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Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder
Journal of Clinical Neuroscience xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Neuroanatomical study
Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder Murad Atmaca a,⇑, Tuba Korucu a, M. Caglar Kilic b, Asli Kazgan a, Hanefi Yildirim b a b
Firat University, School of Medicine, Department of Psychiatry, Elazig, Turkey Firat University, School of Medicine, Department of Radiology, Elazig, Turkey
a r t i c l e
i n f o
Article history: Received 6 May 2019 Accepted 8 July 2019 Available online xxxx Keywords: OCPD Personality disorder Pineal gland Volumes MRI
a b s t r a c t Objective: In the present study, taking into consideration our previous studies showing an association on the neuroanatomy of OCD and obsessive-compulsive personality disorders (OCPD), we also decided to examine pineal gland volumes in patients with obsessive-compulsive personality disorder and hypothesized that gland volumes would be found as altered in comparison with those of healthy subjects. Methods: Sixteen patients with OCPD and eighteen healthy control subjects underwent magnetic resonance imaging (MRI). We compared the volumes of pineal gland by using MRI between groups. Results: As compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs. 108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01.When controlling for gender distribution, age and whole brain volumes in the General Linear Model, we saw that patients with OCPD had still statistically significant smaller pineal volumes compared to those of healthy control subjects. Conclusion: Finally, the findings of the present study revealed that patients with OCPD had reduced pineal gland volumes compared to those of healthy control subjects, supporting the fact that OCPD might be included in the OCD spectrum disorders, since we have previously found same result in patients with OCPD. Ó 2019 Published by Elsevier Ltd.
1. Introduction In the general context, personality disorder describes a severe disturbance in characterological constitution and behavioral tendencies, usually comprising several areas of the personality and leading to considerable personal and social problem. On the other hand, the main clinical features of the personality disorders are resistant, pervasive, and inflexible patterns of inner experience and behaviors that detach from cultural norms and cause to distress or impairment. As a classical knowledge, the features of personality disorders appear in late childhood or adolescence and last in a stable manner in the period of adulthood life. Obsessivecompulsive personality disorder (OCPD) has been classified under the section of personality disorders in the DSM-IV [1] and DSM-5 [2]. However, it has been called as anankastic personality disorder in the ICD-10 classification, organized by the World Health Organization [3]. It is essentially characterized by perfectionism, preoccu⇑ Corresponding author at: Firat (Euphrates) Universitesi, Firat Tip Merkezi, Psikiyatri Anabilim Dali, 23119 Elazig, Turkey. Fax: +90 424 238 8096. E-mail address: [email protected] (M. Atmaca).
pation with orderliness, and mental and interpersonal control, at the expense of flexibility, openness, and efficiency. OCPD has been classified under C Cluster Personality Disorders in last version of DSM, DSM 5. Nestadt et al. [4] reported that OCPD had a prevalence rate of 1–2% in general population. In the personality disorders, to account for psychosocial etiology, psychodynamic and psychosocial explanations have been established [5]. However, our knowledge on pathophysiology of personality disorders has been remained limited. In this context, the pathophysiology of the OCPD has not been well-known. In fact, our knowledge on the occurrence of personality disorders is limited to psychoanalytical approaches. Nevertheless, we have so limited knowledge on neurobiological dimensions of personality disorders including the OCPD. On the other hand, as can be expected, there has not been structural and functional neuroimaging study directly associated with the OCPD. Recently, in a paper, it has been reviewed the relationship between OCPD and OCD, and related disorders, in terms of heritability, environmental risk factors, phenomenology, comorbidity, course of illness, and treatment response and have been reported that it would be to include OCPD within both the personality disorder and Obsessive–Compulsive
https://doi.org/10.1016/j.jocn.2019.07.047 0967-5868/Ó 2019 Published by Elsevier Ltd.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
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M. Atmaca et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
and Related Disorders categories, under a dual parenting status [6]. Our previous studies on the nuroanatomy of OCPD provided an other support for the association of OCPD and Obsessive–Compulsive and Relared Disorders categories. In an unpublished study [7], our study team examined orbito-frontal cortex (OFC) and thalamus volumes in patients with OCPD and found that patients with OCPD had considerably smaller left and right OFC volumes compared to those of healthy control subjects and that thalamus volumes of patients were statistically significantly greater than those of healthy comparisons for both sides of region of interest. In addition, we have aimed to examine the pituitary gland volumes in same group of patients with OCPD and healthy control subjects and to reveal whether similar neuroanatomical changes would exist in patients with obsessive-compulsive disorder (OCD) and have found that patients with OCPD had statistically significantly smaller pituitary gland volumes compared to those of healthy control subjects (0.52 ± 0.13 cm3 for patient group vs. 0.65 ± 0.17 cm3 for the healthy control group; t = 2.44; p = 0.020). These studies supported that OCPD might have similar neuroanatomical alterations seen in OCD. The pineal gland is a small, pinecone-like neuroendocrine organ of the brain which modulates circadian rhythm and sleep by the secretion of melatonin in a circadian manner [8]. It has been well established that melatonin releasing cycle is regulated by an endogenous circadian master clock in the suprachiasmatic nucleus of the hypothalamus, and is secreted according to the twenty four hour cycle of light and darkness [9]. Functions of pineal gland in terms of changed secretion of melatonin, and altered diurnal or nocturnal peaks has been evaluated in patients with schizophrenia, bipolar disorder and majör depressive disorder [10–16].In recent years, examination of circadian rhythms and neurosteroid imbalance have been taken attention in the investigation of OCD [17,18]. In addition, it was reported that there were delayed slow wave sleep phase and increased nocturnal secretion of adrenocorticotropic hormone (ACTH) and cortisol, a melatonin-related stress hormone [19]. Catapano and Monteleone evaluated the secretion of melatonin and cortisol over twenty four hours in OCD patients, compared with healthy control subjects [20,21]. Patients with OCD might exhibit hypervigilance and some problems falling asleep [20–22].On the other hand, biomarkers of circadian rhythms have been reported in patients with OCD. OCD may show hypervigilance and some problems falling asleep [20–23]. Patients with OCDcan have an hyperactivity of the hypothalamo-pituitary-adrenal axis and can show an increased secretion of adreno-corticotropic hormone and cortisol and a reduced secretion of melatonin. This led us to motivate the examination of pineal gland volumes in patients with OCDand thought that those volumes would be changed compared to healthy control comparisons [7]. We determined that the mean pineal volume of patient group was 84.65 ± 35.30 mm3 whereas that of healthy comparison subjects was 111.54 ± 18.99 mm3, with a statistically significantly difference of p < 0.01. In the present study, taking into consideration our previous studies showing an association on the neuroanatomy of OCD and obsessive-compulsive personality disorders, we also decided to examine pineal gland volumes in patients with obsessive-compulsive personality disorder and hypothesized that gland volumes would be found as altered in comparison with those of healthy subjects.
2. Methods 2.1. Subjects Study group was composed of patients who were obsessivecompulsive personality disorder according to the DSM-IV-TR [24]
from the in-patient and out-patient clinics of the Firat University School of Medicine Department of Psychiatry, with the age range of 18–65 years old. The patients investigated in the present study were those of our previous unpublished studies which were performed on same patient group. We realized all study procedures in accordance with the guidelines of Helsinki Declaration. Of course, in addition to this procedure, before starting the investigation, we took the written informed consents from all patients and healthy control subjects to include in the study after obtaining approval from the Local Ethics Committee at the Firat University School of Medicine. All subjects gave the written informed consent to include into the study. Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Version (DSMIV-TR) were performed by using the Turkish version of Structured Clinical Interview for DSM-IV (SCID) [25]. As mentioned in unpublished studies, all patients including in the study were righthanded. The interviews with patients and their first degree relatives were done in separate places and diagnoses were obtained by combining information across both interviews. A group of healthy controls were matched on age, sex, education and handedness. To exclude patients from the study, some exclusion criteria needed. As can be seen in our previous neuroimaging studies on various psychiatric disorders, exclusion criteria included the presence of any current or history of comorbid psychiatric disorder, the existence of current severe medical problems, existence of any congenital malformation in the brain, alcohol/substance abuse within the 6 months preceding the study, any contraindication for suffering from MRI investigation such as cardiac stent, and use of psychoactive medication within four weeks of the study. Healthy control subjects were chosen among well-being people who had been taken from the hospital staff and had been invited to suffer from their magnetic resonance imagings of brains for our study. For healthy subjects, exclusion criteria were: (i) existence of any current or history of psychiatric disorder in self and in their first-degree relatives, (ii) the presence of current medical problems, (iii) alcohol/substance abuse within the 6 months preceding the study, and (iv) any contrendication for suffering from MRI investigation such as cardiac stent. 2.2. Procedure Brain images of pineal gland of patients with OCPD and healthy control subjects were obtained by utilizing a Signa 1.5 Tesla MRI scanner (General Electric Medical Systems, Milwaukee, WI, USA) in a manner of high-resolution T1-weighted spoiled gradient recalled acquisitionsequence. Imagings were taken under following parameters: Flip angle = 20°, slice thickness = 2.4 mm, bandwidth = 20.8, echo spacing = 15.6 ms, Field of view [FOV] = 240 mm, echo time [TE] = 15.6 ms, repetition time [TR] = 2000 msf, 8 echoes, resolution = 0.9375 0.9375 2.4 mm). The GE Volume Viewer voxtool 4.6 64q program, a semi-automated one, was used to measure the region which was traced. Manual tracing procedures were performed by a neuroradiologist researcher (HY) who were blind to diagnosis of subjects, and also verified by a second (CK) blinded one. Boundaries of the pineal gland were determined by using standard brain anatomy atlases [25–28] and were adapted from Sumida et al. [28] and Findikli et al. [29]. For the determination of the axial cuts, superior colliculus, the quadrigeminal cisterna, and the posterior portion of the third ventricle were used as guides. The pineal boundary was determined exactly on the sagittal sections taken in addition to the coronal and axial views. The maximum height (H) and width (W) of the pineal gland were measured on the medial coronal images and the length (L) was measured on the axial images. All images obtained were transferred to Voxtool 4.6 semi-automated program aforementioned to obtain volumetric results.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
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Example scanning of the pineal gland is presented in Fig. 1. On the other hand, the interrater reliability (intraclass correlation coefficient) was calculated as 0.90 (r = 0.90). 2.3. Statistical analysis The Statistical Package for Social Sciences (SPSS for Windows, version 16.0, SPSS, Chicago, IL, USA) was used to obtain statistical results. We used Student’s t test to compare the mean age and volumetric differences of patients with OCPD and healthy control comparisons. Chi-square test was done to assess the gender distribution between groups. On the other hand, for volumetric comparisons, the General Linear Model under the covariates of age, gender, and total brain volume was also utilized. In addition, the Spearman’s correlation test was used to detect correlations between pineal gland volumes and various demographic and clinical parameters.
Table 1 Clinical and demographic characteristics of the groups. Item Age (years) Gender (Female/Male) Education High school High school Elementary school First school Handedness (right) Length of illness (years) Hamilton Depression Rating Score
Control group (n = 18)
p
32.5 ± 8.9 11/5
29.5 ± 5.1 10/8
>0.05 >0.05 >0.05
9 3 4 16 6.4 ± 4.1 9.8 ± 2.2
15 3 18 – 3.3 ± 1.7
>0.05 <0.01
Table 2 The volumes of the structures evaluated in patients with OCPD versus controls subjects (Mean ± Standard Error).
3. Results Data for demographic variables are presented in Table 1. We did not detect any considerable differences patients with OCPD and healthy control comparisons (p > 0.05). In addition, we did not detect any difference with regard to whole brain, gray and white matter volumes between patients with OCPD and healthy control subjects (p > 0.05) (see Table 2).
OCPD Group (n = 16)
Healthy Control Group (n = 18)
p
87.34 ± 19.72
108.62 ± 22.56
<0.01
Pineal Volumes Volumes presented are in mm3.
Fig. 1. Anatomic landmarks for the tracing of the pineal gland.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
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As compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs.108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01. When controlling for gender distribution, age and whole brain volumes in the General Linear Model, we saw that patients with OCPD had still statistically significant smaller pineal volumes compared to those of healthy control subjects (p < 0.01, for gender distribution as covariate, p < 0.01, for age as covariate, p < 0.01, or for whole brain volume as covariate). When utilizing the Spearman’s correlation test, we seen that there were no correlational relationship between any socio-demographical and clinical variables and pineal gland volumes both in patients with OCPD and healthy control subjects (p > 0.05).
4. Discussion First of all, we should implicate that this one is the first study on pineal volumes of patients with OCPD. We hope that our findings presented here could provide a support for understanding of OCPD. In this context, at the beginning of the Discussion section, it will be good to emphasize the most important findings of the present study. As compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs. 108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01. When controlling for gender distribution, age and whole brain volumes in the General Linear Model, we saw that patients with OCPD had still statistically significantsmaller pineal volumes compared to those of healthy control subjects. Although OCPD is classified as a personality disorder in DSM classification, increasing evidence caused the fact that OCPD may be a neurocognitive function disorder rather than a personality disorder [30]. On the other hand, when compared to other personality disorders according to DSM 5, it is less associated with functional disability [31]. As mentioned in the Introduction section, it was reviewed the relationship between OCPD and OCD, and related disorders, with regard to phenomenology, comorbidity, heritability, environmental risk factors, course of illness, and treatment response and was reported that it would be to include OCPD within both the personality disorder and Obsessive–Compulsive and Relared Disorders categories, under a dual parenting status [6]. Our previous studies on the neuroanatomy of OCPD provided an other support for the association of OCPD and Obsessive–Compulsive and Relared Disorders categories. In association with this, our study team evaluated OFC and thalamus volumes of patients with OCPD and detected that patients with OCPD had smaller OFC and greater thalamus volumes compared to those of healthy control subjects [7], just like the findings found in OCD [32,33].That study led us to consider that OCPD might be associated with OCD with respect to the base of neuroanatomy, suggesting that OCPD may be related to OCD spectrum disorders. After this study, we examined pituitary gland volumes in patients with OCPD and found that patients with OCPD had significantly smaller pituitary gland volumes compared to those of healthy control subjects [7], just like the findings found in OCD [34]. This study was another support the notion that OCPD might be related to OCD spectrum disorders, also supporting that OCPD could be included in both the personality disorder and Obsessive–Compulsive and Relared Disorders categories, under a dual parenting status [6]. Finally, our study team also measured pineal gland volumes in patients with OCD and healthy control subjects and detected that pineal gland volumes of patients with OCD were statistically significant reduced compared to those of healthy control comparisons [7]. When taking into consideration that there were considerable
neuroanatomical relationships between OCPD and OCD, this association caused us to motivate the examination of pineal gland volumes in patients with OCPD and thought that those volumes would be changed compared to healthy control comparisons. In the present study, like the findings observed in OCD patients, when compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs. 108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01) and when checking for gender distribution, age and whole brain volumes in the General Linear Model, we observed that patients with OCPD had still statistically significantsmaller pineal volumes compared to those of healthy control subjects (p < 0.01, for gender distribution as covariate, p < 0.01, for age as covariate, p < 0.01, or for whole brain volume as covariate). Our these findings further support the notion that OCPD might be associated with OCD spectrum disorders in regard to neuroanatomy. Probably, it can be considered that OCPD may be included in the OCD and related disorders, at least as one of dual diagnosis, in addition to personality disorder. There are a number of methodological and clinical constraints of the present investigation. On the other hand, when the very preliminary nature of the results should be taken into consideration. Further controlled studies are warranted to reveal the role of pineal gland volume changes in patients with OCPD. First of all, sample size was so limited. But, when considering that OCPD has frequent comorbid situations, it is hard to perform a study on OCPD patients with strict comorbidity criteria. For this reason, this sample size can be accepted. Second, manual tracing method was used in the present study. Manual tracing has some advantages but also some disadvantages. This may be accepted as a limitation of the study. Third, we just detected the volumes of the pineal gland in patients with OCPD, and did not evaluate the measurements of associated hormonal changes such as melatonin values. This was another limitation of the study. Lastly, as mentioned by our previous investigation in OCD patients [34] and by Findikli et al. [29], when measuring it was not include pineal calcifications. This might have influenced on our findings. When commenting our results presented here, these limitations should be taken into account. Finally, the findings of the present study revealed thatpatients with OCPD had reduced pineal gland volumes compared to those of healthy control subjects, supporting the fact that OCPD might be included in the OCD spectrum disorders, since we have previously found same result in patients with OCPD [7]. Our present findings should be accepted as preliminary and novel studies with a larger sample are required. Acknowledgement This study was supported by FUBAP. Declaration of Competing Interest Authors declare that there is no conflict of interest. References [1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. (DSM-IV). Arlington: American Psychiatric Pub; 1994. [2] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5). American Psychiatric Pub; 2013. [3] World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization; 1992. [4] Nestadt G, Romanoski AJ, Brown CH, Chahal R, Merchant A, Folstein MF, et al. DSM-III compulsive personality disorder: an epidemiological survey. Psychol Med 1991;21(2):461–71.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
M. Atmaca et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx [5] Fineberg NA, Reghunandanan S, Kolli S, Atmaca M. Obsessive-compulsive (anankastic) personality disorder: toward the ICD-11 classification. Braz J Psych 2014;36:40–50. [6] Stein DJ, Kogan CS, Atmaca M, Fineberg NA, Fontenelle LF, Grant JE, et al. The classification of obsessive–compulsive and related disorders in the ICD-11. J Affect Disord 2016;190:663–74. [7] Atmaca M, Korucu T, Tabara MF, Yildirim H, Kılıc MC. Volumetric MRI study of orbito-frontal cortex and thalamus in obsessive-compulsive personality disorder. J Clin Neurosci 2019. https://doi.org/10.1016/j.jocn.2019.03.062. [8] Acer N, Turgut M, Yalcin SS, Duvernoy HM. Anatomy of the human pineal gland. In: Turgut M, Kumar R, editors. Pineal Gland and Melatonin: Recent Advances in Development, Imaging, Disease and Treatment. Nova Science; 2011. [9] Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, et al. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 2003;34(1):75–8. [10] Brown R, Kocsis JH, Caroff S, Amsterdam J, Winokur A, Stokes PE, et al. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. Am J Psych 1985;142:811–6. [11] Khaleghipour S, Masjedi M, Ahade H, Enayate M, Pasha G, Nadery F, et al. Morning and nocturnal serum melatonin rhythm levels in patients with major depressive disorder: an analytical cross-sectional study. Sao Paulo Med J 2012;130(3):167–72. [12] Rubin RT, Heist EK, McGeoy SS, Hanada K, Lesser IM. Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects. Arch Gen Psych 1992;49(7):558–67. [13] Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR, et al. Melatonin in mood disorders. World J Biol Psych 2006;7(3):138–51. [14] Whalley LJ, Perini T, Shering A, Bennie J. Melatonin response to bright light in recovered, drug-free, bipolar patients. Psych Res 1991;38(1):13–9. [15] Vigano D, Lissoni P, Rovelli F, Roselli MG, Malugani F, Gavazzeni C, et al. A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. Neuro Endocrinol Lett 2001;22(2):137–41. [16] Rao ML, Gross G, Strebel B, Halaris A, Huber G, Braunig P, et al. Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. Biol Psych 1994;35(3):151–63. [17] Zinder O, Dar DE. Neuroactive steroids: their mechanism of action and their function in the stress response. Acta Physiol Scand 1999;167(3):181–8. [18] Kartalci S, Esel E. Neurosteroids: psychopharmacological and behavioral effects. Bull Clin Psychopharm 2004;14:38–49. [19] Kluge M, Schüssler P, Künzel HE, Dresler M, Yassouridis A, Steiger A. Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder. J Psych Res 2006. Epub 2006 Oct 17.
5
[20] Catapano F, Monteleone P, Fuschino A, Maj M, Kemali D. Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Psych Res 1992;44(3):217–25. [21] Monteleone P, Catapano F, Del Buono G, Maj M. Circadian rhythms of melatonin, cortisol, and prolactin in patients with obsessive-compulsive disorder. Acta Psych Scand 1994;89(6):411–5. [22] Millet B, Touitou Y, Poirier MF, Bourdel MC, Hantouche E, Bogdan A, et al. Plasma melatonin and cortisol in patients with obsessive-compulsive disorder: relationship with axillary temperature, physical activity, and clinical symptoms. Biol Psych 1998;44(9):874–81. [23] Kluge M, Schüssler P, Künzel HE, Dresler M, Yassouridis A, Steiger A. Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder. J Psych Res 2007;41(11):928–33. [24] American Psychiatric Association. Text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000. [25] Jackson GD, Duncan JS. MRI neuroanatomy: a new angle on the brain. WB Saunders Company; 1996. [26] Patel VH, Friedman L. MRI of the brain: normal anatomy and normal variants. Saunders; 1997. [27] Yuh WTC. MRI of head & neck anatomy. New York: Churchill Livingstone; 1994. [28] Sumida M, Barkovich AJ, Newton TH. Development of the pineal gland: measurement with MR. AJNR Am J Neuroradiol 1996;17(2):233–6. [29] Findikli E, Inci MF, Gokce M, Findikli HA, Altun H, Karaaslan MF. Pineal gland volume in schizophrenia and mood disorders. Psych Danub 2015;27(2):153–8. [30] Fineberg NA, de Koenigswarter N, Reghunandanan S, Kolli S, Jefferies K, Laws K. The neurocognitive profile of obsessive compulsive personality disorder; a preliminary analysis. Barcelona Spain: Abstract for a poster ICOCS annual scientific meeting, 2013. [31] Skodol AE, Gunderson JG, McGlashan TH, Dyck IR, Stout RL, Bender DS, et al. Functional impairment in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder. Am J Psych 2002;159(2):276–83. [32] Atmaca M, Yildirim H, Ozdemir H, Aydin A, Tezcan E, Ozler S. Volumetric MRI assessment of brain regions in patients with refractory obsessive-compulsive disorder. Prog Neuropsychopharm Biol Psych 2006;30(6):1051–7. [33] Atmaca M, Yildirim H, Ozdemir H, Tezcan E, Poyraz AK. Volumetric MRI study of key brain regions implicated in obsessive–compulsive disorder. Prog Neuropsychopharm Biol Psych 2007;31(1):46–52. [34] Atmaca M, Yildirim H, Ozler S, Koc M, Kara B, Sec S. Smaller pituitary volume in adult patients with obsessive–compulsive disorder. Psych Clin Neurosc 2009;63(4):516–20.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Neuroanatomical study
Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder Murad Atmaca a,⇑, Tuba Korucu a, M. Caglar Kilic b, Asli Kazgan a, Hanefi Yildirim b a b
Firat University, School of Medicine, Department of Psychiatry, Elazig, Turkey Firat University, School of Medicine, Department of Radiology, Elazig, Turkey
a r t i c l e
i n f o
Article history: Received 6 May 2019 Accepted 8 July 2019 Available online xxxx Keywords: OCPD Personality disorder Pineal gland Volumes MRI
a b s t r a c t Objective: In the present study, taking into consideration our previous studies showing an association on the neuroanatomy of OCD and obsessive-compulsive personality disorders (OCPD), we also decided to examine pineal gland volumes in patients with obsessive-compulsive personality disorder and hypothesized that gland volumes would be found as altered in comparison with those of healthy subjects. Methods: Sixteen patients with OCPD and eighteen healthy control subjects underwent magnetic resonance imaging (MRI). We compared the volumes of pineal gland by using MRI between groups. Results: As compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs. 108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01.When controlling for gender distribution, age and whole brain volumes in the General Linear Model, we saw that patients with OCPD had still statistically significant smaller pineal volumes compared to those of healthy control subjects. Conclusion: Finally, the findings of the present study revealed that patients with OCPD had reduced pineal gland volumes compared to those of healthy control subjects, supporting the fact that OCPD might be included in the OCD spectrum disorders, since we have previously found same result in patients with OCPD. Ó 2019 Published by Elsevier Ltd.
1. Introduction In the general context, personality disorder describes a severe disturbance in characterological constitution and behavioral tendencies, usually comprising several areas of the personality and leading to considerable personal and social problem. On the other hand, the main clinical features of the personality disorders are resistant, pervasive, and inflexible patterns of inner experience and behaviors that detach from cultural norms and cause to distress or impairment. As a classical knowledge, the features of personality disorders appear in late childhood or adolescence and last in a stable manner in the period of adulthood life. Obsessivecompulsive personality disorder (OCPD) has been classified under the section of personality disorders in the DSM-IV [1] and DSM-5 [2]. However, it has been called as anankastic personality disorder in the ICD-10 classification, organized by the World Health Organization [3]. It is essentially characterized by perfectionism, preoccu⇑ Corresponding author at: Firat (Euphrates) Universitesi, Firat Tip Merkezi, Psikiyatri Anabilim Dali, 23119 Elazig, Turkey. Fax: +90 424 238 8096. E-mail address: [email protected] (M. Atmaca).
pation with orderliness, and mental and interpersonal control, at the expense of flexibility, openness, and efficiency. OCPD has been classified under C Cluster Personality Disorders in last version of DSM, DSM 5. Nestadt et al. [4] reported that OCPD had a prevalence rate of 1–2% in general population. In the personality disorders, to account for psychosocial etiology, psychodynamic and psychosocial explanations have been established [5]. However, our knowledge on pathophysiology of personality disorders has been remained limited. In this context, the pathophysiology of the OCPD has not been well-known. In fact, our knowledge on the occurrence of personality disorders is limited to psychoanalytical approaches. Nevertheless, we have so limited knowledge on neurobiological dimensions of personality disorders including the OCPD. On the other hand, as can be expected, there has not been structural and functional neuroimaging study directly associated with the OCPD. Recently, in a paper, it has been reviewed the relationship between OCPD and OCD, and related disorders, in terms of heritability, environmental risk factors, phenomenology, comorbidity, course of illness, and treatment response and have been reported that it would be to include OCPD within both the personality disorder and Obsessive–Compulsive
https://doi.org/10.1016/j.jocn.2019.07.047 0967-5868/Ó 2019 Published by Elsevier Ltd.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
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and Related Disorders categories, under a dual parenting status [6]. Our previous studies on the nuroanatomy of OCPD provided an other support for the association of OCPD and Obsessive–Compulsive and Relared Disorders categories. In an unpublished study [7], our study team examined orbito-frontal cortex (OFC) and thalamus volumes in patients with OCPD and found that patients with OCPD had considerably smaller left and right OFC volumes compared to those of healthy control subjects and that thalamus volumes of patients were statistically significantly greater than those of healthy comparisons for both sides of region of interest. In addition, we have aimed to examine the pituitary gland volumes in same group of patients with OCPD and healthy control subjects and to reveal whether similar neuroanatomical changes would exist in patients with obsessive-compulsive disorder (OCD) and have found that patients with OCPD had statistically significantly smaller pituitary gland volumes compared to those of healthy control subjects (0.52 ± 0.13 cm3 for patient group vs. 0.65 ± 0.17 cm3 for the healthy control group; t = 2.44; p = 0.020). These studies supported that OCPD might have similar neuroanatomical alterations seen in OCD. The pineal gland is a small, pinecone-like neuroendocrine organ of the brain which modulates circadian rhythm and sleep by the secretion of melatonin in a circadian manner [8]. It has been well established that melatonin releasing cycle is regulated by an endogenous circadian master clock in the suprachiasmatic nucleus of the hypothalamus, and is secreted according to the twenty four hour cycle of light and darkness [9]. Functions of pineal gland in terms of changed secretion of melatonin, and altered diurnal or nocturnal peaks has been evaluated in patients with schizophrenia, bipolar disorder and majör depressive disorder [10–16].In recent years, examination of circadian rhythms and neurosteroid imbalance have been taken attention in the investigation of OCD [17,18]. In addition, it was reported that there were delayed slow wave sleep phase and increased nocturnal secretion of adrenocorticotropic hormone (ACTH) and cortisol, a melatonin-related stress hormone [19]. Catapano and Monteleone evaluated the secretion of melatonin and cortisol over twenty four hours in OCD patients, compared with healthy control subjects [20,21]. Patients with OCD might exhibit hypervigilance and some problems falling asleep [20–22].On the other hand, biomarkers of circadian rhythms have been reported in patients with OCD. OCD may show hypervigilance and some problems falling asleep [20–23]. Patients with OCDcan have an hyperactivity of the hypothalamo-pituitary-adrenal axis and can show an increased secretion of adreno-corticotropic hormone and cortisol and a reduced secretion of melatonin. This led us to motivate the examination of pineal gland volumes in patients with OCDand thought that those volumes would be changed compared to healthy control comparisons [7]. We determined that the mean pineal volume of patient group was 84.65 ± 35.30 mm3 whereas that of healthy comparison subjects was 111.54 ± 18.99 mm3, with a statistically significantly difference of p < 0.01. In the present study, taking into consideration our previous studies showing an association on the neuroanatomy of OCD and obsessive-compulsive personality disorders, we also decided to examine pineal gland volumes in patients with obsessive-compulsive personality disorder and hypothesized that gland volumes would be found as altered in comparison with those of healthy subjects.
2. Methods 2.1. Subjects Study group was composed of patients who were obsessivecompulsive personality disorder according to the DSM-IV-TR [24]
from the in-patient and out-patient clinics of the Firat University School of Medicine Department of Psychiatry, with the age range of 18–65 years old. The patients investigated in the present study were those of our previous unpublished studies which were performed on same patient group. We realized all study procedures in accordance with the guidelines of Helsinki Declaration. Of course, in addition to this procedure, before starting the investigation, we took the written informed consents from all patients and healthy control subjects to include in the study after obtaining approval from the Local Ethics Committee at the Firat University School of Medicine. All subjects gave the written informed consent to include into the study. Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Version (DSMIV-TR) were performed by using the Turkish version of Structured Clinical Interview for DSM-IV (SCID) [25]. As mentioned in unpublished studies, all patients including in the study were righthanded. The interviews with patients and their first degree relatives were done in separate places and diagnoses were obtained by combining information across both interviews. A group of healthy controls were matched on age, sex, education and handedness. To exclude patients from the study, some exclusion criteria needed. As can be seen in our previous neuroimaging studies on various psychiatric disorders, exclusion criteria included the presence of any current or history of comorbid psychiatric disorder, the existence of current severe medical problems, existence of any congenital malformation in the brain, alcohol/substance abuse within the 6 months preceding the study, any contraindication for suffering from MRI investigation such as cardiac stent, and use of psychoactive medication within four weeks of the study. Healthy control subjects were chosen among well-being people who had been taken from the hospital staff and had been invited to suffer from their magnetic resonance imagings of brains for our study. For healthy subjects, exclusion criteria were: (i) existence of any current or history of psychiatric disorder in self and in their first-degree relatives, (ii) the presence of current medical problems, (iii) alcohol/substance abuse within the 6 months preceding the study, and (iv) any contrendication for suffering from MRI investigation such as cardiac stent. 2.2. Procedure Brain images of pineal gland of patients with OCPD and healthy control subjects were obtained by utilizing a Signa 1.5 Tesla MRI scanner (General Electric Medical Systems, Milwaukee, WI, USA) in a manner of high-resolution T1-weighted spoiled gradient recalled acquisitionsequence. Imagings were taken under following parameters: Flip angle = 20°, slice thickness = 2.4 mm, bandwidth = 20.8, echo spacing = 15.6 ms, Field of view [FOV] = 240 mm, echo time [TE] = 15.6 ms, repetition time [TR] = 2000 msf, 8 echoes, resolution = 0.9375 0.9375 2.4 mm). The GE Volume Viewer voxtool 4.6 64q program, a semi-automated one, was used to measure the region which was traced. Manual tracing procedures were performed by a neuroradiologist researcher (HY) who were blind to diagnosis of subjects, and also verified by a second (CK) blinded one. Boundaries of the pineal gland were determined by using standard brain anatomy atlases [25–28] and were adapted from Sumida et al. [28] and Findikli et al. [29]. For the determination of the axial cuts, superior colliculus, the quadrigeminal cisterna, and the posterior portion of the third ventricle were used as guides. The pineal boundary was determined exactly on the sagittal sections taken in addition to the coronal and axial views. The maximum height (H) and width (W) of the pineal gland were measured on the medial coronal images and the length (L) was measured on the axial images. All images obtained were transferred to Voxtool 4.6 semi-automated program aforementioned to obtain volumetric results.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
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Example scanning of the pineal gland is presented in Fig. 1. On the other hand, the interrater reliability (intraclass correlation coefficient) was calculated as 0.90 (r = 0.90). 2.3. Statistical analysis The Statistical Package for Social Sciences (SPSS for Windows, version 16.0, SPSS, Chicago, IL, USA) was used to obtain statistical results. We used Student’s t test to compare the mean age and volumetric differences of patients with OCPD and healthy control comparisons. Chi-square test was done to assess the gender distribution between groups. On the other hand, for volumetric comparisons, the General Linear Model under the covariates of age, gender, and total brain volume was also utilized. In addition, the Spearman’s correlation test was used to detect correlations between pineal gland volumes and various demographic and clinical parameters.
Table 1 Clinical and demographic characteristics of the groups. Item Age (years) Gender (Female/Male) Education High school High school Elementary school First school Handedness (right) Length of illness (years) Hamilton Depression Rating Score
Control group (n = 18)
p
32.5 ± 8.9 11/5
29.5 ± 5.1 10/8
>0.05 >0.05 >0.05
9 3 4 16 6.4 ± 4.1 9.8 ± 2.2
15 3 18 – 3.3 ± 1.7
>0.05 <0.01
Table 2 The volumes of the structures evaluated in patients with OCPD versus controls subjects (Mean ± Standard Error).
3. Results Data for demographic variables are presented in Table 1. We did not detect any considerable differences patients with OCPD and healthy control comparisons (p > 0.05). In addition, we did not detect any difference with regard to whole brain, gray and white matter volumes between patients with OCPD and healthy control subjects (p > 0.05) (see Table 2).
OCPD Group (n = 16)
Healthy Control Group (n = 18)
p
87.34 ± 19.72
108.62 ± 22.56
<0.01
Pineal Volumes Volumes presented are in mm3.
Fig. 1. Anatomic landmarks for the tracing of the pineal gland.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
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As compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs.108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01. When controlling for gender distribution, age and whole brain volumes in the General Linear Model, we saw that patients with OCPD had still statistically significant smaller pineal volumes compared to those of healthy control subjects (p < 0.01, for gender distribution as covariate, p < 0.01, for age as covariate, p < 0.01, or for whole brain volume as covariate). When utilizing the Spearman’s correlation test, we seen that there were no correlational relationship between any socio-demographical and clinical variables and pineal gland volumes both in patients with OCPD and healthy control subjects (p > 0.05).
4. Discussion First of all, we should implicate that this one is the first study on pineal volumes of patients with OCPD. We hope that our findings presented here could provide a support for understanding of OCPD. In this context, at the beginning of the Discussion section, it will be good to emphasize the most important findings of the present study. As compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs. 108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01. When controlling for gender distribution, age and whole brain volumes in the General Linear Model, we saw that patients with OCPD had still statistically significantsmaller pineal volumes compared to those of healthy control subjects. Although OCPD is classified as a personality disorder in DSM classification, increasing evidence caused the fact that OCPD may be a neurocognitive function disorder rather than a personality disorder [30]. On the other hand, when compared to other personality disorders according to DSM 5, it is less associated with functional disability [31]. As mentioned in the Introduction section, it was reviewed the relationship between OCPD and OCD, and related disorders, with regard to phenomenology, comorbidity, heritability, environmental risk factors, course of illness, and treatment response and was reported that it would be to include OCPD within both the personality disorder and Obsessive–Compulsive and Relared Disorders categories, under a dual parenting status [6]. Our previous studies on the neuroanatomy of OCPD provided an other support for the association of OCPD and Obsessive–Compulsive and Relared Disorders categories. In association with this, our study team evaluated OFC and thalamus volumes of patients with OCPD and detected that patients with OCPD had smaller OFC and greater thalamus volumes compared to those of healthy control subjects [7], just like the findings found in OCD [32,33].That study led us to consider that OCPD might be associated with OCD with respect to the base of neuroanatomy, suggesting that OCPD may be related to OCD spectrum disorders. After this study, we examined pituitary gland volumes in patients with OCPD and found that patients with OCPD had significantly smaller pituitary gland volumes compared to those of healthy control subjects [7], just like the findings found in OCD [34]. This study was another support the notion that OCPD might be related to OCD spectrum disorders, also supporting that OCPD could be included in both the personality disorder and Obsessive–Compulsive and Relared Disorders categories, under a dual parenting status [6]. Finally, our study team also measured pineal gland volumes in patients with OCD and healthy control subjects and detected that pineal gland volumes of patients with OCD were statistically significant reduced compared to those of healthy control comparisons [7]. When taking into consideration that there were considerable
neuroanatomical relationships between OCPD and OCD, this association caused us to motivate the examination of pineal gland volumes in patients with OCPD and thought that those volumes would be changed compared to healthy control comparisons. In the present study, like the findings observed in OCD patients, when compared to healthy control subjects, patients with OCPD had statistically significant smaller pineal gland volumes by using independent sample t test (87.34 ± 19.72 mm3 for patients with OCPD vs. 108.62 ± 22.56 mm3, with a statistically significantly difference of p < 0.01) and when checking for gender distribution, age and whole brain volumes in the General Linear Model, we observed that patients with OCPD had still statistically significantsmaller pineal volumes compared to those of healthy control subjects (p < 0.01, for gender distribution as covariate, p < 0.01, for age as covariate, p < 0.01, or for whole brain volume as covariate). Our these findings further support the notion that OCPD might be associated with OCD spectrum disorders in regard to neuroanatomy. Probably, it can be considered that OCPD may be included in the OCD and related disorders, at least as one of dual diagnosis, in addition to personality disorder. There are a number of methodological and clinical constraints of the present investigation. On the other hand, when the very preliminary nature of the results should be taken into consideration. Further controlled studies are warranted to reveal the role of pineal gland volume changes in patients with OCPD. First of all, sample size was so limited. But, when considering that OCPD has frequent comorbid situations, it is hard to perform a study on OCPD patients with strict comorbidity criteria. For this reason, this sample size can be accepted. Second, manual tracing method was used in the present study. Manual tracing has some advantages but also some disadvantages. This may be accepted as a limitation of the study. Third, we just detected the volumes of the pineal gland in patients with OCPD, and did not evaluate the measurements of associated hormonal changes such as melatonin values. This was another limitation of the study. Lastly, as mentioned by our previous investigation in OCD patients [34] and by Findikli et al. [29], when measuring it was not include pineal calcifications. This might have influenced on our findings. When commenting our results presented here, these limitations should be taken into account. Finally, the findings of the present study revealed thatpatients with OCPD had reduced pineal gland volumes compared to those of healthy control subjects, supporting the fact that OCPD might be included in the OCD spectrum disorders, since we have previously found same result in patients with OCPD [7]. Our present findings should be accepted as preliminary and novel studies with a larger sample are required. Acknowledgement This study was supported by FUBAP. Declaration of Competing Interest Authors declare that there is no conflict of interest. References [1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. (DSM-IV). Arlington: American Psychiatric Pub; 1994. [2] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5). American Psychiatric Pub; 2013. [3] World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization; 1992. [4] Nestadt G, Romanoski AJ, Brown CH, Chahal R, Merchant A, Folstein MF, et al. DSM-III compulsive personality disorder: an epidemiological survey. Psychol Med 1991;21(2):461–71.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047
M. Atmaca et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx [5] Fineberg NA, Reghunandanan S, Kolli S, Atmaca M. Obsessive-compulsive (anankastic) personality disorder: toward the ICD-11 classification. Braz J Psych 2014;36:40–50. [6] Stein DJ, Kogan CS, Atmaca M, Fineberg NA, Fontenelle LF, Grant JE, et al. The classification of obsessive–compulsive and related disorders in the ICD-11. J Affect Disord 2016;190:663–74. [7] Atmaca M, Korucu T, Tabara MF, Yildirim H, Kılıc MC. Volumetric MRI study of orbito-frontal cortex and thalamus in obsessive-compulsive personality disorder. J Clin Neurosci 2019. https://doi.org/10.1016/j.jocn.2019.03.062. [8] Acer N, Turgut M, Yalcin SS, Duvernoy HM. Anatomy of the human pineal gland. In: Turgut M, Kumar R, editors. Pineal Gland and Melatonin: Recent Advances in Development, Imaging, Disease and Treatment. Nova Science; 2011. [9] Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, et al. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 2003;34(1):75–8. [10] Brown R, Kocsis JH, Caroff S, Amsterdam J, Winokur A, Stokes PE, et al. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. Am J Psych 1985;142:811–6. [11] Khaleghipour S, Masjedi M, Ahade H, Enayate M, Pasha G, Nadery F, et al. Morning and nocturnal serum melatonin rhythm levels in patients with major depressive disorder: an analytical cross-sectional study. Sao Paulo Med J 2012;130(3):167–72. [12] Rubin RT, Heist EK, McGeoy SS, Hanada K, Lesser IM. Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects. Arch Gen Psych 1992;49(7):558–67. [13] Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR, et al. Melatonin in mood disorders. World J Biol Psych 2006;7(3):138–51. [14] Whalley LJ, Perini T, Shering A, Bennie J. Melatonin response to bright light in recovered, drug-free, bipolar patients. Psych Res 1991;38(1):13–9. [15] Vigano D, Lissoni P, Rovelli F, Roselli MG, Malugani F, Gavazzeni C, et al. A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. Neuro Endocrinol Lett 2001;22(2):137–41. [16] Rao ML, Gross G, Strebel B, Halaris A, Huber G, Braunig P, et al. Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. Biol Psych 1994;35(3):151–63. [17] Zinder O, Dar DE. Neuroactive steroids: their mechanism of action and their function in the stress response. Acta Physiol Scand 1999;167(3):181–8. [18] Kartalci S, Esel E. Neurosteroids: psychopharmacological and behavioral effects. Bull Clin Psychopharm 2004;14:38–49. [19] Kluge M, Schüssler P, Künzel HE, Dresler M, Yassouridis A, Steiger A. Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder. J Psych Res 2006. Epub 2006 Oct 17.
5
[20] Catapano F, Monteleone P, Fuschino A, Maj M, Kemali D. Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Psych Res 1992;44(3):217–25. [21] Monteleone P, Catapano F, Del Buono G, Maj M. Circadian rhythms of melatonin, cortisol, and prolactin in patients with obsessive-compulsive disorder. Acta Psych Scand 1994;89(6):411–5. [22] Millet B, Touitou Y, Poirier MF, Bourdel MC, Hantouche E, Bogdan A, et al. Plasma melatonin and cortisol in patients with obsessive-compulsive disorder: relationship with axillary temperature, physical activity, and clinical symptoms. Biol Psych 1998;44(9):874–81. [23] Kluge M, Schüssler P, Künzel HE, Dresler M, Yassouridis A, Steiger A. Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder. J Psych Res 2007;41(11):928–33. [24] American Psychiatric Association. Text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000. [25] Jackson GD, Duncan JS. MRI neuroanatomy: a new angle on the brain. WB Saunders Company; 1996. [26] Patel VH, Friedman L. MRI of the brain: normal anatomy and normal variants. Saunders; 1997. [27] Yuh WTC. MRI of head & neck anatomy. New York: Churchill Livingstone; 1994. [28] Sumida M, Barkovich AJ, Newton TH. Development of the pineal gland: measurement with MR. AJNR Am J Neuroradiol 1996;17(2):233–6. [29] Findikli E, Inci MF, Gokce M, Findikli HA, Altun H, Karaaslan MF. Pineal gland volume in schizophrenia and mood disorders. Psych Danub 2015;27(2):153–8. [30] Fineberg NA, de Koenigswarter N, Reghunandanan S, Kolli S, Jefferies K, Laws K. The neurocognitive profile of obsessive compulsive personality disorder; a preliminary analysis. Barcelona Spain: Abstract for a poster ICOCS annual scientific meeting, 2013. [31] Skodol AE, Gunderson JG, McGlashan TH, Dyck IR, Stout RL, Bender DS, et al. Functional impairment in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder. Am J Psych 2002;159(2):276–83. [32] Atmaca M, Yildirim H, Ozdemir H, Aydin A, Tezcan E, Ozler S. Volumetric MRI assessment of brain regions in patients with refractory obsessive-compulsive disorder. Prog Neuropsychopharm Biol Psych 2006;30(6):1051–7. [33] Atmaca M, Yildirim H, Ozdemir H, Tezcan E, Poyraz AK. Volumetric MRI study of key brain regions implicated in obsessive–compulsive disorder. Prog Neuropsychopharm Biol Psych 2007;31(1):46–52. [34] Atmaca M, Yildirim H, Ozler S, Koc M, Kara B, Sec S. Smaller pituitary volume in adult patients with obsessive–compulsive disorder. Psych Clin Neurosc 2009;63(4):516–20.
Please cite this article as: M. Atmaca, T. Korucu, M. Caglar Kilic et al., Pineal gland volumes are changed in patients with obsessive-compulsive personality disorder, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.07.047