Low prevalence of depression and anxiety is linked to statutory retirement ages rather than personal work exit: a national survey

BACKGROUND: Common mental disorder prevalence decreases substantially around the conventional retirement age for men in the UK, but trends for older women are more continuous. Prevalence changes in depression and anxiety around retirement are less clear, as is the role of risk factors. The aim of this study was to establish whether work status, age or other known risk factors account for the reduced prevalence of depressive episode and anxiety disorder around retirement ages for men and for women. METHOD: The British Psychiatric Morbidity Survey (BPMS) 2000 was analysed, including 1875 men and 2253 women aged 45-75 years. Diagnoses were from the Revised Clinical Interview Schedule (CIS-R). Logistic models were adjusted for sociodemographic factors, social network, work status, life events, physical illness and disability. RESULTS: There are marked reductions in the prevalence of depressive episode after 60 years for women [60% lower prevalence, 95% confidence interval (CI) 40-80] and 65 years for men (90% lower prevalence, 95% CI 70-100), compared to the youngest age groups. For anxiety disorder, the reduction in prevalence was 80% (95% CI 60-90) for men and 40% (95% CI 20-60) for women. In fully adjusted multivariate models, the strong association between diagnoses and age groups remained, for both genders. Work status was a significant factor for men but not for women. CONCLUSION: There is a discontinuity in the prevalence of depressive episode for both men and women, coinciding with statutory retirement ages. No studied risk factor reduced the associations between age group and disorders. This population scale recovery may provide a model for understanding non-genetic factors.     

Medial gastrocnemius muscle growth during adolescence is mediated by increased fascicle diameter rather than by longitudinal fascicle growth

Using a cross-sectional design, the purpose of this study was to determine how pennate gastrocnemius medialis (GM) muscle geometry changes as a function of adolescent age. Sixteen healthy adolescent males (aged 10–19 years) participated in this study. GM muscle geometry was measured within the mid-longitudinal plane obtained from a 3D voxel-array composed of transverse ultrasound images. Images were taken at footplate angles corresponding to standardised externally applied footplate moments (between 4 Nm plantar flexion and 6 Nm dorsal flexion). Muscle activity was recorded using surface electromyography (EMG), expressed as a percentage of maximal voluntary contraction (%MVC). To minimise the effects of muscle excitation, EMG inclusion criteria were set at < 10% of MVC. In practice, however, normalised EMG levels were much lower. For adolescent subjects with increasing ages, GM muscle (belly) length increased due to an increase in the length component of the physiological cross-sectional area measured within the mid-longitudinal plane. No difference was found between fascicles at different ages, but the aponeurosis length and pennation angle increased by 0.5 cm year⁻¹ and 0.5 ° per year, respectively. Footplate angles corresponding to externally applied 0 and 4 Nm plantarflexion moments were not associated with different adolescent ages. In contrast, footplate angles corresponding to externally applied 4 and 6 Nm dorsal flexion moments decreased by 10 ° between 10 and 19 years. In conclusion, we found that in adolescents'' pennate GM muscles, longitudinal muscle growth is mediated predominantly by increased muscle fascicle diameter.     

Shrimp interferon is rather a portion of the mitochondrial F0-ATP synthase than a true alpha-interferon

Type I interferon (IFN) is a multimember cytokine family commonly known by its involvement in antiviral defense. Recently (2005), an interferon-like protein (IntlP) homologue to mammalian IFN-alpha was identified for the first time in crustaceans, in the shrimp Penaeus (Marsupenaeus) japonicus. IntlP was expressed only in WSSV-resistant shrimps (but not in na?ve shrimps) and was capable to induce an unspecific antiviral effect on infected fish cells. In the present paper we show that IntlP is in reality a portion of the mitochondrial F0-ATP synthase (60-73% identity with insect F0-ATP synthase beta-chain) and not a homologue of mammalian type I interferon. In our hands, sequences corresponding to IntlP/F0-ATP synthase beta-chain were equally amplified in na?ve and WSSV-infected Litopenaeus vannamei and also in two wild Brazilian shrimp species. From the obtained results we assumed that type I IFN homologues have not yet been demonstrated in any shrimp or crustacean.     

Diversification of response to hsp65 during the course of autoimmune arthritis is regulatory rather than pathogenic

Summary: Determinant spreading has been implicated in the pathogenesis of certain autoimmune diseases in animal models. We have observed that during the course of adjuvant arthritis (AA) in the Lewis rat, there is 'diversification' of response to the bacterial 65-kDa heat shock protein (Bhsp65) towards its carboxy-terminal determinants (BCTD). Strikingly, pretreatment of naive Lewis rats with BCTD affords significant protection from AA. Our preliminary studies indicate that the diversification of response to BCTD in the Lewis rat is probably triggered in vivo by the induction and enhanced processing of self(rat) hsp65. Thus, the self hsp65-directed T-cell responses appear to be involved in mediating natural remission from acute inflammatory arthritis induced by a foreign antigen, Myco-bacterium tuberculosis. This the first report describing that the new T-cell specificities arising during the course of an autoimmune disease are regulatory/protective rather than pathogenic. Moreover, our results suggest that a final common mechanism involving BCTD might be recruited by other rac strains which either are resistant to AA (WKY rats) or whose susceptibility to AA is modulated significantly by microbial flora (Fisher rats). The results of this study would contribute significantly to understanding of the pathogenesis of human rheumatoid arthritis, and in devising new therapeutic strategies for this disease.     

Severe melancholic depression is more vulnerable than non-melancholic depression to minor precipitating life events

BACKGROUND: The present study examines the moderating role of global depression severity on the relation of melancholic versus non-melancholic depression to severe and non-severe levels of stress. METHOD: A community sample of 50 women with unipolar major depressive disorder, of which 54% met Research Diagnostic Criteria for melancholic depression, were interviewed regarding stressful life events experienced prior to onset. Events were coded as severe or non-severe based on the rigorous Bedford College contextual rating system. RESULTS: Greater severity of depression was related to a higher likelihood of a severely stressful event prior to onset only for women with non-melancholic major depression. By contrast, greater severity of depression was related to a higher likelihood of a non-severe, more minor, stressful event prior to onset only for women with melancholic major depression. LIMITATIONS: The present study was limited by its use of a female volunteer sample, which might not be entirely representative of the population of individuals with major depression. In addition, the study employed a cross-sectional design, which limits conclusions relating to the causal relation of stress to melancholic versus non-melancholic depression. CONCLUSIONS: Far from being autonomous of stress, individuals with severe melancholic depression may be especially sensitive to stress, such that their episodes are influenced by more minor stressors than those of individuals with non-melancholic depression.     

Placental ischaemia is a consequence rather than a cause of pre-eclampsia

The aetiology or pre-eclampsia remains unknown, but it is widely accepted that the disorder is placental in origin. Failed trophoblast invasion of the maternal spiral arteries is accepted to be a central pathogenetic mechanism. However, the concept of failed trophoblast invasion is based on an assumption rather than direct scientific observation and there are other likely explanations for this phenomenon. The criteria for disease causation, such as the Bradford-Hill criteria are central to the ascertainment of causal relationships in modern medicine and these criteria are used here to assess the relationship between the placenta and pre-eclampsia. There is a strong association between pre-eclampsia and small (rather than large) placentas and an appropriate dose-response relationship does not exist. Failed trophoblast invasion of the spiral arteries is not specific to pre-eclampsia and occurs in other pregnancy complications and in up to 40% of biopsies from normal pregnancies and the relationship between placental ischaemia and pre-eclampsia is very inconsistent. A placental cause for pre-eclampsia is not consistent with the pathogenesis of other pregnancy complications like gestational diabetes mellitus. If pre-eclampsia was a disease of trophoblast origin, the risk of the disease should be determined by trophoblast rather than maternal factors. However, evidence from assisted reproduction shows that the risk of a woman developing pre-eclampsia is almost entirely dependent on maternal factors and independent of the embryo from which the placenta develops. There is currently no plausible proven mechanism by which the placenta causes pre-eclampsia. The syndrome typically gets worse, and can arise de-novo after the placenta has been removed, calling into question the role of the placenta in its causation. Uterine artery ligation in humans, unlike in animal experiments, is not associated with an increased incidence of pre-eclampsia, calling into question the role of poor utero-placental perfusion in the cause of the disease in humans. The signals that initiate maternal adaptive responses during pregnancy come from or through the placenta into the maternal milieu but as is the case with gestational diabetes mellitus, are not necessarily the cause of maternal disease. Pre-eclampsia causes renal, hepatic, myocardial, cerebral and adrenal ischaemia--that is ischaemia in all highly vascular organs. Placental ischaemia, like ischaemia in all other organs, is a consequence rather than a causal factor in the development of the syndrome and this has profound consequences for research strategies.     

Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy

Indoleamine 2,3 dioxygenase (IDO) activity during pregnancy protects developing fetuses from maternal immune responses in CBA mice. We show here that fetal allografts were rejected only in mating combinations where paternally inherited tissue antigens elicited potent maternal T cell responses after exposure to IDO inhibitor. IDO inhibitor treatment triggered extensive inflammation at the maternal-fetal interface in susceptible mating combinations, which was characterized by complement deposition and hemorrhagic necrosis. Identical inflammatory responses occurred in B cell-deficient (RAG-I-/-) mothers that carried a monoclonal cohort of CD8+ T cells specific for a single paternally inherited fetal major histocompatibility complex antigen. Thus, fetal allograft rejection was accompanied by a unique form of inflammation that was characterized by T cell-dependent, antibody-independent activation of complement. In contrast, no inflammation, complement deposition or T cell infiltration was elicited when mice carrying syngeneic fetuses were exposed to IDO inhibitor. These data show that IDO activity protects the fetus by suppressing T cell-driven local inflammatory responses to fetal alloantigens.     

Synaptic vesicle retrieval time is a cell-wide rather than individual-synapse property

Although individual nerve terminals from the same neuron often differ in neurotransmitter release characteristics, the extent to which endocytic retrieval of synaptic vesicle components differs is unknown. We used high-fidelity optical recordings to undertake a large-scale analysis of endocytosis kinetics of individual boutons in hippocampal rat neurons. Our data indicate that endocytosis kinetics do not differ substantially across boutons from the same cell but instead appear to be controlled at a cell-wide level.     

Recurrent melioidosis in patients in northeast Thailand is frequently due to reinfection rather than relapse

Human melioidosis is associated with a high rate of recurrent disease, despite adequate antimicrobial treatment. Here, we define the rate of relapse versus the rate of reinfection in 116 patients with 123 episodes of recurrent melioidosis who were treated at Sappasithiprasong Hospital in Northeast Thailand between 1986 and 2005. Pulsed-field gel electrophoresis was performed on all isolates; isolates from primary and recurrent disease for a given patient different by one or more bands were examined by a sequence-based approach based on multilocus sequence typing. Overall, 92 episodes (75%) of recurrent disease were caused by the same strain (relapse) and 31 episodes (25%) were due to infection with a new strain (reinfection). The interval to recurrence differed between patients with relapse and reinfection; those with relapses had a median time to relapse of 228 days (range, 15 to 3,757 days; interquartile range [IQR], 99.5 to 608 days), while those with reinfection had a median time to reinfection of 823 days (range, 17 to 2,931 days; IQR, 453 to 1,211 days) (P = 0.0001). A total of 64 episodes (52%) occurred within 12 months of the primary infection. Relapse was responsible for 57 of 64 (89%) episodes of recurrent infection within the first year after primary disease, whereas relapse was responsible for 35 of 59 (59%) episodes after 1 year (P < 0.0001). Our data indicate that in this setting of endemicity, reinfection is responsible for one-quarter of recurrent cases. This finding has important implications for the clinical management of melioidosis patients and for antibiotic treatment studies that use recurrent disease as a marker for treatment failure.     

Hypercortisolemic depression is associated with increased intra-abdominal fat

OBJECTIVE: Similar to patients with a metabolic syndrome, patients with major depression are at increased risk of developing cardiovascular disorders. Interestingly, both disorders share a specific endocrine syndrome that promotes the accumulation of visceral fat, which again is considered a marker of increased cardiovascular morbidity and mortality. METHODS: Intra-abdominal fat was measured in 22 postmenopausal depressed women and 23 age-matched healthy women by computer tomography at the level of lumbar vertebrae 1 (L1) and 4 (L4). Saliva was taken in patients and control subjects at 08:00 hours over a period of 7 drug-free days for the measurement of free cortisol. In patients only we performed an oral glucose tolerance test. RESULTS: Compared with control subjects, depressed patients with elevated free cortisol concentrations showed similar visceral fat depots at L1 (113.0 +/- 41.6 vs. 94.3 +/- 53.2 cm(2)). Hypercortisolemic depressed patients also showed greater fat depots in this area (74.5 +/- 55.5 cm(2), p =.04) than the normocortisolemic patients. However, a comparison of all patients with control subjects revealed no difference in fat accumulation at either L1 or L4. Finally, glucose concentrations during the glucose tolerance test were higher in hypercortisolemic than in normocortisolemic patients, whereas their insulin levels showed only a tendency toward being increased. CONCLUSIONS: Hypercortisolemic depressed patients suffer from resistance to insulin and increased visceral fat. The fact that hypercortisolemia reverses depression-related fat loss, particularly in the visceral area, might partially explain why major depression can be considered a risk factor for cardiovascular disorders.     

Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration

Long-term potentiation (LTP) of excitatory transmission is a likely candidate for the encoding and storage of information in the mammalian brain. There is a general agreement that LTP involves an increase in synaptic strength, but the mechanisms underlying this persistent change are unclear and controversial. Synaptic efficacy may be enhanced because more transmitter glutamate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular glutamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection of any putative change in extracellular glutamate associated with LTP, our experimental strategy included the following features. 1) Two separate series of experiments were carried out with animals under pentobarbital or urethan anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsynaptic potential evoked by activation of the perforant path were recorded precisely at the same site. Tetanic stimulation of the perforant path increased persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results do not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data supporting the notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft conflict with the hypothesis that LTP could also involve a broad synaptic spillover of glutamate.     

Subthreshold depression is linked to the functional polymorphism of the 5HT transporter gene

BACKGROUND: The functional polymorphism of the serotonin transporter gene (5HTTLPR) has been earlier associated with affective disorders. No research has however been carried out to identify the relationship between this polymorphism and depressive traits and subclinical depressive symptoms within a psychiatrically healthy population. METHODS: One hundred and twenty-eight female subjects with no lifetime or current history of DSM-IV Axis I disorders participated in the study. All subjects completed the Zung Self-Rating Depression Scale and were genotyped for the 5HTTLPR polymorphism. RESULTS: Significant differences were found on the Zung SDS and also on the physical-vegetative subscale of the Zung SDS according to both phenotype and genotype. Subjects carrying the s allele scored significantly higher on the Zung SDS and had also significantly higher scores on the physical-vegetative symptom subscale. Furthermore, subjects carrying the ss genotype scored highest and subjects carrying the ll genotype scored the lowest on both scales. CONCLUSION: Subclinical depressive symptoms (i.e. DSM-IV subthreshold depression) are associated with the functional polymorphism of the serotonin transporter gene. The main association between this polymorphism and subclinical depression is primarily carried by the physical symptoms of depression. The s allele of the 5HTTLPR gene is associated with a "low mood endophenotype".