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Item A critical review of front-loading: A maladaptive drinking pattern driven by alcohol's rewarding effects(Wiley, 2022) Ardinger, Cherish E.; Lapish, Christopher C.; Czachowski, Cristine L.; Grahame, Nicholas J.; Psychology, School of ScienceFront‐loading is a drinking pattern in which alcohol intake is skewed toward the onset of reward access. This phenomenon has been reported across several different alcohol self‐administration protocols in a wide variety of species, including humans. The hypothesis of the current review is that front‐loading emerges in response to the rewarding effects of alcohol and can be used to measure the motivation to consume alcohol. Alternative or additional hypotheses that we consider and contrast with the main hypothesis are that: (1) front‐loading is directed at overcoming behavioral and/or metabolic tolerance and (2) front‐loading is driven by negative reinforcement. Evidence for each of these explanations is reviewed. We also consider how front‐loading has been evaluated statistically in previous research and make recommendations for defining this intake pattern in future studies. Because front‐loading may predict long‐term maladaptive alcohol drinking patterns leading to the development of alcohol use disorder (AUD), several future directions are proposed to elucidate the relationship between front‐loading and AUD.Item Acceptance and commitment therapy for fatigue interference in advanced gastrointestinal cancer and caregiver burden: protocol of a pilot randomized controlled trial(BMC, 2021-04-20) Mosher, Catherine E.; Secinti, Ekin; Kroenke, Kurt; Helft, Paul R.; Turk, Anita A.; Loehrer, Patrick J., Sr.; Sehdev, Amikar; Al-Hader, Ahmad A.; Champion, Victoria L.; Johns, Shelley A.; Psychology, School of ScienceBackground: Fatigue interference with activities, mood, and cognition is one of the most prevalent and bothersome concerns of advanced gastrointestinal (GI) cancer patients. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing responsibilities. Evidence-based interventions jointly addressing cancer patient fatigue interference and caregiver burden are lacking. In pilot studies, acceptance and commitment therapy (ACT) has shown promise for addressing symptom-related suffering in cancer patients. The current pilot trial seeks to test a novel, dyadic ACT intervention for both advanced GI cancer patients with moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden or distress. Methods: A minimum of 40 patient-caregiver dyads will be randomly assigned to either the ACT intervention or an education/support control condition. Dyads in both conditions attend six weekly 50-min telephone sessions. Outcomes are assessed at baseline as well as 2 weeks and 3 months post-intervention. We will evaluate the feasibility, acceptability, and preliminary efficacy of ACT for improving patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities, psychological flexibility, and quality of life. We will also explore the effects of ACT on patient and caregiver physical and mental health service use. Discussion: Findings will inform a large-scale trial of intervention efficacy. Results will also lay the groundwork for further novel applications of ACT to symptom interference with functioning and caregiver burden in advanced cancer.Item Acceptance and commitment therapy for patient fatigue interference and caregiver burden in advanced gastrointestinal cancer: Results of a pilot randomized trial(Sage, 2022) Mosher, Catherine E.; Secinti, Ekin; Wu, Wei; Kashy, Deborah A.; Kroenke, Kurt; Bricker, Jonathan B.; Helft, Paul R.; Turk, Anita A.; Loehrer, Patrick J., Sr.; Sehdev, Amikar; Al-Hader, Ahmad A.; Champion, Victoria L.; Johns, Shelley A.; Psychology, School of ScienceBackground: Fatigue often interferes with functioning in patients with advanced cancer, resulting in increased family caregiver burden. Acceptance and commitment therapy, a promising intervention for cancer-related suffering, has rarely been applied to dyads coping with advanced cancer. Aim: To examine the feasibility, acceptability, and preliminary efficacy of acceptance and commitment therapy for patient-caregiver dyads coping with advanced gastrointestinal cancer. Primary outcomes were patient fatigue interference and caregiver burden. Design: In this pilot trial, dyads were randomized to six weekly sessions of telephone-delivered acceptance and commitment therapy or education/support, an attention control. Outcomes were assessed at baseline and at 2 weeks and 3 months post-intervention. Setting/participants: Forty patients with stage III-IV gastrointestinal cancer and fatigue interference and family caregivers with burden or distress were recruited from two oncology clinics and randomized. Results: The eligibility screening rate (54%) and retention rate (81% at 2 weeks post-intervention) demonstrated feasibility. At 2 weeks post-intervention, acceptance and commitment therapy participants reported high intervention helpfulness (mean=4.25/5.00). Group differences in outcomes were not statistically significant. However, when examining within-group change, acceptance and commitment therapy patients showed moderate decline in fatigue interference at both follow-ups, whereas education/support patients did not show improvement at either follow-up. Acceptance and commitment therapy caregivers showed medium decline in burden at 2 weeks that was not sustained at 3 months, whereas education/support caregivers showed little change in burden. Conclusions: Acceptance and commitment therapy showed strong feasibility, acceptability, and promise and warrants further testing.Item Acceptance and Commitment Therapy for Symptom Interference in Advanced Lung Cancer and Caregiver Distress: A Pilot Randomized Trial(Elsevier, 2019) Mosher, Catherine E.; Secinti, Ekin; Hirsh, Adam T.; Hanna, Nasser; Einhorn, Lawrence H.; Jalal, Shadia I.; Durm, Gregory; Champion, Victoria L.; Johns, Shelley A.; Psychology, School of ScienceContext Advanced lung cancer patients typically have a poor prognosis and many symptoms that interfere with functioning, contributing to high rates of emotional distress in both patients and family caregivers. There remains a need for evidence-based interventions to improve functional outcomes and distress in this population. Objectives This pilot trial examined the feasibility and preliminary efficacy of telephone-based Acceptance and Commitment Therapy (ACT) for symptomatic, advanced lung cancer patients and their distressed family caregivers. Primary outcomes were patient symptom interference with functioning and patient and caregiver distress. Methods Symptomatic, advanced lung cancer patients and distressed caregivers (n = 50 dyads) were randomly assigned to six sessions of ACT or an education/support condition. Patients completed measures of symptom interference and measures assessing the severity of fatigue, pain, sleep disturbance, and breathlessness. Patients and caregivers completed measures of distress and illness acceptance and struggle. Results The eligibility screening rate (51%) and retention rate (76% at six weeks postintervention) demonstrated feasibility. No group differences were found with respect to patient and caregiver outcomes. Both groups showed a small, significant decrease in struggle with the illness over the study period, but did not show meaningful change in other outcomes. Conclusion Findings suggest that telephone-based ACT is feasible for many advanced lung cancer patients and caregivers, but may not substantially reduce symptom interference and distress. Low baseline levels of certain symptoms may have contributed to null findings. Next steps include applying ACT to specific, clinically meaningful symptom interference and varying intervention dose and modality.Item Acceptance and commitment therapy for symptom interference in metastatic breast cancer patients: a pilot randomized trial(Springer Nature, 2018-06) Mosher, Catherine E.; Secinti, Ekin; Li, Ruohong; Hirsh, Adam T.; Bricker, Jonathan; Miller, Kathy D.; Schneider, Bryan; Storniolo, Anna Maria; Mina, Lida; Newton, Erin V.; Champion, Victoria L.; Johns, Shelley A.; Psychology, School of SciencePURPOSE: Breast cancer is the leading cause of cancer mortality in women worldwide. With medical advances, metastatic breast cancer (MBC) patients often live for years with many symptoms that interfere with activities. However, there is a paucity of efficacious interventions to address symptom-related suffering and functional interference. Thus, this study examined the feasibility and preliminary efficacy of telephone-based acceptance and commitment therapy (ACT) for symptom interference with functioning in MBC patients. METHODS: Symptomatic MBC patients (N = 47) were randomly assigned to six telephone sessions of ACT or six telephone sessions of education/support. Patients completed measures of symptom interference and measures assessing the severity of pain, fatigue, sleep disturbance, depressive symptoms, and anxiety. RESULTS: The eligibility screening rate (64%) and high retention (83% at 8 weeks post-baseline) demonstrated feasibility. When examining within-group change, ACT participants showed decreases in symptom interference (i.e., fatigue interference and sleep-related impairment; Cohen's d range = - 0.23 to - 0.31) at 8 and 12 weeks post-baseline, whereas education/support participants showed minimal change in these outcomes (d range = - 0.03 to 0.07). Additionally, at 12 weeks post-baseline, ACT participants showed moderate decreases in fatigue and sleep disturbance (both ds = - 0.43), whereas education/support participants showed small decreases in these outcomes (ds = - 0.24 and - 0.18 for fatigue and sleep disturbance, respectively). Both the ACT and education/support groups showed reductions in depressive symptoms (ds = - 0.27 and - 0.28) at 12 weeks post-baseline. Group differences in all outcomes were not statistically significant. CONCLUSIONS: ACT shows feasibility and promise in improving fatigue and sleep-related outcomes in MBC patients and warrants further investigation.Item Accuracy of Electronic Health Record Food Insecurity, Housing Instability, and Financial Strain Screening in Adult Primary Care(American Medical Association, 2023) Harle, Christopher A.; Wu, Wei; Vest, Joshua R.; Psychology, School of ScienceItem Activation of extrasynaptic δ-GABAA receptors globally or within the posterior-VTA has estrous-dependent effects on consumption of alcohol and estrous-independent effects on locomotion(Elsevier, 2017-09) Melón, Laverne C.; Nolan, Zachary T.; Colar, Delphine; Moore, Eileen M.; Boehm II, Stephen L.; Psychology, School of ScienceRecent reports support higher than expected rates of binge alcohol consumption among women and girls. Unfortunately, few studies have assessed the mechanisms underlying this pattern of intake in females. Studies in males suggest that alcohol concentrations relevant to the beginning stages of binge intoxication may selectively target tonic GABAergic inhibition mediated by GABAA receptor subtypes expressing the δ-subunit protein (δ-GABAARs). Indeed, administration of agonists that interact with these δ-GABAARs prior to alcohol access can abolish binge drinking behavior in male mice. These δ-GABAARs have also been shown to exhibit estrous-dependent plasticity in regions relevant to drug taking behavior, like the hippocampus and periaqueductal gray. The present experiments were designed to determine whether the estrous cycle would alter binge drinking, or our ability to modulate this pattern of alcohol use with THIP, an agonist with high selectivity and efficacy at δ-GABAARs. Using the Drinking-in-the-Dark (DID) binge-drinking model, regularly cycling female mice were given 2h of daily access to alcohol (20%v/v). Vaginal cytology or vaginal impedance was assessed after drinking sessions to track estrous status. There was no fluctuation in binge drinking associated with the estrous cycle. Both Intra-posterior-VTA administration of THIP and systemic administration of the drug was also associated with an estrous cycle dependent reduction in drinking behavior. Pre-treatment with finasteride to inhibit synthesis of 5α-reduced neurosteroids did not disrupt THIP's effects. Analysis of δ-subunit mRNA from posterior-VTA enriched tissue samples revealed that expression of this GABAA receptor subunit is elevated during diestrus in this region. Taken together, these studies demonstrate that δGABAARs in the VTA are an important target for binge drinking in females and confirm that the estrous cycle is an important moderator of the pharmacology of this GABAA receptor subtype.Item Acute Alcohol and Cognition: Remembering What It Causes Us to Forget(Elsevier, 2019) Van Skike, Candice E.; Goodlett, Charles; Matthews, Douglas B.; Psychology, School of ScienceAddiction has been conceptualized as a specific form of memory that appropriates typically adaptive neural mechanisms of learning to produce the progressive spiral of drug-seeking and drug-taking behavior, perpetuating the path to addiction through aberrant processes of drug-related learning and memory. From that perspective, to understand the development of alcohol use disorders it is critical to identify how a single exposure to alcohol enters into or alters the processes of learning and memory, so that involvement of and changes in neuroplasticity processes responsible for learning and memory can be identified early on. This review characterizes the effects produced by acute alcohol intoxication as a function of brain region and memory neurocircuitry. In general, exposure to ethanol doses that produce intoxicating effects causes consistent impairments in learning and memory processes mediated by specific brain circuitry, whereas lower doses either have no effect or produce a facilitation of memory under certain task conditions. Therefore, acute ethanol does not produce a global impairment of learning and memory, and can actually facilitate particular types of memory, perhaps particular types of memory that facilitate the development of excessive alcohol use. In addition, the effects on cognition are dependent on brain region, task demands, dose received, pharmacokinetics, and tolerance. Additionally, we explore the underlying alterations in neurophysiology produced by acute alcohol exposure that help to explain these changes in cognition and highlight future directions for research. Through understanding the impact acute alcohol intoxication has on cognition, the preliminary changes potentially causing a problematic addiction memory can better be identified.Item Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice(Elsevier, 2017-12) Kasten, C.R.; Zhang, Y.; Boehm II, S.L.; Psychology, School of ScienceUse of exogenous cannabinoids disrupts the fine-tuned endocannabinoid receptor system, possibly leading to alterations in cognition, memory, and emotional processes that endure long after cannabinoid use has stopped. Long-term adolescent use may uniquely disrupt these behaviors when compared to adult use. The current study explored the acute and long-term behavioral effects of six 10mg/kg Δ9-tetrahydrocannabinol (THC) injections across the adolescent or early adult period in male inbred C57Bl/6J and DBA/2J mice. The acute and prolonged effects of THC on object memory using the novel object recognition task, unconditioned anxiety in the elevated plus maze and open field, and sedative effects in the open field were examined. Acute THC treatment resulted in anxiogenic activity in both strains, but only caused sedation in B6 mice. Repeated THC treatment resulted in a protracted effect on object recognition, but not unconditioned anxiety, assessed 4weeks later. In both strains, an adolescent history of THC treatment disrupted later object recognition. Interestingly, in B6 mice an adult history of THC exposure appeared to rescue a deficit in object recognition observed in vehicle-treated adults. Repeated THC administration also produced a protracted effected on CB1R protein expression. Animals treated with THC in adolescence maintained increased levels of CB1R protein expression compared to their adult THC-treated counterparts at five weeks following the last injection. These results indicate that THC use may have long-lasting effects with adolescence being a unique period of susceptibility.Item Acute Cannabinoids Produce Robust Anxiety-Like and Locomotor Effects in Mice, but Long-Term Consequences Are Age- and Sex-Dependent(Frontiers Media, 2019-02-20) Kasten, Chelsea R.; Zhang, Yanping; Boehm, Stephen L., II; Department of Psychology, School of ScienceThe rise in cannabinoid legalization and decriminalization in the US has been paired with an increase in adolescents that perceive marijuana as a "no risk" drug. However, a comprehensive review of human literature indicates that cannabinoid usage may have both beneficial and detrimental effects, with adolescent exposure being a critical window for harming cognitive development. Although the cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are often used together for recreational and medical purposes, no study has previously observed the acute and long-lasting effects of THC+CBD in a battery of behavioral assays analogous to subjective human reports. The current study observed the acute and long-term effects of THC, CBD, and THC+CBD on object recognition memory, anxiety-like behavior, and activity levels in adolescent and adult mice of both sexes. Acute THC alone and in combination with CBD resulted in robust effects on anxiety-like and locomotor behavior. A history of repeated cannabinoid treatment followed by a period without drug administration resulted in minimal effects in these behavioral assays. Most notably, the strongest effects of repeated cannabinoid treatment were seen in adult females administered THC+CBD, which significantly impaired their object recognition. No effects of repeated cannabinoid history were present on hippocampal protein expression. These studies represent a detailed examination of age- and sex-effects of acute and repeated cannabinoid administration. However, the acute and long-term effects of THC with and without CBD on additional behaviors in adolescents and adults will need to be examined for a more complete picture of these drug effects.