Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.
description
Transcript of Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.
![Page 1: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/1.jpg)
Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.
Pablo Najt
Department of Psychiatry,
University of Texas,
Health Science Center at San Antonio.
![Page 2: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/2.jpg)
Role of OFC
Neuropsychologic functioning:• exteroreceptive and interoreceptive information coding
• reward-guided behavior
• impulse control
• mood regulation
![Page 3: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/3.jpg)
Anatomical Studies of OFC in Mood Disorders• Rajkoswska et al 1999: significant decrease in the thickness of OFC in MDD patients
compared with healthy controls (post mortem study).
• Lai et al 2000 and Bremner et al 2002: bilateral reductions of OFC volumes in MDD patients compared with controls.
• Lacerda et al 2004: smaller gray matter volumes in right medial and left lateral OFC in MDD patients. And males, but not females patients exhibited smaller left and right medial OFC volumes compared with healthy controls.
• No studies in BP patients, we expect to find OFC reductions in this condition as well.
• Bremner (2002): Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry 51:273-79
• Lacerda et al (2004): Anatomical evaluation of the orbitofrontal cortex in major depressive disorder. Biol Psychiatry 55: 353-58
![Page 4: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/4.jpg)
• 14 children and adolescents with bipolar disorder
(mean age ± S.D. = 15.5 ± 3.2 years)
• 20 healthy controls (mean age ± S.D. = 16.9 ± 3.8
years).
• Structured Clinical Interview for DSM IV (SCID)
for patients aged 18-21
• Schedule for Affective Disorders and
Schizophrenia for School Age Children, Present
and Lifetime Version (K-SADS-PL) interview for
patients younger than 18.
Subjects
![Page 5: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/5.jpg)
Demographics in Bipolar Patients (BP) and Healthy Controls (HC)
Variable BP (n=14) HC (n=20)
Age, mean (S.D.) years
15 (3) 17 (4)
Sex, N (%) female 8 (54) 9 (45)
Race, N (%) White 14 (93) 17 (85)
![Page 6: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/6.jpg)
Clinical characteristics of patients Age at onset Age Dx Mood st. No. episodes
1 19 21 BD I D ?
2 17 19 BD I E 2
3 14 10 BD I E 3
4 12 15 BD I E ?
5 15 21 BD I E 4
6 10 14 BD I E 6
7 8 18 BD I E 7
8 10 14 BD I E 3
9 4 17 BD I E 5
10 12 13 BD I E 3/9
11 14 18 BD I E 4
12 11 14 BD II E 9
13 13 10 BD II E 6
14 7 17 BD NOS D 3
![Page 7: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/7.jpg)
7
Treatment parametersN Minimum Maximum Std. Dev.
Lithium dos(mg/day)
9 675 1350 248.8
Weeks on Lithium 9 8 208 71.3
Dose Valproate 8 500 1109 540.5
VPA blood level(Microgram/ml)
4 49 86 32
Weeks on VPA 7 10 150 51.8
![Page 8: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/8.jpg)
8
MRI Procedures
• A 1.5 T GE Signa Imaging System running version Signa
5.4.3 software was used to acquire the MRI scans.
• TR = 25ms, TE = 5ms, nutation angle = 40°, FOV = 24cm,
slice thickness = 1.5mm, NEX = 1, matrix size=256x192
• Trained raters, who achieved ICC > 0.95, did all anatomical
measurements, blindly, with the BRAINS2 software,
developed at the University of Iowa Hospitals and Clinics
(Andreasen et al 1992).
• We measured the volumes of OFC (total and gray matter)
and its subdivisions.
![Page 9: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/9.jpg)
Delimitation of the Orbitofrontal Cortex
Starting point
Last slice
![Page 10: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/10.jpg)
Superior boundary
![Page 11: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/11.jpg)
Results-1
•Bipolar patients and healthy controls only were compared on demographics (age and race).
•For clinical variables (diagnosis, family psychiatric history, treatment) male and female patients were compared.
•No significant differences regarding demographic or clinical variables.
![Page 12: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/12.jpg)
Results-2
• Analysis of the the young subjects (age<19) only showed the same two effects when analysing the entire sample.
• No significant differences when combining males and females into one group.
![Page 13: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/13.jpg)
(ANCOVA, ICV and age as covariates)
Table1. Orbitofrontal Cortex (OFC), Gray Matter Volumes in Female Patients with Bipolar Disorder and Healthy Subjects.
Gray matter Volumes(cm³) (Mean + SD)
Patients Controls
Region (n = 8)
(n = 9)
p
Total OFC 18.35 + 3.36 14.18 + 4.33 0.110
Right 9.70 + 2.01 7.75 + 2.66 0.300
Left 8.82 + 1.47 6.54 + 1.81 0.034
Medial OFC 7.73 + 1.55 6.13 + 1.56 0.135
Right 4.18 + 0.81 13.32 + 0.90 0.179
Left 3.56 + 0.78 2.82 + 0.72 0.127
Lateral OFC 6.3 + 1.38 4.33 + 1.24 0.012
Right 3.16 + 0.69 2.4 + 0.75 0.072
Left 3.13 + 0.79 1.92 + 0.53 0.007
![Page 14: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/14.jpg)
Table2. Orbitofrontal Cortex (OFC), Gray Matter Volumes in Male Patients with Bipolar Disorder and Healthy Subjects.
Gray matter Volumes(cm³) with in (Mean + SD)
Patients Controls
Region (n= 7)
(n= 11)
p
Total OFC 17.49 + 4.36 19.76 + 3.14 0.105
Right 9.05 + 2.65 10.46 + 1.82 0.069
Left 8.54 + 1.91 9.44 + 1.73 0.228
Medial OFC 5.88 + 2.69 7.97 + 0.78 0.010
Right 3.03 + 1.49 4.17 + 0.47 0.009
Left 3.25 + 1.4 3.89 + 0.42 0.133
Lateral OFC 5.18 + 0.78 6.46 + 1.52 0.047
Right 2.7 + 0.55 3.42 + 0.54 0.014
Left 2.47 + 0.54 3.04 + 1.05 0.193
(ANCOVA, ICV and age as covariates)
![Page 15: Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.](https://reader036.fdocuments.net/reader036/viewer/2022062500/5681598d550346895dc6d73b/html5/thumbnails/15.jpg)
Conclusions• Our findings have similarities with previous
studies, reporting reductions in medial and lateral OFC gray matter in male patients comparing with controls.
• While MDD studies observed no differences within the female subgroup between patients and controls, we found larger OFC volumes in female bipolar patients.
• Further investigation of the OFC in bipolar disorder, confirming these findings is warranted.