Orbitofrontal Cortex Abnormalities in Bipolar Disorder Adolescents.

Pablo Najt

Department of Psychiatry,

University of Texas,

Health Science Center at San Antonio.

Role of OFC

Neuropsychologic functioning:• exteroreceptive and interoreceptive information coding

• reward-guided behavior

• impulse control

• mood regulation

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

• 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

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)

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

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

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.

Delimitation of the Orbitofrontal Cortex

Starting point

Last slice

Superior boundary

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.

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.

(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

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)

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.