DHA Serum Levels Were Significantly Higher in Celiac Disease Patients Compared to Healthy Controls and Were Unrelated to Depression

Objectives

Celiac disease (CD), a genetically predisposed intolerance for gluten, is associated with an increased risk of major depressive disorder (MDD). We investigated whether dietary intake and serum levels of the essential n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) found in fatty fish play a role in this association.

Methods

Cross-sectional study in 71 adult CD patients and 31 healthy volunteers, matched on age, gender and level of education, who were not using n-3 PUFA supplements. Dietary intake, as assessed using a 203-item food frequency questionnaire, and serum levels of EPA and DHA were compared in analyses of covariance, adjusting for potential confounders. Serum PUFA were determined using gas chromatography.

Results

Mean serum DHA was significantly higher in CD patients (1.72 mass%) than controls (1.28 mass%) after multivariable adjustment (mean diff. 0.45 mass%; 95% CI: 0.22–0.68; p = 0.001). The mean intake of EPA plus DHA did not differ between CD patients and controls after multivariable adjustment (0.15 and 0.22 g/d, respectively; p = 0.10). There were no significant differences in intake or serum levels of EPA and DHA between any of the CD patient groups (never depressed, current MDD, minor/partially remitted MDD, remitted MDD) and controls.

Conclusions

Patients on a long term gluten-free diet had similar intakes of EPA plus DHA compared to controls. Contrary to expectations, DHA serum levels were significantly higher in CD patients compared to healthy controls and were unrelated to MDD status.     

Associations of maternal prenatal dietary intake of n-3 and n-6 fatty acids with maternal and umbilical cord blood levels

Maternal n-3 and n-6 polyunsaturated fatty acid (PUFA) status may influence birth outcomes and child health. We assessed second trimester maternal diet with food frequency questionnaires (FFQs) (n=1666), mid-pregnancy maternal erythrocyte PUFA concentrations (n=1550), and umbilical cord plasma PUFA concentrations (n=449). Mean (SD) maternal intake of total n-3 PUFA was 1.17 g/d (0.43), docosahexaenoic and eicosapentaenoic acids (DHA+EPA) 0.16 g/d (0.17), and total n-6 PUFA 12.25 g/d (3.25). Mean maternal erythrocyte and cord plasma PUFA concentrations were 7.0% and 5.2% (total n-3), 5.0% and 4.6% (DHA+EPA), and 27.9% and 31.4% (total n-6). Mid-pregnancy diet–blood and blood–blood correlations were strongest for DHA+EPA (r=0.38 for diet with maternal blood, r=0.34 for diet with cord blood, r=0.36 for maternal blood with cord blood), and less strong for n-6 PUFA. The FFQ is a reliable measure of elongated PUFA intake, although inter-individual variation is present     

Docosahexaenoic acid: Measurements in food and dietary exposure

The Dietary Reference Intakes (DRIs) were established to be an indicator of adequacy of dietary nutrients as well as providing levels for adequacy in reducing risk of chronic diseases such as neurodegenerative diseases, cardiovascular diseases, cancers, diabetes mellitus, etc. One particular nutrient that is increasingly discussed as a potential candidate for the generation of a DRI is the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA) due to its potential benefits in reducing risk for cardiovascular disease, role in resolution of inflammation, its importance in cognitive function in infants and inhibiting the progression of neurodegenerative diseases in the elderly. Each reference value refers to and is predicated on estimates of daily nutrient intake and the goal of this paper is to review these intakes. The confidence of these values is critical in establishing dose–response relationships. This paper reports intake values for DHA and examines how these data were generated and the relative confidence in these values. The adult US population is estimated to consume 80–100 mg/d of DHA based on a nationally representative sample of >8400 individuals as part of the National Health and Nutrition Examination Survey (NHANES). This value and those presented for women and men at various ages appear reasonable and should be used as the basis for establishing an Adequate Intake (AI) for DHA.     

Affective Disorders among Patients with Borderline Personality Disorder

Background

The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders.

Methods

In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice.

Results

More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders.

Conclusions

The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect an etiological relationship or diagnostic overlapping criteria.     

Extraction of DNA from anostracan cysts (Crustacea,Branchiopoda) for use in RAPD-PCR analyses

The total lipid content in Artemia franciscana (21–23% ofdry weight (DW)) when enriched with either Super Selco or DHA Selco wastwice as high as in the adult copepods Temora longicornis and Eurytemora sp.(9–11% of DW). In Brachionus plicatilis the total lipid contentwas 11 and 6.6% for cultures growing at high and low growth rate,0.12 d^–1 and 0.38 d^–1, respectively. In thecopepodid stages I, II and III of Calanus finmarchicus the total lipid levelwas 12–13%, increasing to 24% in copepodid stage IV, Vand the adults. In T. longicornis and Eurytemora sp. the predominant fattyacids were DHA (22:6n-3), EPA (20:5n-3) and the saturated fatty acid 16:0,which constituted 40–45%, 21–24% and8–12% of total fatty acids, respectively. C. finmarchicuscontained the same dominant fatty acids. In both the cultivated live feedorganisms DHA, EPA and 18:1 were the predominant fatty acids. In A.franciscana the content of these fatty acids varied according to theenrichment medium and in B. plicatilis according to the growth rate.     

A Genetic Variant in 12q13, a Possible Risk Factor for Bipolar Disorder,Is Associated with Depressive State,Accounting for Stressful Life Events

Genome-wide association studies (GWASs) have identified a number of susceptibility genes for schizophrenia (SCZ) and bipolar disorder (BD). However, the identification of risk genes for major depressive disorder (MDD) has been unsuccessful because the etiology of MDD is more influenced by environmental factors; thus, gene–environment (G×E) interactions are important, such as interplay with stressful life events (SLEs). We assessed the G×E interactions and main effects of genes targeting depressive symptoms. Using a case–control design, 922 hospital staff members were evaluated for depressive symptoms according to Beck Depressive Inventory (BDI; “depression” and “control” groups were classified by scores of 10 in the BDI test), SLEs, and personality. A total of sixty-three genetic variants were selected on the basis of previous GWASs of MDD, SCZ, and BD as well as candidate-gene (SLC6A4, BDNF, DBH, and FKBP5) studies. Logistic regression analysis revealed a marginally significant interaction (genetic variant × SLE) at rs4523957 (P_uncorrected = 0.0034) with depression and a significant association of single nucleotide polymorphism identified from evidence of BD GWAS (rs7296288, downstream of DHH at 12q13.1) with depression as the main effect (P_uncorrected = 9.4×10⁻⁴, P_corrected = 0.0424). We also found that SLEs had a larger impact on depression (odds ratio∼3), as reported previously. These results suggest that DHH plays a possible role in depression etiology; however, variants from MDD or SCZ GWAS evidence or candidate genes showed no significant associations or minimal effects of interactions with SLEs on depression.     

n-3 Fatty acids modulate brain glucose transport in endothelial cells of the blood–brain barrier

We have previously shown that glucose utilization and glucose transport were impaired in the brain of rats made deficient in n-3 polyunsaturated fatty acids (PUFA). The present study examines whether n-3 PUFA affect the expression of glucose transporter GLUT1 and glucose transport activity in the endothelial cells of the blood–brain barrier. GLUT1 expression in the cerebral cortex microvessels of rats fed different amounts of n-3 PUFA (low vs. adequate vs. high) was studied. In parallel, the glucose uptake was measured in primary cultures of rat brain endothelial cells (RBEC) exposed to supplemental long chain n-3 PUFA, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, or to arachidonic acid (AA). Western immunoblotting analysis showed that endothelial GLUT1 significantly decreased (−23%) in the n-3 PUFA-deficient microvessels compared to control ones, whereas it increased (+35%) in the microvessels of rats fed the high n-3 PUFA diet. In addition, binding of cytochalasin B indicated that the maximum binding to GLUT1 (Bmax) was reduced in deficient rats. Incubation of RBEC with 15 μM DHA induced the membrane DHA to increase at a level approaching that of cerebral microvessels isolated from rats fed the high n-3 diet. Supplementation of RBEC with DHA or EPA increased the [³H]-3-O-methylglucose uptake (reflecting the basal glucose transport) by 35% and 50%, respectively, while AA had no effect. In conclusion, we suggest that n-3 PUFA can modulate the brain glucose transport in endothelial cells of the blood–brain barrier, possibly via changes in GLUT1 protein expression and activity.     

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Specialized proresolving mediators (SPMs) induce resolution of inflammation. SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their beneficial effects. It is unknown whether supplementation with PUFAs influences the production of SPMs. Alzheimer’s disease (AD) is associated with brain inflammation and reduced levels of SPMs. The OmegAD study is a randomized, double-blind, and placebo-controlled clinical trial on AD patients, in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months. Plasma levels of arachidonic acid decreased, and DHA and EPA levels increased after 6 months of n-3 FA treatment. Peripheral blood mononuclear cells (PBMCs) were obtained before and after the trial. Analysis of the culture medium of PBMCs incubated with amyloid-β 1–40 showed unchanged levels of the SPMs lipoxin A₄ and resolvin D1 in the group supplemented with n-3 FAs, whereas a decrease was seen in the placebo group. The changes in SPMs showed correspondence to cognitive changes. Changes in the levels of SPMs were positively correlated to changes in transthyretin. We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from PBMCs of AD patients, which was associated with changes in cognitive function.     

Docosahexaenoic acid, but not eicosapentaenoic acid, lowers ambulatory blood pressure and shortens interval QT in spontaneously hypertensive rats in vivo

This study was designed to evaluate the effects of individual dietary long-chain n-3 polyunsaturated fatty acids (LCPUFA) on hypertension and cardiac consecutive disorders in spontaneously hypertensive rats (SHR) as compared to Wistar-Kyoto rats (WKY). Rats were fed for 2 months an eicosapentaenoic (EPA)- or docosahexaenoic acid (DHA)-rich diet (240 mg/day) or an n-3 PUFA-free diet. Male SHR (n=6), implanted with cardiovascular telemetry devices, were housed in individual cages for continuous measurements of cardiovascular parameters (blood pressure (BP) and heart rate (HR)) during either activity or rest periods, ECG were recorded during the quiet period. The n-6 PUFA upstream of arachidonic acid was affected in SHR tissues. The cardiac phospholipid fatty acid profile was significantly affected by dietary DHA supply, and EPA in a very lower extent, since DHA only was incorporated in the membranes instead of n-6 PUFAs. Endothelium n-6 PUFA content increased in all SHR groups. Compared to WKY, linoleic acid content decreased in both studied tissues. Cardiac noradrenalin decreased while the adrenal catecholamine stores decreased in SHR as compared to WKY. Both n-3 PUFA supply induced a decrease of adrenal catecholamine stores. Nevertheless after 6 weeks, DHA but not EPA induced a lowering-blood pressure effect and shortened the QT interval in SHR, most probably through its tissue enrichment and a specific effect on adrenergic function. Dietary DHA supply retards blood pressure development and has cardioprotective effect. These findings, showing the cardioprotective effects of DHA in living animals, were obtained in SHR, but may relate to essential hypertension in humans.     

The effects of ancymidol,abscisic acid,uniconazole and paclobutrazol on somatic embryogenesis of asparagus

Summary The effects of ancymidol, abscisic acid (ABA), uniconazole, and paclobutrazol on asparagus somatic embryogenesis were evaluated. Calli induced from seedlings of genotype G447 were transferred to embryo induction medium (MS plus 3% sucrose, 0.1 mg L^–1 NAA, 0.5 mg L^–1 kinetin and 3% gelrite), with different concentrations of these compounds. After 8 weeks, the recovered bipolar or globular embryos were placed on germination medium (MS plus 6% sucrose, 0.1 mg L^–1 NAA, 0.1 mg L^–1 kinetin, 0.75 mg L^–1 ancymidol, 40 mg L^–1 adenine sulphate dihydrate, 0.17 mg L^–1 sodium phosphate monobasic and 3% gelrite) for conversion to plantlets. Inclusion of ancymidol, ABA, uniconazole and paclobutrazol in the embryo induction medium did not affect the total number of somatic embryos produced relative to the control without these compounds. However, ancymidol, ABA and uniconazole significantly improved embryo development by increasing the production of bipolar embryos 250–750% and decreasing that of globular embryos 8–35% relative to the control. The bipolar embryos produced with any of the four compounds in the embryo induction medium converted to plantlets at rates 700–1100% greater than the control. None of the globular embryos converted to plantlets. Ancymidol (0.75 mg L^–1) and ABA (0.05 mg L^–1) were the most effective treatments; 61 and 46 bipolar embryos g^–1 callus were produced, and 38% and 37% of the bipolar embryos converted to plantlets, respectively. These results indicated that ancymidol, ABA, uniconazole and paclobutrazol significantly enhanced the production of asparagus somatic embryos and their conversion to plantlets, and ancymidol and ABA were more effective than uniconazole and paclobutrazol.Abbreviations Ancymidol a-cyclopropyl-a(4-methoxyphenyi)-5-pyrimidine methanol - NAA 1-naphthaleneacetic acid - Paclobutrazol I-(4-chlorophenyl)-4,4-dimethyl-2(1H-1,2,4-triazol-1-yl)-pentan-3-ol - Uniconazole (E)-(p-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-pentan-3-ol - ABA abscisic acid - GA gibberellic acid     

Toxicology and safety of DHA

Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid with activities in both infants and adults. The objective of the current work was to evaluate the published literature concerning the toxicological assessment of DHA-rich oils in animals and the safety profile of DHA consumption in humans. Structured literature searches concerning DHA toxicology and DHA effects on platelet function, lipid levels, oxidative potential, glycemic control, and immune function were conducted. The toxicological profile of DHA derived from single-cell organisms demonstrates that these oils are safe in rats (up to a consumption level of 3290 mg/kg body weight/d) in 90-d toxicology evaluations, as well as in reproductive and developmental toxicology studies. The maximum DHA level in human breast milk exceeds 1% of total fatty acids in high-fish-consuming populations. Consumption of DHA-rich human milk as sole source of nutrition provides approximately 315 mg/d in infants 1–6 months of age, and appears to be a safe level of intake. DHA supplementation studies in adults have employed doses ranging from less than 1 to 7.5 g/d, and have not resulted in any consistent adverse responses in platelet function, lipid levels, in vivo oxidation parameters, glycemic control, or immune function. In conclusion, DHA consumption does not result in consistent adverse events in infants or adults. Safe intake levels may be modeled on DHA intake from human milk in infants, and may be at least as high as the upper doses studied in adults.     

Prevalence of Subthreshold Hypomania and Impact on Internal Validity of RCTs for Major Depressive Disorder: Results from a National Epidemiological Sample

Background

Growing evidence supports the validity of distinguishing major depressive disorder (MDD) plus a lifetime history of subthreshold hypomania (D(m)) from pure MDD in psychiatric classifications. The present study sought to estimate the proportion of individuals with D(m) that would have been included in RCTs for MDD using typical eligibility criteria, and examine the potential impact of including these participants on internal validity.

Methods

Data were derived from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined the proportion of participants with a current diagnosis of pure MDD and D(m) that would have been eligible in clinical trials for MDD with a traditional set of eligibility criteria, and compared it with that of participants with bipolar 2 disorder if the same set of eligibility criteria was applied. We considered 4 models including different definitions of subthreshold hypomania.

Results

We found that more than 7 out of ten participants with pure MDD and with D(m) would have been excluded by at least one classical eligibility criterion. Prevalence rate of individuals with D(m) in RCTs for MDD with traditional eligibility criteria would have ranged from 7.98% to 22.59%. Overall exclusion rate of individuals with MDD plus at least 4 lifetime concomitant hypomanic probes significantly differ from those with pure MDD, whereas it was not significantly different in those with at least 2 lifetime concomitant hypomanic probes compared to those with bipolar 2 disorder.

Conclusions

The current design of clinical trials for MDD may suffer from impaired external validity and potential impaired internal validity, due to the inclusion of a substantial proportion of individuals with subthreshold hypomania presenting with similar pattern of exclusion rates to those with bipolar 2 disorder, possibly resulting in a selection bias.     

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

Background

Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.

Objectives

To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.

Methods

A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.

Results

Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.

Conclusions

The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.     

Double enrichment of chicken eggs with conjugated linoleic acid and n-3 fatty acids through dietary fat supplementation

Yolk fat fatty acid (FA) concentrations, sensory quality and firmness of eggs and laying hen performance were evaluated with respect to the combined inclusion in the diet of conjugated linoleic acid (CLA), high n-3 oil sources and high-oleic sunflower oil (HOSO). Nine diets were arranged factorially, with three levels of n-3 FA supplementation (2.9, 3.7 and 4.5 g/kg) from three different sources (two fish oils highly concentrated in eicosapentanoic (EPA) or docosahexanoic acid (DHA) and one algae oil with a very high-DHA content) in diets added with fixed amounts of CLA (2.5 g/kg) and HOSO (30 g/kg). A commercial feed with no CLA, n-3 or HOSO added, and another one containing 4.5 g/kg of high-DHA fish oil but not CLA or HOSO were also formulated. An increase in n-3 FA supplementation had little effect on proportions of CLA, monounsaturated FA, saturated FA or total polyunsaturated FA in yolk fat, but increased (P<0.005) long-chain n-3 FA and decreased (P<0.001) long-chain n-6 FA. An increment of dietary n-3 FA also impaired linearly (P<0.001) egg acceptability by consumers. An increment in the proportion of DHA with respect to total n-3 FA from 0.28 to 0.96 increased yolk concentrations of DHA (P<0.001) and total n-3 FA (P<0.01), but decreased (P<0.001) concentrations of EPA and docosapentanoic acid FA. Current data indicate that addition of HOSO to diets supplemented with moderate amounts of CLA and n-3 FA allows the production of double enriched eggs while maintaining sensory quality for consumers at acceptable levels.     

Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed.     

Associations of Educational Attainment,Occupation, Social Class and Major Depressive Disorder among Han Chinese Women

Background

The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years.

Principal findings

We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders.

Conclusions

In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.     

Metabolic conversion of intra-amniotically-injected deuterium-labeled essential fatty acids by fetal rats following maternal n-3 fatty acid deficiency

Accumulation of polyunsaturated fatty acids (PUFA) in the fetal brain is accomplished predominantly via a highly selective flow of docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid (20:4n-6, AA) through the placenta. Little is known regarding the endogenous capability of the fetus to generate its own DHA and AA from lower homologues such as linolenic (18:3n-3, ALA) and linoleic (18:2n-6, LA) acids, respectively. Deuterium-labeled d5-ALA and d5-LA at millimolar concentrations were injected directly into the amniotic fluid in order to investigate maternal-independent metabolic conversion of the stable isotopes in brain and liver of the fetus near delivery. After 48 h under adequate maternal diet, the levels of d5-ALA metabolites in the fetal brain and fetal liver were 45 ± 2.2 pmol/mg and 86 ± 4 pmol/mg of which 79% and 63.6% were comprised of d5-DHA. At this time point, incorporation of d5-LA metabolites was 103 ± 5 pmol/mg and 772 ± 46 pmol/mg for brain and liver, of which 50% and 30% were comprised of d5-AA. Following sustained maternal dietary ALA deficiency, the levels of total d5-ALA derived metabolites in the fetal brain and fetal liver were increased to 231 pmol/mg and 696 pmol/mg of which 71% and 26% were comprised of d5-DHA. From the time course and relative rates of d5-ALA precursor displacement by d5-DHA in cellular phosphoglycerides, it is concluded that the fetal rat brain can generate its own DHA from its d5-ALA precursors particularly under dietary stress.     

Further Evidence of Emotional Allodynia in Unmedicated Young Adults with Major Depressive Disorder

Background

Recent evidence suggests that sensitivity to the emotional sequela of experimental thermal pain(measured by emotional unpleasantness) is heightened in individuals with major depressive disorder(MDD), a phenomenon we termed “emotional allodynia”. The aim of this study was to examine whether acute happy and sad mood induction alters emotional allodynia in MDD. We hypothesized that emotional allodynia will be a robust characteristic of individuals with MDD compared to healthy controls. Thus, it would remain following acute mood induction, independent of valence.

Methods

Twenty-one subjects with current MDD and 21 well-matched healthy subjects(HC) received graded brief temperature stimuli following happy and sad mood inductions procedures(MIP). All subjects rated the intensity and affect(pleasantness/unpleasantness) of each stimulus. Sensory(pain intensity) and affective(pain unpleasantness) thresholds were determined by methods of constant stimuli.

Results

The MIPs reliably induced happy and sad mood and the resulting induced mood and subjective arousal were not different between the groups at the time of temperature stimulation. Compared to HC, MDD individuals demonstrated emotional allodynia. We found significantly decreased affective pain thresholds whereby significantly lower temperatures became unpleasant in the MDD compared to the HC group. This was not observed for the sensory pain thresholds. Within the MDD, the affective pain thresholds were significantly lower than the corresponding pain intensity thresholds, whereby non-painful temperatures were already unpleasant for the MDD irrespective of the induced mood. This was not observed for the HC groups where the affective and pain intensity thresholds were comparable.

Conclusions

These findings suggest that emotional allodynia may be a chronic characteristic of current MDD. Future studies should determine if emotional allodynia persists after psychological or pharmacological interventions. Finally, longitudinal work should examine whether emotional allodynia is a result of or vulnerability for depression and the role it plays in the increased susceptibility for pain complaints in this disorder.     

The Combined Effects of Obesity,Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study

Background

Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects.

Methods

We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m²) as normal weight (18.5–24.99), overweight (25–29.9), mild obesity (30–34.9) and moderate/severe obesity (≥ 35); we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses.

Results

The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL.

Conclusions

Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL.     

The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity

Orbitofrontal cortex (OFC, Brodmann area 10) gray matter volume reductions and selective reductions in docosahexaenoic acid (DHA, 22:6n-3) are observed in adult patients with major depressive disorder (MDD). OFC gray matter volume also decreases with advancing age in healthy subjects. To examine if OFC gray matter DHA composition decreases during normal aging, we determined age-related changes in OFC gray matter fatty acid composition by gas chromatography in subjects aged 29-80 years (n=30). We additionally determined elongase (HELO1), delta-5 desaturase (FASD1), delta-6 desaturase (FASD2), peroxisomal (PEX19), and stearoyl-CoA desaturase (SCD) mRNA expression in the same tissues. Increasing age was associated with a progressive decline in polyunsaturated fatty acid (PUFA) composition, including DHA and arachidonic acid (AA, 20:4n-6), and transient, apparently compensatory, elevations in elongase and desaturase gene expression. The age-related reduction in PUFA composition was inversely correlated with SCD expression and activity resulting in elevations in monounsaturated fatty acid composition. These dynamic age-related changes in OFC gray matter fatty acid composition and biosynthetic gene expression may contribute to the progressive decline in OFC gray matter volume found with advancing age. The implications of age-related reductions in OFC PUFA composition for affective dysregulation in the elderly are discussed.