Plasma omega-3 and psychological distress among
Nunavik Inuit (Canada)
Michel Lucasa, Éric Dewaillya,b,⁎, Carole Blancheta, Suzanne Gingrasa, Bruce J. Holubc
aPublic Health Research Unit, Laval University Medical Research Centre (CHUQ), Sainte-Foy, Québec, Canada
bDepartment of Social and Preventive Medicine, Laval University, Sainte-Foy, Québec, Canada
cDepartment of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
Received 20 October 2006; received in revised form 14 December 2007; accepted 12 April 2008
Marine omega-3 (n−3) fatty acid eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have been associated with
beneficial effects in mental health. Cultural and social changes have been related to a decline in mental health of the Inuit, but the
role of diet has received scant attention. We examined the relationship between psychological distress (PD) and plasma n−3 among
368 Nunavik Inuit aged 18–74 years who took part in a survey in 1992. Participants were categorized as high-level PD if they
scored over the 80th percentile of the PD Index Santé-Québec Survey (PDISQS-14), and non-distressed subjects were those who
scored less than this cutoff. Compared with the non-distressed group, n−3 concentrations in the PD group were significantly lower
in women but not in men. Compared with the lowest tertile of EPA+DHA, the odds ratios for high-level PD among women were
0.32 (95% CI: 0.13–0.82) for the second, and 0.30 (95% CI: 0.10–0.90) for the third tertile, after controlling for confounders. In
males, there were no significant associations between EPA+DHA and PDISQS-14 scores. Our findings suggest that marine n−3
may play a role in PD among Inuit women. The gender difference observed in our analysis must be examined more carefully in
© 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Omega-3 fatty acids; Psychological distress; Inuit; Eicosapentaenoic acid; Docosahexaenoic acid; Plasma phospholipids; Women
Before World War II, the majority of the Inuit
populations mainly lived according to a traditional
lifestyle, which was based on subsistence activities
such as hunting and fishing (Santé-Québec, 1994;
Blanchet et al., 2002; Kirmayer et al., 2000a; McGrath-
Hanna et al., 2003). In recent decades, however, changes
in lifestyle and dietary patterns have been observed
among Inuit populations (Kirmayer et al., 2000a;
McGrath-Hanna et al., 2003). Traditional food system
use is declining rapidly, though not uniformly across the
Arctic, but for most circumpolar regions, dietary intake
from market foods exceeds those from traditional foods
(Blanchet et al., 2002). In several native populations, this
Available online at www.sciencedirect.com
Psychiatry Research 167 (2009) 266–278
⁎Corresponding author. Delta Building #2, Office 600, 2875 Laurier
Blvd., 6th Floor, Sainte-Foy, QC, Canada G1V 2M2. Tel.: +1 418 525
4444x46518; fax: +1 418 654 2726.
E-mail address: firstname.lastname@example.org (É. Dewailly).
0165-1781/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
shift away from traditional lifestyle and diet was
associated with increased health problems (Kirmayer
et al., 2000a; McGrath-Hanna et al., 2003). Some
aboriginal groups have reported evidence of severe
suicide, violence, alcoholism and substance abuse), the
most profound impact being seen among the young
Lalonde, 1998; Boothroyd et al., 2000; Haggarty et al.,
2000; Kirmayer et al., 2000a,b).
The Nunavikregion, locatedabove the 55thparallelin
the province of Quebec (Canada), is inhabited primarily
by Inuit. The traditional Inuit diet mainly consists of
caribou, which are eaten fresh (raw or cooked) or dried,
with the skin, blubber, liver, and fat added in different
meals (Santé-Québec, 1994; Blanchet et al., 2000). The
3 (n−3) fatty acids, represented a significant part of the
Inuit diet in 1992 (Santé-Québec, 1994; Blanchet et al.,
2000; Dewailly et al., 2001). Data from 24-h dietary
marine origin was 131.2 g/day (95% confidence interval
evidence points to a decrease in the traditional diet of the
market foods (which generally have a higher content of
trans-fatty acids, lower omega-3, higher omega-6/
omega-3 ratio, etc.) appear to be more attractive. We
reported earlier that young adults (18–34 years) had one-
half the eicosapentaenoic acid (EPA)+docosahexaenoic
acid (DHA) concentrations in plasma phospholipids
compared with Inuit aged 50 years and over (6.5% vs.
11.5%, Pb0.0001) (Dewailly et al., 2003).
Several studies have identified EPA and DHA con-
centrations in blood as indicators of past individual
dietary intake of marine n−3 fatty acids (Hjartaker et al.,
1997; Kobayashi et al., 2001; Kuriki et al., 2002, 2003;
Kobayashi etal.,2003). Ithas beensuggested thatdietary
changes occurring in our societies, mainly a decrease in
marine n−3 and an increase in omega-6 (n−6), could be
contributing to the increasing incidence of depression
shown that the prevalence of major depression (Hibbeln,
1998), bipolar depression (Noaghiul and Hibbeln, 2003),
post-partum depression (De Vriese et al., 2003; Hibbeln,
2002), hostility (Iribarren et al., 2004) and suicidal
ideation (De Vriese et al., 2004) is associated with lower
The Omega-3 Fatty Acids Subcommittee, assembled by
the Committee on Research of Psychiatric Treatment of
the American Psychiatric Association, has concluded that
studies support a protective effect of marine omega-3 in
mood disorders (Freeman et al., 2006). Human (Hama-
zaki et al., 2000; Maes et al., 2000; Delarue et al., 2003)
and animal (Takeuchi et al., 2003) investigations suggest
that marine n−3 may have an anti-stress function.
among the Inuit of Nunavik are lacking (Santé-Québec,
1994). This population and the representatives of various
sectors of activity recognize that psychological and social
has been associated with cultural and social changes,
increased chronic diseases (obesity, cardiovascular dis-
orders and diabetes) as well as a decline in mental health
(Kirmayer et al., 2000a; McGrath-Hanna et al., 2003).
However, the role of their traditional diet has received
scant attention in regard to mental health. A generalized
measure of PD was used in a cross-sectional survey
undertaken by the Government of Quebec among the
Inuit of Nunavik in 1992 (Santé-Québec, 1994). We
considered it important to examine the potential role of
marine n−3 fatty acids in PD among the Nunavik Inuit.
2.1. Study design and population
The Santé-Québec Health Survey among the Inuit of
Nunavik in 1992 has been described in detail elsewhere
(Santé-Québec, 1994; Dewailly et al., 2001). Briefly,
Santé-Québec, an organization of the Quebec Health
and Social Services Ministry, undertook a health survey
among the Inuit population of Nunavik in 1992. The
primary objective of the survey was to collect relevant
information on the physical, social and psychosocial
health of the Inuit population (Santé-Québec, 1994).
These data were gathered in several stages. Face-to-face
interviews were conducted in English and/or Inuktitut
(the Inuit language) at each participant's home to fill out
a lifestyle questionnaire along with a confidential and a
self-administrated socio-demographic questionnaire. A
clinical session was organized for the same participants,
in the village health clinic to obtain physiological and
anthropometric measurements. Information on demo-
graphic characteristics was collected from the Santé-
Québec data files. Our team was responsible for ana-
lyzing the fatty acids in blood samples.
The target population of the survey comprised all
permanent residents of Nunavik aged 18–74 years,
excluding households consisting of only non-Inuit
persons, individuals not related to an Inuit, and insti-
hold respondents, 560 participants submitted to clinical
267M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
measurements and blood tests. Of these, 183 did not have
them were therefore excluded from the present analysis.
the study subjects before inclusion. The study protocol
was approved by the Ethics Committee of Maisonneuve-
Rosemont Hospital (Montreal).
2.2. Psychological distress
PD among the Inuit was measured via a modified
version of the 14-Item PD Index used in the 1987 Santé-
The PDISQS-14 is an adaptation of the Psychiatric
Symptom Index (PSI), developed and validated by Ilfeld
(1976, 1978). The self-administered PDISQS-14 con-
tained 14 statements addressing psychological symptoms
experienced in the previous week (Table 1). The structure
of the PSI is based on the existence of four distinct
dimensions (depression, anxiety, aggressiveness and
psychomotor perturbations) connected at a second level
Scores range from a minimum of 0 to a maximum of
100. The internal consistency of the scale within the
Inuit sample was found to be satisfactory (Cronbach's
Québec master survey, a high level of PD was defined by
any score above the 80th percentile of index distribution
observed in the Inuit (Boyer et al., 1993). Participants
were categorized as having high-level PD if they scored
Non-distressed participants were those scoring less than
men and 52 women.
2.3. Plasma phospholipid fatty acids
measured for the fatty acid composition of phospholipids
(PLs). Fatty acid analysis of these plasma biomarkers
(PLs) was based on previously published methods (Stark
and Holub, 2004). The results and methods have been
described in detail elsewhere (Dewailly et al., 2001).
Briefly, the fatty acid composition of plasma PLs was
determined by capillary gas–liquid chromatography.
Fatty acid concentrations in plasma PLs were expressed
14:0 to 24:1. In this study, plasma PL concentrations of
fatty acids corresponded to the relative percentages of
total fatty acids by weight. The concentrations of only
polyunsaturated fatty acids (PUFAs) are reported for the
CAGE (Cutting down, Annoyance by criticism, Guilty
feelings, and Eye-openers) alcoholism risk questionnaire
(Ewing, 1984). A total score of 2 orgreater, considered to
be clinically significant, was the recommended standard
cutoff (Ewing, 1984).
Subjects were asked if they had experienced any of six
stressful events during the past 12 months: moved away
of by the community, suffered a serious illness, lost a
family member (death of husband/wife/common law
spouse), or lost a relative (death of father/mother/family
member when they were under the age of 12 years). A
favourable answer (yes) was coded as 1 for each of these
events (on scores between 0 and 7). The variable “Recent
stress events” was dichotomized, meaning that they either
represented persons who answered no to smoking
cigarettes on a daily basis. Subjects were also asked:
“How would you describe your relationship with other
chosen: “1 — very satisfactory, 2 — somewhat
satisfactory, 3 — somewhat unsatisfactory, 4 — very
unsatisfactory”. Subjects were considered to have a good
relationship with the community if they answered “very
2.5. Statistical analysis
The statistical distribution of plasma fatty acid con-
centrations was checked and found to be skewed for
some fatty acids. Therefore, we used log transformation
The Psychological Distress Index Santé-Québec Survey (PDISQS-14)
used in the Santé-Québec Health Survey among the Inuit of Nunavik
How often, during the past week, did you…
• feel hopeless about the future?
• have your mind go blank?
• feel down or blue?
• feel tense or under pressure?
• lose your temper?
• feel bored or have little interest in things?
• feel fearful or afraid?
• have trouble remembering things?
• cry easily or feel like crying?
• feel nervous or shaky inside?
• feel critical of others?
• feel easily annoyed or irritated?
• get angry over things that are not too important?
• feel like being alone?
268M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
Arithmetic means were also calculated for the fatty acid
t test was performed to compare fatty acids between PD
groups. Analysis of variance (ANOVA) with Bonferroni
correction for multiple comparisons served to compare
EPA+DHA plasma PL concentrations according to
quintiles of PDISQS-14 scores. All analyses were
stratified by gender. Since only 18 men presented high-
level PD, logistic regression analysis was conducted only
among the women. In all subjects and women, the
distribution of n−3 fatty acids was taken to compute
cutoff points for tertiles ofn−3. Associations between the
tertiles of n−3 fatty acids and the risk of high-level PD
were expressed as odds ratios (ORs), with the lowest
were discerned by assigning the log-transformed median
al., 1996; Steyerberg et al., 2001; Babyak, 2004). These
studies suggest a minimum number of events per variable
(minimally 10–15 events were needed per covariate).
were: age, good relationship with the community, abused
sexually, depression in lifetime, no recent stressful events,
coastal region, total plasma cholesterol (b5.2 mmol/l),
maternal language (non-native vs. native), education,
occupation, alcoholism, smoking and marital status. The
final models satisfied collinearity criteria. Statistical ana-
lyses were performed with the SAS program for Windows
v.9 (SAS Institute, Inc., Cary, NC). Differences between
groups and associations were considered significant at
Table 2 reports the prevalence of PD according to
study subject characteristics. Fig. 1 shows EPA+DHA
plasma PL concentrations according to PDISQS-14
quintiles for men and women. Higher PDISQS-14 quin-
tiles indicate higher PD scores, and the fifth quin-
tile corresponds to the high-level PD category. In all
participants, a lower EPA+DHA concentration (P for
trend=0.0028) was observed according to quintiles of
PDISQS-14 scores, especially among those categorized
as high-level PD. Stratification analysis revealed that
Prevalence of psychological distress (PD) according to characteristics of the study subjects.
CharacteristicsPD prevalence (%)
Total plasma cholesterol
Good relationship with community
Depression in lifetimec
Recent stress events
Drugs in lifetimee
18–24 years (n=84) 29.8, 25–44 years (n=188) 18.6, ≥45 years (n=94) 9.5
Female (n=221) 23.1, Male (n=145) 12.4
b5.2 mmol/l (n=211) 23.2, ≥5.2 mmol/l (n=155) 12.9
Yes (n=102) 30.4, No (n=248) 14.5
Hudson (n=204) 23.5, Ungava (n=164) 13.4
Single (n=93) 25.8, Others (n=254) 16.5
No education or on job training (n=75) 12.0, Others (n=270) 21.5
Yes (n=138) 10.9, No (n=221) 24.0
Non-native (n=29) 10.3, Native (Inuktitut) (n=339) 19.8
Yes (n=13) 38.5, No (n=353) 18.1
Yes (n=114) 25.4, No (n=229) 15.3
Remunerated employment (n=199) 15.1, Others (n=140) 21.4
Abstinent (n=130) 15.4, Users (n=176) 21.6, No response or refused to answer (n=62) 19.4
b2 (n=208) 16.4, ≥2 (n=160) 22.5
Never (n=32) 18.8, Ex-smokers (n=61) 11.5, Occasionally (n=23) 21.7, Regularly (n=242) 20.7
b25 kg/m2(n=134) 22.4, 25–30 kg/m2(n=149) 16.8, ≥30 kg/m2(n=70) 12.9
aThe category “others” combines married/cohabiting, divorced/separated and widowed.
bThe category “others” combines persons who reach (completed or not) the elementary or secondary school grade.
cSelf-reported by the principal respondent of the household who answered each chronic health problem listed in the questionnaire for every
member of the household.
dRemunerated employment group combines professionals, executives, white and blue collar workers. The category “others” combines trappers,
houseworkers, students, unemployed, retired and independent workers.
eThe category “users” combines users and ex-users of marijuana, hashish, cocaine, substance sniffing (solvents, glue, gasoline) and other illicit
drugs. To be considered “abstinent”, the subject must never have consumed any illicit drugs.
fCAGE (Cutting down, Annoyance by criticism, Guilty feelings, and Eye-openers) alcoholism risk questionnaire.
269M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
trends in EPA+DHA concentrations across quintiles of
PDISQS-14 scores were significant in women (P for
trend=0.0003) but not in men (P for trend=0.3932).
PUFA concentrations in plasma PLs are enumerated in
Table 3. Mean concentrations of n−3 fatty acids, except
linolenic acid (LNA), were significantly lower in the PD
group compared with the non-distressed group. Strati-
fication established that these differences were signifi-
cant only among women.
Table4 presents the ORs for high-level PD according
to plasma PL concentration tertiles of n−3, with the
lowest tertile group as the reference group. In all sub-
jects, EPA+DHA concentration was inversely related to
the risk of high-level PD in analyses adjusted for age
and gender (P for trend=0.0403), and was of borderline
significance by multivariate model analysis (P for
trend=0.0545). Compared with EPA+DHA concentra-
tions in the lowest tertile (median=4.2), the ORs for
high-level PD were 0.60 (95% CI: 0.29–1.24) for the
second tertile (median=7.3), and 0.44 (95% CI: 0.18–
1.03) for the third tertile (median=12.9), after control-
ling for confounders in the multivariate model. How-
ever, for women, EPA+DHA concentrations were
inversely related to the risk of high-level PD in all
analyses. Compared with women with EPA+DHA
concentrations in the lowest tertile (median=4.6), the
ORs for high-level PD were 0.32 (95% CI: 0.13–0.82)
for women with concentrations in the second tertile
(median=8.0) and 0.30 (95% CI: 0.10–0.90) for women
in the third tertile (median=13.1), after controlling for
confounders in the multivariate model.
There is accumulating evidence of the beneficial
effects of marine n−3 on mental health. In this cross-
sectional study of Nunavik Inuit, we found that women
in the high-level PD group had lower marine n−3 con-
centrations in plasma PLs than women in the non-
distressed group. However, we did not observe this
difference among men. Our main finding was that
women in the second and third tertiles of EPA+DHA
concentrations in plasma PLs had a 3 times lower risk of
having a high-level PD score than women in the lowest
tertile. Neither EPA nor DHA was significantly
associated in the multivariate model among women,
indicating that the combination of these fatty acids may
be a better independent variable to assess the health
effects of marine n−3 consumption (Harris and Von
4.1. Relationship between omega-3 and depressive
mood in other cross-sectional and cohort studies
Our results are in line with the studies of Tanskanen et
was significantly associated with depression among
Fig. 1. Mean concentrations of EPA+DHA in plasma PLs according to
quintiles of PDISQS-14 scores in all subjects, men and women. Higher
quintiles signify higher PD scores. The bars represent mean values
with the SEM shown as a positive error bar. The black bar is the high-
level PD group, andthe grey bars are the non-distressedgroups. Values
with different superscript letters are significantly different (Pb0.05).
270M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
women only (Tanskanen et al., 2001b; Timonen et al.,
2004). In a random sample of the Finnish population
participating in a health survey (n=3204), Tanskanen et
al.discerned a higherrisk(OR: 1.31, 95% CI:1.10–1.56)
of having mild depressive symptoms (score≥10 on the
21-item Beck Depression Inventory) among infrequent
fish consumers (less than once a week) (Tanskanen et al.,
depressive symptoms were only significantly associated
with infrequent fish consumption in women (OR: 1.40,
Timonen et al. found a 2.6-fold higher risk of being
depressed (Hopkins Symptom Checklist-25 depression
lifetime depression) among women who rarely ate fish
(monthly or more seldom) compared with regular eaters
(Timonen et al.,2004). However, this association was not
significant among males. In a sample drawn from the
general Finnish population (n=1767), Tanskanen et al.
fish consumers compared with infrequent consumers
(Tanskanen et al., 2001a). A longitudinal study among
29,133 Finnish men failed to find an association between
marine n−3 and self-reported depressed mood or hospital
However, it had several limitations that could explain
these negative findings (Sontrop and Campbell, 2006). In
771 patients with newly diagnosed lung cancer, Suzuki et
al. reported no association between EPA+DHA intake
and the Depression Subscale of the Hospital Anxiety and
Depression Scale (cutoff≥5) (Suzuki et al., 2004).
However, they observed a 2 times lower risk (Pb0.05)
in the fourth quartile of LNA intake compared with the
between LNA and PDISQS-14 scores.
4.2. Omega-3 effects on the nervous system
It has been shown that n−3 deficiency is associated
with increased violent behaviour, more anxiety, and
reduced attention and motivation (Haag, 2003). A
decrease in n−3 fatty acids in neuronal cell membranes
may affect membrane fluidity, signal transduction pro-
cesses, ion channel modulation, and gene expression,
possibly leading to changes in the synthesis of neuro-
transmitters involved in depression (Bruinsma and Taren,
2000; Locke and Stoll, 2001; Horrobin, 2002; Haag,
2003). Animal studies have indicated that n−3 deficiency
alters serotonin neurotransmission (Delion et al., 1994,
1996, 1997; de la Presa Owens and Innis, 1999; Kodas
et al., 2004). In humans, higher plasma n−3 has been
demonstrated to predict concentrations of serotonin and
dopamine metabolites in cerebrospinal fluid (Hibbeln
etal.,1998a,b). Dysfunction ofthe serotonergic systemis
a considerable risk factor for suicidality (Mann, 2003).
Two studies indicate that low n−3 blood levels, mainly of
DHA, are associated with higher suicide attempt risk
(Huan et al., 2004; Sublette et al., 2006). In a cross-
Polyunsaturated fatty acid concentrations in plasma PLs.
Fatty acids (% of total)Yes NoPYes NoPYesNoP
Linoleic (LA, 18:2 n−6)
Arachidonic (AA, 20:4 n−6)
Linolenic (LNA, 18:3 n−3)
Eicosapentaenoic (EPA, 20:5 n−3)
Docosapentaenoic (DPA, 22:5 n−3)
Docosahexaenoic (DHA, 22:6 n−3)
Total n−3/total n−6 ratio
Plus–minus values are means±S.D. P values were calculated for log-transformed fatty acids.
aParticipants were included as high-level PD if they scored over the 80th percentile on the PD Index Santé-Québec Survey (PDISQS-14). Non-
distressed participants were those scoring less than this cutoff.
bSum of n−6 polyunsaturated fatty acids (18:2+18:3+20:2+20:3+20:4+22:2+22:4+22:5).
cSum of n−3 polyunsaturated fatty acids (18:3+18:4+20:3+20:4+20:5+22:5+22:6).
271M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
healthy (although hypercholesterolemic) community
sample of adults (n=105), serum EPA and DHA were
inversely associated with neuroticism, depressive symp-
tomatology and cognitive impulsivity, after multivariate
adjustment (Conklin et al., 2007). A recent meta-analysis
Odds ratios (ORs) for high-level PD according to tertiles of n−3 fatty acids in plasma PLs of Nunavik Inuit.
Fatty acid tertilesPDa
Odds ratio (95% confidence interval)
T1: 0.9 (0.1–1.3)
T2: 2.3 (1.4–3.8)
T3: 5.8 (3.9–19.9)
P for trend
T1: 3.1 (0.5–3.9)
T2: 4.8 (4.0–5.9)
T3: 7.4 (6.0–11.9)
P for trend
T1: 4.2 (1.4–5.4)
T2: 7.3 (5.5–9.9)
T3: 12.9 (10.1–27.6)
P for trend
T1: 5.6 (2.2–6.9)
T2: 9.0 (7.0–11.9)
T3: 15.4 (12.0–30.4)
P for trend
Women only (n=221)
T1: 0.87 (0.12–1.53)
T2: 2.7 (1.6–4.1)
T3: 6.9 (4.2–17.3)
P for trend
T1: 3.5 (0.6–4.3)
T2: 5.3 (4.3–6.2)
T3: 7.3 (6.30–11.9)
P for trend
T1: 4.6 (1.4–5.9)
T2: 8.0 (6.0–10.8)
T3: 13.1 (10.8–26.5)
P for trend
T1: 6.0 (2.2–7.5)
T2: 9.8 (7.5–12.6)
T3: 15.3 (12.7–29.3)
P for trend
aParticipants were included as high-level PD if they scored over the 80th percentile on the PD Index Santé-Québec Survey (PDISQS-14). Non-
distressed participants were those scoring less than this cutoff.
bMultivariate model 1 controlled for age and gender. For women, model 1 included only age.
cMultivariate model 2 included the variables in multivariate model 1 and good relationship with the community.
dMultivariate model 3 included the variables in multivariate model 2 and CAGE score≥2, depression in lifetime, no recent stress events, coastal
region and abused sexually.
272M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
omega-3 significantly improved symptoms in patients
with clearly defined depression (Lin and Su, 2007).
However, no major clinical trial has been published
(Appleton et al., 2006), and the most significant trials
(Nemets et al., 2002; Peet and Horrobin, 2002) tested
therapy. Moreover, two recent meta-analyses on omega-3
and depression noted significant heterogeneity and
4.3. Strengths and limitations
Our results must be interpreted in the context of
limitations andstrengths ofany cross-sectional study,and
therefore, cannot ascertain any causal relationship. Since
we excluded 183 persons who did not have information
on PD, our results are probably not representative of the
Nunavik Inuit population. This might have introduced an
external validity bias. However, several strengths of our
clinic sessions and multiple validated instruments admi-
nistered by well-trained interviewers (Santé-Québec,
1994, 1995; Santé-Québec et al., 1994). The use of fatty
acid composition in tissues (adipose tissue, erythrocytes,
serum and plasma) as a biological marker of fatty acid
intake has some advantages. A single measurement of
marine n−3 in blood reflects the ranking of usual marine
2003; Kurikiet al.,2002, 2003). Such biomarkersoffatty
acid intake provide quantitative measurements indepen-
are less likely to be due to social desirability bias than
dietary self-reporting (Hebert et al., 1997).
Therisk offailing tocorrectly controlforall cofactors
associated with frequent fish consumption is highly
to cofactors associated with socio-economic status. Fish
consumption is more frequentamongpeople with higher
socio-economic status (occupation, education and
income) (Galobardes et al., 2001; Barberger-Gateau
et al., 2005). More than half (51.7%) of our respondents
did not answer the question on income (38% answered
“Don't know”, and 13.7% refused to answer) which
makes it impossible to analyze the data according to
income. Therefore, we cannot rule out that failure to
control for income may have biased our results. How-
ever, education and occupation were tested as cofactors
and did not significantly influence the relationship bet-
ween EPA+DHA and PD. Because fish and mammals
came mainly from fishing or hunting but could also have
been obtained for free in the cooperative store in
Nunavik (Kishigami, 2000; Duhaime et al., 2002), the
risk of bias due to uncontrolled socio-economic status
was unlikely in this population. We cannot rule out the
possibility that higher PD (especially if it was character-
ized by depression) influenced marine n−3 intake.
In a populations such as the Inuit of Nunavik, where
marineproductsplaya major roleintheirculturalidentity
(Blanchet et al., 2000, 2002), analysis of plasma EPA+
DHA is not only a measure of traditional food con-
sumption but also a yardstick of adherence to traditional
behaviours. It is, therefore, difficult to separate the bio-
logical effect of social behaviour adherence to Inuit
culture when EPA+DHA concentrations are measured.
Modification of the traditional diet of Nunavik Inuit has
been linked with market food integration, especially
among the younger generation for whom market foods
appear to be more attractive (Dewailly et al., 2001;
Blanchet et al., 2002). The Santé-Québec Health Survey
indicated that younger Inuit (15–24 years) suffered 3
times as much PD as older Inuit (more than 45 years)
(Santé-Québec, 1994). The suicide rate among Inuit in
1987–1994 was 6.5 times higher than in the rest of
Québec, and the rate in the younger age group (15–
24 years) was 20 times higher (Boothroyd et al., 2000).
The nature of communities and how they deal with
ongoing stressors (loss of cultural practices, loss of
traditional food resources and habitats, sedentary living,
economic disparity, environmental change, etc.) have
been mentioned as factors that explain different rates of
(Berry, 1997; Kirmayer et al., 2000a).
4.4. PD questionnaire
be used to establish specific psychiatric disorders. How-
ever, the present analysis did not aim to assess the pre-
valence of specific psychiatric disorders but rather to
identifyifmarinen−3 could be associatedwith the global
index of PD. This measure of distress probably cannot be
adapted culturally to the Inuit and, moreover, its sen-
and age is unknown for this population. The PDISQS-14
of quantitative variations recorded in the symptoms often
experienced by individuals suffering from anxiety or
validity of PDISQS-14 criteria showed that this PD index
was correlated with overall individual health, with the
of suicidal ideation and gestures (Preville et al., 1995).
273 M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
Using epidemiological data where 15 to 20% of the
general population presented high-level PD, an arbitrary
threshold defining high PD symptomatology has been
adopted inSanté-Québecsurveys tocategorizehigh-level
1978; Boyer et al., 1993; Santé-Québec, 1994). This
threshold may not reflect the Inuit reality since the
prevalence of mental disorders has never been accurately
estimated in that population. However, establishing
a cutoff based on score distribution appears to be an
interesting way to compare the risk of being in a category
with much more symptoms. Analyses of PDISQS-14
reliability and validity indicated that it could be used
among the Inuit with a view to identifying sub-groups
experiencing more PD (Santé-Québec, 1994). However,
led to non-differential misclassification and, therefore,
biased ORs to the null hypothesis.
It is possible that the outcomes noted in the PDISQS-
14 were due not only to omega-3 effects on depres-
literature on the relationship between omega-3 and
anxiety and hostility is less abundant than for depression.
Indeed, some studies show the benefits of omega-3 in
anxiety disorders (Buydens-Branchey and Branchey,
2006; Green et al., 2006) but others do not (Fux et al.,
2004; Raeder et al., 2007). According to Hibbeln et al., it
is reasonable to expect that DHA and EPA might reduce
aggression and/or hostility (Hibbeln et al., 2006).
4.5. Gender difference in the relationship between
marine n−3 and PD
The gender difference in relation to marine n−3 and
PD is intriguing. Since only 18 men were classified in the
high-level PD group, we were unable to perform logistic
regression analysis among males. However, the trend in
EPA+DHA concentration according to quintiles of
PDISQS-14 scores was not significant in men, only in
common among women than men, with a female/male
ratio between 1 1/2 to 3 (Kessler et al., 1993; Weissman
rate of major depression in women, but none seems to
fully explain it (Nolen-Hoeksema et al., 1999; Cahill,
2005; Altemus, 2006; Nes et al., 2007; Pohl et al., 2007).
Women seem to be more sensitive to the depressogenic
effects of stressful situations involving interpersonal con-
cerns (Taylor et al., 2000; Kendler et al., 2001). Gender
differences in activation of the hypothalamic–pituitary–
adrenal (HPA)axisinresponsetostressful stimulimaybe
another mechanism underlying sex differences in depres-
Nolen-Hoeksema et al. suggested that women are more
vulnerable to chronic negative circumstances (e.g. sexual
(Nolen-Hoeksema et al., 1999). Moreover, ovarian
hormones could affect brain systems, such as the HPA
axis, that are involved in depression and anxiety
(McEwen and Alves, 1999; Young et al., 2000; Becker
et al., 2005; Altemus, 2006). Some authors have also
particular vulnerability to mood disturbances during
periods of intense hormonal fluctuations (such as pre-
menstrual periods, puerperium or menopausal transition)
(Studd, 1992; Arpels, 1996). Young et al. proposed that
women are more willing than men to admit their de-
pression (Young et al., 1990). However, Kessler sug-
gested that men are as likely to be depressed as women,
dysphoria or anhedonia (Kessler, 2003). Due to different
effects of omega-3 on the nervous system, higher omega-
3 status might permit better mood adaptation (lower
depression, anxiety and hostility symptoms) among more
vulnerable women and/or during hormonal fluctuations.
Gender and hormonal factors have been proposed as
determinants of DHA synthesis (Burdge and Calder,
2005). Estrogen seems to play a role in upregulating the
conversionpathwayofLNA to DHA (Giltayetal.,2004).
This is unlikely among Inuit women because their high
intakes of marine n−3 (24-h dietary recall established
EPA+DHA intake to be 2031 mg/day) should down-
regulate enzymes implicated in this pathway (Lefkowitz
et al.,2005). Indeed, Pawlosky et al. observed that gender
had a stronger effect when humans were on a beef-based
diet, whereas it had a lesser effect when they were on
a fish-based diet (Pawlosky et al., 2003). Women in
the high-level PD group were those who had the lowest
EPA+DHA concentrations. This observation is also
intriguing since it is not explained by differences in age,
smoking status and alcohol consumption. However, the
lower EPA+DHA concentrations in women with high-
intake and/or by perinatal depletion. Since the fetus is
unable to synthesize sufficient DHA for the development
of its nervous system, it thus depends on the mother for
DHA (Crawford, 2000). Therefore, women can become
depleted of DHA during pregnancy and lactation if their
dietary intakes are insufficient (Al et al., 1995, 1996; Van
Houwelingen et al., 1999; Hornstra, 2000). This rela-
tive depletion may increase women's risk of developing
depressive symptoms or of having disturbing moods.
274 M. Lucas et al. / Psychiatry Research 167 (2009) 266–278
In this retrospective, cross-sectional study we found
that EPA+DHA concentrations in plasma PLs, a marker
of marine n−3 consumption, were inversely associated
with PD among women only. Women with higher EPA+
DHA plasma concentrations had a lower risk of severe
PD. Another extensive cross-sectional survey was con-
ducted in 2004 among the Nunavik Inuit (n=1000 par-
ticipants) and the data gathered will allow us to know if
is a sex difference in this relationship.
The research reported was supported by Indian and
Northern Affairs Canada. The authors acknowledge the
contributions of Santé-Québec for providing access to
health survey databases on the Inuit of Nunavik. The
authors express their gratitude to the Nunavik Health
Centre personnel and to all the participants of the Santé-
Québec Health Survey. The editorial assistance of Ovid
Da Silva is acknowledged.
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