Table 19.
Functional Analyses of the Ventro-Medial Prefrontal Cortex in MDD.
| Study | Sample | Age | Method | Age of Onset |
Duration of Illness/# Episodes |
Family History of Illness |
Clinical Status at Testing |
Medication Status |
Comorbidity | Findings | Brodmann Map/Stereotaxic Coordinates |
|---|---|---|---|---|---|---|---|---|---|---|---|
| (Drevets et al 1992) | 13 depressed MDD 10 remitted MDD 33 HC |
36.2±8.9 33.6±10.0 30.1±7.8 |
15O-H2O Voxel-wise | NR | NR | Yes | Depressed + euthymic | Depressed unmediated for 3+ weeks before scan. Remitted unmedicated for 4+ months | No co-morbid conditions | Depressed patients showed increased rCBF of L pregenual ACC. Effects not seen in remitted group. | BA 32 7; 55; 6 |
| (Drevets et al 1997) | 10 MDD 21 HC |
39±7.3 34±8.2 |
1.5T 1mm slice ROI |
NR | NR | Yes | Depressed | Not treated for 4 weeks prior to scans | NR | Decreased metabolism of L sgACC in MDD group. | BA 24 1; 25; −6 |
| (Wu et al 1999) | 12 MDD responders 24 MDD non-responders 26 HC |
28.8±9.2 30.8±9.9 29.4±9.5 |
18 F-FDG | NR | NR | NR | Depressed | No medication for 2+ weeks | No axis I diagnoses or physical disorders | Responders had higher metabolic rates in sgACC at baseline. Change in metabolic rate of L mPFC correlated with Ham-D scores after sleep deprivation. ie metabolism = improved symptoms. | BA 24; 25 3; 25; −4 5; 48; −4 |
| (Mayberg et al 2000) | 17 MDD | 49±9 | 18 F-FDG | NR | 2±1 episodes | NR | Depressed | Scanned before and after treatment with fluoxetine | No history of psychosis or substance abuse. No other axis I disorders. No dementia, head injury, cerebrovascular illness | Improvement associated with decreased activity of sgACC. No subgenual cingulate changes in non-responders to fluoxetine. | BA 25 4; 2; −4 2; 26; −8 |
| (Kennedy et al 2001) | 13 MDD 24 HC |
36±10 31.7±6.7 |
18 F-FDG | NR | 2.84±3.95 episodes | NR | Depressed | Scanned before and after treatment with paroxetine | No patients with concurrent DSM diagnosis. | Depressed group had higher activity in R pregenual cingulate which increased further with treatment | BA 24 8; 36; −4 |
| (Drevets et al 2002a) | 20 MDD 14 HC |
36±10 34±9.1 |
18 F-FDG | NR | NR | NR | Depressed | Patients medication free for 3+ weeks prior to study | No other psychiatric disorders or substance abuse | At baseline metabolism decreased in sgACC anteromedial PFC. After treatment with sertraline significant decreases in activity of L sgACC | 3; 31; −10 |
| (Dunn et al 2002) | 31 MDD | 42.4±13.6 | 18 F-FDG | 15.9±13.1 | 26.7±14.6 | NR | Mildly to severely depressed | Unmedicated for 2+ weeks | No active substance abuse, eating disorder, OCD, dementia, medical illness | Anhedonia associated with greater activity of the L pgACC and mPFC | pgACC BA 24, 25, 32 −16; 44; 4 BA 10 |
| (Liotti et al 2002) | 10 remitted MDD 7 ill MDD 8 HC |
37±9 42±15 36±6 |
15O-H2O 6.5mm |
NR | NR | NR | Euthymic | AD | No other primary psychiatric or neurological disorder. No head injury, substance abuse | Decrease in rCBF to medial PFC and pregenual cingulate in acutely depressed and remitted group, respectively | BA 9 + 10 8; 54; 12 6; 40; 27 BA 24 12; 38; 16 |
| (Davidson et al 2003) | 12 MDD 5 HC |
38.17±9.3 27.8±10.4 |
fMRI 1.5T 1mm ROI Block design with alternating negative-neutral or positive-neutral visual stimuli |
NR | NR | NR | Depressed | NR for baseline | No other axis I disorders except specific phobia or dysthymia. No neurological disorders | Less activation of the L ACC at baseline which improved with treatment | NR |
| (Holthoff et al 2004) | 41 MDD No Controls |
45.1±15.66 |
18 F-FDG Voxel-wise ROI |
NR | 1st episode in 54% of sample. 10 patients had more than 2 episodes | NR | Moderate to severely depressed | Treated with AD. BZ discontinued 3 days before baseline. | No substance abusers, axis II disorders | Remission associated with decreased metabolism of L ventral PFC | −16; 40; −2 −14; 70; 0 −14; 68; −12 |
| (Pizzagalli et al 2004) | 38 MDD (20 melancholic) 18 non-melancholic 18 HC |
33.1±8.8 36.5±12.9 38.1±13.6 |
18 F-FDG MRI 1.5T Voxel-wise |
NR | NR | Yes - in 12 melancholic + 7 non-melancholic subjects | Depressed | Free of medication for 2+ months | No other axis I disorders except simple phobias and dysthymia. No history of psychosis + current substance abuse. No axis II assessment. | Decreased (16%) metabolism of sgACC in melancholic patients only | BA25 −3; 9; −6 |
| (Gotlib et al 2005) | 18 MDD 18 HC |
35.2 30.8 |
3T Voxel-wise | NR | NR | NR | Depressed | 9 on AD | No brain injury, psychosis, social phobia, panic disorder + substance abuse in last 6 months | Greater BOLD response to sad faces in L sgACC (BA 25) in MDD. Also greater perfusion of L BA 32/24 in response to happy faces | BA 25 – coordinates not given BA 32/24 −8; 31; 7 |
| (Mayberg et al 2005) | 6 MDD | 46±8 | 15O-H2O | 29.5±12 | 4.7±5 (episodes) | Yes - in 5 out of 6 subjects | Depressed | NR | No psychotic symptoms, substance abuse in last 3 months | Elevated CBF to the sgACC but decreased CBF BA 24b at baseline in MDD. Treatment with deep brain stimulation associated with reduced activity of BA 25 and elevated metabolism of BA 24b | Baseline: sgACC ~BA 24 −10; 28; −12 −2; 18; 28 Treatment: 3 months sgACC BA25 −2; 8; −10 BA 24 −2; 10; 28 6 months BA 25 10; 20; −4 BA24 −4; 4; 34 |
| (Clark et al 2006) | 5 MDD responders 17 MDD non-responders 8 HC |
43.4±6.1 42.0±10.8 35.0±9.5 |
fMRI 1.5T ASL At Rest |
NR | NR | NR | Depressed | Patients medication free for 2+ weeks prior to study; rescanned after sleep deprivation | No patients with history of substance abuse, concurrent axis I disorders. | At baseline, responders had higher activity of L ventral ACC (including sgACC) that correlated with depressed mood. After sleep deprivation perfusion decreased in L + R ventral ACC cingulate in responders | NR |
| (Kumano et al 2006) | 19 cancer patients followed longitudinally | 58.4±15.7 (deterioration group) 57.9±16.4 (no change sample) |
18 F-FDG | NR | NR | No | Depressed + euthymic | Cancer medication | NR | Patients who became more depressed over time showed prodromal hypermetabolism of R ACC + L subcallosal gyrus | BA 25 −4; 9; −12 2; 11; −7 |
| (Chen et al 2007a) | 17 MDD No Controls |
44.06±8.36 | MRI 1.5T 3mm Sad facial stimuli |
NR | NR | NR | Depressed | Scanned before and after treatment with fluoxetine. Patients off medication 4+ weeks before study. | No current axis I comorbidity or substance abuse within 2 months of study. Personality disorders not assessed. | Increased functional activation of pregenual ACC and medial frontal cortex associated with decreased symptom severity at baseline | BA 32 −2; 40; 15 BA 10 −1; 53; 4 |
| (Fales et al 2008b) | 27 MDD 24 HC |
33.4±8 36.4±9 |
3T fMRI ROI Emotional interference task: houses and faces. |
NR | NR | NR | Depressed | No medication for 4+ weeks | No axis I disorders preceding onset of MDD, acute physical illness, trauma with loss of consciousness, current neurological disorder. | Elevated activity of sgACC in MDD | BA 24: −10; 35; −2 0; 13; 29 0; 13; 34 |
| (Nahas et al 2007) | 17 MDD | 46.8±6.3 | fMRI 1.5T |
NR | 71.2±57.3 months (current episode) | NR | Depressed | Yes – not specified | NR | VNS decreased activity of the R sgACC | BA 25 0; 8; −16 |