Psychiatry - Research Publications
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ItemBaseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).(Wiley, 2013-03)AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.
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ItemClinical subtypes of core premenstrual disorders: a Delphi survey(SPRINGER WIEN, 2013-06)The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.
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ItemPossible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach(PUBLIC LIBRARY SCIENCE, 2013-06-04)BACKGROUND: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. METHODS: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. RESULTS: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (Pcorr = .018, Pcorr = .015 and Pcorr = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. CONCLUSIONS/LIMITATIONS: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies.
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ItemChanges in Insulin Resistance and HbA1c Are Related to Exercise-Mediated Changes in Body Composition in Older Adults With Type 2 Diabetes(AMER DIABETES ASSOC, 2013-08)OBJECTIVE: To investigate changes in body composition after 12 months of high-intensity progressive resistance training (PRT) in relation to changes in insulin resistance (IR) or glucose homeostasis in older adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: One-hundred three participants were randomized to receive either PRT or sham exercise 3 days per week for 12 months. Homeostasis model assessment 2 of insulin resistance (HOMA2-IR) and glycosylated hemoglobin (HbA1c) were used as indices of IR and glucose homeostasis. Skeletal muscle mass (SkMM) and total fat mass were assessed using bioelectrical impedance. Visceral adipose tissue, mid-thigh cross-sectional area, and mid-thigh muscle attenuation were quantified using computed tomography. RESULTS: Within the PRT group, changes in HOMA2-IR were associated with changes in SkMM (r = -0.38; P = 0.04) and fat mass (r = 0.42; P = 0.02). Changes in visceral adipose tissue tended to be related to changes in HOMA2-IR (r = 0.35; P = 0.07). Changes in HbA1c were related to changes in mid-thigh muscle attenuation (r = 0.52; P = 0.001). None of these relationships were present in the sham group (P > 0.05). Using ANCOVA models, participants in the PRT group who had increased SkMM had decreased HOMA2-IR (P = 0.05) and HbA1c (P = 0.09) compared with those in the PRT group who lost SkMM. Increases in SkMM in the PRT group decreased HOMA2-IR (P = 0.07) and HbA1c (P < 0.05) compared with those who had increased SkMM in the sham group. CONCLUSIONS: Improvements in metabolic health in older adults with type 2 diabetes were mediated through improvements in body composition only if they were achieved through high-intensity PRT.
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ItemTreating depression and depression-like behavior with physical activity: an immune perspective(FRONTIERS MEDIA SA, 2013-02-04)The increasing burden of major depressive disorder makes the search for an extended understanding of etiology, and for the development of additional treatments highly significant. Biological factors may be useful biomarkers for treatment with physical activity (PA), and neurobiological effects of PA may herald new therapeutic development in the future. This paper provides a thorough and up-to-date review of studies examining the neuroimmunomodulatory effects of PA on the brain in depression and depression-like behaviors. From a neuroimmune perspective, evidence suggests PA does enhance the beneficial and reduce the detrimental effects of the neuroimmune system. PA appears to increase the following factors: interleukin (IL)-10, IL-6 (acutely), macrophage migration inhibitory factor, central nervous system-specific autoreactive CD4+ T cells, M2 microglia, quiescent astrocytes, CX3CL1, and insulin-like growth factor-1. On the other hand, PA appears to reduce detrimental neuroimmune factors such as: Th1/Th2 balance, pro-inflammatory cytokines, C-reactive protein, M1 microglia, and reactive astrocytes. The effect of other mechanisms is unknown, such as: CD4+CD25+ T regulatory cells (T regs), CD200, chemokines, miRNA, M2-type blood-derived macrophages, and tumor necrosis factor (TNF)-α [via receptor 2 (R2)]. The beneficial effects of PA are likely to occur centrally and peripherally (e.g., in visceral fat reduction). The investigation of the neuroimmune effects of PA on depression and depression-like behavior is a rapidly developing and important field.
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ItemEarly experiences and the development of emotional learning systems in rats.(Springer Science and Business Media LLC, 2013)Research first reported nearly 50 years ago demonstrated that infant and young animals (including humans) exhibit profoundly faster rates of forgetting (i.e., infantile amnesia) than do adults. In addition to these differences in retention, more recent research has shown that inhibition of fear learning is also very different in infancy than in adulthood. Specifically, extinction of fear early in life is much more resistant to relapse than is extinction later in life. Both of these findings suggest that young animals should be especially resilient to the emergence of mental health disorders, which appears to be at odds with the view that early-life experiences are particularly important for the development of later psychopathologies (such as anxiety disorders) and with the finding that the majority of anxiety disorders first emerge in adolescence or childhood. This apparent paradox might be resolved, however, if exposure to chronic stress early in life affects the maturation of the fear retention and extinction systems, leading to a faster transition to the adult form of each (i.e., long-lasting fear memories and relapse-prone extinction). In several recent studies we have found exactly this pattern; that is, infant rats exposed to maternal-separation stress exhibit adult-like fear and extinction learning early in development. Further, we have demonstrated that some of these effects can be mimicked by exposing the mother to the stress hormone corticosterone in their drinking water (in lieu of the separation procedure). These findings suggest that early-life exposure to stress and stress hormones may act as a general signal that can alter the developmental trajectory of emotional systems and potentially place animals at greater risk for the development of anxiety. The implications of these recent findings for our understanding of the developmental origins of health and disease, and for enhancing preventative and therapeutic treatments across the lifespan, are considered.
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ItemFrom resilience to vulnerability: mechanistic insights into the effects of stress on transitions in critical period plasticity.(Frontiers Media SA, 2013)While early experiences are proposed to be important for the emergence of anxiety and other mental health problems, there is little empirical research examining the impact of such experiences on the development of emotional learning. Of the research that has been performed in this area, however, a complex picture has emerged in which the maturation of emotion circuits is influenced by the early experiences of the animal. For example, under typical laboratory rearing conditions infant rats rapidly forget learned fear associations (infantile amnesia) and express a form of extinction learning which is relapse-resistant (i.e., extinction in infant rats may be due to fear erasure). In contrast, adult rats exhibit very long-lasting memories of past learned fear associations, and express a form of extinction learning that is relapse-prone (i.e., the fear returns in a number of situations). However, when rats are reared under stressful conditions then they exhibit adult-like fear retention and extinction behaviors at an earlier stage of development (i.e., good retention of learned fear and relapse-prone extinction learning). In other words, under typical rearing conditions infant rats appear to be protected from exhibiting anxiety whereas after adverse rearing fear learning appears to make those infants more vulnerable to the later development of anxiety. While the effects of different experiences on infant rats' fear retention and extinction are becoming better documented, the mechanisms which mediate the early transition seen following stress remain unclear. Here we suggest that rearing stress may lead to an early maturation of the molecular and cellular signals shown to be involved in the closure of critical period plasticity in sensory modalities (e.g., maturation of GABAergic neurons, development of perineuronal nets), and speculate that these signals could be manipulated in adulthood to reopen infant forms of emotional learning (i.e., those that favor resilience).
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ItemAcute effects of different multivitamin mineral preparations with and without Guaraná on mood, cognitive performance and functional brain activation.(MDPI AG, 2013-09-13)Previous work has identified the positive effects of the acute administration of a multivitamin-guaraná preparation during an effortful executive/working memory task. Here, we aimed to differentiate the effects of multivitamins with and without guaraná and to examine the neural substrates of such effects using functional magnetic resonance imaging (fMRI). Following a double-blind, placebo-controlled, randomised, balanced crossover design, 20 participants (mean age 29 ± 5.54 years) consumed multivitamin preparations with or without guaraná (Berocca® Performance and Boost, respectively) and a placebo. Thirty minutes post-treatment, they underwent neurocognitive assessment, consisting of a 10 min Cognitive Demand Battery, with mood ratings taken immediately before and after the battery. Five additional participants underwent post-treatment fMRI scanning during Rapid Visual Information Processing and Inspection Time activation tasks. The multivitamin with guaraná treatment was associated with significantly enhanced Serial Threes performance and self-rated contentment. fMRI revealed that both multivitamin treatments increased activation in areas associated with working memory and attentional processing, with the effect being greater in the multivitamin with guaraná condition. These data confirm the acute benefits of multivitamins with guaraná on mood and cognitive performance. Furthermore, they demonstrate for the first time increased brain activation from multivitamin preparations both with and without guaraná, as measured using fMRI.
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ItemNo Preview AvailableCognitive training and cognitive rehabilitation for persons with mild to moderate dementia of the Alzheimer's or vascular type: a review(BMC, 2013)Cognitive impairments, and particularly memory deficits, are a defining feature of the early stages of Alzheimer's disease and vascular dementia. Interventions that target these cognitive deficits and the associated difficulties with activities of daily living are the subject of ever-growing interest. Cognitive training and cognitive rehabilitation are specific forms of non-pharmacological intervention to address cognitive and non-cognitive outcomes. The present review is an abridged version of a Cochrane Review and aims to systematically evaluate the evidence for these forms of intervention in people with mild Alzheimer's disease or vascular dementia. Randomized controlled trials (RCTs), published in English, comparing cognitive rehabilitation or cognitive training interventions with control conditions and reporting relevant outcomes for the person with dementia or the family caregiver (or both), were considered for inclusion. Eleven RCTs reporting cognitive training interventions were included in the review. A large number of measures were used in the different studies, and meta-analysis could be conducted for several primary and secondary outcomes of interest. Several outcomes were not measured in any of the studies. Overall estimates of the treatment effect were calculated by using a fixed-effects model, and statistical heterogeneity was measured by using a standard chi-squared statistic. One RCT of cognitive rehabilitation was identified, allowing the examination of effect sizes, but no meta-analysis could be conducted. Cognitive training was not associated with positive or negative effects in relation to any of the reported outcomes. The overall quality of the trials was low to moderate. The single RCT of cognitive rehabilitation found promising results in relation to some patient and caregiver outcomes and was generally of high quality. The available evidence regarding cognitive training remains limited, and the quality of the evidence needs to improve. However, there is still no indication of any significant benefits from cognitive training. Trial reports indicate that some gains resulting from intervention may not be captured adequately by available standardized outcome measures. The results of the single RCT of cognitive rehabilitation show promise but are preliminary in nature. Further well-designed studies of cognitive training and cognitive rehabilitation are required to provide more definitive evidence. Researchers should describe and classify their interventions appropriately by using the available terminology.
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ItemNo Preview AvailableA Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research(IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2013)Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.