Pathways contributing to the Risk of Substance Use Disorders after Adverse Childhood Experiences

Substance use disorders are a major global health problem. Worldwide, over 35 million individuals suffer from substance use disorders, adding to 283 million individuals who are affected by alcohol use disorder. Being both a risk factor and consequence of substance use, alterations in the structure and function of the brain take place, for example, in regions rele-vant for reward, stress, and emotion processing. However, merely considering neurobiological aspects does not do justice to the complexi-ty of the disorder. Previous research suggests that adverse childhood experiences, for instance, childhood maltreatment (i.e., emotional, physical, and sexual abuse, as well as emotional and physical neglect), are an important risk factor in the etiopathology of substance use disorders. As such, these experiences also affect the neurobiology of an individual, which might just as well lead to alterations in reward, stress, and emotion processing – and, thus, result in an earlier onset of substance use disorders or hamper treatment success. In this context, substance craving and impaired emotion processing are of importance as they may facilitate relapse, which, in turn, maintains a substance use disorder. This dissertation, therefore, integrates neurobiological and societal aspects to address pathways contributing to the risk of substance use disorders. To this end, an individual’s his-tory of childhood maltreatment – one major aspect of adverse childhood experience – will be explored in depth. Study 1 examined 655 treatment-seeking individuals with substance use disorders and revealed high prevalence and severity of all subtypes of childhood maltreatment. In this sam-ple, women and individuals with cannabis use disorder were most severely affected, especially by emotional abuse. Emotional abuse, but not other subtypes of childhood maltreatment, posi-tively related to substance craving at admission to treatment. However, symptoms of depres-siveness, anxiety, and perceived stress influenced craving severity at admission and craving reduction during treatment rather than childhood maltreatment severity. The results revealed a subtype-specific influence of childhood maltreatment, and, furthermore, demonstrated the significance of type of substance and sex/gender. This study illustrated the importance of in-cluding the aspect of childhood maltreatment in individualized treatment approaches. Study 2 addressed neural correlates of emotion processing and expanded previous find-ings of altered amygdala functioning in individuals with alcohol use disorder by applying a habituation index. Further, the relation between amygdala habituation to repeated aversive emotional stimuli and childhood maltreatment was examined. Individuals with alcohol use disorder exhibited not only deficient amygdala habituation, compared to healthy individuals. Beyond that, the temporal pattern of habituation resembled neural sensitization, thus, showing a unique amygdala habituation pattern compared to other mental disorders such as post-traumatic stress disorder. While no relation between childhood maltreatment and amygdala habituation was observed for individuals with alcohol use disorder, healthy individuals exhib-ited increase habituation in relation to more severe physical and emotional neglect. Lastly, a significant relation between higher alcohol intake and reduced amygdala habituation was ob-served to be independent of the clinical status of the participants, which might indicate short-term substance effects. The study revealed, thus, novel evidence regarding alterations in emo-tion processing in alcohol use disorder that might open a new avenue for treatment targets. Taken together, the two studies demonstrated the relevance of addressing adverse child-hood experiences, and informed about pathways leading to substance use disorders. Integrat-ing this societal aspect into neurobiological research reveals new opportunities for treatment strategies

Effects of polyploidy on female call preference in gray treefrogs, Hyla chrysoscelis

Abstract only availableThe gray treefrog complex consists of two cryptic species; Hyla versicolor is a tetraploid (N=48) species that arose from the polyploidization of its diploid counter-part, H. chrysoscelis (N=24) and two other extinct treefrog species. Speciation via polyploidy is almost instantaneous because polyploid species are isolated reproductively from their non-polyploid ancestors. However, the establishment of newly arisen polyploid lineages requires assortative mating between polyploids. Genome duplication has been shown to affect the quality of the male's species-specific mate-attraction signal, thus polyploids could be reproductively isolated from their diploid ancestors through the action of female mating preferences. Autopolyploid individuals I generated last summer (polyploidy was verified by initial karyotyping) are currently reaching sexual maturity. Once sexually mature, the acoustic mate-choice preferences of female polyploids will be tested using playback experiments. The experimental tests will compare preferences for call traits that vary between the two species, including frequency, pulse shape, and pulse rate. We hypothesize that these changes in the communication system result from ploidy-induced changes in tissue and cellular dimensions. Thus, as a related experiment, we will also look for effects of larval density on blood cell size, male calls and female preferences. We expect to find that polyploidy affects the advertisement-call preferences of female H. chrysoscelis treefrogs, independent of other factors. Preliminary results indicate that autopolyploid individuals are able to reach sexual maturity and that there is an effect of polyploidy on blood cell size.Life Sciences Undergraduate Research Opportunity Progra

Temperature-dependent preferences for advertisement-call frequency in females of Hyla versicolor

Abstract only availableMale treefrogs produce loud and persistent acoustic signals called advertisement calls to attract mates. Ectothermic animals like frogs face an interesting challenge, in that temperature can significantly impact characteristics of the species-specific advertisement call. The mate-choice preferences of female gray treefrogs (H. versicolor) have been extensively studied (reviewed by Gerhardt & Huber 2002). It has been found that females prefer calls with standard frequency peaks of 1.1 kHz + 2.2 kHz over calls with higher and lower frequencies at 20º C. However, it is not known how this preference is affected by temperature. To determine whether acoustic preferences based on frequency are temperature-dependent, I collected female frogs during their breeding season and tested them in a temperature-controlled anechoic testing chamber. I generated ten different computer-synthesized advertisement calls that ranged in frequency between 0.55 + 1.1 kHz to 1.5 + 3.0 kHz. In two-speaker choice tests conducted at three different temperatures (15º C, 20º C and 25º C), females "chose" (moved within 10 cm of a speaker) between a call with standard frequency peaks of 1.1 + 2.2 kHz and one of the nine alternative calls. Preliminary results indicate the preferred frequencies appeared to remain 1.1 + 2.2 kHz at lower temperatures. However, at higher temperatures, female frogs were more likely to approach high-frequency calls. These results will be discussed in the context of known temperature-dependent physiological processes in the inner ear of frogs.NIH grant to H.C. Gerhard

Male phonotactic responses in gray treefrogs (Hyla versicolor) [abstract]

Abstract only availableFaculty Mentor: Dr. Sarah Humfeld, Biological SciencesMany anuran amphibians, better known as frogs and toads, use acoustic signals as a means of communication. Female frogs choose mates by moving towards males making a particular call (phonotaxis). Non-calling males, which have been termed satellites, may also associate with these calling males as a result of male-male competition for mates.  My project addressed the question of whether male frogs have phonotactic preferences similar to those of females.  Most Hyla versicolor females prefer calls with a faster-than-average call rate, longer-than-average call duration and low frequency.  My main goal was to verify whether H. versicolor males demonstrate phonotactic behavior, and if so, to determine whether they have preferences similar to females.  I also wanted to learn if non-calling males were inferior to calling males.  I used two methods to answer these questions. During field observations, H. versicolor males (calling and non-calling) were weighed, their calls recorded and body temperature taken. We found no evidence to indicate that non-calling males are smaller or produce less attractive calls than callers. In laboratory phonotaxis experiments, synthetic signals from two speakers were played and the successive movements of individual males were observed. The results indicated that H. versicolor males express phonotactic responses and also have acoustic preferences, which are similar to female preferences. Fourteen of 22 males moved within 20cm of a speaker, and most of these (13) chose the call with characteristics favored by females. Based on these results we speculate that the ability of males to recognize attractive calls may maximize the reproductive success of satellite males

The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind randomized controlled trial in alcohol use disorder

Background: Alcohol Use Disorder is a highly prevalent mental disorder which puts a severe burden on individuals, families, and society. The treatment of Alcohol Use Disorder is challenging and novel and innovative treatment approaches are needed to expand treatment options. A promising neuroscience-based intervention method that allows targeting cortical as well as subcortical brain processes is real-time functional magnetic resonance imaging neurofeedback. However, the efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a clinical setting is hitherto unclear and will be assessed in the Systems Biology of Alcohol Addiction (SyBil-AA) neurofeedback study. Methods: N = 100 patients with Alcohol Use Disorder will be randomized to 5 parallel groups in a single-blind fashion and receive real-time functional magnetic resonance imaging neurofeedback while they are presented pictures of alcoholic beverages. The groups will either downregulate the ventral striatum, upregulate the right inferior frontal gyrus, negatively modulate the connectivity between these regions, upregulate, or downregulate the auditory cortex as a control region. After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks, participants will be followed up monthly for a period of 3 months and relapse rates will be assessed as the primary outcome measure. Discussion: The results of this study will provide insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use Disorder as well as in the involved brain systems. This might help to identify predictors of successful neurofeedback treatment which could potentially be useful in developing personalized treatment approaches. Trial registration: The study was retrospectively registered in the German Clinical Trials Register (trial identifier: DRKS00010253 ; WHO Universal Trial Number (UTN): U1111–1181-4218) on May 10th, 2016

Choirs, HI galaxy groups: Catalogue and detection of star-forming dwarf group members

Hα observations centred on galaxies selected from the HI Parkes All-Sky Survey (HIPASS)typically show one and sometimes two star-forming galaxies within the ~15 arcmin beam of the Parkes 64 m HI detections. In our Survey for Ionization in Neutral Gas Ga

ER Stress-Induced Aggresome Trafficking of HtrA1 Protects Against 1! Proteotoxicity

High temperature requirement A1 (HtrA1) belongs to an ancient protein family that is linked to various human disorders. The precise role of exon 1-encoded N-terminal domains and how these influence the biological functions of human HtrA1 remain elusive. In this study, we traced the evolutionary origins of these N-terminal domains to a single gene fusion event in the most recent common ancestor of vertebrates. We hypothesized that human HtrA1 is implicated in unfolded protein response. In highly secretory cells of the retinal pigmented epithelia, endoplasmic reticulum (ER) stress upregulated HtrA1. HtrA1 co-localized with vimentin intermediate filaments in highly arborized fashion. Upon ER stress, HtrA1 tracked along intermediate filaments, which collapsed and bundled in an aggresome at the microtubule organizing center. Gene silencing of HtrA1 altered the schedule and amplitude of adaptive signaling and concomitantly resulted in apoptosis. Restoration of wild-type HtrA1, but not its protease inactive mutant, was necessary and sufficient to protect from apoptosis. A variant of HtrA1 that harbored exon 1 substitutions displayed reduced efficacy in rescuing cells from proteotoxicity. Our results illuminate the integration of HtrA1 in the toolkit of mammalian cells against protein misfolding and the implications of defects in HtrA1 in proteostasis