Prospective longitudinal voxel-based morphometry study of major depressive disorder in young individuals at high familial risk.
Previous neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development.



Unaffected individuals (16-25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls ('low risk', n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures.



Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline.



These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
T
T
Nickson
Clinical Psychology,University of Edinburgh,Edinburgh,UK.
S W Y
SW
Chan
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
M
M
Papmeyer
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
L
L
Romaniuk
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
A
A
Macdonald
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
T
T
Stewart
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
S
S
Kielty
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
S M
SM
Lawrie
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
J
J
Hall
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
J E
JE
Sussmann
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
A M
AM
McIntosh
Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
H C
HC
Whalley
D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000473:pathology*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D012306:Risk; D055815:Young Adult
Amygdala; bipolar disorder; hippocampus; major depressive disorder; voxel-based morphometry