Publications by authors named "David Fleck"

Background: Response to pharmacotherapy varies considerably among youths with bipolar disorder (BD) and is poorly predicted by clinical or demographic features. It can take several weeks to determine whether medication for BD is clinically effective. Although neuroimaging biomarkers are promising predictors, few studies examined the predictive value of the brain connectomic topology.

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In most mammals, conspecific chemosensory communication relies on semiochemical release within complex bodily secretions and subsequent stimulus detection by the vomeronasal organ (VNO). Urine, a rich source of ethologically relevant chemosignals, conveys detailed information about sex, social hierarchy, health, and reproductive state, which becomes accessible to a conspecific via vomeronasal sampling. So far, however, numerous aspects of social chemosignaling along the vomeronasal pathway remain unclear.

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The physiological performance of any sensory organ is determined by its anatomy and physical properties. Consequently, complex sensory structures with elaborate features have evolved to optimize stimulus detection. Understanding these structures and their physical nature forms the basis for mechanistic insights into sensory function.

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Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD.

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Article Synopsis
  • A study looked at the brains of young people (ages 10-18) with ADHD, some with a family history of bipolar disorder (BD) and some without.
  • The results showed that those at higher risk (with a family history) had more severe symptoms and smaller brain areas compared to those at lower risk and healthy controls.
  • These changes in brain structure may be linked to how serious their ADHD symptoms are, showing that having a family history of BD can affect brain development in kids with ADHD.
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Background: Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent among youth with or at familial risk for bipolar-I disorder (BD-I), and ADHD symptoms commonly precede and may increase the risk for BD-I; however, associated neuropathophysiological mechanisms are not known. In this cross-sectional study, we sought to investigate brain structural network topology among youth with ADHD, with and without familial risk of BD-I.

Methods: We recruited 3 groups of psychostimulant-free youth (aged 10-18 yr), namely youth with ADHD and at least 1 biological parent or sibling with BD-I (high-risk group), youth with ADHD who did not have a first- or second-degree relative with a mood or psychotic disorder (low-risk group) and healthy controls.

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Attention-deficit/hyperactivity disorder (ADHD) commonly precedes the initial onset of mania in youth with familial risk for bipolar disorder (BD). Although ADHD youth with and without BD familial risk exhibit different clinical features, associated neuropathophysiological mechanisms remain poorly understood. This study aimed to identify brain functional network abnormalities associated with ADHD in youth with and without familial risk for BD.

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Objectives: To characterize the neuroanatomy of BD in youth and its correlation to clinical characteristics.

Methods: The current study includes a sample of 105 unmedicated youth with first-episode BD, aged between 10.1 and 17.

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Introduction: While pain self-management programs can significantly improve patient outcomes, poor adherence is common and the need for research on predictors of adherence has been noted. A potential, but commonly overlooked, predictor is cognitive function. Our aim, then, was to examine the relative influence of various cognitive functional domains on engagement with an online pain self-management program.

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Background: Having a first-degree relative with bipolar I disorder (BD) in conjunction with prodromal attention deficit/hyperactivity disorder (ADHD) may represent a unique phenotype that confers greater risk for developing BD than ADHD alone. However, underlying neuropathoetiological mechanisms remain poorly understood. This cross-sectional study compared regional microstructure in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC).

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Background: In order to identify biomarkers of prodromal mood disorders, we examined functional brain activation in children and adolescent at familial risk for bipolar disorder.

Methods: Offspring of parents with bipolar I disorder (at-risk youth; N = 115, mean ± SD age: 13.6 ± 2.

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Disruptions in the limbic system, and in emotion regulation circuitry that supports affect modulation, have been reported during acute manic episodes of bipolar disorder (BD). The impact of pharmacological treatment on these deficits, especially in youth, remains poorly characterized. 107 youths with acute manic or mixed episodes of bipolar I disorder and 60 group-matched healthy controls were recruited.

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Unlabelled: Disrupted topological organization of brain functional networks has been widely reported in bipolar disorder. However, the potential clinical implications of structural connectome abnormalities have not been systematically investigated. The present study included 109 unmedicated subjects with acute mania who were assigned to 8 weeks of treatment with quetiapine or lithium and 60 healthy controls.

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Background: Identification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.

Methods: A total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine ( = 71) or lithium ( = 50).

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Objective: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established.

Method: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies.

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Precise information flow from the hippocampus (HP) to prefrontal cortex (PFC) emerges during early development and accounts for cognitive processing throughout life. On flip side, this flow is selectively impaired in mental illness. In mouse models of psychiatric risk mediated by gene-environment interaction (GE), the prefrontal-hippocampal coupling is disrupted already shortly after birth.

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The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions.

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The mouse vomeronasal system controls several social behaviors. Pheromones and other social cues are detected by sensory neurons in the vomeronasal organ (VNO). Stimuli activate a transduction cascade that leads to membrane potential depolarization, increase in cytosolic Ca level, and increased firing.

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The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63).

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Spermatogenesis, the complex process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined.

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This pilot study explores the possibility of predicting post-concussion symptom recovery at one week post-injury using only objective diffusion tensor imaging (DTI) data inputs to a novel artificial intelligence (AI) system composed of Genetic Fuzzy Trees (GFT). Forty-three adolescents age 11 to 16 years with either mild traumatic brain injury or traumatic orthopedic injury were enrolled on presentation to the emergency department. Participants received a DTI scan three days post-injury, and their symptoms were assessed by the Post-Concussion Symptom Scale (PCSS) at 6 h and one week post-injury.

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Objectives: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, was previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after 8 weeks of treatment compared to those who did not.

Methods: Forty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received 8 weeks of treatment.

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Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time.

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