Publications by authors named "David Riddle"

This study tested two versions of parent-led, Internet-delivered cognitive behavioral therapy for anxiety among autistic youth; one that provided weekly email support (iCBT-Email), and one that provided alternating bi-weekly emails and video calls (iCBT-Video) across 12 weeks. It was expected that those in the iCBT-Video condition would complete more treatment content, which in turn would lead to more anxiety improvement. Fifty-seven autistic youth (7-15 years-old) with anxiety disorders were randomized to iCBT-Email or iCBT-Video.

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Background: Major depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth.

Methods: A sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis.

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Obsessive-compulsive disorder (OCD), anxiety disorders, and depressive disorders are highly comorbid, and each contribute to significant functional impairment for affected youth. Comorbid anxiety disorders in depressed youth have been associated with greater depressive symptom severity and impairment, but the impact of comorbid OCD in this population remains unclear. Accordingly, the present study examined the differential clinical characteristics of youth with depression and comorbid OCD relative to age/gender matched depressed youth with no such comorbidity and to those with depression and a comorbid (non-OCD) anxiety disorder.

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Article Synopsis
  • Cognitive behavioral therapy (CBT) adapted for autistic youth with anxiety and OCD shows strong evidence for effectiveness, but accessibility is a major issue.
  • A 12-week Internet-delivered CBT program was developed for autistic youth aged 7-15, incorporating feedback from parents, youth, and clinicians before a pilot trial.
  • The pilot trial indicated a 39% average reduction in anxiety severity among participants, suggesting that this family-based approach is promising and warrants further research.
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Unlabelled: A case-based laboratory event integrating neuroanatomy, neuroscience, and psychiatry was implemented into a pre-clerkship psychiatry-based course for second-year medical students. Learners rotating through lab stations to work on different cases to make interdisciplinary connections among these fields is an innovative way for them to integrate foundational neurology, neuroanatomy, and psychiatry concepts.

Supplementary Information: The online version contains supplementary material available at 10.

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The first U.S. case of non-travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was detected in late February 2020 in California, but the prevailing delay in diagnostic testing and initial stringent testing criteria made it difficult to identify those who could have acquired the virus through community spread.

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Rater-mediated assessments, such as teacher behavior rating scales, measure student behavior indirectly through the lens of a rater. As a result, scores from rater-mediated assessments can be influenced by rater effects- individual differences in rater perspectives, attitudes, beliefs, and interpretation of rating scale items. Rater effects are a fundamental aspect of all rater-mediated assessments.

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We describe herein a novel P447_L455 deletion in the C2 domain of in a patient with an ER breast cancer with an excellent response to the PI3Kα inhibitor alpelisib. Although deletions are relatively rare, a significant portion of deletions cluster within amino acids 446-460 of the C2 domain, suggesting these residues are critical for p110α function. A computational structural model of in complex with the p85 regulatory subunit and MCF10A cells expressing and were used to understand the phenotype of C2 domain deletions.

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Acquired resistance to cyclin-dependent kinases 4 and 6 (CDK4/6) small-molecule inhibitors in breast cancer arises through mechanisms that are yet uncharacterized. In this study, we used a kinome-wide siRNA screen to identify kinases that, when downregulated, yield sensitivity to the CDK4/6 inhibitor ribociclib. In this manner, we identified 3-phosphoinositide-dependent protein kinase 1 (PDK1) as a key modifier of ribociclib sensitivity in estrogen receptor-positive MCF-7 breast cancer cells.

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The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release.

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Purpose: To assess the long-term effects of fractionated whole brain irradiation (fWBI) using diffusion tensor imaging (DTI) and behavior in a pediatric rodent model for the clinical presentation of adult pediatric cancer survivors.

Materials And Methods: Five-week-old, male F344xBN rats were randomized to receive 0, 5, or 6.5 Gy fractions biweekly for 3 weeks, resulting in Sham, Irradiated-30 (IR-30) and IR-39 Gy total dose groups.

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We hypothesized that dietary administration of the peroxisomal proliferator-activated receptor α agonist, fenofibrate, to young adult male rats would prevent the fractionated whole-brain irradiation (fWBI)-induced reduction in cognitive function and neurogenesis and prevent the fWBI-induced increase in the total number of activated microglia. Eighty 12-14-week-old young adult male Fischer 344 × Brown Norway rats received either: (1) sham irradiation, (2) 40 Gy of fWBI delivered as two 5 Gy fractions/week for 4 weeks, (3) sham irradiation + dietary fenofibrate (0.2% w/w) starting 7 days prior to irradiation, or (4) fWBI + fenofibrate.

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Background: The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. More women are clinically depressed than men, yet the depressed female brain is little studied. We reported reduced anterior hippocampal volume in behaviorally depressed adult female cynomolgus macaques; the mechanisms contributing to that reduction are unknown.

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Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations.

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We hypothesized that chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, to young adult male rats would prevent/ameliorate fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment. Eighty 12-14-week-old young adult male Fischer 344 rats received either: (1) sham irradiation, (2) 40 Gy of fractionated whole-brain irradiation delivered as two 5 Gy fractions/week for 4 weeks, (3) sham irradiation plus continuous administration of 15 mg/L of ramipril in the drinking water starting 3 days before irradiation, or (4) fractionated whole-brain irradiation plus ramipril. Cognitive function was assessed using a perirhinal cortex-dependent version of the novel object recognition task 26 weeks after irradiation.

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Article Synopsis
  • Blockers of the RAAS, specifically the angiotensin II type 1 receptor antagonist L-158,809, can help protect cognitive function in rats after whole-brain radiation therapy.
  • In a study, L-158,809 was administered before, during, and after radiation exposure to measure its effects on neuroinflammation and neurogenesis in the hippocampus.
  • Findings showed that while the treatment improved cognitive outcomes, it did not significantly reduce neuroinflammation or promote neurogenesis in the brain after radiation injury.
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Radiation effectively treats brain tumors and other pathologies but dose and treatment plans are limited by normal tissue injury, a major cause of morbidity in survivors. Clinically significant normal tissue injury can occur even with therapies that target pathological tissue and limit out-of-target irradiation. Elucidating the mechanisms underlying normal tissue injury is facilitated by studying the effects of focal irradiation and comparing irradiated and un-irradiated tissue in experimental animals.

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Fish oil (FO) mediates a number of cardioprotective benefits in patients with cardiovascular disease. In the absence of cardiovascular disease, however, the effects of FO on cardiac structure and function are not clear. In addition, it is not known if an effective dosing strategy for attenuating age-related cardiac dysfunction is also effective at limiting cognitive dysfunction.

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Degeneration of the cholinergic neurons in the basal forebrain and elevation of inflammatory markers are well-established hallmarks of Alzheimer's disease; however, the interplay of these processes in normal aging is not extensively studied. Consequently, we conducted a neuroanatomical investigation to quantify cholinergic neurons and activated microglia in the medial septum/vertical diagonal band (MS/VDB) of young (6 months) and aged (28 months) Fisher 344 × Brown Norway F(1) rats. Aged rats in this study were impaired relative to the young animals in spatial learning ability as assessed in the Morris water maze.

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