Interaction between the MTHFR C677T polymorphism and traumatic childhood events predicts depression

Childhood trauma is associated with the onset and recurrence of major depressive disorder (MDD). The thermolabile T variant of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) is associated with a limited (oxidative) stress defense. Therefore, C677T MTHFR could be a potential predictor for depressive symptomatology and MDD recurrence in the context of traumatic stress during early life. We investigated the interaction between the C677T MTHFR variant and exposure to traumatic childhood events (TCEs) on MDD recurrence during a 5.5-year follow-up in a discovery sample of 124 patients with recurrent MDD and, in an independent replication sample, on depressive syniptomatology in 665 healthy individuals from the general population. In the discovery sample, Cox regression analysis revealed a significant interaction between MTHFR genotype and TCEs on MOD recurrence (P = 0.017). Over the 5.5-year follow-up period, median time to recurrence was 191 days for T-allele carrying patients who experienced TCEs (T + and TCE +); 461 days for T - and TCE + patients; 773 days for T + and TCE - patients and 866 days for T - and TCE - patients. In the replication sample, a significant interaction was present between the MTHFR genotype and TCEs on depressive symptomatology (P = 0.002). Our results show that the effects of TCEs on the prospectively assessed recurrence of MOD and self-reported depressive symptoms in the general population depend on the MTHFR genotype. In conclusion, T-allele carriers may be at an increased risk for depressive symptoms or MOD recurrence after exposure to childhood trauma

Land conflict in peri-urban areas: Exploring the effects of land reform on informal settlement in Mexico

Peri-urban areas are often subject to intensive construction, through both formal and informal processes. As land transitions from rural to urban status, different land tenure and administration systems may come into conflict, leading to disputes, contestation and, in some cases, violence. However, little is known about the precise causes of peri-urban land conflict. In Mexico, peri-urban growth has historically proceeded peacefully, owing to the control exerted by a corporatist system of government, and the political use of land tenure regularisation. However, the effects of land reforms on transactions at the peri-urban fringe, in the context of wider processes of liberalisation, may be increasing vulnerability to conflict over land. This paper explores these issues through a case study of an irregular settlement on the peri-urban fringe of the provincial Mexican city of Xalapa, where contestations over informally developed land have escalated into violent encounters between groups of settlers and the state. The findings show that vulnerability to conflict in peri-urban areas can be attributed to the interaction of macro-level processes with local-level factors, including diverse claims, overlapping legal and governance frameworks and, critically, local power relations

An Insight into Life at Geometric Zagora Provided by the Animal Bones

This thesis is a study of the animal bone distribution at the Geometric period settlement of Zagora (ca. 850-700 BC), on the island of Andros. The animal bones were excavated during the 1967-74 University of Sydney excavations and analysed in 1977 by a specialist who compiled a report of her findings. The report is currently in preparation for publication and is the primary source for this thesis. The data it provided was limited but enough could be extracted to identify patterns that permitted a tentative reconstruction of social life and the economy at Zagora. There is a paucity of excavated settlements from the Greek EIA and few of these have published faunal material, an essential element in reconstructing past lifeways. Those preserved settlements from which animal bones have been published are not extensive with good domestic contexts but usually sites of minimal extent. Hence, it has not been possible to conduct an analysis of the spatial distribution of animal bones from such a settlement. Zagora, being an extensive settlement containing mainly domestic structures, is therefore unique and the animal bone report provided the opportunity for such a study to be undertaken. A number of analyses were performed using both statistical and non-statistical methods. Through these it was discovered that there is a relationship between the animal size and the size of the architectural unit within which it was found. Similarly, there appeared to be a relationship between larger architecture and the presence of fish, postulated as being a pelagic species. The patterns observed were interpreted as evidence of ‘special’ meals with a larger than usual number of diners in attendance and hence the need for a larger space to host them. Using the animal bones’ distribution and architectural evidence it is proposed that feasting was an important event at Zagora, conducted at the household level to possibly reinforce bonds of kinship and friendship. The evidence also suggests that the H area could have been inhabited by people of better means than elsewhere in the settlement, particularly by the hypaethral sanctuary. Ideally the animal bones would have been studied in conjunction with associated artefacts, but this was not possible and so this would be something desirable to be performed in the near future. With 21st century excavation techniques, the future Zagora excavations should provide greater granularity in the faunal information obtained from the settlement to allow better precision in subsequent analyses

Plasma and Erythrocyte Fatty Acid Patterns in Patients with Recurrent Depression: A Matched Case-Control Study

The polyunsaturated fatty acid (PUFA) composition of (nerve) cell membranes may be involved in the pathophysiology of depression. Studies so far, focussed mainly on omega-3 and omega-6 PUFAs. In the present study, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and PUFAs of the omega-3, -6 and -9 series in plasma and erythrocytes of patients with recurrent major depressive disorder (MDD-R) were compared with controls.We carried out a case-control study. The sample consisted of 137 patients with MDD-R and 65 matched non-depressed controls. In plasma and erythrocytes of patients with MDD-R the concentrations of most of the SFAs and MUFAs, and additionally erythrocyte PUFAs, all with a chain length > 20 carbon (C) atoms, were significantly lower than in the controls. In contrast, the concentrations of most of the shorter chain members (< or = 18C) of the SFAs and MUFAs were significantly higher in the patients. Estimated activities of several elongases in plasma of patients were significantly altered, whereas delta-9 desaturase activity for C14:0 and C18:0 was significantly higher.The fatty acid status of patients with MDD-R not only differs with regard to omega-3 and omega-6 PUFAs, but also concerns other fatty acids. These alterations may be due to: differences in diet, changes in synthesizing enzyme activities, higher levels of chronic (oxidative) stress but may also result from adaptive strategies by providing protection against enhanced oxidative stress and production of free radicals

Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder

Contains fulltext : 167940.pdf (publisher's version ) (Open Access)Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (beta=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (beta=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (beta=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored

Statistical Methodological Issues in Handling of Fatty Acid Data: Percentage or Concentration, Imputation and Indices

Basic aspects in the handling of fatty acid-data have remained largely underexposed. Of these, we aimed to address three statistical methodological issues, by quantitatively exemplifying their imminent confounding impact on analytical outcomes: (1) presenting results as relative percentages or absolute concentrations, (2) handling of missing/non-detectable values, and (3) using structural indices for data-reduction. Therefore, we reanalyzed an example dataset containing erythrocyte fatty acid-concentrations of 137 recurrently depressed patients and 73 controls. First, correlations between data presented as percentages and concentrations varied for different fatty acids, depending on their correlation with the total fatty acid-concentration. Second, multiple imputation of non-detects resulted in differences in significance compared to zero-substitution or omission of non-detects. Third, patients’ chain length-, unsaturation-, and peroxidation-indices were significantly lower compared to controls, which corresponded with patterns interpreted from individual fatty acid tests. In conclusion, results from our example dataset show that statistical methodological choices can have a significant influence on outcomes of fatty acid analysis, which emphasizes the relevance of: (1) hypothesis-based fatty acid-presentation (percentages or concentrations), (2) multiple imputation, preventing bias introduced by non-detects; and (3) the possibility of using (structural) indices, to delineate fatty acid-patterns thereby preventing multiple testing

Is dietary pattern of schizophrenia patients different from healthy subjects?

<p>Abstract</p> <p>Background</p> <p>There are limited findings about dietary patterns and food preferences among patients suffering from schizophrenia. The main objective of this study was therefore to compare the nutritional pattern of schizophrenia patients with that of matched healthy subjects.</p> <p>Methods</p> <p>The dietary pattern of 30 hospitalized 16–67 years old schizophrenic patients (11 female) was compared with that of 30 healthy age and sex matched individuals as control group. Subjects' anthropometric measurements including weight, height and body mass index (BMI), semi-quantitative food frequency (FFQ), medical and food history questionnaires were also collected and FFQs were then scored using Food Guide Pyramid to obtain the dietary scores. Percent body fat (%BF) was measured using bioelectrical impedance analysis (BIA) method.</p> <p>Results</p> <p>Female patients had more %BF and lower dietary pattern scores than that of their controls (32 ± 3.6 vs 27.7 ± 4.6 percent and 43.2 ± 11.9 vs 54.5 ± 10.7 points; respectively, p < 0.05 for both). They also consumed less milk and dairy products, fresh vegetables, fruits, chicken, and nuts compared with the female controls (p < 0.03). However, these patients used to eat more full-fat cream and carbonated drinks (p < 0.05). Male patients had lower BMI (22 ± 4.7 vs 25.6 ± 4.4; p < 0.05) than their counterpart controls but there was no significant difference between their %BFs. Moreover, they used to have more full-fat cream, hydrogenated fats, less red meat and nuts compared with the male controls (p < 0.05).</p> <p>Conclusion</p> <p>Schizophrenia patients have poor nutritional patterns. In particular, female patients have more percent body fat and lower dietary pattern scores compared with their healthy controls. All patients used to consume more fats and sweet drinks frequently. The findings of this study suggest that schizophrenia patients need specific medical nutrition therapies through limiting dietary fats and sugars intakes and weight control. Whether obesity is the consequence of disease, dietary preference or medications used remains to be cleared.</p

Vulnerability for new episodes in recurrent major depressive disorder: protocol for the longitudinal DELTA-neuroimaging cohort study

Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission.In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35-65 years) with ≥ 2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5 years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3 T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination.The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings.NTR3768

Vulnerability for new episodes in recurrent major depressive disorder:protocol for the longitudinal DELTA-neuroimaging cohort study

Introduction Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission.Methods and analysis In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35-65years) with 2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination.Ethics and dissemination The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings.Trial registration number NTR3768.</p