There is a limited number of studies investigating the basophil cell levels in mental disorders. In a study conducted on the patients with developmental stuttering, it was reported that the basophil and platelet counts were higher, while the MPV value was lower in the patient group than the control group (29). Impulsivity and aggression are common findings in ASD, and an increase in basophils and eosinophils was observed in a study conducted in ASD (13). The ability of basophils to recognize and to react to antigen suggests that they may be involved in the development of memory immune responses. Allergic conditions have been reported to occur more frequently in developmental disorders. Strom and Silverberg (30) reported that paediatric eczema may be associated with an increased risk of speech disorder. For these reasons, basophil suggests a possible association between developmental psychiatric disorders and previous infections (29). In another study investigating the basophil counts in mental disorders, it was reported that the complete blood count parameters such as basophil have been usually interpreted as part of acute inflammatory events, but basophils had a memory response. Hence the values identified in the disease might probably reflect a chronic event (31). The basophil levels were found higher in the patient group than the control group in our study, supporting that inflammation may influence APD as a chronic process.
In our study, no significant difference was found in the NLR, PLR, MLR, and MPV values between the patient and control groups. There are numerous studies investigating the NLR, PLR, MLR and MPV values in mental disorders. In children with ADHD, another disease in which impulsivity and aggression are very common, some studies found no relationship between inflammation parameters and ADHD (32), while some studies found an increase in ADHD (33).
In a study on the NLR, PLR, MPV values in panic disorder as an anxiety disorder, it was reported that there was no statistically significant difference (25), while another study reported that the WBC and, MPV levels were higher in the patient group than the control group (26). It was seen that the results obtained for MDD, a mental disorder for which the inflammation parameters have been mostly examined, were inconsistent. However, the majority of the studies suggested that the inflammation parameters were elevated (28, 34).
The majority of the studies confirm that inflammation plays a role in schizophrenia and bipolar patients. In a study comparing patients with schizophrenia, BD and MDD, it was reported that the haematological inflammatory parameters were elevated in these three patient groups, but the inflammatory parameters were higher in schizophrenia than BD and MDD (7). In a study examining the relationship between violent behavior, crime, and inflammation parameters; it has been determined that inflammatory parameters are higher in patients with BD who are involved in crime than the group not involved in crime and the healthy control group (35).
In a study on heroin addicts, it was reported that the NLR and PLR values were significantly higher in the patient group than the control group, which showed a positive correlation with the duration of disease (36). In a study on alcohol addicts, it was reported that there was a negative correlation between the BLR and the duration of alcohol use (37). However, Örüm et al. (30) reported no association between basophil and opioid use. In our study, the BLR values were found significantly higher in the participants with alcohol use than those without alcohol use.
As expected, the anxiety, depression, motor impulsivity, and aggression levels were found significantly higher in the patients with APD than the controls. The literature reviews also showed that the depression and anxiety levels were elevated in APD patients (38). The impulsivity and aggression levels were found elevated in the APD patients due to the DSM-5 criteria (1).
The negative correlation between the MPV values among laboratory parameters and the depression and impulsivity levels, and the positive correlation between the lymphocyte, monocyte, basophil, and RDW values and the anxiety, depression, impulsivity, and aggression levels suggested that inflammation might influence psychiatric symptoms.
Limitations of the Study
The study sample consisted of male participants only, and the number of participants is relatively low, making it difficult to generalize and interpret the results. Also, smoking, alcohol, substance abuse, lifestyle, and diet of the individuals were confounding factors that might affect the blood parameters. Alcohol and substance use is very common in people with APD. In our study, 37.5% of patients with APD have alcohol use and 25% have substance use. The results we obtained in our study may also be a result of alcohol and substance use. For this reason, our study is a preliminary study to conduct comprehensive studies comparing individuals with alcohol and substance use but not diagnosed with APD and individuals with alcohol and substance use but diagnosed with APD. In order to verify these results and to make the underlying mechanism clear, further studies should be performed on larger sample groups including both genders, taking into account these confounding factors.
CONCLUSION
Our study is the first study in the literature, where the effect of peripheral inflammation parameters on the etiopathogenesis of APD has been examined. The basophil, a type of white blood cell, and RDW values were found higher in the APD patients. The depression, anxiety, motor impulsivity, and aggression levels were found significantly higher in the patient group. We found a positive correlation between the RDW, basophil, monocyte, lymphocyte levels and the anxiety, depression, impulsivity, and aggression levels and a negative correlation between the MPV values and the depression and impulsivity levels. In this regard, inflammation has been suggested to have an influence on the etiopathogenesis of APD. However, further studies are needed to clarify the association between APD and inflammatory markers.
Footnotes
Ethics Committee Approval: The study was approved by the Fırat University Clinical Research Ethics Committee with the decision number 03 dated 11.04.2019.
Informed Consent: Written informed consent was obtained from all participants.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept– SK; Design– ŞK; Supervision– GT; Resources– GT; Materials– ŞK, GT; Data Collection and/or Processing– ŞK, GT; Analysis and/or Interpretation– SK, GT; Literature Search– GT; Writing Manuscript– GT; Critical Review– SK, MA.
Conflict of Interest: The authors declared that there is no conflict of interest.
Financial Disclosure: The authors declared that this study has received no financial support.
REFERENCES
- 1.American Psychiatric Association. 5th ed. Arlington: American Psychiatric Publishing; 2013. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [Google Scholar]
- 2.Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC. Psychiatric aspects of impulsivity. Am J Psychiatry. 2001;158:1783–1793. doi: 10.1176/appi.ajp.158.11.1783. [DOI] [PubMed] [Google Scholar]
- 3.Volavka J. Violence schizophrenia and bipolar disorder. Psychiatr Danub. 2013;25:24–33. http: //www.psychiatria-danubina.com/UserDocsImages/pdf/dnb_vol25_no1/dnb_vol25_no1_24.pdf . [PubMed] [Google Scholar]
- 4.Corrigan PW, Watson AC. Findings from the National Comorbidity Survey on the frequency of violent behavior in individuals with psychiatric disorders. Psychiatry Res. 2005;136:153–162. doi: 10.1016/j.psychres.2005.06.005. [DOI] [PubMed] [Google Scholar]
- 5.Moffitt TE. Genetic and enviromental influences on antisocial behaviors: evidence from behavioral-genetic research. In: Hall JC, Dunlap JC, Friedmann T, van Heyningen V, editors. Advances in Genetics. Vol. 55. USA: Elsevier, ScienceDirect; 2005. pp. 41–104. [DOI] [PubMed] [Google Scholar]
- 6.Mazza MG, Lucchi S, Tringali AGM, Rossetti A, Botti ER, Clerici M. Neutrophil/lymphocyte ratio and platelet/lymphocyte. Int J Med Biochem ratio in mood disorders: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84:229–236. doi: 10.1016/j.pnpbp.2018.03.012. [DOI] [PubMed] [Google Scholar]
- 7.Catak Z, Uzmez E, Ozturk N, Ugur K. Research Article Comparison of neutrophil-to-lymphocyte, platelet-to-lymphocyte, and monocyte-to-lymphocyte ratios in patients with schizophrenia, bipolar disorder, and major depressive disorder. Int J Med Biochem. 2018;1:106–110. [Google Scholar]
- 8.Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology. 2017;42:254–270. doi: 10.1038/npp.2016.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Bauer ME, Teixeira AL. Inflammation in psychiatric disorders: what comes first? Ann N Y Acad Sci. 2019;1437:57–67. doi: 10.1111/nyas.13712. [DOI] [PubMed] [Google Scholar]
- 10.Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry. 2008;65:409–415. doi: 10.1001/archpsyc.65.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Müller N, Ackenheil M. Psychoneuroimmunology and the cytokine action in the CNS. implications for psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22:1–33. doi: 10.1016/s0278-5846(97)00179-6. [DOI] [PubMed] [Google Scholar]
- 12.Mazza M, Capellazzi M, Tagliabue I, Lucchi S, Rossetti A, Clerici M. Neutrophil-lymphocyte, monocyte-lymphocyte and platelet-lymphocyte ratio in schizoaffective disorder compared to schizophrenia. Gen Hosp Psychiatry. 2019;61:86–87. doi: 10.1016/j.genhosppsych.2019.06.013. [DOI] [PubMed] [Google Scholar]
- 13.Trottier G, Srivastava L, Walker CD. Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. J Psychiatry Neurosci. 1999;24:103–115. https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC1188990/ [PMC free article] [PubMed] [Google Scholar]
- 14.Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561–571. doi: 10.1001/archpsyc.1961.01710120031004. [DOI] [PubMed] [Google Scholar]
- 15.Hisli N. Effect of patients'evaluation of group behavior on therapy outcome. Int J Group Psychother. 1987;37:119–124. doi: 10.1080/00207284.1987.11491045. [DOI] [PubMed] [Google Scholar]
- 16.Beck AT, Epstein N, Brown G, Steer RA. An inventory form easuring clinical anxiety: Psychometric properties. J Consult Clin Psychol. 1988;56:893–897. doi: 10.1037//0022-006x.56.6.893. [DOI] [PubMed] [Google Scholar]
- 17.Ulusoy M, Hisli Sahin N, Erkmen H. Turkish Version of the Beck Anxiety Inventory: Psychometric Properties. J Cogn Psychother. 1998;12:163–172. https: //www.researchgate.net/publication/233792003_Turkish_Version_of_the_Beck_Anxiety_Inventory_Psychometric_Properties . [Google Scholar]
- 18.Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. J Clin Psychol. 1995;51:768–774. doi: 10.1002/1097-4679(199511)51:6<768::aid-jclp2270510607>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- 19.Güleç H, Tamam L, Güleç MY, Turhan M, Karakuş G, Zengin M, et al. Psychometric properties of the Turkish version of the Barratt Impulsivity Scale-11. Bull Clin Psychopharmacol. 2008;18:251–258. https: //scholars.houstonmethodist.org/en/publications/psychometric-properties-of-the-turkish-version-of-the-barratt-imp . [Google Scholar]
- 20.Buss AH, Durkee A. An inventory for assessing different kinds of hostility. J Consult Psychol. 1957;21:343–349. doi: 10.1037/h0046900. [DOI] [PubMed] [Google Scholar]
- 21.Can S. “Aggression questionnaire”AdlıÖlçeğin Türk Popülasyonunda Geçerlilik ve Güvenilirlik Çalışması Genel Kurmay Başkanlığı, Gülhane Askeri Tıp Akademisi Haydarpaşa Eğitim Hastanesi Ruh Sağlığıve HastalıklarıServis Şefliği. İstanbul: Unpublished Dissertation Thesis; 2002. [Google Scholar]
- 22.Zalawadiya SK, Veeranna V, Panaich SS, Afonso L, Ghali JK. Gender and ethnic differences in red cell distribution width and its association with mortality among low risk healthy United State adults. Am J Cardiol. 2012;109:1664–1670. doi: 10.1016/j.amjcard.2012.01.396. [DOI] [PubMed] [Google Scholar]
- 23.Yesil A, Şenateş E, Bayoğlu İV, Erdem ED, Demirtunç R, Övünç AOK. Red cell distribution width: a novel marker of activity in inflammatory bowel disease. Gut Liver. 2011;5:460–467. doi: 10.5009/gnl.2011.5.4.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Seretis C, Seretis F, Lagoudianakis E, Gemenetzis G, Salemis NS. Is red cell distribution width a novel biomarker of breast cancer activity?Data from a pilot study. J Clin Med Res. 2013;5:121–126. doi: 10.4021/jocmr1214w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Gunduz N, Timur O, Erzincan E, Tural U. The mean platelet volume, neutrophil lymphocyte ratio, platelet lymphocyte ratio and red cell distribution width in panic disorder. Anadolu Psikiyatri Derg. 2018;19:5–12. [Google Scholar]
- 26.Asoglu M, Aslan M, Imre O, Kivrak Y, Akil O, Savik E, et al. Mean platelet volume and red cell distribution width levels in initial evaluation of panic disorder. Neuropsychiatr Disease Treat. 2016;12:2435–2348. doi: 10.2147/NDT.S111108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Gündüz N, Timur Ö, Erzincan E, Turgut C, Turan H, Yıldız Akbey Z. Major depresif bozukluk tanılıhastalarda ortalama trombosit hacmi, nötrofil lenfosit oranı, platelet lenfosit oranı, kırmızıküre dağılım genişliğinin belirlenmesi. Medeniyet Med J. 2017;32:230–237. [Google Scholar]
- 28.Demircan F, Gözel N, Kılınç F, Ulu R, Atmaca M. The impact of red blood cell distribution width and neutrophil/lymphocyte ratio on the diagnosis of major depressive disorder. Neurol Ther. 2016;5:27–33. doi: 10.1007/s40120-015-0039-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Kara MZ, Örüm MH, Sekmen E. Is there a relationship between basophil, platelet-related parameters and developmental stuttering? Anadolu Psikiyatri Derg. 2020;21:187–194. [Google Scholar]
- 30.Strom MA, Silverberg JI. Eczema is associated with childhood speech disorder: A retrospective analysis from the National Survey of Children's Health and the National Health Interview Survey. J Pediatr. 2016;168:185–192. e4. doi: 10.1016/j.jpeds.2015.09.066. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Orüm MH. Basophil Count, Percentage of Basophil and Basophil Lymphocyte Ratio in Psychiatry Practice: Current Approaches and Future Directions. J Contemp Med. 2020;10:295–296. [Google Scholar]
- 32.Binici NC, Kutlu A. Is ADHD an inflammation-related disorder? Anadolu Psikiyatri Derg. 2019;20:313–321. [Google Scholar]
- 33.Avcil S. Evaluation of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as inflammatory markers in children with attention-deficit hyperactivity disorder. Psychiatry Clin Neurosci. 2018;72:522–530. doi: 10.1111/pcn.12659. [DOI] [PubMed] [Google Scholar]
- 34.Korkmaz S, Denk A, Gundoğan B, Korucu T, Dulkadir Z E, Telo S, et al. Neutrophil lymphocyte ratio in patients with major depressive disorder. Acta Medica Mediterranea. 2016;32:795–798. [Google Scholar]
- 35.Özsoy F, Ünal Demir F, Taşcı G. Inflammation in bipolar affective disorder patients who committed or did not commit a crime: neutrophil/lymphocyte, platelet/lymphocyte, monocyte/lymphocyte ratios and mean platelet volume. J Forensic Psychiatr Psychol. 2021;32 [Google Scholar]
- 36.Cicek E, Demirel B, Cicek IE, Kirac AS, Eren I. Increased Neutrophil-Lymphocyte And Platelet-Lymphocyte Ratios In Male Heroin Addicts: A Prospective Controlled Study. Clin. Psychopharmacol Neurosci. 2018;16:190–196. doi: 10.9758/cpn.2018.16.2.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Orum MH, Kara MZ, Egilmez OB. Relationship between immune cells and alcohol dependents and controls: what about the lymphocyte-related ratios? J Immunoassay Immunochem. 2018;39:348–350. doi: 10.1080/15321819.2018.1488728. [DOI] [PubMed] [Google Scholar]
- 38.Coid J, Ullrich S. Antisocial personality disorder and anxiety disorder: A diagnostic variant? J Anxiety Disord. 2010;24:452–460. doi: 10.1016/j.janxdis.2010.03.001. [DOI] [PubMed] [Google Scholar]
