Department of Psychiatry & Behavioral Sciences, University of California-Davis, Sacramento, CA, 2230 Stockton Blvd., Sacramento, CA 95817.
We investigated how cognitive neuroscientific studies during the last decade have advanced understanding of cognitive control from adolescence to young adulthood in individuals with autism spectrum disorder (ASD). To do so, we conducted a selective review of the larger structural, resting state, and diffusion imaging studies of brain regions and networks related to cognitive control that have been conducted since 2007 in individuals with ASD and typical development (TYP) ages 10 to 30 years that examined how these regions and networks support behavioral and task-based fMRI performance on tasks assessing cognitive control during this period. Longitudinal structural studies reveal overgrowth of the anterior cingulate (ACC) and slower white matter development in the parietal cortex in adolescents with ASD versus TYP. Read More
Center for Affective Science, Binghamton University (SUNY).
Background: Attentional biases, particularly difficulty inhibiting attention to negative stimuli, are implicated in risk for major depressive disorder (MDD). The current study examined a neural measure of attentional bias using a continuous index of visuocortical engagement (steady-state visual evoked potentials [SSVEPs]) before and after a negative mood induction in a population at high-risk for MDD recurrence due to a recently remitted MDD (rMDD) episode. Additionally, we examined working memory (WM) capacity as a potential moderator of the link between rMDD and visuocortical responses. Read More
The genetic evidence implicating amyloid-β in the initial stage of Alzheimer's disease is unequivocal. However, the long biochemical and cellular prodromal phases of the disease suggest that dementia is the result of a series of molecular and cellular cascades whose nature and connections remain unknown. Therefore, it is unlikely that treatments directed at amyloid-β will have major clinical effects in the later stages of the disease. Read More
Department of Psychiatry, Yale University School of Medicin, New Haven, Connecticut; Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut; Psychiatry and Behavioral Health Services, Yale New Haven Hospital, New Haven, Connecticut; Clinical Neuroscience Division, VA National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, Connecticut. Electronic address:
Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. Read More
School of Epidemiology, Public Health, and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address:
Background: It has been suggested that prenatal maternal stress may increase the risk of childhood externalizing disorders, yet no large cohort study has investigated this association across a large range of acute stressors. Our objective was to estimate the association between prenatal stressful events and risk of offspring conduct disorder and hyperactivity.
Methods: We used data from 10,184 mother-offspring pairs from the United Kingdom-based Avon Longitudinal Study of Parents and Children. Read More
Background: Individuals with Major Depressive Disorder (MDD) are characterized by biases in attention to negative emotional material. While there is evidence that anomalous functioning in frontocingulate regions may underlie these biases, we know little about the neural correlates of negative emotional biases in depressed adolescents.
Methods: Eighteen adolescents diagnosed with MDD and 21 matched healthy control (CTL) adolescents underwent fMRI while performing an emotional distractor task. Read More
Background: Stress is a prevailing risk factor for mood-related illnesses, wherein women represent the majority of those affected by major depression. Despite the growing literature suggesting that affective disorders can arise after a traumatic event is vicariously experienced, this relationship remains understudied in female subjects at the preclinical level. Thus, the objective of the current investigation was to examine whether exposure to emotional and/or psychological stress (ES) mediates depression-related outcomes in female mice. Read More
Background: Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Read More
Background: Chronic stress-induced inflammatory responses occur in part via danger-associated molecular pattern (DAMP) molecules, such as high mobility group box 1 protein (HMGB1), but the receptor(s) underlying DAMP signaling have not been identified.
Methods: Microglia morphology and DAMP signaling in enriched rat hippocampal microglia were examined during the development and expression of chronic unpredictable stress (CUS)-induced behavioral deficits, including long-term, persistent changes after CUS.
Results: The results show that CUS promotes significant morphological changes and causes robust upregulation of HMGB1 messenger RNA in enriched hippocampal microglia, an effect that persists for up to 6 weeks after CUS exposure. Read More
Background: Trait anxiety is reliably associated with enhanced neural responses following errors: meta analyses have described how the electrophysiological response to errors known as the Error-Related Negativity (ERN) is increased in anxious individuals, particularly in relation to worry. The ERN has been related to a broader class of control signals, particularly via a common theta band denominator, but it is unknown whether worry relates to these alternative medial frontal metrics. Moreover, it is unclear if increased ERN in anxiety relates to altered cognitive control. Read More
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany; Development, Health, and Disease Research Program, University of California, Irvine, Irvine, California; Department of Pediatrics, School of Medicine, University of California, Irvine, Irvine, California. Electronic address:
Background: Childhood maltreatment (CM) confers deleterious long-term consequences, and growing evidence suggests some of these effects may be transmitted across generations. We examined the intergenerational effect of maternal CM exposure on child brain structure and also addressed the hypothesis that this effect may start during the child's intrauterine period of life.
Methods: A prospective longitudinal study was conducted in a clinical convenience sample of 80 mother-child dyads. Read More
Background: Anxious hypervigilance is marked by sensitized sensory-perceptual processes and attentional biases to potential danger cues in the environment. How this is realized at the neurocomputational level is unknown but could clarify the brain mechanisms disrupted in psychiatric conditions such as posttraumatic stress disorder. Predictive coding, instantiated by dynamic causal models, provides a promising framework to ground these state-related changes in the dynamic interactions of reciprocally connected brain areas. Read More
Background: Differentiating whether an action leads to an outcome by chance or by an underlying statistical regularity that signals environmental change profoundly affects adaptive behavior. Previous studies have shown that anxious individuals may not appropriately differentiate between these situations. This investigation aims to precisely quantify the process deficit in anxious individuals and determine the degree to which these process dysfunctions are specific to anxiety. Read More
Computational psychiatry aims to apply mathematical and computational techniques to help improve psychiatric care. To achieve this, the phenomena under scrutiny should be within the scope of formal methods. As emotions play an important role across many psychiatric disorders, such computational methods must encompass emotions. Read More
Background: Problematic alcohol use in adolescence and adulthood is a common and often debilitating correlate of childhood attention-deficit/hyperactivity disorder (ADHD). Converging evidence suggests that ADHD and problematic alcohol use share a common additive genetic basis, which may be mechanistically related to reward-related brain function. In the current study, we examined whether polygenic risk for childhood ADHD is linked to problematic alcohol use in young adulthood through alterations in reward-related activity of the ventral striatum, a neural hub supporting appetitive behaviors and reinforcement learning. Read More
Program in Neuroscience, Indiana University, Bloomington, Indiana; Psychological and Brain Sciences, Indiana University, Bloomington, Indiana; Gill Center for Biomolecular Science, Bloomington, Indiana. Electronic address:
Background: Activation of cannabinoid CB1 receptors suppresses pathological pain but also produces unwanted central side effects. We hypothesized that a positive allosteric modulator of CB1 signaling would suppress inflammatory and neuropathic pain without producing cannabimimetic effects or physical dependence. We also asked whether a CB1 positive allosteric modulator would synergize with inhibitors of endocannabinoid deactivation and/or an orthosteric cannabinoid agonist. Read More
Background: A recent analysis of 25 historical candidate gene polymorphisms for schizophrenia in the largest genome-wide association study conducted to date suggested that these commonly studied variants were no more associated with the disorder than would be expected by chance. However, the same study identified other variants within those candidate genes that demonstrated genome-wide significant associations with schizophrenia. As such, it is possible that variants within historic schizophrenia candidate genes are associated with schizophrenia at levels above those expected by chance, even if the most-studied specific polymorphisms are not. Read More
Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina. Electronic address:
Background: Studies in rodents provide compelling evidence that microorganisms inhabiting the gut influence neurodevelopment. In particular, experimental manipulations that alter intestinal microbiota impact exploratory and communicative behaviors and cognitive performance. In humans, the first years of life are a dynamic time in gut colonization and brain development, but little is known about the relationship between these two processes. Read More
Background: Medication and psychotherapy treatments for posttraumatic stress disorder (PTSD) provide insufficient benefit for many patients. Substantial preclinical and clinical data indicate abnormalities in the hypothalamic-pituitary-adrenal axis, including signaling by corticotropin-releasing factor, in the pathophysiology of PTSD.
Methods: We conducted a double-blind, placebo-controlled, randomized, fixed-dose clinical trial evaluating the efficacy of GSK561679, a corticotropin-releasing factor receptor 1 (CRF1 receptor) antagonist in adult women with PTSD. Read More
Circulating autoantibodies against glutamatergic N-methyl-D-aspartate receptor (NMDAR) have been reported in a proportion of patients with psychotic disorders, raising hopes for more appropriate treatment for these antibody-positive patients. However, the prevalence of circulating autoantibodies against glutamatergic NMDAR in psychotic disorders remains controversial, with detection prevalence rates and immunoglobulin classes varying considerably between studies, perhaps because of different detection methods. Here, we compared the results of serum assays for a large cohort of patients with first-episode psychosis using classical cell-based assays in three labs and a single molecule-based imaging method. Read More
Background: Disruptions in circadian rhythms are associated with an increased risk for bipolar disorder. Moreover, studies show that the circadian protein CLOCK (circadian locomotor output cycles kaput) is involved in regulating monoaminergic systems and mood-related behavior. However, the molecular and synaptic mechanisms underlying this relationship remain poorly understood. Read More
Background: The limited neurobiological understanding of posttraumatic stress disorder (PTSD) has been partially attributed to the need for improved animal models. Stress-enhanced fear learning (SEFL) in rodents recapitulates many PTSD-associated behaviors, including stress-susceptible and stress-resilient subgroups in outbred rats. Identification of subgroups requires additional behavioral phenotyping, a confound to mechanistic studies. Read More
Background: Posttraumatic stress disorder (PTSD) may contribute to heightened cardiovascular disease risk by promoting a proinflammatory state and impaired endothelial function. Previous research has demonstrated associations of PTSD with inflammatory and endothelial function biomarkers, but most work has been cross-sectional and does not separate the effects of trauma exposure from those of PTSD.
Methods: We investigated associations of trauma exposure and chronic PTSD with biomarkers of inflammation (C-reactive protein and tumor necrosis factor alpha receptor II) and endothelial function (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in 524 middle-aged women in the Nurses' Health Study II. Read More
Background: Learned fear is crucial in the development and maintenance of posttraumatic stress disorder (PTSD) and other anxiety disorders, and extinction of learned fear is necessary for response to exposure-based treatments. In humans, research suggests disrupted sleep impairs consolidation of extinction, though no studies have examined this experimentally using total sleep deprivation.
Methods: Seventy-one healthy controls underwent a paradigm to acquire conditioned fear to a visual cue. Read More
Department of Physiology, Development and Neuroscience, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom. Electronic address:
Background: Impaired regulation of emotional responses to potential threat is a core feature of affective disorders. However, while the subcortical circuitry responsible for processing and expression of fear has been well characterized, the top-down control of this circuitry is less well understood. Our recent studies demonstrated that heightened emotionality, as measured both physiologically and behaviorally, during conditioned fear and innate/social threat was induced, independently, by excitotoxic lesions of either the anterior orbitofrontal cortex (antOFC) or ventrolateral prefrontal cortex (vlPFC). Read More
Development, Health and Disease Research Program, University of California, Irvine, Irvine, California; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany. Electronic address:
Background: Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans.
Methods: Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks' gestation. Read More
Background: Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology and treatment of depression. Recent clinical studies demonstrate that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in patients with depression. Rodent studies demonstrate that scopolamine increases glutamate transmission and synaptogenesis in the medial prefrontal cortex (mPFC). Read More
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington. Electronic address:
Background: The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D2-family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy.
Methods: To better understand how loss of D2-family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. Read More