Table 13.
White Matter Hyperintensities in MDD.
| Study | Sample | Age | Method | Age of Onset | Illness Duration/# Episodes |
Family History of Illness |
Clinical Status at Testing |
Medication Status |
Comorbidity | Findings |
|---|---|---|---|---|---|---|---|---|---|---|
| (Coffey et al 1988) | 67 MDD referred for ECT | 71.6 (60–86) | Both MRI + CT MRI: 5mm (2.5mm gap). CT: 10mm |
After age 60 in 58% of cases | NR | Yes – 43% | Depressed | Tapered off medication | 35 heart disease or hypertension, 8 DM, 4 COPD, 2 DVT, 2 dementia | WMH found in 44 MDD |
| (Krishnan et al 1988) | 35 MDD | NR | 1.5T 10mm |
12<45 23>45 |
NR | NR | Depressed | AD | No dementia. Greater incidence of medical problems in older group. | Higher rate of PVH in late onset group |
| (Coffey et al 1989) | 51 MDD | 71.3 | 1.5T 5mm (2.5mm gap) |
80% > 60 | NR | NR | Depressed | Variety of medication for medical illness. 27% with a previous course of ECT. | 10 patients with history of dementia, 4 alcohol abuse. Cardiovascular risk factors in 58% of sample. | PVH in 100% of sample. WMH in 86% of sample. |
| (Dolan et al 1990) | 10 MDD 13 HC |
47±11 46±7 |
0.08T 12mm ROI |
31±9 | 11±7 | NR | Depressed | AD, BZ | No significant medical illness or alcohol abuse. | Greater mean T1 relaxation times in frontal WH in MDD. |
| (Zubenko et al 1990) | 67 MDD 44 HC |
73.2±6.5 68.0±6.2 |
1.5T 5mm 91-2.5mm gap) |
62.5±16.0 | NR | NR | Depressed | NR | NR | Increased incidence of infarcts + leukoencephalopathy in MDD |
| (Deicken et al 1991) | 90 psychiatric patients (31 MDD) | 43.9±21.5 46.7±21.9 |
0.5T 5mm (2.6mm gap) |
NR | NR | NR | NR | NR | Large variety of cardiovascular risk factors | 42% of patients + 12% of HC showed deep WMH. Mean age for patients with and without WMH was 62 and 32 |
| (Rabins et al 1991) | 21 MDD 14 HC |
23–79 60+ |
1.5T ROI |
54.2±17.1 | NR | NR | Depressed | NR | No neurological disease or head trauma | Greater severity of WMH but not PVH in MDD |
| (Guze and Szuba 1992) | 119 MDD (44 young + 75 old) 60 HC (30 young + 30 old). |
33.4 66.2 34.1 68.7 |
0.3T 7mm (3mm gap) |
21 (young) 43 (old) |
11.6 (young) 24.2 (old) |
NR | Depressed | NR | NR | Old MDD group had more WMH than young MDD and old HC. Young defined as less than 45 years of age |
| (Coffey et al 1993) | 48 MDD 76 HC |
62.4±16.4 61.6±15.9 |
1.5T 5mm (2.5mm gap) ROI |
NR | NR | NR | Severely depressed | 30 free of medication for 2.5 days (median). Remainder on Benz, AD + AP | No substance abuse, neurological disorder. 13 with hypertension or heart disease, 2 with COPD. | Greater number of PVH in MDD |
| (Fujikawa et al 1993) | (1) 31 young, early onset MDD (2) 70 young, late onset MDD (3) 41 old, early onset depression (4). 63 old, late-onset depression |
56.7±3.6 58.2±3.6 67.6±2.4 72.8±5.3 |
0.5T 10mm |
Early-onset < 50 Late-onset > 50 |
NR | NR | Depressed | NR | NR | Frequency of silent cortical infarcts: (1) 22.6% (2) 51.4% (3) 65.9% (4) 93.7% |
| (Howard 1993) | 12 MDD 12 HC |
76.0±6.5 77.7±7.9 |
1.5T 8mm (0.8mm gap) |
>45 | NR | NR | Severely depressed | NR | No neurological disorders, stroke or alcohol abuse. Groups matched for cardiovascular risk factors. | Trend for PVH + WMH to be more severe in MDD. |
| (Dupont et al 1995b) | 33 MDD 32 HC |
38.9±10.2 39.2±8.9 |
1.5T 5mm (2.5mm gaps) |
±25 | NR | Mixed | Depressed | 13 AD, 18 no medication | No substance abuse in last 5 years. No hypertension, head injury | No significant differences |
| (Hickie et al 1995) | 39 MDD | 64.4 | 1.5T 5mm (2.5mm gap) |
NR | 63±54.9 weeks | 19/39 | Severe depression with history of psychosis | AD, lithium, ECT | Positive history of hypertension + cerebrovascular risk factors. 6/39 with alcohol abuse. | Late onset group (>50) showed more WM changes than earlier onset group. WMH associated with negative family history of depression + poor response to treatment. |
| (Lewine et al 1995) | 27 MDD 150 HC |
40±11 33±9 |
1.5T 5–8mm |
±35 | NR | NR | NR | NR | No neurological or medical disorders. No current substance abuse. | Deep WMH more common in MDD |
| (Greenwald et al 1996) | 48 MDD 39 HC |
74.6±6.1 72.6±6.4 |
1T 7mm (0.7mm gap) |
62.4±15.2 | NR | NR | Depressed | NR | No dementia, history of stroke or other DSM diagnosis. 19 MDD with hypertension, 7 heart disease, 6 DM. Similar rates in HC. | No significant differences in WMH |
| (Iidaka et al 1996) | 30 MDD 30 HC |
67.7±5.4 66.3±4.7 |
1.5T 5mm |
61.8±9.4 | NR | 9/30 | Depressed | NR | Matched for cerebrovascular risk factors. | More PVH but not WMH in frontal lobes + BG in MDD |
| (O’Brien et al 1996) | 60 MDD 39 HC |
71.2±7.9 71.4±11.0 |
0.3T 5mm (0.5–2.5mm gap) |
NR | NR | NR | Depressed | NR | No PD, epilepsy, substance abuse, insulin-dependent DM | Deep WMH in BG and frontal lobes more common in MDD group. Patients with late-onset MDD had more WMH than early-onset MDD. |
| (Salloway et al 1996) | 30 MDD | Early onset: 73.3±7.8 Late onset: 77.5±4.4 |
1.5T 5mm (2.5mm gap) |
“Early” onset: 35.8±16.4 “Late” onset: 72.4±7.1 |
± 37 (early onset) ± 5 (late onset) |
NR | Depressed | NR | No neurological disorders or substance abuse | More deep WMH + PVH in late onset group. |
| (Dahabra et al 1998) | 23 MDD | 66.2±5.1 | 0.5T 7mm (1mm gap) |
12 >55 11 <50 |
NR | NR | Euthymic | AD, 7 lithium | No substance abuse, epilepsy, heart disease, neurological or endocrine disorders. | Greater severity of WMH in late-onset MDD |
| (Greenwald et al 1998) | 35 MDD 31 HC |
74.7±6.4 72.9±4.7 |
1T 5mm (2.5mm gap) ROI |
56.5±17.1 | NR | NR | Depressed | NR | No dementia, stroke, other DSM diagnoses. Patients and controls matched for other cerebrovascular risk factors. | Depression associated with L deep frontal and L putaminal WMH |
| (Lenze et al 1999) | 24 MDD 24 HC |
52.7±18.4 | 1.5T 5mm |
19 early onset (25.4±6.4). 5 late onset (59.2±6.6) | 151±147 (weeks) | Yes - 75% (79% early-onset; 60% late-onset) | Depressed | AD | No neurological, endocrine and cerebrovascular disorders. No hypertension. | No significant differences in total number of lesions |
| (Sato et al 1999) | 3371 people drawn from background population | 72.2 | 1.5T 5mm |
NR | NR | NR | NR | NR | No cancer but a variety of cardiovascular risk factors. | WMH associated with depressive symptomatology |
| (Steffens et al 1999) | 3660 people drawn from background population | Approximately 75 | 1.5T | NR | NR | NR | NR | NR | NR | Number of WMH in BG associated with depressive symptoms as measured with a psychometric scale after controlling for hypertension + cardiovascular disease. |
| (de Groot et al 2000) | 1077 non-demented adults. | 60–90 | 1.5T 5–6mm (20% gap) |
NR | NR | NR | NR | NR | No dementia | People with severe WMH were 3–5 times more likely to have symptoms of depression. WMH associated with older age of onset (>60). |
| (Kumar et al 2000) | 51 MDD 30 HC |
74.3±6.56 69.43±6.09 |
1.5T 5mm |
35 patients had onset after age 60 | NR | NR | Depressed | AD, BZ | No neurological disorders, dementia or substance abuse. Both MDD + HC had heart disease, DM | Increase in lesion volume in MDD |
| (MacFall et al 2001) | 88 MDD 47 HC |
72.6±7.9 72.2±6.3 |
1.5 3mm VBM |
49.3±22.6 | NR | NR | Depressed | NR | NR | Trend towards more deep WMH in MDD |
| (Murata et al 2001) | 20 early onset MDD 27 late onset MDD |
62.7±6.7 60.3±6.9 |
1.5T 5mm |
Early onset: 39.7±8.8 Late onset: 65.6±5.4 |
2.78±0.89 episodes (early) 1.47±0.68 episodes (late) |
NR | Depressed | AD, BZ | Incidence of cardiovascular risk factors not different across groups | More severe WMH in late onset group. |
| (Nebes et al 2001) | 92 healthy volunteers | 73.6±3.4 | 1.5T 5mm (1mm gap) |
NR | NR | NR | NR | 1 person on AD | No PD, HD, AD, schizophrenia, BD, alcoholism, head injury | Deep WMH but not PVH associated with level of depression. |
| (Tupler et al 2002) | 115 MDD (69 late-onset, 46 early onset) 37 HC |
66.7±10.9 65.9±9.4 |
1.5T 5mm (2.5mm gap) |
NR | NR | NR | Depressed | NR | No exclusion for comorbid medical illness except dementia | More severe WMH rating in deep frontal regions in late-onset cases. Early-onset defined as <50 |
| (Sassi et al 2003) | 17 MDD 38 HC |
42.8±9.2 36.8±9.7 |
1.5T 5mm |
7/17 <30 10/17 >30 |
NR | Mixed | NR | No medication for 2+ weeks before scan | No neurological disorders, axis I co-morbidity or substance abuse | MDD patients with longer illness duration had more WMH. The early-onset group had more WMH than HC. MDD subjects with a positive-family history had more WMH than their counterparts with no history. |
| (Silverstone et al 2003) | 11 MDD 19 HC |
34.4 35.9 |
0.5T 5mm (2.5mm gaps) |
26.6 | 7.8 | NR | Depressed | NR | No neurological disorders, cardiovascular disease, DM or head injury | No between group differences |
| (Firbank et al 2004) | 29 MDD 32 HC |
75.7±5.9 74.9±7.0 |
1.0T 5mm (1.5mm gap) VBM |
NR | ±21.5 ±4 episodes |
NR | Depressed | NR | No dementia, substance abuse, history of stroke, ischemic attack. Other vascular risk factors allowed. | Greater frontal lobe WM lesion volume in MDD. Differences between groups greater after exclusion of subjects with hypertension, DM and heart disease |
| (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 | No differences in WMH |
| (Kumar et al 2004) | 8 MDD 8 HC |
71.5±5.13 74.1±8.90 |
MT-MRI 1.5T 3mm ROI |
NR | NR | NR | Depressed | Off medication for 2+ weeks | No neurological disorders including dementia | Abnormalities in the WM of the R caudate + R putamen 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, neurological or serious medical disorders. | No differences between groups |
| (Firbank et al 2005) | 629 subjects from background population | NR | 5mm | NR | NR | NR | NR | NR | 439 with hypertension, 184 with history of stroke, | Level of depression associated with severity of WMH |
| (Heiden et al 2005) | 31 MDD | 68.0±6.5 | 1.5T 6mm (0.6mm gap) |
47–51 | NR | NR | NR | AD | NR | Extent of WMH associated with severity of depression after 5 year follow-up. Severity of WMH associated with poorer outcome. |
| (Jorm et al 2005) | 475 background volunteers. 17 classified as MDD. | 60–64 | 1.5T 2mm |
NR | NR | NR | Depressed | NR | NR | Association between total brain WMH + depression. Remitted subjects taking AD intermediate to depressed patients + HC. |
| (Minett et al 2005) | 60 patients attending memory clinic (12 MDD) | 72.6±4.7 | 1.5T 5mm (0.5mm gap) |
NR | NR | NR | NR | NR | No dementia, severe medical or neurological disease, current psychiatric disorders or alcohol abuse | Late-onset depression associated with WMH severity |
| (Taylor et al 2005) | 253 MDD 146 HC |
70.48±6.23 69.85±7.54 |
1.5T 3mm |
NR | NR | NR | Depressed | NR | No other major psychiatric disorders such as BD. No substance abuse or neurological disorders. Hypertension + heart disease more common in MDD | Greater WM lesion volumes in MDD |
| (Bae et al 2006) | 106 MDD 84 HC |
70.4±6.4 71.7±6.0 |
DTI 1.5T 3mm ROI |
NR | NR | NR | Depressed | NR | NR | Loss of WM integrity in middle + superior frontal gyri + ACC |
| (Chen et al 2006) | 164 MDD 126 HC |
68.93±7.04 69.83±6.25 |
1.5T 3mm (3mm gap) |
NR | NR | NR | Depressed | Yes – not specified | No current substance abuse, psychiatric or neurological illness. | Greater volume of WM lesions at baseline + at 2-year + 4-year follow-up in MDD |
| (Hannestad et al 2006) | 182 MDD 62 HC |
70.2±5.8 70.0±7.7 |
1.5T 3mm (3mm gap) ROI |
43.7±20.8 | NR | NR | Depressed | NR | No other DSM disorders, substance abuse, neurological illness. | Greater volume of WML in MDD. |
| (Iosifescu et al 2006) | 84 MDD 35 HC |
40.7±10.2 39.3±9.8 |
1.5T 3mm |
NR | NR | NR | Depressed | No medication | No BD, psychosis, substance abuse within last 21 months, organic mental disorder, seizure disorder, unstable medical illness. | No difference in prevalence of WMH. WMH correlated with cardiovascular risk score. |
| (Nobuhara et al 2006) | 13 MDD 13 HC |
62.8±6.6 61.5±4.8 |
DTI 1.5T 6mm (2mm gap) ROI |
52.9±7.3 | 4.0±2.6 | NR | Depressed | AD | No dementia, severe medical illness, neurological disorders | Loss of integrity of WM frontal and temporal tracts. |
| (Rainer et al 2006) | 51 MDD 204 HC |
75.8 (whole sample) | 1T | >65 – not specified | NR | NR | Depressed | AD, BZ | Groups matched for cardiovascular risk factors. | No differences in incidence of WMH |
| (Versluis et al 2006) | 527 background population | 74.9 | 1.5T 3mm |
NR | NR | NR | NR | NR | Cerebrovascular risk factors not exclusion criterion | Presence of WMH at baseline was not predictive of depression at 33 month follow-up |
| (Godin et al 2007) | 1214 subjects followed for 4 years. 14.5% depressed at baseline | 72.5±4.1 | 1.5T 3.5mm (0.5mm gap) |
NR | NR | NR | Depressed | AD – not specified. | No pacemaker, vulvular prosthesis, history of neurosurgery or aneurysm. | Patients with baseline depression had more WMH at follow-up. Among non-depressed subjects at baseline, the higher the rate of WMH, the greater the risk of depression at follow-up |
| (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 | Greater severity of WMH in late-onset group. |
| (Ma et al 2007) | 14 MDD 14 HC |
28.9±8.0 27.1±6.7 |
1.5T 2mm DTI |
28.1±7.8 | 10.3±8.3 (months) | NR | Depressed | Treatment naive | No LOC, substance abuse in last 9 months, mental retardation, serious medical or neurological illness | Lower FA in WM of R middle frontal gyrus (dorsal PFC), parietal + occipito-temporal lobes |
| (Yang et al 2007) | 31 MDD 15 HC |
64.6±5.21 64.3±4.22 |
1.5T DTI 3mm ROI |
NR | NR | NR | Depressed | 24 AD, 7 drug-free | No substance abuse, major psychiatric or neurological disorders. | Decreased FA values in middle, superior frontal gyri, + R parahippocampal gyrus |
| (Zanetti et al 2008) | 28 MDD 102 HC |
30.5 30.4 |
1.5T 3mm |
NR | 34.1 (28.5) weeks | NR | Psychotic | 16 AP, 14 AD, 4 MS, 7 drug free | No organic, neurological illness, head injury, mental retardation. 6 individuals with substance abuse/dependence, 2 individuals with hypertension | No significant differences in prevalence or severity of WMH between groups. |