Gender differences in automatic thoughts and cortisol and alpha-amylase responses to acute psychosocial stress in patients with obsessive-compulsive personality disorder

Journal of Affective Disorders 217 (2017) 1–7

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Research paper

Gender differences in automatic thoughts and cortisol and alpha-amylase responses to acute psychosocial stress in patients with obsessive-compulsive personality disorder

MARK

Masayuki Kanehisaa, Chiwa Kawashimaa, Mari Nakanishia, Kana Okamotoa, Harumi Oshitab, Koji Masudaa, Fuku Takitaa, Toshihiko Izumia, Ayako Inouea, Yoshinobu Ishitobia, ⁎ Haruka Higumaa, Taiga Ninomiyaa, Jotaro Akiyoshia, a b

Department of Neuropsychiatry, Oita University Faculty of Medicine, Hasama-Machi, Oita 879-5593, Japan Department of Applied Linguistics, Oita University Faculty of Medicine, Hasama-Machi, Oita 879-5593, Japan

A R T I C L E I N F O

A BS T RAC T

Keywords: Obsessive-compulsive personality disorder Stress Cortisol Alpha-amylase Childhood abuse Cognition

Introduction: Obsessive-compulsive personality disorder (OCPD) has a pervasive pattern of preoccupation with orderliness, perfection, and mental and interpersonal control at the expense of flexibility, openness, and efficiency. The aims of the present study were to explore the relationship between OCPD and psychological stress and psychological tests. Methods: We evaluated 63 OCPD patients and 107 healthy controls (HCs). We collected saliva samples from patients and controls before and after a social stress procedure, the Trier Social Stress Test (TSST), to measure the concentrations of salivary alpha-amylase (sAA) and salivary cortisol. The Childhood Trauma Questionnaire (CTQ), Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Social Adaptation Self-Evaluation Scale (SASS), and Depression and Anxiety Cognition Scale (DACS) were administered to patients and HCs. Results: Following TSST exposure, the salivary amylase and cortisol levels were significantly decreased in male patients compared with controls. Additionally, OCPD patients had higher CTQ, POMS, STAI, and BDI scores than HCs and exhibited significantly higher anxiety and depressive states. OCPD patients scored higher on future denial and threat prediction as per the DACS tool. According to a stepwise regression analysis, STAI, POMS, and salivary cortisol responses were independent predictors of OCPD. Conclusions: Our results suggested that attenuated sympathetic and parasympathetic reactivity in male OCPD patients occurs along with attenuated salivary amylase and cortisol responses to the TSST. In addition, there was a significant difference between OCPD patients and HCs in child trauma, mood, anxiety, and cognition. The finding support the modeling role of cortisol (20 min) on the relationships between STAI trait and depression among OCPD.

1. Introduction Obsessive-compulsive personality disorder (OCPD) is characterized by a prevalent pattern of maladaptive behaviors (American Psychiatric Association, 2013). Individuals with OCPD often exhibit the need for mental and interpersonal control, over-conscientiousness, difficulty abandoning items, rigidity, uniformity, and perfectionism. Assessments of the influence of OCPD on OCD (obsessive-compulsive disorder) symptoms have produced discrepant findings regarding the relationship between OCPD and OCD. As an example, one study noted that OCPD was associated with excessive OCD severity and incapacity,

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whereas another found no such association (Garyfallos et al., 2010; Lochner et al., 2011). Variation in personality traits was associated with the neurological response to mental stress (Yamano et al., 2015). This stress reaction is mainly regulated by an axial system consisting of two neuroendocrine systems: the hypothalamic–pituitary–adrenocortical (HPA) axis and the sympathetic adrenomedullary (SAM) system. A treatment regimen combining virtual reality exposure therapy and the administration of yohimbine hydrochloride led to a significant reduction in anxiety compared to pre-treatment, which induced significantly higher levels of salivary amylase (sAA) in the treated group (Meyerbroeker et al., 2012).

Corresponding author. E-mail address: [email protected] (J. Akiyoshi).

http://dx.doi.org/10.1016/j.jad.2017.03.057 Received 16 September 2016; Received in revised form 6 March 2017; Accepted 26 March 2017 Available online 28 March 2017 0165-0327/ © 2017 Elsevier B.V. All rights reserved.

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Table 1 Demographic characteristics. Female

Male

Control (n=41)

OCPD (N=19)

Statistics

Control (n=66)

OCPD (n=44)

Statistics

Age BMI

24.9 ± 3.8 24.2 ± 3.5

23.0 ± 0.9 23.3 ± 3.7

p=0.11 p=0.75

25.4 ± 18.0 23.2 ± 3.6

24.9 ± 9.5 23.8 ± 3.3

p=0.55 p=0.75

Smoking (no. cig) < 10/day > 10/day Education (years)

38 3 12.0 ± 2.5

17 2 13.2 ± 2.4

p=0.65 p=0.65

56 10 12.3 ± 2.5

35 9 13.0 ± 2.2

p=0.67 p=0.58

CTQ Emotional Abuse Physical Abuse Sexual Abuse Emotional Neglect Physical Neglect

5.8 ± 1.7 5.4 ± 1.1 5.5 ± 1.0 11.0 ± 2.8 6.2 ± 2.1

6.4 ± 1.6 5.3 ± 0.8 5.6 ± 1.1 11.6 ± 2.5 6.4 ± 1.9

p < 0.001 p=0.70 p=0.62 p < 0.001 p=0.24

5.4 ± 0.9 5.4 ± 1.1 5.3 ± 0.7 11.8 ± 3.3 6.3 ± 2.0

6.6 ± 3.4 5.6 ± 1.6 5.6 ± 1.1 13.4 ± 4.1 6.8 ± 2.3

p < 0.001 p=0.32 p=0.17 p < 0.001 p < 0.003

OCPD=Obsessive-compulsive personality disorder, BMI=Body Mass Index. CTQ=Childhood trauma Questionnaire.

Manual of Mental Disorders (DSM)-IV-TR criteria for OCPD and 107 Japanese HCs participated in the study. OCPD patients were recruited via advertisement and screened by interviews. In particular, OCPD patients who met the DSM-IV-TR criteria and who did not have axis I disorders were selected for the study. An OCPD diagnosis was determined using the Structured Clinical Interview of DSM-IV-TR for Personality Disorders (SCID-II) (First et al., 1997). The diagnoses of current axis I disorders were made by a trained psychiatrist (JA) using the Mini International Neuropsychiatry Interview (MINI), a standardized psychiatric examination validated in the general population (Sheehan et al., 1998) as per the DSM-IV-TR criteria (Ritchie et al., 2004). We excluded 12 OCPD patients with axis I disorders (8 with major depressive disorder [MDD], 3 with panic disorder, and 1 with bipolar disorder). HCs were enrolled via advertising and confirmed to be free of any axis I or II disorders (as determined by MINI and SCIDII). All participants were free of major illnesses according to their medical history and a physical examination and did not show any substance or alcohol abuse or dependence within 12 months prior to the study. Demographic information (age, body mass index [BMI], smoking, and education) was collected from all participants (Table 1). The participants were instructed to avoid strenuous physical activity for 48 h as well as any form of physical exercise and alcohol consumption 24 h prior to the study. Caffeine, tea, and smoking were not permitted within 3 h prior to the study, and tooth brushing and/or eating was to be avoided 2 h before the study. To diminish the influence of circadian rhythms on physiological variables, all experiments were performed in the afternoon (between 1 and 5 p.m.). All female subjects participated in the experiment during their late luteal phase to reduce the impact of hormonal variations through the menstrual cycle. After receiving a comprehensive explanation of the study, all participants offered their written informed consent. The study was approved by the ethics committee of the Oita University Faculty of Medicine.

We previously reported the association between OCD, sAA, and salivary cortisol (Kawano et al., 2013). The sAA levels in male and female OCD patients were significantly elevated comparted to healthy controls both before and after electrical stimulation. However, there were no marked differences in the salivary cortisol levels between OCD patients and controls. We also reported the association between avoidant personality disorder (OCPD), sAA, and salivary cortisol (Tanaka et al., 2016). Following electrical stimulation, the salivary cortisol levels in female OCPD patients were significantly decreased compared to healthy female controls, but there was no significant difference in the salivary cortisol levels between male OCPD patients and healthy male controls. Additionally, the sAA levels were not significantly different among male and female OCPD patients and male and female controls. Following exposure to a social stress procedure known as the Trier Social Stress Test (TSST), the sAA levels remained nonsignificantly different among male and female OCPD patients and healthy controls, and the salivary cortisol levels were also not markedly different between male and female OCPD patients and controls. We also reported the association between borderline personality disorder (BPD) and sAA and salivary cortisol levels (Inoue et al., 2015). Physical/sexual abuse and emotional abuse/neglect have been shown to be associated with heightened symptoms of all three personality disorder clusters (Tyrka et al., 2009). Enhanced symptoms of several specific personality disorders have also been observed, including paranoid, borderline, avoidant, dependent, obsessive-compulsive, and depressive personality disorders. Cognitive models of OCD suggest that changes in obsessive beliefs are mechanistically important for treatment (Diedrich et al., 2016). Extensive evidence also supports the effectiveness of cognitive behavioral therapy (CBT), with exposure and response prevention as the standard psychotherapeutic intervention for OCD (Skapinakis et al., 2016). Short-term cognitive therapy has been shown to effectively treat patients with cluster C personality disorders (including OCPD, OCPD, and dependent personality disorder) (Johansen et al., 2011; Renner et al., 2013). In this study, we examined the relationship among sAA and salivary cortisol levels before and after the TSST, childhood abuse, and cognitive vulnerability in OCPD patients and healthy controls (HCs). We examined the relationship between psychopathological assessments and endocrine responses to an empirical stress test.

2.2. Stimuli and procedures 2.2.1. TSST stress challenge All participants were TSST stress challenged to reduce the effect of habituation and relaxation in the experimental environment. The participants were divided into small groups consisting of four to five people. All participants were invited to our laboratory on a weekday afternoon between 1 and 5 p.m. After a 30-min resting period intended to minimize the impact of physical activity, prior stress, and emotions as well as to allow the participants to fill out questionnaires, the participants were exposed to the TSST (Kirschbaum et al., 1993). The

2. Methods 2.1. Patients and healthy controls Sixty-three Japanese patients meeting the Diagnostic and Statistical 2

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referred to as respiratory sinus arrhythmia) are highly sensitive to confounding influences, such as respiratory parameters (tidal volume) and other factors (participant’s level of fitness, medication, and position at assessment). Without the assessment of these confounders, it was not possible to perform valid HF calculations.

TSST consisted of a 3-min preparation period; a 5-min speech task, during which the participants had to discuss their personal characteristics; and a 5-min mental arithmetic task. All tasks were performed in front of an audience. After the test, the participants remained in our laboratory for another 20 min for a collection of saliva samples during recovery.

2.5. Statistical analyses 2.3. Psychological measures The data are presented as the mean ± standard deviation (S.D.) and reliability coefficients (Cronbach’s alpha) of the individual values from each test. We performed analyses using the SPSS 19 software program (IBM Corporation, Armonk, NY, USA). We used the χ2 test, Mann– Whitney U test, and Spearman’s rank correlation coefficient for sample characterization. A repeated measures analysis of variance (ANOVA) was used to compare the sAA or cortisol response level means between the patients and controls, followed by Scheffé’s method significant difference tests. The results were analyzed via structural equation modeling (SEM) using SPSS AMOS 21.0. Statistical significance was set at p < 0.05.

The Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 1994), Profile of Mood State (POMS) (McNair et al., 1992), StateTrait Anxiety Inventory (STAI) (Spielberger et al., 1973), Beck Depression Inventory (BDI) (Beck et al., 1961), Social Adaptation Self-Evaluation Scale (SASS) (Bosc et al., 1997), and Depression and Anxiety Cognition Scale (DACS) were administered (Fukui, 1998; Ishitobi et al., 2014). The POMS and STAI were administered once more after the TSST. The CTQ is the most commonly used test for assessing childhood maltreatment. The POMS provides a rapid, economical method of assessing transient, fluctuating active mood states. It is an ideal instrument for measuring and monitoring treatment change in clinical, medical, and addiction counseling centers. The STAI clearly differentiates between the temporary condition of “state anxiety” and the more general and long-standing quality of “trait anxiety” and helps professionals distinguish between a client's feelings of anxiety and depression. The BDI is a well-established measure of depression. The SASS is a scale developed for the evaluation of patients’ social functioning. The DACS is a questionnaire used to measure automatic thoughts that cause depression and anxiety.

3. Results 3.1. Psychological assessment We adjusted all analyses to match ages, and 107 HCs were selected to provide close matches to the 63 patients with respect to age and gender. There was no marked differences between the OCPD and healthy participant groups with regard to gender, age, smoking history, and education level (Table 1). The CTQ profiles of emotional abuse and neglect were significantly increased in OCPD female patients compared with HCs (p < 0.01), while those of emotional abuse and neglect and physical neglect were significantly increased in OCPD male patients compared with HCs (p < 0.001) (Table 1). Regarding the post-POMS testing, OCPD female patients scored significantly higher across three categories (depression–dejection, anger–hostility, and fatigue) than HCs (p < 0.05) (Table 2). There were no marked differences in other categories between the OCPD female patients and the controls prePOMS. Furthermore, there were no marked differences in the categories between the OCPD male patients and the controls either pre- or post-POMS. Regarding pre- and post-STAI testing, OCPD female patients scored significantly higher for trait anxiety than HCs (p < 0.01) in the pre-STAI (Table 3). There were no marked differences in the state anxiety between the OCPD male patients and HCs in pre- and post-STAI. Regarding the BDI, OCPD male patients scored significantly higher than HCs (p < 0.05) (Table 3). There were no marked differences in the BDI scores between OCPD female patients and the HCs. Regarding the HRV, there were no differences in the LF, HF, and LF/HF scores between OCPD patients and HCs (Table 3). Regarding the SASS scores, there were also no marked differences (Table 4). Regarding the DACS, the OCPD female patients scored significantly higher for future denial than HCs (p < 0.01), and OCPD male patients scored significantly higher for threat prediction than HCs (p < 0.05) (Table 4). There were no marked differences in other scores between the OCPD patients and the HCs.

2.4. Physiological measures We measured the sAA and salivary cortisol levels before, immediately after, and 20 min after TSST as per previous reports (Ishitobi et al., 2010; Tanaka et al., 2012a, 2012b, 2013; Maruyama et al., 2012; Kawano et al., 2013; Tamura et al., 2013). To control for circadian variations in the sAA and cortisol levels, the exposure to psychological stressors and collection of saliva were both performed between 1 and 5 p.m. The sAA levels were measured using the Dry Chemistry System (Nipro Corp., Tokyo, Japan) in accordance with the manufacturer’s protocol. Saliva was sampled by holding a saliva-sampling strip under the tongue for 30 s. The strip was immediately placed in an automatic saliva transfer system, and saliva was transferred to the alpha-amylase test paper on the reverse side of the strip sleeve by compression. The alpha-amylase test paper contained the substrate 2-chloro-4-nitrophenyl-4-O-β-D-galactopyranosylmaltoside. The enzymatic reaction was started upon transfer by compression, and the level of free 2-chloro4-nitrophenyl was optically measured after 20 s. The alpha-amylase activity that reduced sugars equivalent to 1 µmol/min of maltose was defined as 1 unit (Robles et al., 2011). The concentration of salivary cortisol (μg/dl) was analyzed by an enzyme-linked immunosorbent assay (ELISA), with intra-assay and inter-assay coefficients of variation of 3% and 10%, respectively. The samples were stored in a freezer at −20 °C until they were thawed for the analysis. We also measured the HRV immediately after the TSST. Lowfrequency (LF; 0.04–0.15 Hz) and high-frequency (HF; 0.15–0.4 Hz) fluctuations in the HR on R-R intervals were calculated using an APG Heart-Rater SA-3000P (Tokyo Iken Co., Ltd., Tokyo, Japan). LF fluctuation has frequently been used in the past as a measure of the sympathetic nervous system activity, but recent pharmacological research has repeatedly questioned its validity, indicating this variable is not a measure of the cardiac sympathetic tone but may instead be a measure of the modulation of cardiac autonomic outflows by baroreflexes (Goldstein et al., 2011). In particular, HF fluctuations (also

3.2. Physiological assessment After TSST exposure, the salivary cortisol levels in male OCPD patients were significantly lower than in male HCs (F (2, 91)=3.98, p < 0.01, Fig. 1B). In contrast, the salivary cortisol levels were not markedly different between female OCPD patients and HCs (F (2, 50)=0.46, p=0.51, Fig. 1A). The sAA levels in OCPD males were significantly decreased compared to those in male HCs (F (2, 91)=6.31, p < 0.01, Fig. 2B) but were not markedly different between female OCPD patients and HCs (F (2, 50)=0.48, p=0.49, Fig. 2A). There were no marked differences in the LF, HF, and LF/HF values between 3

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Table 2 Characteristics of OCPD and Control. Female

Male p

Control (n=41)

OCPD (N=19)

Min-max

Mean ± SD

Min-max

Mean ± SD

Pre-POMS Tension-Anxiety Depression-Dejection Anger-Hostility Vigor Fatigue Confusion

33–73 40–59 37–61 27–75 36–74 32–71

40.5 ± 8.2 43.0 ± 6.6 40.2 ± 5.6 48.1 ± 8.9 40.7 ± 6.3 44.8 ± 8.0

34–59 39–68 37–60 30–77 34–65 33–60

44.4 ± 8.1 45.5 ± 7.4 41.7 ± 6.6 48.3 ± 13.5 44.2 ± 9.3 45.9 ± 8.5

Post-POMS Tension-Anxiety Depression-Dejection Anger-Hostility Vigor Fatigue Confusion

33–75 40–72 37–56 27–73 36–78 32–85

43.8 ± 9.7 42.7 ± 6.4 38.6 ± 4.2 40.8 ± 10.4 43.4 ± 9.1 49.4 ± 10.5

34–75 39–75 37–65 30–67 35–68 36–85

48.1 ± 10.5 47.2 ± 10.6 42.1 ± 7.6 40.5 ± 9.5 48.9 ± 9.9 53.7 ± 12.9

p

Control (n=66)

OCPD (n=44)

Min-max

Mean ± SD

Min-max

Mean ± SD

p=0.09 p=0.19 p=0.36 p=0.95 p=0.09 p=0.60

34–75 39–66 37–60 32–65 35–59 33–75

41.0 ± 8.6 43.1 ± 7.9 39.8 ± 5.3 47.3 ± 10.9 42.7 ± 6.5 43.1 ± 7.7

33–65 39–72 35–64 27–70 35–68 32–71

41.8 ± 8.6 43.6 ± 5.8 42.0 ± 7.3 48.6 ± 11.9 43.5 ± 8.3 44.0 ± 7.2

p=0.63 p=0.72 p=0.07 p=0.57 p=0.56 p=0.58

p=0.13 p < 0.05 p < 0.05 p=0.91 p < 0.05 p=0.17

32–70 39–78 36–85 27–70 36–72 35–71

43.9 ± 9.4 44.3 ± 7.8 40.8 ± 7.3 40.3 ± 10.2 46.7 ± 8.9 48.4 ± 9.2

34–75 39–68 37–60 30–77 35–75 33–78

44.6 ± 10.2 43.8 ± 6.5 40.2 ± 5.4 40.0 ± 13.4 46.5 ± 10.8 48.2 ± 11.8

p = 0.70 p = 0.71 p=0.63 p=0.90 p=0.91 p=0.94

OCPD=Obsessive-compulsive personality disorder.

controls both before and after electrical stimulation. In contrast, there were no marked differences in the salivary cortisol levels between OCD patients and the HCs. The elevated secretion of sAA before and after electrical stimulation may suggest an increased responsiveness to novel and uncontrollable situations in patients with OCD (Kawano et al., 2013). Our present results did not corroborate these previous findings. This may be due to different mechanisms of stress between the studies: electrical stimulation and the TSST. Another possible explanation for the differences might be the pathophysiological states of OCPD and OCD. The duration of stress in OCPD might be longer than that in OCD (Cullen et al., 2008). This longer stress state might suppress the autonomic response. Male OCPD patients exhibited significant sAA and salivary cortisol responses, but female OCPD patients did not show similar sAA or salivary cortisol profiles. Previous studies assessing gender differences have yielded conflicting results, with one study reporting equal rates for men and women (Grant et al., 2012) while other studies have indicated higher frequency rates in men than in women (Coid et al., 2006; Light et al., 2006). Additionally, other studies have consistently shown that OCD patients and comorbid OCPD patients did not differ significantly with respect to gender (Lochner et al., 2011; Gordon et al., 2013; Pinto et al., 2011). Kawano et al. (2013) reported that the sAA levels in male and female OCD patients were significantly higher than in controls

OCPD patients and the HCs (Table 3). As shown in Table 5, according to the stepwise regression analysis of OCPD, three variables were determined as independent predictors of response: trait anxiety (STAI), depression-dejection (Pre-POMS), and salivary cortisol responses (20 min). A structural equation model was run in AMOS to examine the path diagram. The fit statistics for the structural model are shown in Fig. 3. The finding support the modeling role of cortisol (20 min) on the relationships between STAI trait and depression among OCPD. 4. Discussion Decreased parasympathetic reactivity in male OCPD patients occurred with attenuated sAA upon administration of the TSST. The sAA levels were not markedly different between female OCPD patients and HCs. Decreased sympathetic reactivity in OCPD males also occurred with attenuated salivary cortisol levels in response to the TSST, but the salivary cortisol levels were not markedly different between OCPD females and HCs. Both the sympathetic and parasympathetic responses and endocrine responsivity were low in the male OCPDs. This profile may be related to the low penetration of the tests in males with OCPD. We previously reported that sAA levels in both male and female OCD patients were significantly elevated relative to the values in Table 3 Characteristics of OCPD and Control. Female

Male

Control (n=41)

OCPD (N=19)

Min-max

Mean ± SD

Min-max

Mean ± SD

Pre-STAI Trait Anxiety State Anxiety

21–68 20–73

35.5 ± 9.4 35.8 ± 9.6

27–64 22–62

46.3 ± 10.5 41.1 ± 10.7

Post-STAI State Anxiety BDI

20–63 0–12

42.5 ± 10.5 2.7 ± 7.2

34–74 0–14

HRV LF HF LF/HF

7.4–92.2 7.8–83.6 0.2–11.8

52.0 ± 19.4 46.4 ± 20.0 1.9 ± 2.4

17.4–86.7 13.3–82.6 0.2–6.5

p

p

Control (n=66)

OCPD (n=44)

Min-max

Mean ± SD

Min-max

p < 0.01 p=0.06

22–57 26–62

37.7 ± 8.5 36.6 ± 7.4

23–70 22–73

40.1 ± 9.4 38.0 ± 9.7

p=0.17 p=0.39

48.5 ± 9.5 4.8 ± 5.2

p < 0.05 p=0.28

24–63 0–13

43.2 ± 9.3 2.5 ± 3.2

24–69 0–18

44.1 ± 10.8 4.3 ± 4.7

p=0.63 p < 0.05

46.5 ± 19.4 53.5 ± 19.4 1.3 ± 1.5

p=0.34 p=0.20 p=0.32

34.2–88.5 11.5–65.8 0.5–7.7

61.3 ± 16.4 38.7 ± 16.4 2.3 ± 1.9

19.0–86.3 13.7–81.0 0.2–6.3

59.1 ± 17.4 40.9 ± 17.4 2.0 ± 1.5

p=0.51 p=0.51 p=0.37

OCPD=Obsessive-compulsive personality disorder, BDI=Beck Depression Inventory, HRV=Heart Rate Variability.

4

Mean ± SD

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Table 4 Characteristics of OCPD and Control. Female

Male

Control (n=41)

OCPD (N=19)

Min-max

Mean ± SD

Min-max

Mean ± SD

SASS

23–47

38.3 ± 6.3

15–56

40.1 ± 8.8

DACS Future denial Threat prediction Self-denial Past denial Interpersonal threat

38–58 16–71 31–66 30–62 11–61

43.4 ± 6.1 41.3 ± 14.6 46.3 ± 10.4 42.8 ± 9.3 42.5 ± 13.0

39–74 28–65 31–72 32–63 25–62

50.1 ± 10.7 47.4 ± 10.6 52.0 ± 11.6 46.1 ± 9.2 48.9 ± 10.5

p

p

Control (n=66)

OCPD (n=44)

Min-max

Mean ± SD

Min-max

Mean ± SD

p=0.38

22–52

40.9 ± 6.6

26–56

40.7 ± 5.6

p=0.86

p < 0.01 p=0.12 p=0.07 p=0.22 p=0.07

38–56 17–70 30–65 28–60 11–65

41.6 ± 5.0 39.0 ± 13.5 42.3 ± 9.2 38.8 ± 8.7 40.1 ± 15.0

39–56 20–68 31–75 30–68 11–65

43.4 ± 5.4 45.3 ± 13.1 43.9 ± 11.7 43.0 ± 12.0 44.3 ± 13.4

p=0.09 p < 0.05 p=0.45 p=0.06 p=0.16

OCPD=Obsessive-compulsive personality disorder, DACS=Depression and Anxiety Cognition Scale.

In our study, there was a significant difference between OCPD patients and HCs in mood. Specifically, the BDI in male OCPD patients was higher than in HCs. However, the BDI level was just shy of the cutoff point for depression (10). This indicates minimal depression and excludes moderate and severe depression. The most common comorbidities were major depression, generalized anxiety, and social anxiety disorder. (Miguel et al., 2008). Patients with first-episode depression were screened using the BDI scale, with a cut-off point of > 9. Onethird of the participants had OCPD. It is important to identify comorbid OCPD when evaluating persons of employable age suffering from depression (Raiskila et al., 2013). Interestingly, a study dissecting OCPD and depression noted a relationship between obsessive-compulsive traits and a genetic variation in the dopamine D3 receptor in patients with major depressive disorder (Light et al., 2006). Thus, OCPD might be associated with depression. Regarding the DACS, OCPD female patients scored significantly higher in future denial than HCs, and OCPD male patients scored significantly higher in threat prediction than HCs. Dysfunctional beliefs in OCD patients and disquiet are thought to give rise to vulnerability and the maintenance of pathological anxiety (Calleo et al., 2010). Overestimation of threat/responsibility and intolerance of uncertainty were significantly correlated with obsession and worry severity. The compulsive style is susceptible to dysfunctional cognition (BlasczykSchiep et al., 2016). There is a relationship between obsessive–

before and after electrical stimulation. In contrast, there were no differences in the salivary cortisol levels between male and female OCD patients and controls. The elevated secretion of sAA before and after electrical stimulation may suggest an increased responsiveness to new and uncontrollable situations in OCD patients, and an increase in the sAA might be a distinctive aspect of OCD. However, our results obtained in the present study show that OCPD and OCD have distinct pathophysiologies. The CTQ (emotional abuse, emotional neglect) scores were significantly increased in OCPD female patients compared with controls. Similarly, the CTQ (emotional abuse, emotional neglect, and physical neglect) scores were also significantly increased in OCPD male patients compared with controls. As stated previously, physical/sexual abuse and emotional abuse/neglect have been shown to be associated with elevated symptoms of all three personality disorder clusters, including OCPD (Tyrka et al., 2009). Another study reported that physical and emotional abuse were more likely to manifest subclinical symptoms of paranoid, narcissistic, borderline, antisocial, OCPD, passive-aggressive, and depressive personality disorders (Grover et al., 2007). A significant relationship was noted between obsessive-compulsive symptoms and childhood trauma, specifically emotional abuse and physical neglect, all of which were due to co-occurring anxiety symptoms (Mathews et al., 2008). These results suggest that child trauma is likely associated with OCPD.

Fig. 1. Salivary cortisol responses to the Trier Social Stress Test (TSST) in patients with obsessive-compulsive personality disorder and healthy matched control subjects. (A) Female, (B) male. After TSST exposure, the salivary cortisol levels in male OCPD patients were significantly lower than in male HCs. In contrast, the salivary cortisol levels were not markedly different between female OCPD patients and female HCs. The values are presented as the mean ± standard deviation.

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Fig. 2. Salivary alpha‐amylase (sAA) responses to the Trier Social Stress Test in patients with obsessive-compulsive personality disorder and healthy matched control subjects. (A) Female, (B) male. After TSST exposure, the sAA levels in OCPD males were significantly lower than in male HCs. In contrast, the sAA levels were not markedly different between female OCPD patients and female HCs. The values are presented as the mean ± standard deviation.

shown that the sAA and salivary cortisol levels can differ according to the length of time that a participant spends in the hospital (Balodis et al., 2010). Lastly, our findings cannot be generalized to other ethnic groups. Thus, it will be necessary to conduct further studies in larger and more diverse populations to confirm the reproducibility of our data. In conclusion, our findings suggested that attenuated sympathetic and parasympathetic reactivity in male OCPD patients occurs with attenuated sAA and cortisol responses to the TSST. Additionally, there were significant differences between the OCPD patients and HCs in child trauma, mood, anxiety, and cognition. The finding support the modeling role of cortisol (20 min) on the relationships between STAI trait and depression among OCPD.

Table 5 The multiple regression analysis of OCPD. β

Significance

STAI Trait Anxiety

−0.227

0.036

Post-POMS Depression-Dejection

0.221

0.063

0.222

0.065 < 0.00001

Salivary Cortisol 20 min R2

OCPD=Obsessive-compulsive personality disorder, STAI=State-Trait Anxiety Inventory; POMS=Profile of Modd State.

Role of funding sources The study was supported by a Grant-in-Aid for Scientific Research (C: 23591719) from the Ministry of Health and Welfare. References American Psychiatric Association, 2013. Diagnostic and Statistical Manual of Mental Disorders 5th ed.. American Psychiatry Publishing, Arlington. Balodis, I.M., Wynne-Edwards, K.E., Olmstead, M.C., 2010. The other side of the curve: examining the relationship between pre-stressor physiological responses and stress reactivity. Psychoneuroendocrinology 35, 1363–1373. Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., Erbaugh, J., 1961. An inventory for measuring depression. Arch. Gen. Psychiatry 4, 561–571. Bernstein, D.P., Fink, L., Handelsman, L., Foote, J., Lovejoy, M., Wenzel, K., Sapareto, E., Ruggiero, J., 1994. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am. J. Psychiatry 151, 1132–1136. Blasczyk-Schiep, S., Sokoła, K., Fila-Witecka, K., Kazén, M., 2016. Are all models susceptible to dysfunctional cognitions about eating and body image? The moderating role of personality styles. Eat. Weight Disord. 21, 211–220. Bosc, M., Dubini, A., Polin, V., 1997. Development and validation of a social functioning scale, the social adaptation self-evaluation scale. Eur. Neuropsychopharmacol. 7 (Suppl. 1), S57–S70. Brakoulias, V., Starcevic, V., Berle, D., Milicevic, D., Hannan, A., Martin, A., 2014. The relationships between obsessive-compulsive symptom dimensions and cognitions in obsessive-compulsive disorder. Psychiatr. Q. 85, 133–142. Calleo, J.S., Hart, J., Björgvinsson, T., Stanley, M.A., 2010. Obsessions and worry beliefs in an inpatient OCD population. J. Anxiety Disord. 24, 903–908. Coid, J., Yang, M., Tyrer, P., Roberts, A., Ullrich, S., 2006. Prevalence and correlates of personality disorder in Great Britain. Br. J. Psychiatry 188, 423–431. Cullen, B., Samuels, J.F., Pinto, A., Fyer, A.J., McCracken, J.T., Rauch, S.L., Murphy, D.L., Greenberg, B.D., Knowles, J.A., Piacentini, J., Bienvenu, O.J., 3rd, Grados, M.A., Riddle, M.A., Rasmussen, S.A., Pauls, D.L., Willour, V.L., Shugart, Y.Y., Liang, K.Y., Hoehn-Saric, R., Nestadt, G., 2008. Demographic and clinical characteristics associated with treatment status in family members with obsessive-compulsive

Fig. 3. Structural model results. ns=not significant; ***p < 0.001.

compulsive symptom dimensions and the specific obsessive–compulsive cognitions (Brakoulias et al., 2014). The symmetry/ordering symptom dimension was associated with increased perfectionism/ intolerance of uncertainty, the unacceptable/taboo thoughts symptom dimension with increased importance/control of thoughts, and the doubt/checking symptom dimension with increased responsibility/ threat estimation. OCPD may bias towards automatic thoughts. Several limitations associated with the present study warrant mention. First, the small population of participants with OCPD prevented us from drawing definite conclusions, meaning that further investigation with a large cohort are warranted. Second, we conducted a limited number of hormonal examinations. Third, we used the time period immediately preceding the stressor as a baseline. It has been 6

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