Cloning of the ferrireductase that may be involved in iron transport in the small intestine: revisiting Crane's controversial oxidoreductase

Abstract

Objectives

Oxidative stress and inflammation have been reported to be higher in subjects with depression, but it is unclear whether this is due to inadequate dietary antioxidant intake or the pathophysiology of depression. The aim of this study was to assess the association between dietary and serum antioxidant status with depression scales in young male university students.

Methods

This research was a case–control study carried out on 60 male university students (30 students diagnosed with depression and 30 matched healthy controls). Beck Depression Inventory-II was used to assess the major depressive disorder (MDD) scales. A semi-quantitative food frequency questionnaire and 2-day 24-h recalls were used for dietary assessment. Dietary and serum total antioxidant capacity (TAC) and high-sensitive C-reactive protein (hs-CRP) concentrations were also measured.

Results

MDD subjects consumed less fruits (P < 0.05), legumes (P < 0.001), nuts and seeds (P = 0.003), vitamin C (P = 0.005), beta carotene (P < 0.001), lutein, and zeaxanthin (P = 0.006) than the controls. Moreover, the depressed group had lower serum TAC levels than their controls (P < 0.05). There were no significant differences in serum hs-CRP concentrations and dietary TAC levels between the study groups.

Discussion

Students with depression had significantly lower intake of dietary antioxidants. However, dietary TAC and serum hs-CRP levels were not significantly different between depressed and normal university male students. Intake of foods rich in antioxidants is encouraged in male students.     

Diferencias en función de la edad y la autopercepción del envejecimiento en ansiedad,tristeza, soledad y sintomatología comórbida ansioso-depresiva durante el confinamiento por la COVID-19

ObjectivesTo analyze differences by age group in anxiety, depression, loneliness and comorbid anxiety and depression in young people, middle aged adults and older adults during the lock-down period at home due to the COVID-19 pandemic, and to explore the association between negative self-perceptions of aging and psychological symptoms controlling by age group.MethodParticipants are 1501 people (age range 18 to 88 years). Anxiety, sadness, loneliness and self-perceptions of aging were assessed. The sample was divided according to the age group and quartiles (lower, intermediate levels, and higher) of anxiety, sadness, loneliness and self-perceptions of aging.ResultsOlder adults reported lower levels of anxiety and sadness than middle aged adults, and middle aged adults reported lower levels than younger participants. Middle aged adults reported the lowest loneliness, followed by older adults and younger participants. For each age group, those with more negative self-perceptions of aging reported higher anxiety, sadness and loneliness. More comorbid anxiety and sadness was found in younger adults and less in older adults; more depressed participants in the middle aged group, and more older adults and less younger participants were found in the group with the lowest levels of anxiety and sadness. For all the age groups, participants with high levels of comorbid anxiety and sadness are those who report the highest scores in negative self-perceptions of aging.ConclusionsOlder adults reported lower psychological anxiety, sadness and loneliness than the other age groups. Having negative self-perceptions of aging damage psychological health irrespective of the chronological age.     

The 3111T/C Polymorphism Interacts With Stressful Life Events to Influence Patterns of Sleep in Females

Genetic variations in clock-relevant genes have been investigated in relation to sleep abnormalities, both in healthy populations and in mood-disorder patients with inconsistent results. Environmental influences may moderate associations between genes and phenotype. The authors examined the CLOCK 3111T/C polymorphism and several variants within the PER3 gene and their possible interaction with stressful life events in a group of female volunteers (n?=?415). Gene-environment (G?×?E) interactions and gene main effects were investigated on depressive symptoms using the Beck Depression Inventory and on change of sleep patterns (Item 16). Results showed a G?×?E interaction on alteration of sleeping pattern: the 3111C homozygous genotype reported greater disruption in sleep pattern after the experience of stressful life events. Within the PER3 gene, one G?×?E interaction was observed with rs228642 on sleep change. These findings show that the 3111T/C polymorphism is not associated with depressive symptoms, but only with symptoms of sleep change in the case of prior stressful life experiences. The combination of a sensitive genotype (3111C/C) and environmental stress increases vulnerability to circadian rhythm disruption in females. (Author correspondence: laura.mandelli@unibo.it)     

EVENING PREFERENCE IS RELATED TO THE INCIDENCE OF DEPRESSIVE STATES INDEPENDENT OF SLEEP-WAKE CONDITIONS

Although evening preference has recently been identified as a risk factor for depression, it has not been substantiated whether evening preference is a direct risk factor for depressive states, or if it is associated secondarily through other factors, such as delayed sleep timing and shortened sleep duration. The objective of this study is to investigate associations in Japanese adult subjects between evening preference and incidence of depressive states, adjusting for various sleep parameters related to depressive states. The Morningness-Eveningness Questionnaire (MEQ), the Pittsburgh Sleep Quality Index (PSQI), and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to 1170 individuals (493 males/677 females; mean and range 38.5 and 20–59 yrs) to assess their diurnal preferences, sleeping states, and presence of depression symptoms. Subjects were classified into five chronotypes based on MEQ scores. Evening preference was associated with delayed sleep timing, shortened sleep duration, deteriorated subjective sleep quality, and worsened daytime sleepiness. Logistic regression analysis demonstrated that the extreme evening type (odds ratio [OR]?=?1.926, p?=?.018) was associated with increased incidence of depressive states and that the extreme morning type (OR?=?0.342, p?=?.038) was associated with the decreased incidence of depressive states, independent of sleep parameters, such as nocturnal awakening (OR?=?1.844, p?<?.001), subjective sleep quality (OR?=?2.471, p?<?.001), and daytime sleepiness (OR?=?1.895, p?=?.001). However, no significant associations were observed between the incidence of depressive states and sleep duration, sleep timing, and sleep debt (levels of insufficient sleep). Although the findings of this study do not demonstrate a causative relationship between evening preference and depression, they do suggest the presence of functional associations between mood adjustment and biological clock systems that regulate diurnal preference. They also suggest that evening preference might increase susceptibility to the induction of mood disorders. (Author correspondence: mishima@ncnp.go.jp)     

Depression in Medical School: The Influence of Morningness‐Eveningness

Medical students are at higher risk for depression, affecting not only their lives but also patient care. This article studied a population of medical students engaged in lecture‐based learning regarding the presence of depressive symptoms and its relation to morningness‐eveningness. Depressive symptoms were assessed by the Beck Depressive Inventory scale (BDI>10), and diurnal preference was assessed by the Horne & Östberg Morningness/Eveningness Questionnaire (MEQ). Family history of depression and involvement in regular physical activity were also investigated. A total of 161 students, 77 (47.8%) males, aged 19 to 30 yrs (22.1±2.1) living in a city close to the equator were evaluated. Fifty‐three individuals (32.9%) had depressive symptoms. Depressive individuals showed a trend to be female (p=0.07). Also, female gender showed a non‐significant shift toward morningness. Fifty‐eight (36.0%) subjects participated in regular physical activity. In 57 cases (35.4%), there was a history of depression in the family. Fifteen individuals (9.3%) were definitely evening type, 42 (26.1%) were moderately evening type, 44 (27.3%) were indifferent, 42 (26.1%) were moderately morning type, and 18 (11.2%) were definitely morning type. Family history of depression (OR=0.29, 95% CI=1.37–6.12) and sedentary life (OR=0.28, 95% CI=0.12–0.65) were associated with depressive symptoms. Eveningness was associated with depressive symptoms (OR=0.66, 95% CI=0.50–0.88), and this association remained significant after adjusting for the presence of familial depression and physical activity (OR=0.71, 95% CI=0.52–0.95). In conclusion, depressive symptoms are independently associated with “eveningness” in medical students. These results should be confirmed by future studies involving a larger number of subjects.     

A Prospective Study of Seasonal Variation in Shift‐Work Tolerance

Seasonal effects on shift‐work tolerance were assessed using the Standardized Shiftwork Index and the 21‐item Hamilton Depression Scale. Participants (N=88) mainly worked a two‐day, two‐night, four‐off rotation with 12 h shifts changing at 06∶00 and 18∶00 h in Vancouver, Canada. At this latitude (～49° N), daylength varies seasonally from ～16 to ～8 h, and both daily commutes occur in the dark in mid‐winter and in sunlight in mid‐summer. Questionnaires were completed twice, near the summer and winter solstices (order counterbalanced). Outcome variables were mood, general psychological health, sleep quality, chronic fatigue, physical health, job satisfaction, and social and domestic disruption. Of these, general psychological health and mood were significantly worse in winter, while sleep was more disturbed in summer. In winter, 31% exceeded the cutoff for psychological distress, and >70% scored in the higher than normal range for depressive symptoms. In summer, the proportions dropped to 19% and 53%, respectively. Measures of physical health and psychosocial well‐being showed no seasonal effects. Relationships among explanatory and outcome variables, assessed by linear regression and canonical correlations, were also stable across season. Neuroticism was the strongest predictor of tolerance to shift work. Age was predictive only of sleep disturbance in both summer and winter. These results indicate that time of year can affect important outcome measures in shift‐work assessment and intervention studies. The high average scores on measures of psychological distress and depression in winter suggest that at northern latitudes, some shift schedules may increase the risk of seasonal‐type depression.     

Depression Scores Associate With Chronotype and Social Jetlag in a Rural Population

In public health, mood disorders are among the most important mental impairments. Patients with depressive episodes exhibit daily mood variations, abnormal patterns in sleep-wake behavior, and in the daily rhythms of several endocrine-metabolic parameters. Although the relationship between the sleep/circadian processes and mood disorders is poorly understood, clock-related therapies, such as light therapy, sleep deprivation, and rigid sleep schedules, have been shown to be effective treatments. Several studies investigated the relationship between circadian phenotype (chronotype) and depression. These focused mainly on urban populations and assessed diurnal preferences (Morningness-Eveningness score) rather than the actual timing of sleep and activity. Here, we used the Beck Depression Inventory (BDI) in an essentially rural population (N?=?4051), and investigated its relation to circadian phenotype (chronotype and social jetlag), assessed with the Munich Chronotype Questionnaire (MCTQ). In our study design, we (i) normalized both chronotype and BDI scores for age and sex (MSF_sas and BDI_as, respectively); (ii) calculated individual social jetlag (misalignment of the biological and social time); and (iii) investigated the relationship between circadian phenotypes and BDI scores in a population homogeneous in respect to culture, socioeconomic factors, and daily light exposure. A 15.65% (N?=?634) of the participants showed mild to severe depressive BDI scores. Late chronotypes had a higher BDI_as than intermediate and early types, which was independent of whether or not the participants were smokers. Both chronotype and BDI_as correlated positively with social jetlag. BDI_as was significantly higher in subjects with >2?h of social jetlag than in the rest of the population—again independent of smoking status. We also compared chronotype and social jetlag distributions between BDI categories (no symptoms, minimal symptoms, and mild to severe symptoms of depression) separately for men and women and for four age groups; specifically in the age group 31–40 yrs, subjects with mild to severe BDI scores were significantly later chronotypes and suffered from higher social jetlag. Our results indicate that misalignment of circadian and social time may be a risk factor for developing depression, especially in 31- to 40-yr-olds. These relationships should be further investigated in longitudinal studies to reveal if reduction of social jetlag should be part of prevention strategies. (Author correspondence: karla.allebrandt@med.uni-muenchen.de)     

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: Modulation of hypothalamic–pituitary–adrenal axis activity and brain-derived neurotrophic factor level

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) were administered during the last 21 days (8–28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1 mg/kg., p.o.) and fluoxetine (20 mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p < 0.05) increased the BDNF level and inhibited the hypothalamic–pituitary–adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level.     

Serum level of brain-derived neurotrophic factor in fibromyalgia syndrome correlates with depression but not anxiety

Brain-derived neurotrophic factor (BDNF) has been known to play a role in fibromyalgia syndrome (FMS) patients. Depression and anxiety are quite common additional symptoms in FMS. However the role of BDNF in these symptoms still needs to be elucidated. Although BDNF has been shown to be relevant in major depression, however studies could not show such differences between FMS patients with and without major depression. As mood-related symptom occurs frequently and differs in its intensity in FMS patients, BDNF level should be measured in subgroup regarding depression and anxiety scale. Therefore the aim of this study was to evaluate the correlation of BDNF in serum of FMS with intensity of depression and anxiety. Additionally, interleukin (IL)-6 was measured.     

Synthesis and biological evaluation of novel 3,4-diaryl lactam derivatives as triple reuptake inhibitors

A series of 3,4-diarylpyrrolidin-2-one was designed, prepared and evaluated as triple reuptake inhibitors for antidepressant. Most compounds exhibited comparable in vitro efficacy as norepinephrine and dopamine transporter reuptake inhibitors. Especially, 2i showed better potency than GBR-12909 (IC₅₀ = 14 nM) which was used as reference compound for dopamine transporter. In addition, 2a and 2b showed inhibition (5.17 μM–85.6 nM) for three transporters.