Supplementary Information
Figure S1 Individual mice clustering of video tracker data using a PhenoChipping approach(1). We
used GeneSpring GX (Agilent Technologies, Palo Alto, CA) a microarray gene expression analysis
software, for the novel use of analyzing and visualizing phenotypic data. Unsupervised two-way
hierarchical clustering of normalized (Z-scored) behavioral data from locomotor pattern test was
carried out, using methodology previously described(2) . (a) Male mice (b) Female mice. Center
Time-time spent in the center zone; Center entry-number of time entering center zone; V.maxmaximal velocity; Red-increased; blue-decreased.
A.
B.
2
Figure S2. Effects of diet on food intake and weight changes.
3
Table S1. Female blood top gene expression changes in response to DHA. Redcandidate biomarkers for human studies, changed in expression by DHA in opposite
direction to that seen in human blood in mood disorders and stress disorders.
Gene Symbol /Name
Blood
Change
Animal Brain Evidence
Animal
Blood
Evidence
Animal Genetic
Evidence
Human
Brain
Evidence
Bipolar (6)
(Transgenic)
Decreased anxietyrelated response,
abnormal frequency of
paradoxical sleep,
(I)
BP
Human Blood
Evidence
Human Genetic
Evidence
CFG
Score
(I)
Alcohol
(3)
FOS
FBJ osteosarcoma
oncogene
D
(D)
MDD
Fluoxetine(4)
(I)
Anxiety
Plaza-Zabala A
2010
(I)
Stress
(7)
(I)
PTSD(8)
(I)
Stress (9)
14q24.3
(Linkage)
BP (10)
Alcohol (11)
5.5
(5)
DBP-STAMY (I) (2)
CD44
CD44 antigen
DUSP1
dual specificity
phosphatase 1
D
Bipolar CP (12)
Bipolar (6)
(I)
Alcohol
(3)
D
Bipolar
(6)
Alcohol AMY,
CP,NAC,PFC (16)
QTL
Abnormal
eating/drinking
behavior;Abnormal
circadian rhythm
QTL
Abnormal
eating/drinking
behavior;Abnormal
circadian rhythm
(I)
BP
(D)
Alcohol
(D)
BP,MDD
(I)
Stress (9)
(17)
(21)
D
(14)
(I)
Anxiety
(I)
Alcohol
Bipolar (6)
(20)
11p13
(Linkage)
Alcohol
(15),
5.0
(13)
(I)
BP
(19)
MBP
myelin basic protein
(I)
BP
(I) MOOD
BIOMARKER (6)
5q35.1
(Linkage)
PD (18)
5.0
18q23
(Association)
BP
(23)
5.0
(22)
DBP-NST PFC (D);DBPSTAMY (I);DBPSTPFC(D); DBPSTAMY(I) (2)
(D)
MDD
(24)
(D)
BP
(27)
PSEN1
presenilin 1
D
Alcohol NAC
QTL
Abnormal
eating/drinking
behavior; Abnormal
circadian rhythm
(16)
(D)
Alcohol
(25)
(D)
Chronic stress
(D)
SuicideMDD
(28)
14q24.2
(Association)
Depression(29)
5.0
(26)
(D)
SPP1
secreted phosphoprotein 1
D
Bipolar VT (12)
Bipolar (6)
(QTL)
Abnormal
emotion/affect behavior
Addiction/drug abuse
(D)
SuicideMDD
(D) Hallucinations(30)
(26)
4q22.1
(Linkage)
Anxiety (31)
BP (10)
(I)
BP
5.0
(17)
ATXN1
ataxin 1
(D)
Alcohol
D
GLO1
glyoxalase 1
I
PBRM1
polybromo 1
I
Bipolar CP(12)
DBP-ST PFC (D) (2)
(QTL)
Abnormal
emotion/affect
behavior;
Addiction/drug abuse
(D)
Anxiety (34)
Bipolar CP(12)
QTL
Abnormal
eating/drinking
behavior; Abnormal
circadian rhythm
(D)
BP
(QTL)
Abnormal
(I)
BP
(32)
DBP-ST AMY (I) (2)
(D)
Alcohol
(33)
(D) Delusion
,Hallucinations (30)
(I) MOOD
BIOMARKER (6)
(D)
Chronic stress(28)
(D)
BP,MDD(36)
6p22.3
(Association)
BP/substance abuse
4.5
(23)
6p21.2
(Association)
PD(37),
(38)
4.5
(35)
(I) MOOD
3p21.1
(Association)
4.5
4
emotion/affect
behavior,
Addiction/drug abuse
SLC6A4
solute carrier family 6
(neurotransmitter
transporter, serotonin),
member 4
(I)
Avoidance learning (fear)
(41)
D
WNK1
WNK lysine deficient
protein kinase 1
(QTL)
Abnormal
emotion/affect behavior
Addiction/drug abuse
(12)
I
(Transgenic)
Abnormal response to
novel object/Abnormal
anxiety-related
response/Behavioal
despair/Abnormal
sleep pattern/ Cocaine
preference
Bipolar VT
DBP-STPFC (D); DBPST AMY (I) (2)
(39)
BIOMARKER (6)
BP/MDD(39)
BP (40)
(D)
SuicideMDD
(42)
(D)
PD
(43)
(I)
MDD(45)
(D)
SuicideMDD
17q11.2
(Association)
Alcohol(46),(47)
Anxiety (48),(49)
BP(50)
MDD
4.5
(51, 52),(53)
(44)
(I)
BP
(D)
Alcohol
(14)
(54)
12p13.33
(Association)
Alcohol(55)
4.5
Table S2. Male blood top gene expression changes in response to DHA. Redcandidate biomarkers for human studies, changed in expression by DHA in opposite
direction to that seen in human blood in mood disorders and stress disorders.
Gene Symbol
/Name
APOE
apolipoprotein E
Blood
Change
Animal Brain
Evidence
D
(I)
Stress(56)
(I)
Alcohol (McBride, Kimpel et al.
Animal
Blood
Evidence
Animal Genetic Evidence
(Transgenic)
Increased anxiety-related
response
2010
(I)
Alcohol
(McBride, Kimpel et al. 2010
D
(Transgenic)
Impaired passive avoidance
behavior, depressionrelated behavior
(I)
Anxiety
(59)
Bipolar CP
MBP
myelin basic protein
D
PTGDS
prostaglandin D2
synthase (brain)
D
(12)
(I)
BP(19)
(I)
Anxiety(20)
(I)
Anxiety;DBP-ST AMY
(I);DBP-ST PFC(D);
DBP-ST AMY(I) (2)
(I)
Anxiety
Human Blood
Evidence
Human Genetic
Evidence
(D) Delusion(30)
19q13.32
(Association)
MDD(51)
PTSD(58)
(D)
Alcohol
Alcohol HIP(16)
GABBR1
gamma-aminobutyric
acid (GABA) B
receptor, 1
Human Brain
Evidence
(13)
Alcohol
(I)
BP
(60)
(I)
Alcohol
(I)
Alcohol
(Transgenic)
Decreased aggression
Bipolar AMY (12)
(D)
PTSD
(8)
5.0
OCD(61)
(I) MOOD
BIOMARKER (6)
(22)
(D)
Alcohol
6p22.1
(Association)
MDD
(52)
(54), (25)
(21)
(34)
5.0
(57)
(I)
BP
Bipolar (6)
CFG
Score
(D)
BP
(62)
(13)
18q23
(Association)
BP
(23)
5.0
9q34.3
(Association)
Anxiety(63)
5.0
4q22.1
(Association)
Alcohol (67)
5.0
6p21.2
(Association)
PD(37),(70)
4.5
(D)
Alcohol
Liang 2010
SNCA
synuclein, alpha
GLO1
glyoxalase 1
GPM6A
glycoprotein m6a
I
I
D
(D)
Response to
antidepressant(64)
(D)BP(65)
DBP ST AMY (D) (2)
Alcohol AMY,HIP(16)
Bipolar (6)
DBP-ST
BLOOD (D)
(2)
(D)
Anxiety(34)
(D)
Anxiety(68),(69)
Bipolar CP (12)
(I)
Alcohol
(3)
(D)
Alcohol
Bipolar (6)
(33),
(66)
QTL
Abnormal eating/drinking
behavior;Abnormal
circadian rhythm
(D)
BP
QTL
Abnormal emotion/affect
behavior Abnormal
circadian rhythm
(D)
Alcohol
(D)
BP
(36)
(35)
(13)
(D) Delusion (30)
4q34.2
(Linkage)
Alcohol MDD(71)
Anxiety (31)
BP (72)
4.5
5
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