TABLE 4.

Volumetric MRI Studies in the Perigenual ACC in Bipolar Disorder¹,⁶,⁴⁷,⁵³–⁶¹

Study (year)	Sample	Age (years)	Method	Age of Onset (years)	Illness Duration/# Episodes	Family History of Illness	Clinical Status at Testing	Medication Status	Comorbidity	Findings*
Drevets et al (1997)1	21 BD 21 HC	35±8.2 34±8.2	1.5T 1 mm ROI	NR	NR	Yes	Depressed	Cohort not treated for 4 weeks prior to scans	NR	Decreased volume of L sgACC in BD group
Hirayasu et al (1999)6	21 BD 17 SCZ 20 HC	23.7±5.1 24.0±4.3	1.5T 1.5mm ROI	23.7±5.1	First hospital	14 familial subjects	First episode affective psychosis	AP	No substance abuse within last 5 years	Decreased volume of L sgACC in familial patients
Brambilla et al (2002)53	27 BD 38 HC	35±11 37±10	1.5T 1.5mm ROI	NR	NR	12 familial, 12 non-familial	11 mildly depressed, 1 hypomanic, 15 euthymic	No medication for ≥2 weeks in 11 subjects, other 16 on lithium alone	No comorbid psychiatric conditions; no current medical problems	No difference in sgACC volumes§; No difference between familial and non-familial subjects
Sharma et al (2003)54	12 BD 8HC	38±6 38±7	4T 3.3mm ROI	21.1±6.4	12±17.2	6 with family history. 6 without	Euthymic	MS, AD	No substance abuse in last 5 years	Decreased volume of R sgACC in BD
Bruno et al (2004)55	39 BD (28 BD-I, 11 BD-II) 35 HC	39.1 34.8	1.5T VBM MTI		13.2 yrs	9 with family history of BD, 10 with family history of other mood disorders	NR	MS, AD, AP	No comorbid conditions	Reduced magnetization transfer ratio in R sgACC and adjacent white matter in BD group; no difference in regional gray matter
Doris et al (2004)56	11 BD-I 11 HC	40.5±11.6 38.1 ±10.8	2T 1 mm VBM	24.3±5.1	16.2±11.1 7.8±3.4 (hospital)	NR	Euthymic	MS, AD, AP	No comorbid conditions	Decreases in gray matter density of R pgACC/medial frontal gyri (peak at 9; 52; −2; BA 10/32)
Lochhead et al (2004)57	11 BD (7 BD-I, 4 BD-II) 31 HC	38±11 36±14	1.5T 1.5 mm VBM	24±9.2	9.0±6.4 episodes	NR	Depressed	2 weeks off meds for 10 subjects	1 with eating disorder, 5 with personality disorder	pgACC smaller bilaterally in BD group
Kaur et al (2005)58	16 BD 21 HC	15.5±3.4 16.9±3.8	1.5T 1.5mm ROI	NR	NR	Yes	2 depressed, 14 euthymic	10 lithium, 3 AD, 1 AP, 1 stimulant, 1 BZ	No substance abuse; 5 ADHD, 1 ODD, 1 CD	Decreased volume of L ACC‡
Sanches et al (2005)59	15 BD(3 BD-II, 1 BD NOS) 21 HC	15.5±3.5 16.9±3.8	1.5T 1.5 mm ROI	NR	3.8±2.4	Yes	13 euthymic, 2 mildly depressed	13 on MS	No substance abuse; 5 ADHD, 1 ODD, 1 CD	No group differences in sgACC volumes; no differences between patients on and off medication
Zimmerman et al (2006)60	27 BD 22 HC	24.0±6.4 23.5±6.5	1.5T 1.5mm ROI	NR	NR	NR	Manic or mixed episode	28 MS, 3 AD, 18 AP, 7 BZ	NR	No volume differences between groups in the combined R and L ACC subregions
Bearden et al (2007}47	28 BD (70% on lithium) 28 HC	36.1±10.5 35.9±8.5	1.5T VBM	18.6±6.1	15.1±18.2	NR	30% depressed 70% euthymic	Lithium for ≥ 2 weeks (treated group); no lithium for ≥1 month (untreated group)	No neurological, medical problems; no substance abuse, other psychiatric disorders	Greater volumes of the LACC, including the sgACC in lithium treated group compared to HC and lithium negative BD
Chiu et al (2007)61	16 BP 24 autism spectrum 15 HC	10.6±4.6 10.5±1.9 10.9±1.7	1.5T 1.5mm	NR	NR	NR	NR	12 AD, 9 MS, 8 AP, 3 adrenergic agents	No CNS disease, serious medical problems, IQ<70	Smaller L sgACC in BD vs both healthy and autism control groups

^*The magnetic field strength for the MRI scanner employed is listed for each study. Differences between groups were identified using either the more sensitive ROI approach or VBM. The image slice thickness is listed.

^†The ROI approach does not generate a set of stereotaxic coordinates that indicates the peak difference between groups, therefore coordinates are listed only where relevant for the studies that assessed regional grey matter using the VBM approach.

^‡The ROI applied for the outcome measures in this study included the perigenual ACC, but also included the more dorsal supragenual ACC.

^§Although this article aimed at defining the sgACC ROI using the same landmarks as Drevets and colleagues, ¹ Botteron and colleagues, ⁵ and Hirayasu and colleagues, ⁸ the volumes obtained in the healthy control subjects in the Brambilla and colleagues⁵³ study were almost two-fold greater than those obtained in these other studies, suggesting that differences existed in the application of these methods in the latter relative to the former studies.

pgACC=pregenual anterior cingulate cortex; BD=biploar disorder; HC=healthy control, ROI=region of interest; NR=not reported; L=left, sgACC=subgenual anterior cingulate cortex; SCZ=schizophrenia; AP=antipsychotics; MS=mood stabilizers; R=right; BD-I=bipolar I disorder; BD-II=bipolar II disorder, VBM=voxel-based morphometry; MTI=magnetization transfer imaging; AD=antidepressants; BA=Brodmann area; BZ=benzodiazepines; NOS=not otherwise specified; ADHD=attention-deficit/hyperactivity disorder; ODD=oppositional defiant disorder; CD=conduct disorder; CNS=central nervous system; IQ=intelligence quotient; MRI=magnetic resonance imaging.