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Journal of Affective Disorders 217 (2017) 1–7

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Journal of Affective Disorders


journal homepage: www.elsevier.com/locate/jad

Research paper

Gender differences in automatic thoughts and cortisol and alpha-amylase MARK


responses to acute psychosocial stress in patients with obsessive-compulsive
personality disorder
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
Department of Neuropsychiatry, Oita University Faculty of Medicine, Hasama-Machi, Oita 879-5593, Japan
b
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: Introduction: Obsessive-compulsive personality disorder (OCPD) has a pervasive pattern of preoccupation
Obsessive-compulsive personality disorder with orderliness, perfection, and mental and interpersonal control at the expense of flexibility, openness, and
Stress efficiency. The aims of the present study were to explore the relationship between OCPD and psychological
Cortisol stress and psychological tests.
Alpha-amylase
Methods: We evaluated 63 OCPD patients and 107 healthy controls (HCs). We collected saliva samples from
Childhood abuse
patients and controls before and after a social stress procedure, the Trier Social Stress Test (TSST), to measure
Cognition
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 whereas another found no such association (Garyfallos et al., 2010;


Lochner et al., 2011).
Obsessive-compulsive personality disorder (OCPD) is characterized Variation in personality traits was associated with the neurological
by a prevalent pattern of maladaptive behaviors (American Psychiatric response to mental stress (Yamano et al., 2015). This stress reaction is
Association, 2013). Individuals with OCPD often exhibit the need for mainly regulated by an axial system consisting of two neuroendocrine
mental and interpersonal control, over-conscientiousness, difficulty systems: the hypothalamic–pituitary–adrenocortical (HPA) axis and the
abandoning items, rigidity, uniformity, and perfectionism. sympathetic adrenomedullary (SAM) system. A treatment regimen com-
Assessments of the influence of OCPD on OCD (obsessive-compulsive bining virtual reality exposure therapy and the administration of yohim-
disorder) symptoms have produced discrepant findings regarding the bine hydrochloride led to a significant reduction in anxiety compared to
relationship between OCPD and OCD. As an example, one study noted pre-treatment, which induced significantly higher levels of salivary
that OCPD was associated with excessive OCD severity and incapacity, amylase (sAA) in the treated group (Meyerbroeker et al., 2012).


Corresponding author.
E-mail address: akiyoshi@oita-u.ac.jp (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.
M. Kanehisa et al. Journal of Affective Disorders 217 (2017) 1–7

Table 1
Demographic characteristics.

Female Male

Control (n=41) OCPD (N=19) Statistics Control (n=66) OCPD (n=44) Statistics

Age 24.9 ± 3.8 23.0 ± 0.9 p=0.11 25.4 ± 18.0 24.9 ± 9.5 p=0.55
BMI 24.2 ± 3.5 23.3 ± 3.7 p=0.75 23.2 ± 3.6 23.8 ± 3.3 p=0.75

Smoking (no. cig)


< 10/day 38 17 56 35
> 10/day 3 2 p=0.65 10 9 p=0.67
Education (years) 12.0 ± 2.5 13.2 ± 2.4 p=0.65 12.3 ± 2.5 13.0 ± 2.2 p=0.58

CTQ
Emotional Abuse 5.8 ± 1.7 6.4 ± 1.6 p < 0.001 5.4 ± 0.9 6.6 ± 3.4 p < 0.001
Physical Abuse 5.4 ± 1.1 5.3 ± 0.8 p=0.70 5.4 ± 1.1 5.6 ± 1.6 p=0.32
Sexual Abuse 5.5 ± 1.0 5.6 ± 1.1 p=0.62 5.3 ± 0.7 5.6 ± 1.1 p=0.17
Emotional Neglect 11.0 ± 2.8 11.6 ± 2.5 p < 0.001 11.8 ± 3.3 13.4 ± 4.1 p < 0.001
Physical Neglect 6.2 ± 2.1 6.4 ± 1.9 p=0.24 6.3 ± 2.0 6.8 ± 2.3 p < 0.003

OCPD=Obsessive-compulsive personality disorder, BMI=Body Mass Index.


CTQ=Childhood trauma Questionnaire.

We previously reported the association between OCD, sAA, and salivary Manual of Mental Disorders (DSM)-IV-TR criteria for OCPD and 107
cortisol (Kawano et al., 2013). The sAA levels in male and female OCD Japanese HCs participated in the study. OCPD patients were recruited
patients were significantly elevated comparted to healthy controls both via advertisement and screened by interviews. In particular, OCPD
before and after electrical stimulation. However, there were no marked patients who met the DSM-IV-TR criteria and who did not have axis I
differences in the salivary cortisol levels between OCD patients and disorders were selected for the study. An OCPD diagnosis was
controls. We also reported the association between avoidant personality determined using the Structured Clinical Interview of DSM-IV-TR for
disorder (OCPD), sAA, and salivary cortisol (Tanaka et al., 2016). Following Personality Disorders (SCID-II) (First et al., 1997). The diagnoses of
electrical stimulation, the salivary cortisol levels in female OCPD patients current axis I disorders were made by a trained psychiatrist (JA) using
were significantly decreased compared to healthy female controls, but there the Mini International Neuropsychiatry Interview (MINI), a standar-
was no significant difference in the salivary cortisol levels between male dized psychiatric examination validated in the general population
OCPD patients and healthy male controls. Additionally, the sAA levels were (Sheehan et al., 1998) as per the DSM-IV-TR criteria (Ritchie et al.,
not significantly different among male and female OCPD patients and male 2004). We excluded 12 OCPD patients with axis I disorders (8 with
and female controls. Following exposure to a social stress procedure known major depressive disorder [MDD], 3 with panic disorder, and 1 with
as the Trier Social Stress Test (TSST), the sAA levels remained nonsigni- bipolar disorder). HCs were enrolled via advertising and confirmed to
ficantly different among male and female OCPD patients and healthy be free of any axis I or II disorders (as determined by MINI and SCID-
controls, and the salivary cortisol levels were also not markedly different II). All participants were free of major illnesses according to their
between male and female OCPD patients and controls. We also reported medical history and a physical examination and did not show any
the association between borderline personality disorder (BPD) and sAA and substance or alcohol abuse or dependence within 12 months prior to
salivary cortisol levels (Inoue et al., 2015). the study.
Physical/sexual abuse and emotional abuse/neglect have been shown to Demographic information (age, body mass index [BMI], smoking,
be associated with heightened symptoms of all three personality disorder and education) was collected from all participants (Table 1). The
clusters (Tyrka et al., 2009). Enhanced symptoms of several specific participants were instructed to avoid strenuous physical activity for
personality disorders have also been observed, including paranoid, border- 48 h as well as any form of physical exercise and alcohol consumption
line, avoidant, dependent, obsessive-compulsive, and depressive personality 24 h prior to the study. Caffeine, tea, and smoking were not permitted
disorders. within 3 h prior to the study, and tooth brushing and/or eating was to
Cognitive models of OCD suggest that changes in obsessive beliefs be avoided 2 h before the study. To diminish the influence of circadian
are mechanistically important for treatment (Diedrich et al., 2016). rhythms on physiological variables, all experiments were performed in
Extensive evidence also supports the effectiveness of cognitive beha- the afternoon (between 1 and 5 p.m.). All female subjects participated
vioral therapy (CBT), with exposure and response prevention as the in the experiment during their late luteal phase to reduce the impact of
standard psychotherapeutic intervention for OCD (Skapinakis et al., hormonal variations through the menstrual cycle. After receiving a
2016). Short-term cognitive therapy has been shown to effectively treat comprehensive explanation of the study, all participants offered their
patients with cluster C personality disorders (including OCPD, OCPD, written informed consent. The study was approved by the ethics
and dependent personality disorder) (Johansen et al., 2011; Renner committee of the Oita University Faculty of Medicine.
et al., 2013). In this study, we examined the relationship among sAA
and salivary cortisol levels before and after the TSST, childhood abuse, 2.2. Stimuli and procedures
and cognitive vulnerability in OCPD patients and healthy controls
(HCs). 2.2.1. TSST stress challenge
We examined the relationship between psychopathological assess- All participants were TSST stress challenged to reduce the effect of
ments and endocrine responses to an empirical stress test. habituation and relaxation in the experimental environment. The
participants were divided into small groups consisting of four to five
2. Methods 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
2.1. Patients and healthy controls to minimize the impact of physical activity, prior stress, and emotions
as well as to allow the participants to fill out questionnaires, the
Sixty-three Japanese patients meeting the Diagnostic and Statistical participants were exposed to the TSST (Kirschbaum et al., 1993). The

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M. Kanehisa et al. Journal of Affective Disorders 217 (2017) 1–7

TSST consisted of a 3-min preparation period; a 5-min speech task, referred to as respiratory sinus arrhythmia) are highly sensitive to
during which the participants had to discuss their personal character- confounding influences, such as respiratory parameters (tidal volume)
istics; and a 5-min mental arithmetic task. All tasks were performed in and other factors (participant’s level of fitness, medication, and
front of an audience. After the test, the participants remained in our position at assessment). Without the assessment of these confounders,
laboratory for another 20 min for a collection of saliva samples during it was not possible to perform valid HF calculations.
recovery.
2.5. Statistical analyses
2.3. Psychological measures
The data are presented as the mean ± standard deviation (S.D.) and
The Childhood Trauma Questionnaire (CTQ) (Bernstein et al., reliability coefficients (Cronbach’s alpha) of the individual values from
1994), Profile of Mood State (POMS) (McNair et al., 1992), State- each test. We performed analyses using the SPSS 19 software program
Trait Anxiety Inventory (STAI) (Spielberger et al., 1973), Beck (IBM Corporation, Armonk, NY, USA). We used the χ2 test, Mann–
Depression Inventory (BDI) (Beck et al., 1961), Social Adaptation Whitney U test, and Spearman’s rank correlation coefficient for sample
Self-Evaluation Scale (SASS) (Bosc et al., 1997), and Depression and characterization. A repeated measures analysis of variance (ANOVA)
Anxiety Cognition Scale (DACS) were administered (Fukui, 1998; was used to compare the sAA or cortisol response level means between
Ishitobi et al., 2014). The POMS and STAI were administered once the patients and controls, followed by Scheffé’s method significant
more after the TSST. difference tests. The results were analyzed via structural equation
The CTQ is the most commonly used test for assessing childhood modeling (SEM) using SPSS AMOS 21.0. Statistical significance was set
maltreatment. The POMS provides a rapid, economical method of at p < 0.05.
assessing transient, fluctuating active mood states. It is an ideal
instrument for measuring and monitoring treatment change in clinical, 3. Results
medical, and addiction counseling centers. The STAI clearly differenti-
ates between the temporary condition of “state anxiety” and the more 3.1. Psychological assessment
general and long-standing quality of “trait anxiety” and helps profes-
sionals distinguish between a client's feelings of anxiety and depres- We adjusted all analyses to match ages, and 107 HCs were selected
sion. The BDI is a well-established measure of depression. The SASS is to provide close matches to the 63 patients with respect to age and
a scale developed for the evaluation of patients’ social functioning. The gender. There was no marked differences between the OCPD and
DACS is a questionnaire used to measure automatic thoughts that healthy participant groups with regard to gender, age, smoking history,
cause depression and anxiety. and education level (Table 1). The CTQ profiles of emotional abuse and
neglect were significantly increased in OCPD female patients compared
2.4. Physiological measures with HCs (p < 0.01), while those of emotional abuse and neglect and
physical neglect were significantly increased in OCPD male patients
We measured the sAA and salivary cortisol levels before, immedi- compared with HCs (p < 0.001) (Table 1). Regarding the post-POMS
ately after, and 20 min after TSST as per previous reports (Ishitobi testing, OCPD female patients scored significantly higher across three
et al., 2010; Tanaka et al., 2012a, 2012b, 2013; Maruyama et al., 2012; categories (depression–dejection, anger–hostility, and fatigue) than
Kawano et al., 2013; Tamura et al., 2013). To control for circadian HCs (p < 0.05) (Table 2). There were no marked differences in other
variations in the sAA and cortisol levels, the exposure to psychological categories between the OCPD female patients and the controls pre-
stressors and collection of saliva were both performed between 1 and POMS. Furthermore, there were no marked differences in the cate-
5 p.m. gories between the OCPD male patients and the controls either pre- or
The sAA levels were measured using the Dry Chemistry System post-POMS. Regarding pre- and post-STAI testing, OCPD female
(Nipro Corp., Tokyo, Japan) in accordance with the manufacturer’s patients scored significantly higher for trait anxiety than HCs (p <
protocol. Saliva was sampled by holding a saliva-sampling strip under 0.01) in the pre-STAI (Table 3). There were no marked differences in
the tongue for 30 s. The strip was immediately placed in an automatic the state anxiety between the OCPD male patients and HCs in pre- and
saliva transfer system, and saliva was transferred to the alpha-amylase post-STAI. Regarding the BDI, OCPD male patients scored significantly
test paper on the reverse side of the strip sleeve by compression. The higher than HCs (p < 0.05) (Table 3). There were no marked differences
alpha-amylase test paper contained the substrate 2-chloro-4-nitrophe- in the BDI scores between OCPD female patients and the HCs.
nyl-4-O-β-D-galactopyranosylmaltoside. The enzymatic reaction was Regarding the HRV, there were no differences in the LF, HF, and
started upon transfer by compression, and the level of free 2-chloro- LF/HF scores between OCPD patients and HCs (Table 3). Regarding
4-nitrophenyl was optically measured after 20 s. The alpha-amylase the SASS scores, there were also no marked differences (Table 4).
activity that reduced sugars equivalent to 1 µmol/min of maltose was Regarding the DACS, the OCPD female patients scored significantly
defined as 1 unit (Robles et al., 2011). higher for future denial than HCs (p < 0.01), and OCPD male patients
The concentration of salivary cortisol (μg/dl) was analyzed by an scored significantly higher for threat prediction than HCs (p < 0.05)
enzyme-linked immunosorbent assay (ELISA), with intra-assay and (Table 4). There were no marked differences in other scores between
inter-assay coefficients of variation of 3% and 10%, respectively. The the OCPD patients and the HCs.
samples were stored in a freezer at −20 °C until they were thawed for
the analysis. 3.2. Physiological assessment
We also measured the HRV immediately after the TSST. Low-
frequency (LF; 0.04–0.15 Hz) and high-frequency (HF; 0.15–0.4 Hz) After TSST exposure, the salivary cortisol levels in male OCPD
fluctuations in the HR on R-R intervals were calculated using an APG patients were significantly lower than in male HCs (F (2, 91)=3.98, p <
Heart-Rater SA-3000P (Tokyo Iken Co., Ltd., Tokyo, Japan). LF 0.01, Fig. 1B). In contrast, the salivary cortisol levels were not
fluctuation has frequently been used in the past as a measure of the markedly different between female OCPD patients and HCs (F (2,
sympathetic nervous system activity, but recent pharmacological 50)=0.46, p=0.51, Fig. 1A). The sAA levels in OCPD males were
research has repeatedly questioned its validity, indicating this variable significantly decreased compared to those in male HCs (F (2,
is not a measure of the cardiac sympathetic tone but may instead be a 91)=6.31, p < 0.01, Fig. 2B) but were not markedly different between
measure of the modulation of cardiac autonomic outflows by barore- female OCPD patients and HCs (F (2, 50)=0.48, p=0.49, Fig. 2A). There
flexes (Goldstein et al., 2011). In particular, HF fluctuations (also were no marked differences in the LF, HF, and LF/HF values between

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M. Kanehisa et al. Journal of Affective Disorders 217 (2017) 1–7

Table 2
Characteristics of OCPD and Control.

Female Male

Control (n=41) OCPD (N=19) p Control (n=66) OCPD (n=44) p

Min-max Mean ± SD Min-max Mean ± SD Min-max Mean ± SD Min-max Mean ± SD

Pre-POMS
Tension-Anxiety 33–73 40.5 ± 8.2 34–59 44.4 ± 8.1 p=0.09 34–75 41.0 ± 8.6 33–65 41.8 ± 8.6 p=0.63
Depression-Dejection 40–59 43.0 ± 6.6 39–68 45.5 ± 7.4 p=0.19 39–66 43.1 ± 7.9 39–72 43.6 ± 5.8 p=0.72
Anger-Hostility 37–61 40.2 ± 5.6 37–60 41.7 ± 6.6 p=0.36 37–60 39.8 ± 5.3 35–64 42.0 ± 7.3 p=0.07
Vigor 27–75 48.1 ± 8.9 30–77 48.3 ± 13.5 p=0.95 32–65 47.3 ± 10.9 27–70 48.6 ± 11.9 p=0.57
Fatigue 36–74 40.7 ± 6.3 34–65 44.2 ± 9.3 p=0.09 35–59 42.7 ± 6.5 35–68 43.5 ± 8.3 p=0.56
Confusion 32–71 44.8 ± 8.0 33–60 45.9 ± 8.5 p=0.60 33–75 43.1 ± 7.7 32–71 44.0 ± 7.2 p=0.58

Post-POMS
Tension-Anxiety 33–75 43.8 ± 9.7 34–75 48.1 ± 10.5 p=0.13 32–70 43.9 ± 9.4 34–75 44.6 ± 10.2 p = 0.70
Depression-Dejection 40–72 42.7 ± 6.4 39–75 47.2 ± 10.6 p < 0.05 39–78 44.3 ± 7.8 39–68 43.8 ± 6.5 p = 0.71
Anger-Hostility 37–56 38.6 ± 4.2 37–65 42.1 ± 7.6 p < 0.05 36–85 40.8 ± 7.3 37–60 40.2 ± 5.4 p=0.63
Vigor 27–73 40.8 ± 10.4 30–67 40.5 ± 9.5 p=0.91 27–70 40.3 ± 10.2 30–77 40.0 ± 13.4 p=0.90
Fatigue 36–78 43.4 ± 9.1 35–68 48.9 ± 9.9 p < 0.05 36–72 46.7 ± 8.9 35–75 46.5 ± 10.8 p=0.91
Confusion 32–85 49.4 ± 10.5 36–85 53.7 ± 12.9 p=0.17 35–71 48.4 ± 9.2 33–78 48.2 ± 11.8 p=0.94

OCPD=Obsessive-compulsive personality disorder.

OCPD patients and the HCs (Table 3). As shown in Table 5, according controls both before and after electrical stimulation. In contrast, there
to the stepwise regression analysis of OCPD, three variables were were no marked differences in the salivary cortisol levels between OCD
determined as independent predictors of response: trait anxiety (STAI), patients and the HCs. The elevated secretion of sAA before and after
depression-dejection (Pre-POMS), and salivary cortisol responses electrical stimulation may suggest an increased responsiveness to novel
(20 min). A structural equation model was run in AMOS to examine and uncontrollable situations in patients with OCD (Kawano et al.,
the path diagram. The fit statistics for the structural model are shown 2013). Our present results did not corroborate these previous findings.
in Fig. 3. The finding support the modeling role of cortisol (20 min) on This may be due to different mechanisms of stress between the studies:
the relationships between STAI trait and depression among OCPD. 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
4. Discussion
(Cullen et al., 2008). This longer stress state might suppress the
autonomic response.
Decreased parasympathetic reactivity in male OCPD patients
Male OCPD patients exhibited significant sAA and salivary cortisol
occurred with attenuated sAA upon administration of the TSST. The
responses, but female OCPD patients did not show similar sAA or
sAA levels were not markedly different between female OCPD patients
salivary cortisol profiles. Previous studies assessing gender differences
and HCs. Decreased sympathetic reactivity in OCPD males also
have yielded conflicting results, with one study reporting equal rates for
occurred with attenuated salivary cortisol levels in response to the
men and women (Grant et al., 2012) while other studies have indicated
TSST, but the salivary cortisol levels were not markedly different
higher frequency rates in men than in women (Coid et al., 2006; Light
between OCPD females and HCs. Both the sympathetic and parasym-
et al., 2006). Additionally, other studies have consistently shown that
pathetic responses and endocrine responsivity were low in the male
OCD patients and comorbid OCPD patients did not differ significantly
OCPDs. This profile may be related to the low penetration of the tests in
with respect to gender (Lochner et al., 2011; Gordon et al., 2013; Pinto
males with OCPD.
et al., 2011). Kawano et al. (2013) reported that the sAA levels in male
We previously reported that sAA levels in both male and female
and female OCD patients were significantly higher than in controls
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) p Control (n=66) OCPD (n=44) p

Min-max Mean ± SD Min-max Mean ± SD Min-max Mean ± SD Min-max Mean ± SD

Pre-STAI
Trait Anxiety 21–68 35.5 ± 9.4 27–64 46.3 ± 10.5 p < 0.01 22–57 37.7 ± 8.5 23–70 40.1 ± 9.4 p=0.17
State Anxiety 20–73 35.8 ± 9.6 22–62 41.1 ± 10.7 p=0.06 26–62 36.6 ± 7.4 22–73 38.0 ± 9.7 p=0.39

Post-STAI
State Anxiety 20–63 42.5 ± 10.5 34–74 48.5 ± 9.5 p < 0.05 24–63 43.2 ± 9.3 24–69 44.1 ± 10.8 p=0.63
BDI 0–12 2.7 ± 7.2 0–14 4.8 ± 5.2 p=0.28 0–13 2.5 ± 3.2 0–18 4.3 ± 4.7 p < 0.05

HRV
LF 7.4–92.2 52.0 ± 19.4 17.4–86.7 46.5 ± 19.4 p=0.34 34.2–88.5 61.3 ± 16.4 19.0–86.3 59.1 ± 17.4 p=0.51
HF 7.8–83.6 46.4 ± 20.0 13.3–82.6 53.5 ± 19.4 p=0.20 11.5–65.8 38.7 ± 16.4 13.7–81.0 40.9 ± 17.4 p=0.51
LF/HF 0.2–11.8 1.9 ± 2.4 0.2–6.5 1.3 ± 1.5 p=0.32 0.5–7.7 2.3 ± 1.9 0.2–6.3 2.0 ± 1.5 p=0.37

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

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Table 4
Characteristics of OCPD and Control.

Female Male

Control (n=41) OCPD (N=19) p Control (n=66) OCPD (n=44) p

Min-max Mean ± SD Min-max Mean ± SD Min-max Mean ± SD Min-max Mean ± SD

SASS 23–47 38.3 ± 6.3 15–56 40.1 ± 8.8 p=0.38 22–52 40.9 ± 6.6 26–56 40.7 ± 5.6 p=0.86

DACS
Future denial 38–58 43.4 ± 6.1 39–74 50.1 ± 10.7 p < 0.01 38–56 41.6 ± 5.0 39–56 43.4 ± 5.4 p=0.09
Threat prediction 16–71 41.3 ± 14.6 28–65 47.4 ± 10.6 p=0.12 17–70 39.0 ± 13.5 20–68 45.3 ± 13.1 p < 0.05
Self-denial 31–66 46.3 ± 10.4 31–72 52.0 ± 11.6 p=0.07 30–65 42.3 ± 9.2 31–75 43.9 ± 11.7 p=0.45
Past denial 30–62 42.8 ± 9.3 32–63 46.1 ± 9.2 p=0.22 28–60 38.8 ± 8.7 30–68 43.0 ± 12.0 p=0.06
Interpersonal threat 11–61 42.5 ± 13.0 25–62 48.9 ± 10.5 p=0.07 11–65 40.1 ± 15.0 11–65 44.3 ± 13.4 p=0.16

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

before and after electrical stimulation. In contrast, there were no In our study, there was a significant difference between OCPD
differences in the salivary cortisol levels between male and female OCD patients and HCs in mood. Specifically, the BDI in male OCPD patients
patients and controls. The elevated secretion of sAA before and after was higher than in HCs. However, the BDI level was just shy of the cut-
electrical stimulation may suggest an increased responsiveness to new off point for depression (10). This indicates minimal depression and
and uncontrollable situations in OCD patients, and an increase in the excludes moderate and severe depression. The most common comor-
sAA might be a distinctive aspect of OCD. However, our results bidities were major depression, generalized anxiety, and social anxiety
obtained in the present study show that OCPD and OCD have distinct disorder. (Miguel et al., 2008). Patients with first-episode depression
pathophysiologies. were screened using the BDI scale, with a cut-off point of > 9. One-
The CTQ (emotional abuse, emotional neglect) scores were sig- third of the participants had OCPD. It is important to identify
nificantly increased in OCPD female patients compared with controls. comorbid OCPD when evaluating persons of employable age suffering
Similarly, the CTQ (emotional abuse, emotional neglect, and physical from depression (Raiskila et al., 2013). Interestingly, a study dissecting
neglect) scores were also significantly increased in OCPD male patients OCPD and depression noted a relationship between obsessive-compul-
compared with controls. As stated previously, physical/sexual abuse sive traits and a genetic variation in the dopamine D3 receptor in
and emotional abuse/neglect have been shown to be associated with patients with major depressive disorder (Light et al., 2006). Thus,
elevated symptoms of all three personality disorder clusters, including OCPD might be associated with depression.
OCPD (Tyrka et al., 2009). Another study reported that physical and Regarding the DACS, OCPD female patients scored significantly
emotional abuse were more likely to manifest subclinical symptoms of higher in future denial than HCs, and OCPD male patients scored
paranoid, narcissistic, borderline, antisocial, OCPD, passive-aggressive, significantly higher in threat prediction than HCs. Dysfunctional beliefs
and depressive personality disorders (Grover et al., 2007). A significant in OCD patients and disquiet are thought to give rise to vulnerability
relationship was noted between obsessive-compulsive symptoms and and the maintenance of pathological anxiety (Calleo et al., 2010).
childhood trauma, specifically emotional abuse and physical neglect, all Overestimation of threat/responsibility and intolerance of uncertainty
of which were due to co-occurring anxiety symptoms (Mathews et al., were significantly correlated with obsession and worry severity. The
2008). These results suggest that child trauma is likely associated with compulsive style is susceptible to dysfunctional cognition (Blasczyk-
OCPD. Schiep et al., 2016). There is a relationship between obsessive–

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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M. Kanehisa et al. Journal of Affective Disorders 217 (2017) 1–7

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.

Table 5 shown that the sAA and salivary cortisol levels can differ according to
The multiple regression analysis of OCPD. the length of time that a participant spends in the hospital (Balodis
et al., 2010). Lastly, our findings cannot be generalized to other ethnic
β Significance
groups. Thus, it will be necessary to conduct further studies in larger
STAI and more diverse populations to confirm the reproducibility of our
Trait Anxiety −0.227 0.036 data.
In conclusion, our findings suggested that attenuated sympathetic
Post-POMS
and parasympathetic reactivity in male OCPD patients occurs with
Depression-Dejection 0.221 0.063
attenuated sAA and cortisol responses to the TSST. Additionally, there
Salivary Cortisol were significant differences between the OCPD patients and HCs in
20 min 0.222 0.065 child trauma, mood, anxiety, and cognition. The finding support the
R2 < 0.00001
modeling role of cortisol (20 min) on the relationships between STAI
OCPD=Obsessive-compulsive personality disorder, STAI=State-Trait Anxiety Inventory;
trait and depression among OCPD.
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
Fig. 3. Structural model results. ns=not significant; ***p < 0.001.
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
compulsive symptom dimensions and the specific obsessive–compul- susceptible to dysfunctional cognitions about eating and body image? The
moderating role of personality styles. Eat. Weight Disord. 21, 211–220.
sive cognitions (Brakoulias et al., 2014). The symmetry/ordering
Bosc, M., Dubini, A., Polin, V., 1997. Development and validation of a social functioning
symptom dimension was associated with increased perfectionism/ scale, the social adaptation self-evaluation scale. Eur. Neuropsychopharmacol. 7
intolerance of uncertainty, the unacceptable/taboo thoughts symptom (Suppl. 1), S57–S70.
dimension with increased importance/control of thoughts, and the Brakoulias, V., Starcevic, V., Berle, D., Milicevic, D., Hannan, A., Martin, A., 2014. The
relationships between obsessive-compulsive symptom dimensions and cognitions in
doubt/checking symptom dimension with increased responsibility/ obsessive-compulsive disorder. Psychiatr. Q. 85, 133–142.
threat estimation. OCPD may bias towards automatic thoughts. Calleo, J.S., Hart, J., Björgvinsson, T., Stanley, M.A., 2010. Obsessions and worry beliefs
Several limitations associated with the present study warrant 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
mention. First, the small population of participants with OCPD personality disorder in Great Britain. Br. J. Psychiatry 188, 423–431.
prevented us from drawing definite conclusions, meaning that further Cullen, B., Samuels, J.F., Pinto, A., Fyer, A.J., McCracken, J.T., Rauch, S.L., Murphy,
investigation with a large cohort are warranted. Second, we conducted 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,
a limited number of hormonal examinations. Third, we used the time K.Y., Hoehn-Saric, R., Nestadt, G., 2008. Demographic and clinical characteristics
period immediately preceding the stressor as a baseline. It has been associated with treatment status in family members with obsessive-compulsive

6
M. Kanehisa et al. Journal of Affective Disorders 217 (2017) 1–7

disorder. Depress. Anxiety 25, 218–224. yohimbine hydrochloride facilitate fear extinction in virtual reality treatment of fear
Diedrich, A., Sckopke, P., Schwartz, C., Schlegl, S., Osen, B., Stierle, C., Voderholzer, U., of flying? A randomized placebo-controlled trial. Psychother. Psychosom. 81, 29–37.
2016. Change in obsessive beliefs as predictor and mediator of symptom change Miguel, E.C., Ferrão, Y.A., Rosário, M.C., Mathis, M.A., Torres, A.R., Fontenelle, L.F.,
during treatment of obsessive-compulsive disorder – a process-outcome study. BMC Hounie, A.G., Shavitt, R.G., Cordioli, A.V., Gonzalez, C.H., Petribú, K., Diniz, J.B.,
Psychiatry 16, 220. Malavazzi, D.M., Torresan, R.C., Raffin, A.L., Meyer, E., Braga, D.T., Borcato, S.,
First, M.B., Gibbon, M., Spitzer, R.L., Williams, J.B.W., Benjamin, L.S., 1997. Structured Valério, C., Gropo, L.N., Prado Had, S., Perin, E.A., Santos, S.I., Copque, H., Borges,
Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). American M.C., Lopes, A.P., Silva, E.D., 2008. The Brazilian Research Consortium on
Psychiatric Press, Washington, DC. obsessive-compulsive spectrum disorders: recruitment, assessment instruments,
Fukui, I., 1998. Development of depression and anxiety cognition scale – toward the methods for the development of multicenter collaborative studies and preliminary
construction of a cognitive-behavioral model of depression and anxiety. Jpn. J. results. Rev. Bras. Psiquiatr. 30, 185–196.
Behav. Ther. 24, 57–70. Pinto, A., Liebowitz, M.R., Foa, E.B., Simpson, H.B., 2011. Obsessive compulsive
Garyfallos, G., Katsigiannopoulos, K., Adamopoulou, A., Papazisis, G., Karastergious, A., personality disorder as a predictor of exposure and ritual prevention outcome for
Bozikas, V., 2010. Comorbidity of obsessive– compulsive disorder with obsessive– obsessive compulsive disorder. Behav. Res. Ther. 49, 453–458.
compulsive personality disorder: does it imply a specific subtype of obsessive– Raiskila, T., Sequeiros, S.B., Kiuttu, J., Kauhanen, M.L., Läksy, K., Rissanen, P.,
compulsive disorder? Psychiatry Res. 177, 156–160. Vainiemi, K., Tuulio-Henriksson, A., Veijola, J., Joukamaa, M., 2013. Obsessive-
Goldstein, D.S., Bentho, O., Park, M.Y., Sharabi, Y., 2011. Low-frequency power of heart compulsive personality disorder is common among occupational health care clients
rate variability is not a measure of cardiac sympathetic tone but may be a measure of with depression. J. Occup. Environ. Med. 55, 168–171.
modulation of cardiac autonomic outflows by baroreflexes. Exp. Physiol. 96, Renner, F., van Goor, M., Huibers, M., Arntz, A., Butz, B., Bernstein, D., 2013. Short-
1255–1261. term group schema cognitive-behavioral therapy for young adults with personality
Gordon, O.M., Salkovskis, P.M., Oldfield, V.B., Carter, N., 2013. The association between disorders and personality disorder features: associations with changes in
obsessive compulsive disorder and obsessive compulsive personality disorder: symptomatic distress, schemas, schema modes and coping styles. Behav. Res. Ther.
prevalence and clinical presentation. Br. J. Clin. Psychol. 52, 300–315. 51, 487–492.
Grant, J.E., Mooney, M.E., Kushner, M.G., 2012. Prevalence, correlates, and comorbidity Ritchie, K., Artero, S., Beluche, I., Ancelin, M.L., Mann, A., Dupuy, A.M., Malafosse, A.,
of DMS-IV obsessive-compulsive personality disorder: results from the National Boulenger, J.P., 2004. Prevalence of DSM-IV psychiatric disorder in the French
Epidemiologic Survey on Alcohol and Related Conditions. J. Psychiatr. Res. 46, elderly population. Br. J. Psychiatry 184, 147–152.
469–475. Robles, T.F., Shetty, V., Zigler, C.M., Glover, D.A., Elashoff, D., Murphy, D., Yamaguchi,
Grover, K.E., Carpenter, L.L., Price, L.H., Gagne, G.G., Mello, A.F., Mello, M.F., Tyrka, M., 2011. The feasibility of ambulatory biosensor measurement of salivary alpha
A.R., 2007. The relationship between childhood abuse and adult personality disorder amylase: relationships with self-reported and naturalistic psychological stress. Biol.
symptoms. J. Pers. Disord. 21, 442–447. Psychol. 86, 50–56.
Inoue, A., Oshita, H., Maruyama, Y., Tanaka, Y., Ishitobi, Y., Kawano, A., Ikeda, R., Ando, Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E.,
T., Aizawa, S., Masuda, K., Higuma, H., Kanehisa, M., Ninomiya, T., Akiyoshi, J., Hergueta, T., Baker, R., Dunbar, G.C., 1998. The mini-international neuropsychiatric
2015. Gender determines cortisol and alpha-amylase responses to acute physical and interview (M.I.N.I.): the development and validation of a structured diagnostic
psychosocial stress in patients with borderline personality disorder. Psychiatry Res. psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59 (Suppl. 20),
228, 46–52. 22–33.
Ishitobi, Y., Inoue, A., Aizawa, S., Masuda, K., Ando, T., Kawano, A., Ikeda, R., Skapinakis, P., Caldwell, D.M., Hollingworth, W., Bryden, P., Fineberg, N.A., Salkovskis,
Maruyama, Y., Kanehisa, M., Ninomiya, T., Tanaka, Y., Tsuru, J., Akiyoshi, J., 2014. P., Welton, N.J., Baxter, H., Kessler, D., Churchill, R., Lewis, G., 2016.
Association of microcephalin 1, syntrophin-beta 1, and other genes with automatic Pharmacological and psychotherapeutic interventions for management of obsessive-
thoughts in the Japanese population. Am. J. Med. Genet. B Neuropsychiatr. Genet. compulsive disorder in adults: a systematic review and network meta-analysis.
165B, 492–501. Lancet Psychiatry 3, 730–739.
Ishitobi, Y., Akiyoshi, J., Tanaka, Y., Ando, T., Okamoto, S., Kanehisa, M., Kohno, K., Spielberger, C.D., Edwards, C.D., Montuori, J., Lushene, R.E., Platzek, D., 1973. State-
Ninomiya, T., Maruyama, Y., Tsuru, J., Kawano, A., Hanada, H., Isogawa, K., Trait Anxiety Inventory for Children. Mind Garden Inc..
Kodama, K., 2010. Elevated salivary α-amylase and cortisol levels in unremitted and Tanaka, Y., Ishitobi, Y., Inoue, A., Oshita, H., Okamoto, K., Kawashima, C., Nakanishi,
remitted depressed patients. Int. J. Psychiatry Clin. Pract. 14, 268–273. M., Aizawa, S., Masuda, K., Maruyama, Y., Higuma, H., Kanehisa, M., Ninomiya, T.,
Johansen, P.Ø., Krebs, T.S., Svartberg, M., Stiles, T.C., Holen, A., 2011. Change in Akiyoshi, J., 2016. Sex determines cortisol and alpha-amylase responses to acute
defense mechanisms during short-term dynamic and cognitive therapy in patients physical and psychosocial stress in patients with avoidant personality disorder. Brain
with cluster C personality disorders. J. Nerv. Ment. Dis. 199, 712–715. Behav. 6, e00506.
Kawano, A., Tanaka, Y., Ishitobi, Y., Maruyama, Y., Ando, T., Inoue, A., Okamoto, S., Tamura, A., Maruyama, Y., Ishitobi, Y., Kawano, A., Ando, T., Ikeda, R., Inoue, A.,
Imanaga, J., Kanehisa, M., Higuma, H., Ninomiya, T., Tsuru, J., Akiyoshi, J., 2013. Imanaga, J., Okamoto, S., Kanehisa, M., Ninomiya, T., Tanaka, Y., Tsuru, J.,
Salivary alpha-amylase and cortisol responsiveness following electrical stimulation Akiyoshi, J., 2013. Salivary alpha-amylase and cortisol responsiveness following
stress in obsessive-compulsive disorder patients. Psychiatry Res. 209, 85–90. electrical stimulation stress in patients with the generalized type of social anxiety
Kirschbaum, C., Pirke, K.M., Hellhammer, D.H., 1993. The ‘Trier Social Stress Test’ – a disorder. Pharmacopsychiatry 46, 225–260.
tool for investigating psychobiological stress responses in a laboratory setting. Tanaka, Y., Ishitobi, Y., Maruyama, Y., Kawano, A., Ando, T., Okamoto, S., Kanehisa, M.,
Neuropsychobiology 28, 76–81. Higuma, H., Ninomiya, T., Tsuru, J., Hanada, H., Kodama, K., Isogawa, K., Akiyoshi,
Light, K.J., Joyce, P.R., Luty, S.E., Mulder, R.T., Frampton, C.M., Joyce, L.R., 2006. J., 2012a. Salivary alpha-amylase and cortisol responsiveness following electrical
Preliminary evidence for an association between a dopamine D3 receptor gene stimulation stress in major depressive disorder patients. Prog.
variant and obsessive-compulsive personality disorder in patients with major Neuropsychopharmacol. Biol. Psychiatry 36, 220–224.
depression. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 409–413. Tanaka, Y., Ishitobi, Y., Maruyama, Y., Kawano, A., Ando, T., Imanaga, J., Okamoto, S.,
Lochner, C., Serebro, P., van der Merwe, L., Hemmings, S., Kinnear, C., Seedat, S., Stein, Kanehisa, M., Higuma, H., Ninomiya, T., Tsuru, J., Hanada, H., Isogawa, K.,
D.J., 2011. Comorbid obsessive–compulsive personality disorder in obsessive– Akiyoshi, J., 2012b. Salivary α-amylase and cortisol responsiveness following
compulsive disorder (OCD): a marker of severity. Prog. Neuropsychopharmacol. electrical stimulation stress in panic disorder patients. Neurosci. Res. 73, 80–84.
Biol. Psychiatry 35, 1087–1092. Tanaka, Y., Maruyama, Y., Ishitobi, Y., Kawano, A., Ando, T., Ikeda, R., Inoue, A.,
Maruyama, Y., Kawano, A., Okamoto, S., Ando, T., Ishitobi, Y., Tanaka, Y., Inoue, A., Imanaga, J., Okamoto, S., Kanehisa, M., Ninomiya, T., Tsuru, J., Akiyoshi, J., 2013.
Imanaga, J., Kanehisa, M., Higuma, H., Ninomiya, T., Tsuru, J., Hanada, H., Salivary alpha-amylase and cortisol responsiveness following electrically stimulated
Akiyoshi, J., 2012. Differences in salivary alpha-amylase and cortisol responsiveness physical stress in bipolar disorder patients. Neuropsychiatr. Dis. Treat. 8,
following exposure to electrical stimulation versus the Trier Social Stress Tests. PLoS 1899–1905.
One 7, e39375. Tyrka, A.R., Wyche, M.C., Kelly, M.M., Price, L.H., Carpenter, L.L., 2009. Childhood
Mathews, C.A., Kaur, N., Stein, M.B., 2008. Childhood trauma and obsessive-compulsive maltreatment and adult personality disorder symptoms: influence of maltreatment
symptoms. Depress. Anxiety 25, 742–751. type. Psychiatry Res. 165, 281–287.
McNair, D.M., Lorr, M., Droppleman, L.F., 1992. POMS manual: Profile of Mood States. Yamano, E., Ishii, A., Tanaka, M., Nomura, S., Watanabe, Y., 2015. Neural basis of
Multi-Health Systems Inc., San Diego, CA. individual differences in the response to mental stress: a magnetoencephalography
Meyerbroeker, K., Powers, M.B., van Stegeren, A., Emmelkamp, P.M., 2012. Does study. Brain Imaging Behav., (Epub ahead of print).

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