Etiology Of Depressive Disorder Research Articles

Interrelationships between affective disorders in the form of depression and obesity and overweight - A systematic review

Both depression and obesity are significant health, social and economic problems. Depressive disorders were the second most common psychiatric disorder in 2017 after anxiety disorders. According to data published by the World Health Organization (WHO), depression affects about 280 million people worldwide, which is about 3.8 percent of the population. The etiology of depressive disorders is very complex and still not fully understood. The theories described so far complement each other. The factors underlying the development of depressive disorders can be divided into biological, psychological and other factors. Eating disorders in the form of overweight and obesity result from a loss of balance between anabolic and catabolic processes. This is most often led by insufficient physical activity and excess caloric intake. Hormonal disorders, genetic factors and environmental factors may also play an important role in the pathogenesis of obesity. The steadily increasing number of people suffering from depression and obesity prompts the search for links between these two seemingly unrelated disease entities. According to current knowledge, these diseases are bi-directionally linked by genetic, psychological, metabolic and social factors. Depression is associated with an increase in the risk of obesity by about 37% relative to those without depression. Obesity is associated with an increase in the risk of depressive disorders by about 18%. Understanding the links that exist between depressive disorders and obesity enables the search for new therapeutic options. The most important conclusion from the scientific research conducted so far is the advantage of simultaneous treatment of obesity and depression over treating these disease entities individually.

Omega-3 fatty acids and major depression: a Mendelian randomization study

Omega-3 fatty acids have been implicated in the aetiology of depressive disorders, though trials supplementing omega-3 to prevent major depressive disorder (MDD) have so far been unsuccessful. Whether this association is causal remains unclear. We used two sample Mendelian randomization (MR) to investigate causality. Genetic variants associated with circulating omega-3 and omega-6 fatty acids in UK Biobank (UKBB, n = 115,078) were selected as exposures. The Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWAS) of MDD (n = 430,775; cases = 116,209; controls = 314,566) and recurrent depression (rMDD, n = 80,933; cases = 17,451; controls = 62,482), were used as outcomes. Multivariable MR (MVMR) models were used to account for biologically correlated lipids, such as high- and low-density cholesterol and triglycerides, and to explore the relative importance of longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) using data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, n = 8866). Genetic colocalization analyses were used to explore the presence of a shared underlying causal variant between traits. Genetically predicted total omega-3 fatty acids reduced the odds of MDD (ORIVW 0.96 per standard deviation (SD, i.e. 0.22 mmol/l) (95% CIs 0.93–0.98, p = 0.003)). The largest point estimates were observed for eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid (OREPA 0.92; 95% CI 0.88–0.96; p = 0.0002). The effect of omega-3 fatty acids was robust to MVMR models accounting for biologically correlated lipids. ‘Leave-one-out’ analyses highlighted the FADS gene cluster as a key driver of the effect. Colocalization analyses suggested a shared causal variant using the primary outcome sample, but genomic confounding could not be fully excluded. This study supports a role for omega-3 fatty acids, particularly EPA, in the aetiology of depression, although pleiotropic mechanisms cannot be ruled out. The findings support guidelines highlighting the importance of EPA dose and ratio for MDD and question whether targeted interventions may be superior to universal prevention trials, as modest effect sizes will limit statistical power.

Identification of Key Modules and Genes Associated with Major Depressive Disorder in Adolescents.

Major depressive disorder (MDD) is a leading cause of disability worldwide. Adolescence is a crucial period for the occurrence and development of depression. There are essential distinctions between adolescent and adult depression patients, and the etiology of depressive disorder is unclear. The interactions of multiple genes in a co-expression network are likely to be involved in the physiopathology of MDD. In the present study, RNA-Seq data of mRNA were acquired from the peripheral blood of MDD in adolescents and healthy control (HC) subjects. Co-expression modules were constructed via weighted gene co-expression network analysis (WGCNA) to investigate the relationships between the underlying modules and MDD in adolescents. In the combined MDD and HC groups, the dynamic tree cutting method was utilized to assign genes to modules through hierarchical clustering. Moreover, functional enrichment analysis was conducted on those co-expression genes from interested modules. The results showed that eight modules were constructed by WGCNA. The blue module was significantly associated with MDD after multiple comparison adjustment. Several Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with stress and inflammation were identified in this module, including histone methylation, apoptosis, NF-kappa β signaling pathway, and TNF signaling pathway. Five genes related to inflammation, immunity, and the nervous system were identified as hub genes: CNTNAP3, IL1RAP, MEGF9, UBE2W, and UBE2D1. All of these findings supported that MDD was associated with stress, inflammation, and immune responses, helping us to obtain a better understanding of the internal molecular mechanism and to explore biomarkers for the diagnosis or treatment of depression in adolescents.

Association of BDNF Gene (rs6265/G196A) Polymorphism with Depression

Depression affects an individual’s feelings, thoughts, and behavior. It is known as the most common mental illness worldwide with complex origin. The risk factors for depression include both genetic as well as environmental factors. Depression is affecting more than 300 million individuals globally and is categorized as a major cause of the global burden of disease. Several studies demonstrate the involvement of the brain-derived neurotrophic factor (BDNF) gene in the etiology of depressive disorder. This study was designed to assess the association of (rs6265/G196A) polymorphism of the BDNF gene in the pathogenesis of depression. The cross-sectional study was conducted consisting of 357 samples from Rawalpindi, Pakistan. Depression was determined through questionnaire, using DSM-Ⅳ (Diagnostic and Statistical Manual for Mental Disorders-Version Ⅳ). DNA was extracted from the blood samples of study participants. The conventional polymerase chain reaction was performed to amplify the BDNF gene and to detect the frequency of rs6265/ G196A SNP in the samples of subjects under study. Statistical analysis was done using Pearson’s Chi-Squared test. It was observed that the homozygous GG genotype is more prevalent in study subjects than the homozygous AA or heterozygous AG genotypes. However, depression is likely to be more prevalent in AA genotype i.e., 37.8%, less prevalent in AG genotype i.e., 34.0%, and least prevalent in GG genotype i.e., 28.2%. This data shows the A allele of the BDNF gene to be more associated with depression than the G allele, suggesting this polymorphism to be a somewhat potential target for anti-depressants.

Elucidating the Possible Role of FoxO in Depression.

Forkhead box-O (FoxO) transcriptional factors perform essential functions in several physiological and biological processes. Recent studies have shown that FoxO is implicated in the pathophysiology of depression. Changes in the upstream mediators of FoxOs including brain-derived neurotrophic factor (BDNF) and protein kinase B have been associated with depressive disorder and the antidepressant agents are known to alter the phosphorylation of FoxOs. Moreover, FoxOs might be regulated by serotonin or noradrenaline signaling and the hypothalamic-pituitary-adrenal (HPA)-axis,both of them are associated with the development of the depressive disorder. FoxO also regulates neural morphology, synaptogenesis, and neurogenesis in the hippocampus, which accounts for the pathogenesis of the depressive disorder. The current article underlined the potential functions of FoxOs in the etiology of depressive disorder and formulate few essential proposals for further investigation. The review also proposes that FoxO and its signal pathway might establish possible therapeutic mediators for the management of depressive disorder.

Inflammation predicts new onset of depression in men, but not in women within a prospective, representative community cohort

Depression has been associated with increased inflammation. However, only few large-scale, prospective studies have evaluated whether inflammation leads to new cases of depression and whether this association can be found in men and women. Longitudinal data of N = 10,357 adult participants with no evidence of depression at baseline (based on Patient Health Questionnaire (PHQ-9), lifetime diagnoses, and current antidepressant medication) were evaluated for depression 5 years later. Multivariate logistic regression models were used to predict the onset of depression based on C-reactive protein (CRP) and white blood cell count (WBC). We used interaction terms and separate analyses in men and women to investigate gender-dependent associations. Based on both markers, inflammation was predictive of new cases of depression 5 years later, even when adjusting for sociodemographic, physical health, health behavior variables, and baseline depression symptoms. As established by interaction terms and separate analyses, inflammatory markers were predictive of depression in men, but not in women. Additional predictors of new onset of depression were younger age, loneliness, smoking (only in men), cancer and less alcohol consumption (only in women). The study indicates gender differences in the etiology of depressive disorders within the community, with a greater role of physical factors in men.

Maternal Separation Model of Postpartum Depression: Potential Role for Nucleus Accumbens Dopamine D1-D2 Receptor Heteromer.

Postpartum depression is a mood disorder with a distinct neurobiological and behavioural profile occurring during and after the postpartum period. Dopamine pathways in the limbic regions of the brain such as the nucleus accumbens (NAc) have been shown to be involved in the etiology of depressive disorders. Selective activation of the dopamine D1-D2 receptor heteromer has been demonsrated to cause depressive- and anxiogenic-like behaviours in rats. The maternal separation model involving three hour daily maternal separation (MS) from pups on PPD 2-15 on anxiety-, depression- and anhedonia-like behaviors in the dams was investigated, together with plasma corticosterone, oxytocin and D1-D2 heteromer expression in the NAc core and shell in non-MS and MS dams. Depression, anxiety and anhedonia-like behaviours were measured using the forced swim test, elevated plus maze and sucrose preference test, respectively. In comparison to non-MS controls, MS dams displayed slightly higher depressive and anxiety-like behaviours with no difference in anhedonia-like behaviours. The MS dams displayed significantly increased care of pups after their retrieval with higher bouts of nursing, lower latency to nurse, lower bouts of out nest behaviour and decreased self-care. There was no significant alteration in D1-D2 heteromer expression in NAc core and shell between mothers of either group (MS, non-MS) or between postpartum rats and nonpregnant female rats, remaining higher than in male rats. This data provides evidence for the maternal separation model in producing a postpartum depression-like profile, but with maternal resilience able to modify behaviours to counteract any potential deleterious consequences to the pups.

Comparative analysis of restraint stress-induced depressive-like phenotypes in C57BL/6N mice derived from three different sources

C57BL/6NKorl mice are a novel mouse stock recently developed by the National Institute of Food and Drug Safety Evaluation in Korea. Extensive research into the nature of C57BL/6NKorl mice is being conducted. However, there is no scientific evidence for the phenotypic response to restraint stress (RST), a stress paradigm for modeling depressive disorders, in rodents. In this study, we investigated the repeated RST-induced depressive-like phenotypes in C57BL/6 N mouse substrains (viz., C57BL/6NKorl mice from Korea, C57BL/6NA mice from the United States, and C57BL/6NB mice from Japan) obtained from different sources. The results showed that C57BL/6 N mice derived from various sources exposed to repeated RST resulted in depressive-like phenotypes reflected by a similar degree of behavioral modification and susceptibility to oxidative stress in a duration-dependent manner, except for the distinctive features (increased body weight (BW) and tolerance to the suppression of BW gain by exposure to repeated RST) in C57BL/6NKorl mice. Taken together, the duration-dependent alteration in depressive-like phenotypes by repeated exposure to RST observed in this study may provide valuable insights into the nature of C57BL/6NKorl mice as an alternative animal resource for better understanding of the etiology of depressive disorders and the mechanisms of antidepressant actions.

The role of the endoplasmic reticulum stress in depression.

Depression is an important health problem around the world. There are several effective methods for its treatment, but it is estimated that one-third of patients with depression do not respond adequately to conventional antidepressants. There is, therefore, an urgent need to identify the biological mechanism of depression and the pharmacological action of antidepressants. The participation of broadly understood inflammatory factors in the etiology of depressive disorders no longer raises doubts. In recent years, a lot of attention has also been devoted to changes in the endoplasmic reticulum, suggesting that the so-called endoplasmic reticulum stress gives rise to many diseases. The endoplasmic reticulum stress is activated in response to the increasing amount of unfolded or improperly folded proteins in the ER. Research on the so-called endoplasmic reticulum stress inspire hope not only in the context of amore thorough understanding of the pathophysiology of diseases, but it can also be an inspiration to search for new, more effective drugs. This paper presents the connections between changes of the endoplasmic reticulum and inflammatory states and oxidative-reduction balance. Both the occurrence of inflammation and so-called oxidative stress have been confirmed in depressive disorders.

Genetic basis of depressive disorders

Depression is a common mental disorder being one of the main causes of disability and mortality worldwide. Despite an intensive research during the past decades, the etiology of depressive disorders (DDs) remains incompletely understood; however, genetic factors are significantly involved in the liability to depression. The present review is focused on the studies based on a candidate gene approach, genome-wide association studies (GWAS) and whole exome sequencing (WES), which previously demonstrated associations between gene polymorphisms and DDs. According to the first approach, DD development is affected by serotonergic (TPH1, TPH2, HTR1A, HTR2A, and SLC6A4), dopaminergic (DRD4, SLC6A3) and noradrenergic (SLC6A2) system genes, and genes of enzymatic degradation (MAOA, COMT). In addition, there is evidence of the involvement of HPA-axis genes (OXTR, AVPR1A, and AVPR1B), sex hormone receptors genes (ESR1, ESR2, and AR), neurotrophin (BDNF) and methylenetetrahydrofolate reductase (MTHFR) genes, neuronal apoptosis (CASP3, BCL-XL, BAX, NPY, APP, and GRIN1) and inflammatory system (TNF, CRP, IL6, IL1B, PSMB4, PSMD9, and STAT3) genes in DD development. The results of the second approach (GWAS and WES) revealed that the PCLO, SIRT1, GNL3, GLT8D1, ITIH3, MTNR1A, BMP5, FHIT, KSR2, PCDH9, and AUTS2 genes predominantly responsible for neurogenesis and cell adhesion are involved in liability to depression. Therefore, the findings discussed suggest that genetic liability to DD is a complex process, which assumes simultaneous functioning of multiple genes including those reported previously, and requires future research in this field.

Vitamin D and the Risk of Depression: A Causal Relationship? Findings from a Mendelian Randomization Study.

While observational studies show an association between 25(OH)vitamin D concentrations and depressive symptoms, intervention studies, which examine the preventive effects of vitamin D supplementation on the development of depression, are lacking. To estimate the role of lowered 25(OH)vitamin D concentrations in the etiology of depressive disorders, we conducted a two-sample Mendelian randomization (MR) study on depression, i.e., “depressive symptoms” (DS, n = 161,460) and “broad depression” (BD, n = 113,769 cases and 208,811 controls). Six single nucleotide polymorphisms (SNPs), which were genome-wide significantly associated with 25(OH)vitamin D concentrations in 79,366 subjects from the SUNLIGHT genome-wide association study (GWAS), were used as an instrumental variable. None of the six SNPs was associated with DS or BD (all p > 0.05). MR analysis revealed no causal effects of 25(OH)vitamin D concentration, either on DS (inverse variance weighted (IVW); b = 0.025, SE = 0.038, p = 0.52) or on BD (IVW; b = 0.020, SE = 0.012, p = 0.10). Sensitivity analyses confirmed that 25(OH)vitamin D concentrations were not significantly associated with DS or BD. The findings from this MR study indicate no causal relationship between vitamin D concentrations and depressive symptoms, or broad depression. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

Depressive symptoms and serum levels of polyunsaturated fatty acids omega-3 and omega-6 among college students from Northern Mexico

Previous studies suggest that low consumption as well as low serum levels of polyunsaturated fatty acids (PUFA) omega-3 and a high omega-6/omega-3 ratio may be implicated in the etiology of depressive disorders, however, epidemiologic evidence is inconclusive. To assess the relationship of serum levels of omega-3 fatty acids (docosahexaenoic [DHA], eicosapentaenoic [EPA], alpha-linolenic fatty acid [ALA]) and the omega-6 (arachidonic acid [AA])/EPA ratio with depressive symptoms among Mexican college students. A cross-sectional study that included 60 male and female participants (ages 18 to 24 years) with serum levels of EPA, DHA, ALA and AA. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression (CES-D) scale validated for Mexican students. Linear regression was used to assess the relationship between depressive symptoms and serum PUFA omega-3 and omega-6. Serum levels of EPA, DHA and EPA/DHA ratio were not related to depressive symptoms, high serum ALA was related with lower depressive symptoms before and after covariate adjustment; however, these results were not statistically significant. Among women, 1% increase in EPA resulted in 5.5. (p = 0.57) increase in the depressive scale scores while 1% increase in ALA resulted in 6.7 decrease (p = 0.39) in the scores. Our results did not confirm the relationship of serum levels of PUFA omega-3 and omega-6/omega-3 ratio with depressive symptoms; the negative correlation of serum ALA with depressive symptoms remains to be confirmed in prospective studies.

Depressive-like behavior is elevated among offspring of parents exposed to dim light at night prior to mating

Rates of major depressive disorder (MDD) have steadily increased over the past 50 years. Many factors have been implicated in the etiology of depressive disorders and environmental influences are being increasingly recognized. The increase in depression rates has coincided with increased artificial nighttime lighting. Exposure to light at night (LAN) has been associated with increased depressive-like behavior in rodents and decreased mood in humans. However, relatively little is known on the multigenerational effects of dLAN on affect. In this study, we exposed adult male and female Siberian hamsters (Phodopus sungorus) to either DARK (0lx) or dim LAN (5lx) for 9 weeks, then paired animals in a full factorial design; all animals were thereafter housed in dark nights. Offspring were gestated and reared in dark nights, then tested in adulthood for depressive-like behaviors and hippocampal expression of glucocorticoid (GR) and melatonin (MT1) receptor expression. Maternal exposure to dLAN decreased sucrose preference, time to first float bout in the Porsolt swim test, and GR expression in the hippocampus. Paternal exposure to dLAN increased time spent floating, and increased hippocampal GR expression. Overall, our results suggest that chronic exposure of parents to light at night has multigenerational effects on offspring depressive-like behavior. If these results pertain to humans, then our data suggest that LAN may contribute to the rapidly rising rates of major depressive disorder in industrialized and developing countries.

Daylight Savings Time Transitions and the Incidence Rate of Unipolar Depressive Episodes.

Daylight savings time transitions affect approximately 1.6 billion people worldwide. Prior studies have documented associations between daylight savings time transitions and adverse health outcomes, but it remains unknown whether they also cause an increase in the incidence rate of depressive episodes. This seems likely because daylight savings time transitions affect circadian rhythms, which are implicated in the etiology of depressive disorder. Therefore, we investigated the effects of daylight savings time transitions on the incidence rate of unipolar depressive episodes. Using time series intervention analysis of nationwide data from the Danish Psychiatric Central Research Register from 1995 to 2012, we compared the observed trend in the incidence rate of hospital contacts for unipolar depressive episodes after the transitions to and from summer time to the predicted trend in the incidence rate. The analyses were based on 185,419 hospital contacts for unipolar depression and showed that the transition from summer time to standard time were associated with an 11% increase (95% CI = 7%, 15%) in the incidence rate of unipolar depressive episodes that dissipated over approximately 10 weeks. The transition from standard time to summer time was not associated with a parallel change in the incidence rate of unipolar depressive episodes. This study shows that the transition from summer time to standard time was associated with an increase in the incidence rate of unipolar depressive episodes. Distress associated with the sudden advancement of sunset, marking the coming of a long period of short days, may explain this finding. See video abstract at, http://links.lww.com/EDE/B179.

The importance of TCF4 gene in the etiology of recurrent depressive disorders

BackgroundA recurrent depressive disorder is one of the most commonly diagnosed disease entities among psychiatric disorders. The prevalence and morbidity of depression are constantly increasing. Numerous studies have demonstrated the role of genetic factors in the etiology of depressive disorders. Many studies are being conducted to identify genes that predispose to depression. The purpose of this study was to investigate the role of TCF4 gene in the etiology of recurrent depressive disorders and, in particular, to assess expression of the TCF4 gene at the mRNA and protein level in patients with recurrent depressive disorders versus healthy individuals. Material and methodsThe examined population consisted of 170 individuals suffering from depression and 90 healthy individuals. The expressions of the TCF4 gene at the mRNA and protein level were assessed. ResultsDecreased TCF4 expression at the mRNA and protein level was found in patients with depressive disorder versus healthy individuals. Expression of the studied gene was not affected by the patients' sex and age.The statistical analysis also showed no correlation between the expression of TCF4 at the mRNA and protein level and the number of episodes or the severity of symptoms. Among the clinical manifestations of depression, only the duration of the illness correlated with the expression of TCF4 at the mRNA level. ConclusionsExpression of TCF4 at the mRNA and protein level may be significant in the pathomechanism of recurrent depressive disorder and it is not dependent on sex and age.

Ethiopathogenesis of depressive disorders.

Etiology of depressive disorders is still unknown. Several factors are involved in its pathophysiology such as neurotransmitters and neuroendocrine alterations, genetics, life events and their appraisal. Some of these components are strictly linked. Subjects with a family member affected by mood disorders are more prone to suffer from depressive disorders. It is also true that receiving feedbacks of indifference or neglect during childhood from one parent who suffer from depression may represent a factor of vulnerability. Indeed, reaction to a specific negative event may determine an increased allostasis which lead to a depressive episode. Thus, a psychological cause does not exclude a neurobiological cascade. Whereas in other cases recurrent depressive episodes appear in absence of any negative life event. This review provides a set of data regarding the current etiopathogenesis models of depression, with a particular attention to the neurobiological correlates and vulnerability factors.

SEMIOTICS, DIAGNOSTICS AND THERAPY TACTICS OF DEPRESSIVE DISORDERS IN CLINICAL MEDICINE

Study objectives are dedicated to brief synthesized establishment of diagnostics general standard, management and therapy of major depressive disorders (MDD) in clinical medicine to provide education in medical practice.Study methods are based on short-term, medium-term and long-term educational programs in 24 Russian and Ukraine cities, which were based on original educational programs under the direction of World Psychiatric Association (WPA) and International Committee For Prevention and Treatment of Depression (PTD). There, about 1450 doctors of different occupations were acquainted with the detection, management and treatment of MDD. The Russian version of WPA/PTD programs was created. The program of education included 4 modules. The Core module included an overview of the epidemiology, impact, concepts and classification, and etiology of depressive disorders as well as their recognition, diagnosis, and management in the primary care setting. The second module focused on depressive disorders in physical illness and covered those major illnesses for which is reasonable evidence for an association with depressive disorders. The third module included the development of the depressive disorders in older persons. The forth module included training physicians in mental health skills. 39 theme improvements for 858 primary care setting physicians within the framework of faculty training program of physicians’ development were the part of other programs of physicians’ occupations.Results. A number of highlights were included in the general algorithm of the educational programs. The creation of optimum «physician-depressive patient» contact demands a number of new skills to establish effective communication. These skills involve training of meeting of depressive patient and physician, the ability to follow a certain communication style; identify emotional, cognitive, psychomotor and nonverbal patterns of behavior. Besides that, the education included adherence to therapy and therapeutic alliance during the period of informed agreement. There was an education of fluent grasp of medicaments, which are the first choice in therapy. Integration of this knowledge is done during the periods of repeated interactive discussions of antidepressants’ effectiveness in depression therapy which is based on three-phased MDD therapy model. The process of working out the depressive patients’ management was based on systematization and diagnostic of depression disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, or International Classification of Diseases, Revision 10); detailed discussions of manifestation and thorough depression symptomatology; management approaches in depression disorders, different in manifestation.Conclusion. The basis of physicians' education was the idea that depressive disorder in holistic approach can't be considered as an independent psychiatric disease in its mild and moderate forms of manifestation. Depression, along with coronary artery disease, cerebrovascular diseases, diabetes, osteoporosis, obesity and fatness should be considered by clinical medicine within one cluster of noninfectious multifactorial chronic diseases.

Potential link between caffeine consumption and pediatric depression: A case-control study.

BackgroundEarly-onset depressive disorders can have severe consequences both from developmental and functional aspects. The etiology of depressive disorders is complex and multi-factorial, with an intricate interaction among environmental factors and genetic predisposition. While data from studies on adults suggest that caffeine is fairly safe, effects of caffeine in children, who are in period of rapid brain development, are currently unknown. Furthermore, systematic research addressing the relationship between depressive symptoms in children and caffeine consumption is lacking.The present study examined the effects of caffeine consumption on depressed mood in children with depression and non-depressed participants.MethodsChildren and adolescents (n = 51) already enrolled in an ongoing longitudinal study, aged 9-12 years, were assessed for depressive symptoms with the Children Depressive Inventory (CDI). Psychopathological symptoms were assessed with the Child Behavioral Checklist (CBCL) and eating habits were assessed with the Nutrition-Behavior Inventory (NBI) [1]. The children were compared to control children without psychopathology attending public schools in a Southern Brazilian city.ResultsParticipants with CDI scores ≥ 15 (mean = 19; S.D. = 4) also had high NBI scores (mean = 52; S.D. = 19, p < 0.001) suggestive of a relationship between depressive symptoms and environmental factors, in this case nutrition/behavior. Additional linear regression adjusted statistical analysis, considering the factors of consumption of sweets and caffeine individually, showed that caffeine, but not sweets, was associated with depressive symptoms.ConclusionsThese findings indicate that depressed children consume more caffeinated drinks than non-depressed children. Nonetheless while a strong association between depressive symptoms and caffeine consumption among children was found, further research should investigate whether or not this association is due to a cause and effect relationship.

The GABAergic deficit hypothesis of major depressive disorder

Increasing evidence points to an association between major depressive disorders (MDDs) and diverse types of GABAergic deficits. In this review, we summarize clinical and preclinical evidence supporting a central and causal role of GABAergic deficits in the etiology of depressive disorders. Studies of depressed patients indicate that MDDs are accompanied by reduced brain concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and by alterations in the subunit composition of the principal receptors (GABA(A) receptors) mediating GABAergic inhibition. In addition, there is abundant evidence that suggests that GABA has a prominent role in the brain control of stress, the most important vulnerability factor in mood disorders. Furthermore, preclinical evidence suggests that currently used antidepressant drugs (ADs) designed to alter monoaminergic transmission and nonpharmacological therapies may ultimately act to counteract GABAergic deficits. In particular, GABAergic transmission has an important role in the control of hippocampal neurogenesis and neural maturation, which are now established as cellular substrates of most if not all antidepressant therapies. Finally, comparatively modest deficits in GABAergic transmission in GABA(A) receptor-deficient mice are sufficient to cause behavioral, cognitive, neuroanatomical and neuroendocrine phenotypes, as well as AD response characteristics expected of an animal model of MDD. The GABAergic hypothesis of MDD suggests that alterations in GABAergic transmission represent fundamentally important aspects of the etiological sequelae of MDDs that are reversed by monoaminergic AD action.

Ghrelin, paraoxonase and arylesterase levels in depressive patients before and after citalopram treatment

Objectives The purpose of this study was to examine alterations in lipid profiles and in the serum concentrations of acylated and desacylated ghrelin, paraoxonase and arylesterase in psychiatric patients before and after treatment with 40 mg citalopram daily for 3 months. Design and methods Samples were collected from 22 healthy controls and 24 psychiatric patients before and after citalopram treatment. Blood levels of acylated and desacylated ghrelin were measured by radioimmunoassay. Paraoxonase and arylesterase activities were determined spectrophotometrically. Lipid parameters were measured on the OLYMPUS-AU400. Results It was found that the levels of acylated, desacylated ghrelin, paraoxonase arylesterase, total cholesterol and triglyceride were lower in depressive patients before citalopram treatment than in the control group. Those parameters were not restored after citalopram treatment except for the arylesterase level. Conclusion Decreased PON1 and ghrelin levels as well as fluctuations in lipid profiles may be involved in the etiology of depressive disorders.