Brain Structure and Function in Emotion Processing, Emotion Regulation, and Reward Processing Neural Circuitries in Offspring at Risk for Bipolar Disorder

Bipolar Disorder (BD) is a serious psychiatric illness with demonstrated structural and functional abnormalities in emotion processing, emotion regulation, and reward processing neural circuitries. BD is also a highly heritable disorder, placing first-degree relatives of patients with BD at great risk for developing the disorder, themselves. There are many similarities, however, between BD and other psychiatric illnesses, such as Major Depressive Disorder, Attention Deficit/Hyperactive Disorder, and Anxiety Disorders, which often makes it difficult to diagnose BD. By detecting abnormalities in neural measures and symptomatology that uniquely distinguish youth at risk for BD, we have the potential to identify objective biological markers of BD risk that may aid in the development of improved diagnostic and therapeutic strategies for BD. In this dissertation, we use elastic net regression analyses to examine structural, functional, and symptomatic measures in offspring of bipolar parents (OBP) compared with offspring of comparison parents with non-BD psychiatric disorders (OCP) and offspring of healthy parents (OHP). In chapter 3, we present findings demonstrating greater rostral anterior cingulate cortex (ACC) activity when regulating attention away from positive (i.e. happy) emotions, as well as greater bilateral amygdala-left caudal ACC functional connectivity (FC) when regulating attention away from all (i.e. fearful, happy, and neutral) emotions in OBP compared with OCP. In chapter 4, we demonstrate lower right ventral striatum-left caudal ACC FC when processing loss and greater right pars orbitalis-orbitofrontal cortex FC when processing reward in OBP compared with both OCP and OHP. In chapter 5, we demonstrate inverse relationships between right cingulum-cingulate gyrus length and bilateral caudal ACC activity, as well as between forceps minor radial diffusivity and bilateral rostral ACC activity, when processing positive emotions in OBP compared with OCP. Throughout these analyses, significant relationships were observed between the ACC and affective lability severity. Together, these studies identify the ACC as a key neural region that may help distinguish youth at risk for BD from youth at risk for other psychiatric disorders. These findings provide specific neural and symptomatic targets which may improve the diagnosis and treatment of BD, leading to overall better outcomes for youth at risk for BD

A Review of Application Strategies and Efficacy of Probiotics in Pet Food

In companion animal nutrition, probiotics (direct-fed microbials) are marketed as functional ingredients that add value to pet foods due to the impact they have on gastrointestinal and immune health of dogs and cats. The nature of the beneficial effect each probiotic strain exerts depends on its metabolic properties and perhaps most importantly, the arrival of a sufficient number of viable cells to the large bowel of the host. Pet food manufacturing processes are designed to improve food safety and prolong shelf-life, which is counterproductive to the survival of direct-fed microbials. Therefore, a prerequisite for the effective formulation of pet foods with probiotics is an understanding of the conditions each beneficial bacterial strain needs to survive. The aims of this chapter are: (1) To summarize the inherent characteristics of probiotic strains used in commercial pet foods, and (2) To review recently published literature on the applications of probiotics to pet foods and their associated challenges to viability

White Matter Structure in Youth With Behavioral and Emotional Dysregulation Disorders: A Probabilistic Tractographic Study

Psychiatric disorders in youth characterized by behavioral and emotional dysregulation are often comorbid and difficult to distinguish. An alternative approach to conceptualizing these disorders is to move toward a diagnostic system based on underlying pathophysiologic processes that may cut across conventionally defined diagnoses. Neuroimaging techniques have potentials for the identification of these processes

Effects of Bacillus coagulans GBI-30, 6086 probiotic added to extruded pet food on apparent nutrient digestibility, stool quality, intestinal health indicators, and fecal microbiota of healthy adult dogs

Doctor of PhilosophyDepartment of Grain Science and IndustryGreg AldrichBacillus coagulans GBI-30, 6086 is a spore-forming bacterium reported to survive environmental stresses, heat processing, and extreme-pH conditions, which are characteristics that support its utility in commercial food applications. Extrusion is the most widely used method to produce commercial dog foods, however no previous studies have examined the survivability of this strain through extrusion or its efficacy with regards to gastrointestinal health of dogs. Thus, the objectives were to determine the viability of Bacillus coagulans GBI-30, 6086 through extrusion cooking and drying, and its effects on nutrient utilization, intestinal health, and the fecal microbiota of healthy adult dogs. Two experiments were conducted to determine the reduction in viability of the organism at graded flour inoculation doses (0, 6.2, 6.7, and 7.3 log₁₀ CFU/g) through extrusion with varying levels of extruder water inputs (10, 12, and 20 kg/h), extruder screw speeds (400, 500, and 600 rpm), and dryer settings (49 °C for 10 min; 107 °C for 16 min; and 66 °C for 46 min). The low SME extrusion conditions (in-barrel moisture of 35%, extruder screw speed of 400 rpm, and specific mechanical energy of 129 kJ/kg) resulted in the greatest retention (P<0.05), with a mean log₁₀ reduction of viable spores of 0.44, 2.15, and 2.67 for the low, moderate, and severe extrusion conditions, respectively. Viability of spores subjected to three dryer conditions were observed to be similar across all treatments. To evaluate the effects of Bacillus coagulans on nutrient utilization, stool quality, and intestinal health indicators in dogs, extruded diets containing graded levels of probiotic applied either to the base ration before extrusion or to the exterior of the kibble as a topical coating after extrusion were randomly assigned to ten individually housed adult Beagle dogs (7 castrated males, 3 spayed females) of similar age (5.75 ± 0.23 years) and body weight (12.3 ± 1.5 kg). Apparent total tract digestibility of organic matter, crude protein, crude fat, and gross energy calculated by the marker method were numerically greatest for dogs fed 9 log₁₀ CFU/d with increases (P < 0.05) observed in gross energy and organic matter digestibility compared to the negative control. No significant changes were observed in food intake or fecal scores, moisture content, pH, ammonia, short-chain fatty acids, or branched-chain fatty acids for the probiotic-containing treatments compared to a non-probiotic control. To evaluate the effects of Bacillus coagulans on the fecal microbiota of dogs, fresh fecal samples were analyzed by 16S rRNA gene pyrosequencing. Firmicutes comprised the greatest proportion of observational taxonomic units (mean 81.2% ± 5), followed by Actinobacteria (mean 9.9% ± 4.4), Bacteroidetes (mean 4.5% ± 1.7), Proteobacteria (mean 1.3% ± 0.7), and Fusobacteriota (mean 1.1% ± 0.6). No evidence of a shift in predominant phyla, class, family, or genus taxonomic levels were found apart from the Bacillus genus, which was observed to have a greater relative abundance (P=0.0189) in the low probiotic coating (5.92 x 10⁵ CFU/g) and high probiotic coating (6.84 x 10⁶ CFU/g) treatment groups compared to the extruded probiotic (1.06 x 10⁴ CFU/g) and non-probiotic control treatments. Alpha-diversity indices (Richness, Chao1, ACE, Shannon, Simpson, Inverse Simpson, and Fisher) were similar for all treatments. Beta-diversity metrics (principal coordinate analysis) did not provide evidence of clustering for UniFrac distances among treatment groups. Overall, Bacillus coagulans GBI-30, 6086 retained varying degrees of viability during extrusion and drying of pet food. As a functional probiotic, our data supports an improvement in nutrient utilization and maintenance of stool quality, intestinal health indicators, and fecal microbiota in healthy adult dogs at a dose of 9 log₁₀ CFU/day

White matter structure in youth with behavioral and emotional dysregulation disorders a probabilistic tractographic study

Importance: Psychiatric disorders in youth characterized by behavioral and emotional dysregulation are often comorbid and difficult to distinguish. An alternative approach to conceptualizing these disorders is to move toward a diagnostic system based on underlying pathophysiologic processes that may cut across conventionally defined diagnoses. Neuroimaging techniques have potentials for the identification of these processes.Objective: To determine whether diffusion imaging, a neuroimaging technique examining white matter (WM) structure, can identify neural correlates of emotional dysregulation in a sample of youth with different psychiatric disorders characterized by behavioral and emotional dysregulation.Design, Setting, And Participants: Using global probabilistic tractography,we examined relationships betweenWMstructure in key tracts in emotional regulation circuitry (ie, cingulum, uncinate fasciculus, and forceps minor) and (1) broader diagnostic categories of behavioral and emotional dysregulation disorders (DDs) and (2) symptom dimensions cutting across conventional diagnoses in 120 youth with behavioral and/or emotional DDs, a referred sample of the Longitudinal Assessment of Manic Symptoms (LAM) study. Thirty age- and sex-matched typically developing youth (control participants) were included. Multivariate multiple regression models were used. The study was conducted from July 1, 2010, to February 28, 2014.Main Outcomes And Measures: Fractional anisotropy aswell as axial and radial diffusivity were estimated and imported into a well-established statistical package.We hypothesized that (1) youth with emotional DDs and those with both behavioral and emotional DDs would show significantly lower fractional anisotropy compared with youth with behavioral DDs in these WM tracts and (2) that there would be significant inverse relationships between dimensional measures of affective symptom severity and fractional anisotropy in these tracts across all participants.Results: Multivariate multiple regression analyses revealed decreased fractional anisotropy and decreased axial diffusivity within the uncinate fasciculus in youth with emotional DDs vs those with behavioral DDs, those with both DDs, and the controls (F6,160 = 2.4; P = .032; all pairwise comparisons, P 3,85 = 2.8; P = .044).Conclusions And Relevance: These findings suggest that abnormal uncinate fasciculus and cingulumWMstructure may underlie emotional, but not behavioral, dysregulation in pediatric psychiatric disorders and that a different neural mechanism may exist for comorbid emotional and behavioral DDs