White matter volume is decreased in bipolar disorder at early and late stages

Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied.

Objective:

To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls.

Methods:

Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects).

Results:

CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD.

Conclusion:

Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Keywords:
Bipolar disorder; magnetic resonance imaging; affective disorders; staging; biomarkers

		Early stage			Late stage
		BD (n=14)	Controls (n=14)	p-value	BD (n = 15)	Controls (n=12)	p-value
Sex (male/female)		4/10	6/8	0.430^* * Qui-square;	4/8	8/7	0.299^* * Qui-square;
Age (years), mean (SD)		40.79 (14.22)	39.93 (10.03)	0.855^† † Student's t test;	52.07 (11.08)	52.15 (11.08)	0.985^† † Student's t test;
No. years at school, mean (SD)		10.29 (3.17)	11.18 (2.76)	0.434^† † Student's t test;	8.17 (2.04)	8.80 (2.37)	0.470^† † Student's t test;
BMI, mean (SD)		26.80 (5.49)	27.50 (3.85)	0.680^† † Student's t test;	31.31 (6.92)	27.54 (5.67)	0.133^† † Student's t test;
FAST, median (IQR)		12 (18.25)	9 (7.5)	0.151^‡ ‡ Mann-Whitney test.	43 (16)	5 (2)	0.001 ^‡ ‡ Mann-Whitney test.
Marital status, n (%)
	Single	2 (14.29)	2 (12.29)	0.492^* * Qui-square;	5 (33.33)	1 (8.33)	0.367^* * Qui-square;
	Married	10 (71.43)	10 (71.43)		5 (33.33)	7 (58.34)
	Divorced	1 (7.14)	2 (14.28)		3 (20)	3 (25)
	Widowed	1 (7.14)	0		2 (13.34)	1 (8.33)
Work situation, n (%)
	Employed	12 (85.71)	14 (100)	0.379^* * Qui-square;	2 (13.33)	12 (100)	0.001 ^* * Qui-square;
	Unemployed	2 (14.29)	0		2 (13.33)	0
	Medical benefits	0	0		6 (40)	0
	Invalidity	0	0		5 (33.34)	0

		BD early (n = 14)	BD late (n = 15)	p-value
Illness duration (years)		8 (7.5)	18 (23.75)	0.017 ^* * Mann-Whitney test;
No. mood episodes		5 (4)	16 (26.5)	<0.0001 ^* * Mann-Whitney test;
Suicide attempts		2 (0)	1 (1)	0.023 ^* * Mann-Whitney test;
No. hospitalizations		2 (2.5)	3 (4)	0.093^* * Mann-Whitney test;
HAM-D		0 (2)	5 (2.5)	0.011 ^* * Mann-Whitney test;
YMRS		0 (2)	1 (2.5)	0.572
No. patients under…, n (%)				0.003 ^† † Chi-square test.
	One drug	7 (50)	0
	Two drugs	6 (42.9)	5 (33.33)
	Three drugs	0	5 (33.33)
	Four drugs	1 (7.1)	4 (26.67)
	Five or more drugs	0	1 (6.67)
No. patients under clozapine		0	5	0.042 ^† † Chi-square test.
No. patients under…, n (%)		9 (64.3)	5 (41.7)
	Lithium	9 (64.3)	9 (75)
	Anticonvulsants	6 (42.9)	12 (100)
	Atypical antipsychotics	0	4 (33.3)
	Typical antipsychotics	4 (28.6)	2 (16.7)
	Antidepressants	0	4 (33.3)
	Benzodiazepines

Associação de Psiquiatria do Rio Grande do Sul Av. Ipiranga, 5311/202, 90610-001 Porto Alegre RS/ Brasil, Tel./Fax: (55 51) 3024 4846 - Porto Alegre - RS - Brazil
E-mail: trends@aprs.org.br

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[1] Correspondence: Clarissa S Gama, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903 - Porto Alegre, RS - Brazil, Tel.: +55 (51) 33598845 E-mail: cgama@hcpa.edu.br