Table 14.
White Matter Hyperintensities in BD.
| Study | Sample | Age | Method | Age of Onset | Illness Duration/# Episodes |
Family History of Illness |
Clinical Status at Testing |
Medication Status | Medical + Psychiatric Comorbidity |
Findings |
|---|---|---|---|---|---|---|---|---|---|---|
| (Dolan et al 1990) | 14 BD 13 HC |
39±9 46±7 |
0.08T 12mm ROI |
31±9 | 11±7 | NR | Depressed | Lith, AD, BZ | No significant medical illness or alcohol abuse. | No group differences |
| (Dupont et al 1990) | 19 BD 10 HC |
36.5±10 41±10 |
1.5T 5mm (2.5mm gap) |
25±7.5 | NR | Mixed – not specified | Mixed – not specified | Lith, MS. No Benz, ECT, antihypertensives. | No poorly controlled hypertension, head injury with neurological sequelae, substance abuse of greater than 5 years duration. | 9 out of 19 BD subjects and no HC showed deep frontal WMH. No differences in age, age of onset, family history of BD between those patients with WMH and those without, but WMH associated with more hospitalizations. |
| (Swayze et al 1990) | 48 BD 47 HC |
33.9 34.4 |
0.5T 10mm |
22.86±7.82 | 5.89±6.15 (hosp) | NR | Manic | Lithium, AP, ECT | 27 with drug abuse, 33 with alcohol abuse | 9 out of 48 BD and 2 out of 47 HC showed WMH |
| (Figiel et al 1991) | 18 BD 18 HC |
37.5 (26–56) 34.7 |
1.5T 5mm (2.5mm gap) |
NR | ±28 | NR | 12 manic, 6 depressed | NR | No dementia, neurological illnesses. Presence of atherosclerotic risk factors similar in BD and HC. | WMH in 8 out of 18 BD, 1 out of 18 HC. |
| (McDonald et al 1991) | 12 BD 12 HC |
68.3±7 67.7±7 |
1.5T 5mm (2.5mm gap) |
62±6 | NR | 3/12 | manic | NR | 1 patient with ataxia, 1 with peripheral neuropathy, 1 with tardive dyskinesia. All patients had cognitive dysfunction | More BL subcortical WMH in BD group |
| (Brown et al 1992) | 22 BD 154 HC |
37.7±7.6 34±9.5 |
0.5T and 1.5T 7mm |
NR | NR | NR | NR | NR | No history of cardiovascular risk factors, current drug abuse | No inter-group differences in WMH |
| (Strakowski et al 1993) | 18 BD 15 HC |
31±11.8 32.4±8.8 |
1.5T 5mm (2mm gap) |
NR | 1st episode | NR | Manic | Majority of patients medication naive | 5 BD with drug abuse. No major neurological or medical illness. | More WMH in BD but not statistically significant. |
| (Aylward et al 1994) | 30 BD 30 HC |
39.3±11.1 37.6±9.0 |
1.5T 5mm |
24.6±8.4 | NR | NR | 1 depressed, 2 manic, 2 mixed, 27 euthymic. | AD | No “substantial” substance abuse. 7 hypertension, 12 smokers, 3 cardiovascular disease, 3 elevated cholesterol, 1 DM. | Greater prevalence of deep WMH in BD but significant differences due to older BD group. |
| (Altshuler et al 1995) | 29 BD I 26 BD II 20 HC |
41.6±11.6 40.0±10.0 35.2±9.9 |
0.5T 10mm |
28.3±10.9 for BD I, 19.2±7 for BD II. | 14.2±8.7 (BD I) 18.9±7.7 (BD II) |
NR | Euthymic | 30 lithium, 10 carbamazepine, 3 AD | 1 DM, 4 hypertension, | No significant difference between groups in deep frontal WMH. Trend (2x) towards more PVH in BD I. Greater number of PVH was due to BD I subsample >30 years of age. |
| (Botteron et al 1995) | 11 BD 5 HC |
11.3±3.1 11.8±2.9 |
1.5T 4–5mm |
NR | NR | NR | Manic | NR | No autism, pervasive developmental disorder, anorexia, bulimia, major medical or neurological illness, head injury. | WMH in 2 BD patients |
| (Dupont et al 1995b) | 44 BD 32 HC |
36.6±10.7 39.2±8.9 |
1.5T 5mm (2.5mm gaps) |
23±8.0 | NR | Mixed | 28 BD in remission, others depressed or manic. | 26 lithium, 6 AD, 6 AP, 2 anticholinergics | No substance abuse in last 5 years. No hypertension, head injury | Greater number of WMH in BD (46% vs 22%). Not accounted for by age of onset. Higher (but not significant) rate of WMH in subjects with family history. |
| (Lewine et al 1995) | 20 BD 150 HC |
36±7 | 1.5T 5–8mm |
±30 | NR | NR | NR | NR | No neurological or medical disorders. No current substance abuse. | No significant differences |
| (Woods et al 1995) | 52 BD 38 HC |
36.3±15.1 36.3±11.4 |
1.5T 5mm (2.5mm gap) |
NR | 2.1±1.8 (hosp) | NR | NR | NR | NR | More deep WMH and PVH in BD |
| (Persaud et al 1997) | 26 BD 34 HC |
35.6 31.6 |
0.5T 5mm |
25 | NR | NR | Manic | NR | No hypertensives, anorexics, heavy drinkers | No significant differences |
| (Ahearn et al 1998) | 21 family members (9 BD, 2 MDD, 10 unaffected) | 41 (range 12–66) | 1.5T 4–6mm |
18 | NR | Yes | NR | NR | No substantial artherosclerotic risk factors. | WMH in 9 affecteds and 6 unaffecteds. |
| (McDonald et al 1999) | 79 BD 70 HC |
49.9±19.7 53.2±18.1 |
1.5T 5mm (2.5mm gap) |
38±17 | NR | NR | NR | NR | NR | 16% of young BD (35.9±11) vs 0% HC showed WMH. No difference between old (68.2±9) BD and old HC. |
| (Krabbendam et al 2000) | 21 BD 22 HC |
38.3±7.9 41.4±11.3 |
1.5T 5mm (0.5mm gap) |
32.2±9.4 | 6.2±5.1 dep episodes 3.9±3.7 manic episodes |
NR | Remitted | 16 Lith 6 MS |
No cerebrovascular disease; head injury, DM, hypertension; substance abuse in last year. | No significant differences |
| (Moore et al 2001) | 14 BD (good outcome) 15 BD (poor outcome) 15 HC |
47.4±10.10 42.1±13.9 41.9±12.6 |
0.5T 7mm (1mm gap) |
31.4 in good outcome and 26.3 in poor outcome groups | 16±7.9 8.6±6.0 episodes (good outcome) 15.8±10.8 8.9±4.3 episodes (poor outcome) |
4 in each group | Good outcome group euthymic Poor outcome group depressed. | Lithium in good outcome group, not specified in poor outcome. | No axis I comorbidity, learning disorders, neurological or cerebrovascular disease, head injury, hypertension, cardiovascular illness, drug abuse | Greater number of subcortical WMH in poor outcome BD (7/15) group than good outcome sample (1/14) or controls (0/15) |
| (Lopez-Larson et al 2002) | 17 BD 12 HC |
29±8 31±8 |
1.5T 1mm ROI |
NR | 7±6 | NR | Manic | 9 MS, 4 AP, 3 AD | No medical or neurological disorders, head injury, substance abuse in previous 3 months | No WM differences. |
| (Lyoo et al 2002b) | 56 BD 83 HC |
13.6±2.1 9.9±3.3 |
1.5T 5mm (2.5mm gap) |
NR | NR | NR | NR | NR | NR | Greater number of frontal WMH in BD (17.9%) compared with HC (1.2%) |
| (Pillai et al 2002) | 15 BD 16 HC |
15.0±2.4 16.0±1.8 |
1.5T 5mm (2mm gap) |
10±4.2 | 5±3.4 | NR | NR | NR | No significant neurological disorder, head injury with loss of consciousness for more than 20 min. No substance abuse | WMH present in 10 BD (67%) and 5 HC (31%) |
| (Sassi et al 2003) | 24 BD 17 MDD 38 HC |
34.2±9.9 42.8±9.2 36.8±9.7 |
1.5T 5mm |
14/24 <20 10/24 >21 |
NR | 12/24 | NR | Lithium | No neurological disorders, axis I comorbidity or substance abuse | No significant differences |
| (Silverstone et al 2003) | 13 BD 19 HC |
40.2 35.9 |
0.5T 5mm (2.5mm gaps) |
25.9 | 14.2 | NR | Depressed | NR | No neurological disorders, cardiovascular disease, DM or head injury | More BD subjects (56%) had deep frontal WMH than HC (26%). Effect strongest in older subjects. No differences in PVH. |
| (Adler et al 2004) | 9 BD 9 HC |
32±8 31±7 |
3T 5mm ROI |
NR | NR | NR | NR | MS, AP | No concurrent psychiatric or medical illness including substance abuse | Reduced fractional anisotropy in frontal regions of BD indicative of loss of bundle coherence of WM tracts |
| (Ahn et al 2004) | 43 BD 39 HC |
36.9±11.9 35.1±9.7 |
1.5T 3mm |
NR | NR | NR | NR | NR | No axis I disorders, substance abuse within 3 months of study, antisocial PD, neurological illnesses, head injury, seizure, ADHD. | Greater number of deep frontal WMH in BD (27.9%) compared with HC (7.7%) |
| (Beyer et al 2005) | 14 BD 21 HC |
44.0±17.6 44.6±13.5 |
1.5T 5mm (2.5mm gap) ROI |
NR | 13.6±12.1 | NR | 6 depressed, 5 manic, 3 euthymic | NR | No dementia, neurological or medical illnesses, other primary psychiatric diagnosis or recent substance abuse | WM of OFC exhibited higher apparent diffusion coefficients but not FA in BD |
| (Chang et al 2005a) | 20 BD 20 HC |
14.6±2.8 14.1±2.8 |
3T 1.5mm |
NR | 1.7±1.8 | NR | 3 manic, 3 mixed, 1 depressed, 13 euthymic | MS, AD, AP. Psychostimulants discontinued 24 hrs before scan. | No pervasive developmental disorders, neurological conditions, substance abuse. 85% had ADHD, 35% anxiety disorder, 60% ODD. | No difference between groups in prevalence of WMH. |
| (Adler et al 2006a) | 11 BD 17 HC |
14±2 | 3T 5mm ROI |
11±3 | 1st episode | NR | Manic or mixed episode | Nil | No substance abuse in last 3 months. No head trauma, unstable neurological or medical conditions | No differences in FA of medial and inferior frontal regions but FA of superior frontal cortex lower in BD |
| (de Asis et al 2006) | 40 BD 15 HC |
69.8±6.7 66.9±6.5 |
1.5T 5mm |
51.8±18.3 | NR | NR | Manic | NR | No dementia, medical illness | More severe deep frontal WMH in BD. Positive association between age of onset of mania + WMH |
| (El-Badri et al 2006) | 50 BD 26 HC |
30.2±6.2 30.2±6.2 |
0.5T | NR | 8.9±3.3 | NR | Euthymic | NR | No axis I comorbidity, learning disorders, neurological or cerebrovascular disease, head injury, hypertension, cardiovascular illness, drug abuse | Deep WMH found in 5 BD but no HC. |
| (Gulseren et al 2006) | 12 BD 1 12 siblings 12 HC |
30.9±3.6 29.5±5.8 30.4±3.6 |
0.5T 5mm |
24.8±3.6 | 6.1±3.2 | Yes - 2/12 | NR | Lithium | No substance abuse, hypertension, history of neurological disorders or head trauma. All subjects <45 years old | No difference in frequencies of WMH. Number of WMH correlated with # manic episodes |
| (Regenold et al 2006) | 8 severe BD 8 controls with neurological illness |
58.4±12.9 54.5±12.8 |
1.5T 5mm (1mm gap) ROI DTI |
32 | 25±7.2 (episodes) | NR | 4 manic, 3 mixed, 1 depressed | 7 MS, 7 AP, 2 AD, 2 Benz | 6 BD, 1 control smokers. No substance abuse | Elevated apparent diffusion coefficient as evinced by DTI – indicative of decreased integrity of WM in the frontal lobes of BD patients. |
| (Houenou et al 2007) | 16 BD 16 HC |
41.88±12.82 40.50±12.82 |
1.5T 1.3mm DTI |
18.13±3.77 | NR | NR | Euthymic | Lithium, AD | No neurological conditions, substance abuse, head injury. 1 patient with comorbid PD | Increased number of white matter tracts between the L sgACC and the amygdala-hippocampal complex. This result was not influenced by illness duration |
| (Yurgelun-Todd et al 2007) | 11 BPD 1 10 HC |
32.9±10.5 32.4±9.1 |
1.5T 5mm DTI |
21.7±5.4 | 12.0±9.8 | NR | Euthymic | Lith, MS, AP | No organic mental disorder, head injury, CNS disease, substance abuse in previous 6 months | BD patients had significantly higher FA in the midline of the genu but not splenium indicating changes in WM microstructure |
| (Zanetti et al 2008) | 25 BD 102 HC |
28.7 30.4 |
1.5T 3mm |
NR | 27.1±19.3 weeks | NR | Psychotic | 12 AP, 2 AD, 13 MS, 6 drug free | No organic, neurological illness, head injury, mental retardation. 5 individuals with substance abuse/dependence, 2 individuals with hypertension | No significant differences in prevalence or severity of WMH between groups. |