Psychiatry and Clinical Neurosciences 2010; 64: 318–326
doi:10.1111/j.1440-1819.2010.02085.x
Regular Article
Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder pcn_2085
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Tomohide Roppongi, MD, PhD,1 Motoaki Nakamura, MD, PhD,1 Takeshi Asami, MD, PhD,1–4 Fumi Hayano, PhD,1 Tatsui Otsuka, MD, PhD,1–4 Kumi Uehara, MD,1 Akiko Fujiwara, MD,1 Takashi Saeki, MD,1 Shunsuke Hayasaka, MD,1 Takeshi Yoshida, MD, PhD,1 Reina Shimizu, MMSc,1 Tomio Inoue, MD, PhD5 and Yoshio Hirayasu, MD, PhD1* Departments of 1Psychiatry and 5Radiology, Yokohama City University School of Medicine, Yokohama, Japan, 2Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, 3Harvard Medical School and 4Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3-D high-spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age- and gender-matched healthy controls. Optimized voxel-based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State–Trait Anxiety Inventory and Revised Neuroticism-Extraversion-Openness Personality Inventory scores.
HE ORBITOFRONTAL CORTEX (OFC) has direct reciprocal connections with the amygdala,1 which plays an important role in neuroanatomical pathways for panic disorder.2 The amygdala also has
T
Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior–medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait-Anxiety (b = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait-Anxiety (b = -0.394, F = 5.341, P = 0.032) and Neuroticism trait (b = -0.492, F = 6.989, P = 0.017). Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment. Key words: magnetic resonance imaging, orbitofrontal cortex, panic disorder, posterior orbital sulcus, voxel-based morphometry.
connections with a region of the anterior cingulate cortex known as the affective division.3 The OFC mediates anxiety behavior and perception in child and adolescent primates,4 and is involved in emotional
*Correspondence: Yoshio Hirayasu, MD, PhD, Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. Email:
[email protected] Received 5 October 2009; revised 25 January 2010; accepted 30 January 2010.
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© 2010 The Authors Journal compilation © 2010 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences 2010; 64: 318–326
processing in humans.5 Anxiety requires multiple sensory inputs, which enter the posterior region of the OFC from the primary sensory cortex.5 These findings suggest that anatomical differences may be related to OFC dysfunction. The OFC sulcogyral pattern, which exhibits anatomical variability among individuals, is determined in early neurodevelopment,6 and develops during 16–44 weeks gestation.7 It has been reported that the OFC continues to mature longer than other ventral brain regions,5,8 although frontal gray matter volume decreases after the age of 10 years.9 The posterior region of the OFC develops before the anterior region.8,9 A recent volumetric study demonstrated that the OFC sulcogyral pattern was associated with brain volume in schizophrenia.10 These findings indicate a relationship between sulcogyral pattern and OFC gray matter volume. Few magnetic resonance imaging (MRI) volumetric studies of the OFC have involved patients with panic disorder, whereas several MRI volumetric studies of the amygdala11,12 and anterior cingulated cortex13 have been done. Chiavaras and Petrides evaluated OFC sulcogyral patterns of 50 healthy volunteers, and reported considerable pattern differences among individuals.14 Based on these findings, the anatomical pattern of the posterior orbital sulcus (POS) was classified as absent POS, single POS, or double POS, according to the presence/absence and number of POS in the OFC. In the present study we hypothesized that anatomical variability may be associated with dysfunction of the OFC in patients with panic disorder. This study focused on the structure of the OFC posterior region, which receives multiple sensory inputs and modulates the anxiety response. We investigated differences in the distribution of POS subtypes between patients with panic disorder and healthy control subjects. Additionally, we used optimized voxel-based morphometry (VBM) to investigate OFC volume differences between patients and control subjects of each POS subtype group. We also assessed the association of POS subtypes with clinical measures for anxiety and personality traits.
METHODS
Posterior OFC in panic disorder
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Yokohama City University Hospital. Twenty-eight age- and gender-matched healthy control (HC) subjects (male, n = 10; female, n = 18; mean age, 37.8 ⫾ 9.8 years) were also recruited. All subjects were right-handed. The panic disorder diagnosis was based on DSM-IV criteria. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) was used to ascertain the diagnosis.15 Table 1 lists the demographic and clinical characteristics of these groups. Comorbid psychiatric diseases included agoraphobia (n = 15), current major depression (n = 1), previous dysthymia (n = 1), and previous major depression (n = 6). Twenty-five patients were taking antidepressants and benzodiazepine. HC subjects were recruited from the community and the staff of Yokohama City University and were screened using the SCID non-patient edition16 and Mini-International Neuropsychiatric Interview.17 HC subjects had neither previous nor present psychiatric diseases. As part of a comprehensive neuropsychological battery, the total IQ scores of subjects from both groups (patients, n = 24; HC, n = 24) were determined using the Wechsler Adult Intelligence Scale–Revised.18 Anxiety and personality traits were assessed using the Trait-Anxiety subscale of State–Trait Anxiety Inventory (STAI; patients, n = 28; HC, n = 27)19 and the Revised Neuroticism-Extraversion-Openness Personality Inventory (NEO; patients, n = 24; HC, n = 26).20 We also used the Panic Disorder Severity Scale (PDSS)21 as a clinical measure. The present study was approved by the Yokohama City University Review Board. Written informed consent was obtained from all subjects in advance of study participation.
Magnetic resonance imaging MRI was done with a 1.5-T Siemens Magnetom Symphony scanner (Siemens Medical System, Erlangen, Germany) at Yokohama City University Hospital. The 128 contiguous sagittal T1-weighted images were acquired using turbo-FLASH sequences with the following parameters: echo time = 3.93 ms, repetition time = 1960 ms, inversion time = 1100 ms, flip angle = 15°, field of view = 24 cm, matrix = 256 ¥ 256 ¥ 128, and voxel dimension = 0.9375 ¥ 0.9375 ¥ 1.5 mm.
Subjects Twenty-eight patients with panic disorder (male, n = 10; female, n = 18; mean age, 38.4 ⫾ 9.8 years) were recruited from the Department of Psychiatry at
Sulcogyral pattern identification Sulcogyral pattern identification was based on a previous report by Chiavaras and Petrides.14 To clarify the
© 2010 The Authors Journal compilation © 2010 Japanese Society of Psychiatry and Neurology
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Psychiatry and Clinical Neurosciences 2010; 64: 318–326
Table 1. Subject characteristics Patients with panic disorder (n = 28) Variables Age (years) Gender (male/female) Handedness Subject socioeconomic status Parents’ socioeconomic status Total IQ STAI A Trait NEO PI-R Neuroticism NEO PI-R Extraversion NEO PI-R Openness to Experience NEO PI-R Agreeableness NEO PI-R Conscientiousness PDSS Antidepressant dosage (amitriptyline equivalent, mg) Anti-anxiety agent dosage (diazepam equivalent, mg)
Mean 38.4 10/18 1.0 2.43 2.57 103.7 46.5 110.2 101.7 114.7 110.8 106.5 9.0 74.0 6.60
SD 9.8 0.1 0.879 0.879 13.8 10.9 26.1 18.1 17.0 15.6 16.3 4.9 66.3 4.66
Healthy control subjects (n = 28) Mean 37.8 10/18 1.0 2.00 2.23 109.9 35.4 88.0 109.0 113.6 112.6 110.1
SD 9.8 0.1 0.980 0.710 13.4 6.4 22.8 15.6 14.3 13.6 15.6
t-test or c2 †
0.23 0.00‡ 0.24† 1.694† 1.559† -1.59† 4.52† 3.22† -1.53† 0.26† -0.43† -0.78†
d.f.
P
54 1 54 52 52 46 51 48 48 48 48 48
0.82 1.00 0.81 0.096 0.125 0.12
