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Predictors of primary care psychological therapy outcomes for depression and anxiety in people living with dementia: evidence from national healthcare records in England
- Georgia Bell, Celine El Baou, Rob Saunders, Joshua E. J. Buckman, Georgina Charlesworth, Marcus Richards, Caroline Fearn, Barbara Brown, Shirley Nurock, Stuart Michael, Paul Ware, Natalie L. Marchant, Elisa Aguirre, Miguel Rio, Claudia Cooper, Stephen Pilling, Amber John, Joshua Stott
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- Journal:
- The British Journal of Psychiatry / Volume 224 / Issue 6 / June 2024
- Published online by Cambridge University Press:
- 08 February 2024, pp. 205-212
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- June 2024
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Background
Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown.
AimsTo investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD.
MethodNational linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored.
ResultsPeople with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08–8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15–7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92–0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04–2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96–0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51–0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10–3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09–1.16, P < 0.001) were associated with worse therapy outcomes in PLWD.
ConclusionsDementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.
Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project
- Zhenzhen Zhang, Autumn Shafer, Katie Johnson-Camacho, Andrew Adey, Pavana Anur, Kim A. Brown, Casey Conrad, Rachel Crist, Paige E. Farris, Christina A. Harrington, Lisa K. Marriott, Asia Mitchell, Brian O’Roak, Vanessa Serrato, C. Sue Richards, Paul T. Spellman, Jackilen Shannon
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 19 January 2024, e32
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Background:
Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms.
Methods:We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities.
Results:By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18–100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates.
Conclusion:This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.
Associations between psychological therapy outcomes for depression and incidence of dementia
- Amber John, Rob Saunders, Roopal Desai, Georgia Bell, Caroline Fearn, Joshua E. J. Buckman, Barbara Brown, Shirley Nurock, Stewart Michael, Paul Ware, Natalie L. Marchant, Elisa Aguirre, Miguel Rio, Claudia Cooper, Stephen Pilling, Marcus Richards, Josh Stott
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- Journal:
- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 15 September 2022, pp. 4869-4879
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Background
Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia.
MethodsNational psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later.
ResultsImprovements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83–0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77–0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83–1.00).
ConclusionsReliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research.
Relationships among Self-Efficacy, Quality of Life, Perceived Vulnerability, and Readiness to Quit Smoking in People Living with HIV
- Remington E. Donnelly, Haruka Minami, Jacki Hecht, Erika Litvin Bloom, Karen Tashima, Danusha Selva Kumar, Ana Abrantes, Cassandra Stanton, Richard A. Brown, Bar-Zeev Yael
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- Journal:
- Journal of Smoking Cessation / Volume 2021 / 2021
- Published online by Cambridge University Press:
- 01 January 2024, e9
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- 2021
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Smoking-related diseases (e.g., lung cancer) are the leading cause of mortality in HIV-infected patients. While many PLWH who smoke report a desire to quit, a majority of them have low readiness to quit. This study used logistic and linear regression to examine the relations among two (continuous vs. binary) measures of readiness to quit, smoking cessation self-efficacy (SE), quality of life (QoL), and perceived vulnerability (PV) using baseline data from 100 PLWH who smoke who participated in a clinical trial. Results showed no significant main effects (SE, QoL, and PV) or interaction effects (SE × QoL and SE × PV) on a continuous measure of readiness to quit. However, a follow-up analysis revealed that SE had a curvilinear effect on readiness to quit such that self-efficacy was positively associated with readiness to quit except at the highest levels of self-efficacy where readiness to quit declined. Greater SE significantly increased the likelihood of reporting readiness to quit (yes/no) among those with low QoL or high PV. For PLWH who smoke, improving self-efficacy may increase readiness to quit especially among those with lower quality of life. Psychoeducation tailored to PLWH designed to reduce unrealistic invulnerability to smoking-related diseases along with interventions that target self-efficacy may improve readiness to quit.
150 HAM-D6 Outcomes in a Randomized, Controlled Trial Evaluating the Utility of Combinatorial Pharmacogenomics in Depression
- Boadie W. Dunlop, Sagar V. Parikh, Maitrey Patel, Anthony J. Rothschild, Michael E. Thase, Charles DeBattista, Charles R. Conway, Brent P. Forester, Richard C. Shelton, Matthew Macaluso, James Li, Krystal Brown, Lisa Brown, Michael R. Jablonski, John F. Greden
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 295-296
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Background:
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Methods:Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
Results:At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Conclusions:Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Funding Acknowledgements:Assurex Health, Inc.
Heart failure biomarker levels correlate with invasive haemodynamics in pulmonary valve replacement
- Phillip M. Zegelbone, Richard E. Ringel, John D. Coulson, Melanie K. Nies, Meagan E. Stabler, Jeremiah R. Brown, Allen D. Everett
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- Journal:
- Cardiology in the Young / Volume 30 / Issue 1 / January 2020
- Published online by Cambridge University Press:
- 27 November 2019, pp. 50-54
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Background:
Although widely used in cardiology, relation of heart failure biomarkers to cardiac haemodynamics in patients with CHD (and in particular with pulmonary insufficiency undergoing pulmonary valve replacement) remains unclear. We hypothesised that the cardiac function biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity 2, and galectin-3 would have significant associations to right ventricular haemodynamic derangements.
Methods:Consecutive patients ( n = 16) undergoing cardiac catheterisation for transcatheter pulmonary valve replacement were studied. NT-proBNP, soluble suppressor of tumorigenicity 2, and galectin-3 levels were measured using a multiplex enzyme-linked immunosorbent assay from a pre-intervention blood sample obtained after sheath placement. Spearman correlation was used to identify significant correlations (p ≤ 0.05) of biomarkers with baseline cardiac haemodynamics. Cardiac MRI data (indexed right ventricular and left ventricular end-diastolic volumes and ejection fraction) prior to device placement were also compared to biomarker levels.
Results:NT-proBNP and soluble suppressor of tumorigenicity 2 were significantly correlated (p < 0.01) with baseline mean right atrial pressure and right ventricular end-diastolic pressure. Only NT-proBNP was significantly correlated with age. Galectin-3 did not have significant associations in this cohort. Cardiac MRI measures of right ventricular function and volume were not correlated to biomarker levels or right heart haemodynamics.
Conclusions:NT-proBNP and soluble suppressor of tumorigenicity 2, biomarkers of myocardial strain, significantly correlated to invasive pressure haemodynamics in transcatheter pulmonary valve replacement patients. Serial determination of soluble suppressor of tumorigenicity 2, as it was not associated with age, may be superior to serial measurement of NT-proBNP as an indicator for timing of pulmonary valve replacement.
The ablation zone in northeast Greenland: ice types, albedos and impurities
- Carl Egede Bøggild, Richard E. Brandt, Kendrick J. Brown, Stephen G. Warren
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- Journal of Glaciology / Volume 56 / Issue 195 / 2010
- Published online by Cambridge University Press:
- 08 September 2017, pp. 101-113
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Ice types, albedos and impurity content are characterized for the ablation zone of the Greenland ice sheet in Kronprinz Christians Land (80° N, 24° W). Along this ice margin the width of the ablation zone is only about 8 km. The emergence and melting of old ice in the ablation zone creates a surface layer of dust that was originally deposited with snowfall high on the ice sheet. This debris cover is augmented by locally derived wind-blown sediment. Subsequently, the surface dust particles often aggregate together to form centimetre-scale clumps that melt into the ice, creating cryoconite holes. The debris in the cryoconite holes becomes hidden from sunlight, raising the area-averaged albedo relative to surfaces with uniform debris cover. Spectral and broadband albedos were obtained for snow, ice hummocks, debris-covered ice, cryoconite-studded ice and barren tundra surfaces. Broadband ice albedos varied from 0.2 (for ice with heavy loading of uniform debris) to 0.6 (for ice hummocks with cryoconite holes). The cryoconite material itself has albedo 0.1 when wet. Areal distribution of the major surface types was estimated visually from a transect video as a function of distance from the ice edge (330 m a.s.l.). Ablation rates were measured along a transect from the ice margin to the slush zone 8 km from the margin (550 m a.s.l.), traversing both Pleistocene and Holocene ice. Ablation rates in early August averaged 2 cm d−1. Impurity concentrations were typically 4.3 mg L−1 in the subsurface ice. Surface concentrations were about 16 g m−2 on surfaces with low impurity loading, and heavily loaded surfaces had concentrations as high as 1.4 kg m−2. The mineralogical composition of the cryoconite material is comparable with that of the surrounding soils and with dust on a snowdrift in front of the ice margin, implying that much of the material is derived from local sources. A fine mode (clay) is present in the oldest ice but not in the nearby soil, suggesting that its origin is from wind deposition during Pleistocene glaciation.
Summary of the Snowmastodon Project Special Volume A high-elevation, multi-proxy biotic and environmental record of MIS 6–4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA
- Ian M. Miller, Jeffrey S. Pigati, R. Scott Anderson, Kirk R. Johnson, Shannon A. Mahan, Thomas A. Ager, Richard G. Baker, Maarten Blaauw, Jordon Bright, Peter M. Brown, Bruce Bryant, Zachary T. Calamari, Paul E. Carrara, Michael D. Cherney, John R. Demboski, Scott A. Elias, Daniel C. Fisher, Harrison J. Gray, Danielle R. Haskett, Jeffrey S. Honke, Stephen T. Jackson, Gonzalo Jiménez-Moreno, Douglas Kline, Eric M. Leonard, Nathaniel A. Lifton, Carol Lucking, H. Gregory McDonald, Dane M. Miller, Daniel R. Muhs, Stephen E. Nash, Cody Newton, James B. Paces, Lesley Petrie, Mitchell A. Plummer, David F. Porinchu, Adam N. Rountrey, Eric Scott, Joseph J.W. Sertich, Saxon E. Sharpe, Gary L. Skipp, Laura E. Strickland, Richard K. Stucky, Robert S. Thompson, Jim Wilson
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- Quaternary Research / Volume 82 / Issue 3 / November 2014
- Published online by Cambridge University Press:
- 20 January 2017, pp. 618-634
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In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
5 - Neurotransmitters
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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- 04 June 2015, pp 78-119
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Summary
In general terms, neurons communicate with each other through chemical messengers called neurotransmitters. Given the complexity of the brain, it should not be surprising that there are more than 100 known neurotransmitters (Purves et al. 2008). Neurotransmitters are synthesized in nerve cells, sometimes using precursors from the diet (e.g. tyrosine; see Figure 5.8), and are released into the synapse where they bind to specific receptors located on the postsynaptic cell. As discussed in the present chapter, this simple view conceals the many fascinating ways in which neurons communicate with each other. This chapter focuses on the different categories of neurotransmitters, the synthesis, storage, transport and release of neurotransmitters, their action at receptors and their deactivation. The influence of drugs on neurotransmitter function will also be discussed. Chapter 6 examines the specific effects of neurotransmitters in the neuroendocrine system, and Chapter 10 covers the actions of neurotransmitters at their receptors on postsynaptic cells.
The neuron and the synapse
A typical neuron is shown in Figure 5.1. Neurons possess a cell body, which contains the nucleus, and the characteristic dendrites plus an axon. The dendrites receive messages from other cells onto their spines and shafts, while the axon transmits information to other cells. Although each nerve cell has only one axon, this axon may have a number of branches and the nerve terminals at the end of each branch can form synapses with other neurons.
Nerve cells communicate with each other by the release of neurotransmitters from the nerve terminals of the axon into the synapse, the space that separates the presynaptic and postsynaptic cells. Neurotransmitters released into the synapse then bind to their receptors on the postsynaptic cell. As shown in Figure 5.1, synapses can form between the axon of the presynaptic cell and a number of different sites on the postsynaptic cell, including the shafts and/or spines of dendrites (axodendritic synapses), the cell body (axosomatic synapses) and the axons (axoaxonic synapses).
10 - Receptors for peptide hormones, neuropeptides and neurotransmitters
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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- 04 June 2015, pp 236-256
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Summary
Peptide hormones, neuropeptides, neurotransmitters and other non-steroid chemical messengers regulate cellular and biochemical activity by binding to receptors located in the plasma membranes of their target cells. These chemical messengers are generally polar and water soluble and so cannot readily enter their target cells to influence the cell nucleus in the manner described for steroid and thyroid hormones (Chapter 9). In order to induce biochemical changes within the target cell, they act as first messengers to activate a second messenger, such as cAMP, within the cytoplasm of the target cell. The transduction of information from the first to the second messenger is accomplished through the activation of membrane protein transducers (G proteins) and enzymes, such as adenylate cyclase. This chapter discusses membrane receptors for peptide hormones and neurotransmitters, the mechanisms by which signal transduction across the cell membrane occurs, the role of G proteins and receptor tyrosine kinases in this signal transduction, the second messenger systems activated, and the actions of the second messengers in the target cells, with special emphasis on neural target cells.
Some of this material was introduced in Chapter 5 and we will refer to relevant figures where appropriate.
Membrane receptors
Membrane receptors are complex proteins embedded in the cell membrane. The function of these receptors is to recognize specific ligands in the blood (e.g. peptide hormones, neuropeptides) or in the synapse (e.g. neurotransmitters) and bind to them. Once this binding occurs, signal transduction across the cell membrane occurs as described in section 10.2 below. As noted in the description of steroid hormone receptors, modern techniques of immunohistochemistry (using antibodies to receptor proteins) and in situ hybridization (allowing visualization of peptide mRNA) permit the ready localization of membrane receptors in any tissue of interest. Gene cloning and sequencing techniques enabled molecular biologists to develop three-dimensional models of many membrane receptors. There are three distinct types of membrane receptor: (1) ligand-gated ion channel receptors; (2) guanine nucleotide binding protein (G-protein-) coupled receptors; and (3) transmembrane-regulated tyrosine kinases.
6 - Neurotransmitter and neuropeptide control of hypothalamic, pituitary and other hormones
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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- 04 June 2015, pp 120-156
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Summary
Previous chapters have discussed the endocrine glands and their hormones (Chapter 2), the hormones of the pituitary gland (Chapter 3), the hypothalamic hormones (Chapter 4) and neurotransmitters (Chapter 5). This chapter will describe how neurotransmitters influence the release of hypothalamic and pituitary hormones and the hormones of the adrenal medulla, pancreas, thymus and gastrointestinal tract. It will also examine the electrophy-siological properties of neurosecretory cells and the effects of drugs on the release of neurohormones.
The cascade of chemical messengers
As shown in Figure 6.1, and using the adrenal gland as an example, there is a cascade of chemical messengers that regulate target tissue function from the brain to the endocrine glands. For example, neurons release a neurotransmitter that regulates the secretion of neurohormones (such as CRH) from hypothalamic neurosecretory cells. These hypothalamic hormones stimulate the cells of the adenohypophysis (anterior pituitary) to synthesize and release their hormones. Many pituitary hormones, such as ACTH, act on endocrine target cells, such as the adrenal cortex, causing them to synthesize and release their own hormones (e.g. cortisol) which then stimulate biochemical changes in target cells elsewhere in the body, including the brain. In each step of this pathway, the individual neurotransmitters and peptide hormones bind to membrane receptors that activate a second messenger, such as cAMP, within the target cell (see Chapter 10). Steroid hormones (such as cortisol) act on receptors located inside the target cells (see Chapter 9). This chapter describes the effects of neurotransmitters on hypothalamic neurosecretory cells.
Neural control of hypothalamic neurosecretory cells
6.2.1 Neural input to the endocrine hypothalamus
Figure 4.1 illustrates the different nuclei of the hypothalamus, many of which have neurons, or nerve terminals, which release a variety of neurotransmitters including GABA, glutamate, kisspeptin, opioids, dopamine, norepinephrine and serotonin. These neurotransmitters all bind to receptors on hypothalamic neurosecretory cells. This chapter describes the magnocellular hypothalamic neurosecretory cells of the paraventricular and supraoptic nuclei (PVN and SON), whose axons terminate in the posterior pituitary, and the parvicellular hypothalamic neurosecretory cells, whose axons terminate in the median eminence (see Figure 3.1).
15 - An overview of behavioral neuroendocrinology: present, past and future
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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- 04 June 2015, pp 458-468
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Summary
The aim of this book
The aim of this book is to introduce students to the language and concepts of neuroendocrinology, including how the neuroendocrine system influences behavior. It began with a consideration of the many chemical messengers in the body, classified as “true” hormones, neurohormones, neurotransmitters, pheromones, parahormones, prohormones, growth factors, cytokines, adipokines, vitamins and neuropeptides. As more became known about the neuroendocrine system, it became clear that these classifications are not unambiguous and a single chemical might fit into two or more classes of messenger and perform different functions. This means that while the classification of chemical messengers is useful to begin the study of neuroendocrinology, by the end it provides little help in understanding the different actions of peptides, steroids, neuropeptides and neurotransmitters on different target cells, even within the same tissue.
The hormones of the endocrine and pituitary glands are generally accepted as the major components of the neuroendocrine system. However, the traditional endocrine function of hormones being released into the bloodstream to act on peripheral target cells represents only a small part of the neuroendocrine activity of hormones such as testosterone, cholecystokinin or somatostatin. These hormones also have significant effects in the brain, via specific receptors, and can alter neural regulation of autonomic reflexes, behavior and emotional states. The hypothalamus provides the link between the brain and the traditional endocrine system and provides the locus for external factors, such as environmental influences, to regulate endocrine target organs. Thus, while the endocrine system consists of a number of closed-loop feedback systems that maintain homeostatic control over the synthesis, storage, release and deactivation of hormones, external stimuli can alter these systems. For example, environmental stimuli, social interactions and cognitive factors can greatly alter the functioning of the endocrine system by altering the neurotransmitter/neuropeptide pathways that regulate the release of hypothalamic hormones.
Acknowledgements
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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An Introduction to Neuroendocrinology
- 2nd edition
- Michael Wilkinson, Richard E. Brown
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- 05 June 2015
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- 04 June 2015
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How does the brain regulate sexual behavior, or control our body weight? How do we cope with stress? Addressing these questions and many more besides, this thoroughly revised new edition reflects the significant advances that have been made in the study of neuroendocrinology over the last twenty years. The text examines the importance of the hypothalamus in regulating hormone secretion from the endocrine glands, describing novel sites of hormone release including bone, heart, skeletal muscle and liver. The role of steroid hormone, neurotransmitter and peptide receptors, and the molecular responses of target tissues, is integrated into the discussion of the neuroendocrine brain, especially through changes in gene expression. Particular attention is attached to neuropeptides, including their profound influence on behavior. Complete with new full-color figures throughout, along with review and essay questions for each chapter, this is an ideal resource for undergraduate and graduate students of neuroscience, psychology, biology and physiology.
8 - Regulation of hormone levels in the bloodstream
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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- 04 June 2015, pp 170-191
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Summary
As illustrated in Figures 6.5 and 6.11, pituitary (LH, FSH and ACTH) and steroid (cortisol) hormone levels in the bloodstream fluctuate dramatically over short periods of time (minutes to hours). In addition, hormones such as GH, ACTH and melatonin show marked circadian variations in their secretion patterns (Figure 6.5). These patterns are physiologically important; for example, we saw in the case of LH secretion, a continuous release, rather than a pulsatile secretion, will not stimulate the ovaries or testes correctly (Figure 7.4). In other words, fertility is dependent on an appropriate pulsatile LH signal reaching the gonads. This principle might be generally applicable to all pituitary hormone secretions. The measurement, or assay, of hormone levels is therefore an important clinical goal, as well as a crucial aid in understanding how hormone levels in blood are regulated and how the neuroendocrine system functions in health and disease. This chapter thus begins with an examination of the methods for measuring hormone levels in the circulation.
Analysis of hormone levels
The level of a circulating hormone can be measured directly in blood samples or estimated by measuring hormone levels in the saliva, urine or feces, measuring urinary metabolites, or by using bioassays. The determination of glucocorticoids levels in hair, for example, is a way to detect long-term exposure to stress.
8.1.1 Direct measurement of circulating hormones
In the past 20 years, there have been striking changes in the analytical techniques used to estimate hormone levels. Until recently, the benchmark in determination of hormone levels was the radioimmunoassay. However, this method, employing antibodies specific to each hormone, and radioactively labeled hormones, is slow, labor-intensive and raised safety problems in the use and disposal of radioactive materials. It is now routine to analyze hormone levels using rapid and automated chemiluminescent or immunometric assays that produce data in a matter of hours, rather than days.
A widely used assay is the Enzyme-linked Immunosorbent Assay (ELISA).
3 - The pituitary gland and its hormones
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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Summary
The pituitary gland
The pituitary gland, which is also called the hypophysis, is attached to the hypothalamus at the base of the brain (Figure 3.1). Secretion of the hormones of the pituitary gland is regulated by the hypothalamus and it is through the hypothalamic-pituitary connection that external and internal stimuli can influence the release of the pituitary hormones, thus producing the neural-endocrine interaction. The pituitary has been called the body's “master gland” because its hormonal secretions stimulate a variety of endocrine glands to synthesize and secrete their own hormones. However, it is really the hypothalamus that is the master gland, because it controls the pituitary.
The pituitary gland consists of two primary organs: the anterior pituitary (adenohypophysis or pars distalis) which is a true endocrine gland, and the posterior pituitary (neurohypophysis) which is formed from neural tissue and is an extension of the hypothalamus (Figure 3.1). The pituitary gland is attached to the hypothalamus by the pituitary (hypophyseal) stalk. Further details of the anatomy and physiology of the pituitary gland can be found elsewhere (Norman and Litwack 1997; Amar and Weiss 2003; Boron and Boulpaep 2005; Gardner and Shoback 2011).
The neurohypophysis (posterior pituitary)
The neurohypophysis consists of neural tissue and contains the nerve terminals (about 100,000) of axons whose cell bodies are located in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. The axons of these large magnocellular neurosecretory cells project down from the hypothalamus through the part of the pituitary stalk called the infundibulum and terminate in the posterior pituitary gland (Figure 3.2). The neurosecretory cells of the PVN and SON manufacture the hormones oxytocin and vasopressin (also called antidiuretic hormone, ADH), which are transported down the axons and stored in nerve terminals in the posterior pituitary. The axon terminals in the posterior pituitary are surrounded by supporting cells called pituicytes.
Dedication
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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Preface to the second edition
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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- 05 June 2015
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Summary
In this second edition of An Introduction to Neuroendocrinology, we have rewritten and greatly extended the original content. The revised text includes entirely new reference lists and a complete new set of illustrations. The book reflects the many advances that have occurred in the study of neuroendocrinology during the past 20 years. Nevertheless, and although the text is based largely on modern references, our primary aim is to provide an introductory description of mammalian neuroendocrine control systems. Several books are available that cover this topical and clinically relevant field, but, although valuable, these tend to be advanced texts of the edited, multi-author type. Our book is designed to provide the basic principles necessary to understand how the brain controls, and responds to, the endocrine hormones. It will be suitable for a variety of different students and especially those who might not have been previously exposed to a focused course in neuroendocrinology. Thus, students in psychology, biology and science should be able to master much of the basic material. However, the book is also highly appropriate for honors students and first-year graduate students in physiology, anatomy, neuroscience and medicine. This book is therefore designed for students in two levels of classes: introductory classes, in which all of the material will be new to the student, and more advanced classes, in which the students will be familiar with many of the terms and concepts through courses in biology, physiology, psychology or neuroscience, but who have not studied neuroendocrinology as an integrated discipline.
This book offers an overall outline of the neuroendocrine system and will provide the vocabulary necessary to understand the interaction between hormones and the brain. In addition, we provide a concise description of those topics that must underpin any attempt to learn, and to teach, neuroendocrinology. For example, there are chapters on basic neuroscience (neurotransmitters and neuropeptides), the physiology of the endocrine glands (hormones), receptors and receptor signaling mechanisms (e.g. G proteins; nuclear receptors), hormone assay and gene expression techniques (e.g. ELISA; in situ hybridization) and a description of the immune system, with particular emphasis on the integration of immune and neuroendocrine pathways.
Index
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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2 - The endocrine glands and their hormones
- Michael Wilkinson, Dalhousie University, Nova Scotia, Richard E. Brown, Dalhousie University, Nova Scotia
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- An Introduction to Neuroendocrinology
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Summary
The endocrine glands
The location of the human endocrine glands is shown in Figure 2.1. The pineal gland is a small gland lying deep between the cerebral cortex and the cerebellum at the posterior end of the third ventricle in the middle of the brain. The hypothalamus exerts some degree of control over most of the endocrine glands through the release of neurohormones, neuropeptides and neurotransmitters. The pituitary gland hangs from the bottom of the hypothalamus at the base of the brain and sits in a small cavity of bone above the roof of the mouth.
The thyroid gland is located in the neck and the small parathyroid glands are embedded in the surface of the thyroid. In the chest is the thymus gland, which is very important for the production of T lymphocytes that play a critical role in the immune response. The heart and lungs also act as endocrine glands that secrete hormones. The gastrointestinal (GI) tract, consisting of the stomach and intestines, is also an important source of hormones. The liver secretes several hormones such as somatomedin (also called IGF-1), important for growth. The adrenal glands are complex endocrine glands situated on top of the kidneys. The pancreas secretes hormones involved in regulating blood sugar levels and the kidney also produces hormone-like chemicals. The testes and ovaries produce gonadal hormones, or sex hormones, which, in addition to the maintenance of fertility and sex characteristics, have important effects on behavior. During pregnancy, the placenta acts as an endocrine gland. The endocrine glands occur in similar locations in all vertebrates. A large endocrine gland is fat (adipose tissue) which can be found beneath the skin (subcutaneous), in the abdominal cavity surrounding the heart and GI tract (see Figure 2.1), and within tissues such as liver and muscle. Fat secretes a variety of hormones called adipokines. Finally, two of the largest tissues in the body – skeletal muscle and bone – secrete factors that act in an endocrine fashion.