EXPLAINING DEPRESSION: A DISCOURSE ANALYSIS OF FAMILY PHYSICIANS’ AND NEUROSCIENTISTS’ ACCOUNTS OF EXPLANATORY MODELS AND THE CHEMICAL IMBALANCE HYPOTHESIS OF DEPRESSION

The etiological explanations for depression, along with the received views of the way the brain and body function, have shifted from an excess of black bile to impaired neuroplasticity and neuroimmune functions. A common biological explanation for depression is the chemical imbalance hypothesis, which posits that depression is caused by a deficiency of monoamines, particularly serotonin, in the depressed person’s brain. Many scholars have argued that the chemical imbalance hypothesis is unable to adequately explain depression and antidepressant treatment. However, while the etiological understanding of depression is complex and incomplete, the chemical imbalance hypothesis remains pervasive and persuasive among laypersons and clinicians. I begin this dissertation with an introduction to biological psychiatry and neuroscience. The dissertation includes a brief history of Western/English approaches to the diagnosis and etiology of depression, a chapter on my ontological, epistemological, and methodological assumptions, two manuscript-style research studies, and concludes with a general discussion. In the two studies, I demonstrate how a sample of family physicians and neuroscientists accounted for using the chemical imbalance hypothesis of depression and other explanations of depression, the persuasive rhetorical features in their arguments, and the functions achieved by these accounts. In study 1, I analyzed an interview data set with 11 family physicians. Using a discursive analytic approach, I argue that these physicians are utilizing the chemical imbalance hypothesis as a persuasive rhetorical device to motivate patients toward treatment, to attempt to minimize self-blame and stigma, to instill hope and confidence in the treatment, and to contribute generally to scientific knowledge among patients. In the discussion I provide a critique of the general assumptions upon which their arguments rely. For study 2, I interviewed 10 neuroscientists who conduct depression research. Using a discursive analytic approach, I present how a sample of neuroscientists working on a biological understanding of depression argue for and/or against the chemical imbalance hypothesis of depression. I argue that they maintain support for the chemical imbalance hypothesis through the construction of depression as a brain-based disorder and the brain as functioning through chemical transmissions, and that they argue against the chemical imbalance hypothesis by defining this hypothesis as a specific deficiency of serotonin and drawing attention to the failings and shortcomings of the hypothesis. I argue that their rhetorical construction of a distinction between a general chemical imbalance and a specific serotonin deficiency allows for the maintenance and support of the fundamental assumption that depression is a brain-based disorder, while simultaneously denying that depression is exclusively a problem with the serotonin system. I discuss alternative explanations of depression proposed by the scientists and show how they construct the serotonin hypothesis as a persuasive rhetorical device resistant to replacement. The results of studies 1 and 2 suggest that the chemical imbalance hypothesis of depression, while limited in its specific form to explain the cause of depression, has value and merit in scientific and lay discourses. In the general discussion, I summarize the arguments for and against the chemical imbalance hypothesis and suggest ways that the general chemical imbalance explanation can be augmented with additional ideas from contemporary neuroscience. I discuss the discipline of translational neuroscience, which aims to bridge the gap between science and practice, and provide commentary using extracts from the interviews. I conclude with a reflexive examination of my position

Cosmic 21-cm Delensing of Microwave Background Polarization and the Minimum Detectable Energy Scale of Inflation

The curl (B) modes of cosmic microwave background (CMB) polarization anisotropies are a unique probe of the primordial background of inflationary gravitational waves (IGWs). Unfortunately, the B-mode polarization anisotropies generated by gravitational waves at recombination are confused with those generated by the mixing of gradient-mode (E-mode) and B-mode polarization anisotropies as CMB photons propagate through the Universe and are gravitationally lensed. We describe here a method for delensing CMB polarization anisotropies using observations of anisotropies in the cosmic 21-cm radiation emitted or absorbed by neutral hydrogen atoms at redshifts 10 to 200. While the detection of cosmic 21-cm anisotropies at high resolution is challenging, a combined study with a relatively low-resolution (but high-sensitivity) CMB polarization experiment could probe inflationary energy scales well below the Grand Unified Theory (GUT) scale of 10^{16} GeV -- constraining models with energy scales below 10^{15} GeV (the detectable limit derived from CMB observations alone). The ultimate theoretical limit to the detectable inflationary energy scale via this method may be as low as 3 \times 10^{14} GeV.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

Значение специфических инфекций у беременных в развитии хронической плацентарной недостаточности

ПЛАЦЕНТАРНАЯ НЕДОСТАТОЧНОСТЬБЕРЕМЕННОСТИ ОСЛОЖНЕНИЯПОЛОВЫМ ПУТЕМ ПЕРЕДАВАЕМЫЕ БОЛЕЗНИИНФЕКЦИ

Measuring the Primordial Deuterium Abundance During the Cosmic Dark Ages

We discuss how measurements of fluctuations in the absorption of cosmic microwave background (CMB) photons by neutral gas during the cosmic dark ages, at redshifts z ~ 7--200, could reveal the primordial deuterium abundance of the Universe. The strength of the cross-correlation of brightness-temperature fluctuations due to resonant absorption of CMB photons in the 21-cm line of neutral hydrogen with those due to resonant absorption of CMB photons in the 92-cm line of neutral deuterium is proportional to the fossil deuterium to hydrogen ratio [D/H] fixed during big bang nucleosynthesis (BBN). Although technically challenging, this measurement could provide the cleanest possible determination of [D/H], free from contamination by structure formation processes at lower redshifts, and has the potential to improve BBN constraints to the baryon density of the Universe \Omega_{b} h^2. We also present our results for the thermal spin-change cross-section for deuterium-hydrogen scattering, which may be useful in a more general context than we describe here.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let

Cryo-EM analysis of the effect of seeding with brain-derived Aβ amyloid fibrils

Aβ amyloid fibrils from Alzheimer’s brain tissue are polymorphic and structurally different from typical in vitro formed Aβ fibrils. Here, we show that brain-derived (ex vivo) fibril structures can be proliferated by seeding in vitro. The proliferation reaction is only efficient for one of the three abundant ex vivo Aβ fibril morphologies, which consists of two peptide stacks, while the inefficiently proliferated fibril morphologies contain four or six peptide stacks. In addition to the seeded fibril structures, we find that de novo nucleated fibril structures can emerge in seeded samples if the seeding reaction is continued over multiple generations. These data imply a competition between de novo nucleation and seed extension and suggest further that seeding favours the outgrowth of fibril morphologies that contain fewer peptide stacks

Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein

Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized

A GPU-based Correlator X-engine Implemented on the CHIME Pathfinder

We present the design and implementation of a custom GPU-based compute cluster that provides the correlation X-engine of the CHIME Pathfinder radio telescope. It is among the largest such systems in operation, correlating 32,896 baselines (256 inputs) over 400MHz of radio bandwidth. Making heavy use of consumer-grade parts and a custom software stack, the system was developed at a small fraction of the cost of comparable installations. Unlike existing GPU backends, this system is built around OpenCL kernels running on consumer-level AMD GPUs, taking advantage of low-cost hardware and leveraging packed integer operations to double algorithmic efficiency. The system achieves the required 105TOPS in a 10kW power envelope, making it among the most power-efficient X-engines in use today.Comment: 6 pages, 5 figures. Accepted by IEEE ASAP 201

Solvation-guided design of fluorescent probes for discrimination of amyloids

The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with ab initio computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer's-related beta-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment