Table 5.
Morphometric Studies of the Hippocampal Complex 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| (Axelson et al 1993) | 19 MDD 30 HC |
46.7±7.4 56.6±19.1 |
1.5T 5mm ROI |
34±17 | 12.7±13.1 | NR | Depressed | NR | NR | No difference in hippocampal-amygdala complex volumes. Age negatively correlated with volume. |
| (Sheline et al 1996) | 10 MDD 10 HC |
68.5±10.4 68.0±9.5 |
1.5T 1.25mm ROI |
NR | 1293±1067 (days) | NR | Partially remitted | 8 AD | No drug or alcohol abuse | Smaller BL hippocampal volumes in MDD. Volume correlated negatively with duration of depression. |
| (Pantel et al 1997) | 19 MDD 13 HC |
72.4±8.8 68.2±5.3 |
1.5T 1.25mm |
64.2±9.2 | 26.7±6.6 (months) | NR | Depressed | NR | NR | No difference in hippocampal-amygdala complex volumes. |
| (Shah et al 1998) | 20 MDD (chronic) 20 MDD (remitted) 20 HC |
21–65 | VBM | NR | NR | NR | Depressed and remitted | AD | No mania, significant substance abuse, organic pathology or neurological illness | Chronic MDD group showed trend towards reduced GM density in the L hippocampus. −29; −18; −16 |
| (Ashtari et al 1999) | 40 MDD 40 HC |
74.3±6.0 71.4±0.3 |
1T 3.1mm ROI |
61.5±5.5 | 1.8±0.5 | NR | Depressed | NR | NR | No difference in hippocampal volumes. No relationship between # episodes + volume |
| (Sheline et al 1999) | 24 MDD 24 HC |
52.8±18.4 52.8±17.8 |
1.5T 1.25mm ROI |
NR | 1058±1032 (days) 4.8 (episodes) |
NR | Depressed | 16 on AD | No substance abuse, medical or neurological conditions | Smaller BL hippocampal volumes in MDD. No correlation between volume and age but duration of depression associated with volume |
| (Bremner et al 2000) | 16 MDD 16 HC |
43±8 45±10 |
ROI | NR | 2±3 (episodes) | NR | Remitted | AD | No PTSD. 5 patients with history of substance abuse/dependence. 1 PD. | Reduced L hippocampal volume in MDD. Trend for R hippocampus. No associationbetween volume and # episodes or hospitalisations |
| (Mervaala et al 2000) | 34 MDD (6 BD) 17 HC |
42.2±12.2 42.1±14.6 |
1.5T 8mm ROI |
NR | 31 months | NR | Depressed | AD | No substance abuse | Smaller L hippocampal volumes in MDD. Trend for R hippocampus. |
| (Steffens et al 2000) | 66 MDD 18 HC |
71.74±8.42 67.11±5.04 |
1.5T 3mm |
25.6 (N=28) 65.2 (N=38) |
NR | NR | Depressed | NR | No other “major” psychiatric illnesses. | Smaller BL hippocampal volumes in MDD. Weak negative association between age of onset and volume. No association between # of episodes + volume. |
| (Vakili et al 2000) | 38 MDD 20 HC |
38.5±10.0 40.3±10.4 |
1.5T 3mm ROI |
NR | NR | NR | Depressed | Fluoxetine | No active substance abuse | No significant differences in hippocampal volume. Negative correlation between severity of depression and volume. |
| (von Gunten et al 2000) | 14 MDD (with memory complaints) 14 HC |
57.6 58.1 |
1.5T 5mm |
NR | ±6.5 | NR | Depressed | 7 AD, 2 BZ | No neurological disorders, substance abuse | No difference in hippocampal volumes |
| (Rusch et al 2001) | 25 MDD 15 HC |
33.2±9.5 37.4±14.4 |
1.5T 1.2mm ROI |
NR | NR | Yes but not BD | Depressed | Free of medication for 4+ weeks. | No history of mania, psychosis or any other axis I disorder except dysthymia. | No hippocampal volume differences |
| (Bell-McGinty et al 2002) | 30 MDD 47 HC |
69.3±5.7 66.9±7.3 |
1.5T VBM |
NR | 1.8±0.9 (episodes) | NR | Depressed | NR | No other axis I disorders or substance abuse. No neurological disorders, untreated DM or hypertension | Smaller R hippocampal volume in MDD. Volume inversely correlated with age of onset. |
| (Frodl et al 2002) | 30 FE MDD 30 HC |
40.3±12.6 40.6±12.5 |
1.5T 3mm ROI |
40±12.5 | 0.71±0.9 | NR | Depressed | AD | No other axis I conditions, neurological disorders or had injury | Smaller L hippocampal GM volumes in male MDD. No association between illness duration or age and volume. |
| (Vythilingam et al 2002) | 21 MDD with history of childhood abuse 12 MDD without abuse 14 HC |
33±6 34±8 27±5 |
1.5T 1.5mm ROI |
NR | NR | NR | Depressed | NR | Anxiety disorders, especially PTSD more prevalent in abused MDD sample. | Smaller L hippocampal volume in MDD group with history of childhood abuse. |
| (MacQueen et al 2003) | 20 FE MDD. 17 multi-episode MDD. 20 HC 17HC |
28.4±11.8 35.9±11.1 28.4±11.5 36.2±11.9 |
1.5T 1.2mm ROI |
26.3±12 24.9±11.6 |
10 years 6 (episodes) |
Mixed | Depressed | FE MDD group medication naïve. AD in multi-episode group. | No substance abuse, anxiety disorders. | Hippocampal volume reduction in multi-episode patients. Correlation between duration of depression & hippocampal volume. |
| (Posener et al 2003) | 27 MDD 42 HC |
33.0±10.7 33.2±10.8 |
1.5T 1mm ROI |
NR | 0.8±1.2 (episodes) | NR | Depressed | Yes – not specified. | No substance abuse in last 3 months. No other axis I or II disorders. No neurological disorders, cardiovascular risk factors. | No differences in hippocampal volume but surface deformation |
| (Caetano et al 2004) | 31 MDD 31 HC |
39.2±11.9 36.7±10.7 |
1.5T 1.5mm ROI |
30.5±12.5 (remitted) 26.7±11.4 |
12.3±8.4 (remitted) 11.0±11.7 (depressed) |
Both | 21 depressed; 10 remitted. | All patients off psychotropics for 2+ weeks. | No comorbid disorders except substance abuse in remission for 6+ months. | Depressed patients had smaller hippocampal volumes than remitted patients. Inverse correlation between length of illness and L hippocampus. |
| (Frodl et al 2004) | 30 MDD 30 HC |
48.4±13.4 45.7±12.9 |
1.5T 1.5mm ROI |
39.3±13.4 | 9.1±10.2 | NR | Depressed | AD + lithium | No co-morbid disorders | No differences between hippocampal volumes in remitted group. Smaller R hippocampal volume in non-remitted group (N=12) at base-line and follow-up. No change in volumes over 1 year. |
| (Hastings et al 2004) | 18 MDD 18 HC |
38.9±11.4 34.8±13.6 |
1.5T 1.5mm ROI |
23±12.3 | 4.7±4.4 | Mixed | Depressed | NR | No current drug abuse | No volume changes of hippocampus. |
| (Inagaki et al 2004) | 17 MDD 51 HC |
47.1±6 48.6±5 |
1.5T 1.5mm |
NR | 1.1±1.0 | No | Remitted | No psychotropic medication for 1+ month. Tamoxifen. | No substance abuse | No hippocampal volume differences in cancer survivors |
| (Janssen et al 2004) | 28 MDD 41 HC |
64.04±10.9 62.37±11.38 |
1.5T 1.2–5mm ROI |
33.04±9.48 | 93.5±17.5 months | NR | Depressed | 22 AD, 4 lithium, 1 BZ. | NR | Smaller R hippocampal volume in MDD. |
| (Lange and Irle 2004) | 17 female MDD 17 female HC |
34±10 34±6 |
1.5T 1.3mm ROI |
29±10 | 5±5 | Yes – in 7 cases but no history of BD | Depressed | AD | No history of psychosis. No PTSD, borderline PD | Reduction in hippocampal volume in MDD |
| (Lloyd et al 2004) | 51 MDD (23 early onset; 28 late-onset) 39 HC |
72.7±6.7 75.1±5.8 73.1±6.7 |
1T 1mm |
38.7 (N=23) 72.0 (N=28) |
88.3 weeks; 5.1 (episodes) 24.3 weeks; 2.0 (episodes) |
NR | Depressed | AD | No drug or alcohol abuse | BL hippocampal atrophy in late-onset MDD compared with early-onset MDD + HC. No relationship between volume + lifetime duration of depression. |
| (MacMaster and Kusumakar 2004) | 17 MDD 17 HC |
16.67±1.83 16.23±1.61 |
1.5T 1.5mm ROI |
14.06±1.98 | 2.89±1.71 | Yes in 9/17 | Depressed | 14 treatment naive. 3 AD or methyphenidate | No neurological or serious medical illness. 2 substance abuse, 1 ODD. | BL (especially L) reduction in hippocampal volume in MDD |
| (O’Brien et al 2004) | 61 MDD 40 HC |
73.9±6.7 73.3±6.7 |
1T 1mm ROI |
NR | 2.2±2.7 (episodes) | NR | Depressed. 20% with psychotic features. | 51 AD, 7 lithium | No substance abuse, stroke, unstable medical illness | Decreased volume of hippocampus in MDD |
| (Hickie et al 2005) | 66 (14 BD) MDD 20 HC |
53.5±13.5 55.8±10.8 |
1.5T 1.5mm ROI |
38.4±16.3 | 15±15.8 | NR | Depressed | NR | No substance abuse | Reduced hippocampal volume. Effect stronger in late onset patients. Increasing age associated with smaller volumes |
| (Neumeister et al 2005) | 31 MDD 57 HC |
40.1±101 38.0±10.9 |
3T 0.6mm |
24.6±10.3 | 3.2±2.1 (episodes) | NR | Remitted | Unmedicated | No history of trauma or substance abuse | Total + posterior hippocampal volume reductions in MDD. |
| (Frodl et al 2006) | 34 MDD 34 HC |
45.5±11.9 43.6±13.2 |
1.5–3mm ROI |
38.8±12.4 | 6.8±8.8 | NR | Depressed | AD, 4 AP | No comorbidity | BL hippocampal GM + WM volume reductions in MDD. No correlation between illness duration + hippocampal volume. |
| (Hickie et al 2006) | 45 MDD 16 HC |
52.0±12.8 55.8±10.3 |
1.5T 1.5mm |
36.1±17.2 | 15.6±16.1 6.9±9.8 episodes |
NR | Depressed | 29/45 AD | No substance abuse but comorbid axis II disorders. No head injury, neurological illness, stroke, dementia | Smaller hippocampal volume in MDD |
| (Rydmark et al 2006) | 29 female MDD 28 HC |
47.7±4.9 47.6±4.2 |
1.5T VBM |
44.1±8.4 | Mostly 1st episode | NR | Partially remitted | AD | No hazardous alcohol or illicit drug use. | No hippocampal differences. |
| (Frodl et al 2007) | 60 MDD 60 HC |
44.2±11.8 41.6±12.3 |
1.5T 1mm ROI |
37.7±11.7 | 6.7±8.7 | NR | Depressed | AD | No head injury, neurological disorders, cortisol medication, substance abuse, and personality disorders, | Smaller hippocampal volumes in MDD. No association between duration of illness and volume |
| (Janssen et al 2007) | 13 early onset MDD 15 late-onset depression 22 HC |
70.38±8.3 72.67±6.7 71.05±7.5 |
1.5T | 33.62±8.8 69.93±6.4 |
NR | NR | Depressed | 4 lithium | Cerebrovascular risk factors not exclusion criterion. No neurological disorders, dementia, substance abuse | Smaller hippocampus in early-onset group only. |
| (Macmaster et al 2007) | 32 MDD 35 HC |
14.08±2.08 14.51±2.72 |
1.5T 1.5mm ROI |
11.77±2.92 | 27.70±27.68 months | Yes | Depressed | Medication naive | No psychosis, BD, OCD, PTSD, eating disorders, substance abuse, autism, learning disorders, medical or neurological conditions | Smaller L+R hippocampal volumes in MDD |
| (Keller et al 2008) | 23 MDD (with psychosis) 19 MDD (without psychosis 22 HC |
36.5±13.2 36.6±11.9 32.2±11.5 |
3T 1.5mm ROI |
27.6±11.7 27.0±14.0 |
2.9±4.4 4.0±9.3 (episodes) |
NR | Depressed | AD, MS, AP, 4 no med 8 no med, 8 AD, 3 other |
No major medical illness, seizures, head trauma, unstable cerebrovascular, endocrine conditions. No treatment with steroids, hormone replacement therapy. No substance abuse within last 6 months | No significant differences |
| (Tae et al 2008) | 21 MDD 20 HC |
41.7±11.0 41.9±10.3 |
1.5T 1.3mm ROI VBM |
33.2±13.0 | 3.9±3.3 (episodes) 80.0±67.0 months (duration) |
4 + 17 − |
Depressed | AD only | No childhood trauma, other axis I disorder, no current or past history of substance abuse/dependence, major medical illness, head trauma, steroid meds. | Smaller L hippocampus in MDD using both manual and VBM methods |