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    11867 results match your criteria Biological psychiatry[Journal]

    1 OF 238

    Role of Striatal Direct Pathway 2-Arachidonoylglycerol Signaling in Sociability and Repetitive Behavior.
    Biol Psychiatry 2017 Dec 28. Epub 2017 Dec 28.
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
    Background: Endocannabinoid signaling plays an important role in regulating synaptic transmission in the striatum, a brain region implicated as a central node of dysfunction in autism spectrum disorder. Deficits in signaling mediated by the endocannabinoid 2-arachidonoylglycerol (2-AG) have been reported in mouse models of autism spectrum disorder, but a causal role for striatal 2-AG deficiency in phenotypes relevant to autism spectrum disorder has not been explored.

    Methods: Using conditional knockout mice, we examined the electrophysiological, biochemical, and behavioral effects of 2-AG deficiency by deleting its primary synthetic enzyme, diacylglycerol lipase α (DGLα), from dopamine Dreceptor-expressing or adenosine A2a receptor-expressing medium spiny neurons (MSNs) to determine the role of 2-AG signaling in striatal direct or indirect pathways, respectively. Read More

    Psychiatric Symptom Dimensions Are Associated With Dissociable Shifts in Metacognition but Not Task Performance.
    Biol Psychiatry 2018 Jan 11. Epub 2018 Jan 11.
    Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, United Kingdom. Electronic address:
    Background: Distortions in metacognition-the ability to reflect on and control other cognitive processes-are thought to be characteristic of poor mental health. However, it remains unknown whether such shifts in self-evaluation are due to specific alterations in metacognition and/or a downstream consequence of changes in decision-making processes.

    Methods: Using perceptual decision making as a model system, we employed a computational psychiatry approach to relate parameters governing both decision formation and metacognitive evaluation to self-reported transdiagnostic symptom dimensions in a large general population sample (N = 995). Read More

    Neurogenetic Approaches to Stress and Fear in Humans as Pathophysiological Mechanisms for Posttraumatic Stress Disorder.
    Biol Psychiatry 2018 Jan 10. Epub 2018 Jan 10.
    Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany. Electronic address:
    In this review article, genetic variation associated with brain responses related to acute and chronic stress reactivity and fear learning in humans is presented as an important mechanism underlying posttraumatic stress disorder. We report that genes related to the regulation of the hypothalamic-pituitary-adrenal axis, as well as genes that modulate serotonergic, dopaminergic, and neuropeptidergic functions or plasticity, play a role in this context. The strong overlap of the genetic targets involved in stress and fear learning suggests that a dimensional and mechanistic model of the development of posttraumatic stress disorder based on these constructs is promising. Read More

    Glutamatergic Ventral Pallidal Neurons Modulate Activity of the Habenula-Tegmental Circuitry and Constrain Reward Seeking.
    Biol Psychiatry 2018 Jan 12. Epub 2018 Jan 12.
    Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address:
    Background: The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modulate these behaviors is not known. Read More

    Genes and Pathways Regulated by Androgens in Human Neural Cells, Potential Candidates for the Male Excess in Autism Spectrum Disorder.
    Biol Psychiatry 2018 Jan 9. Epub 2018 Jan 9.
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Centre National de la Recherche Scientifique, UMR 7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Université de Strasbourg, Illkirch, France; Laboratory of Genetic Diagnostics, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address:
    Background: Prenatal exposure to androgens during brain development in male individuals may participate to increase their susceptibility to develop neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability. However, little is known about the action of androgens in human neural cells.

    Methods: We used human neural stem cells differentiated from embryonic stem cells to investigate targets of androgens. Read More

    Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving.
    Biol Psychiatry 2017 Dec 29. Epub 2017 Dec 29.
    Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland.
    Background: Methamphetamine (meth) seeking progressively increases after withdrawal (incubation of meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in the rat dorsal striatum and incubation of meth craving. Here we used viral constructs to study the causal role of dorsal striatum HDAC5 in this incubation. Read More

    Transcription Factor E2F3a in Nucleus Accumbens Affects Cocaine Action via Transcription and Alternative Splicing.
    Biol Psychiatry 2017 Dec 5. Epub 2017 Dec 5.
    Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:
    Background: Lasting changes in gene expression in brain reward regions, including nucleus accumbens (NAc), contribute to persistent functional changes in the addicted brain. We and others have demonstrated that altered expression of several candidate transcription factors in NAc regulates drug responses. A recent large-scale genome-wide study from our group predicted transcription factor E2F3 (E2F3) as a prominent upstream regulator of cocaine-induced changes in gene expression and alternative splicing. Read More

    Neural Mechanisms of Early-Life Social Stress as a Developmental Risk Factor for Severe Psychiatric Disorders.
    Biol Psychiatry 2017 Dec 28. Epub 2017 Dec 28.
    Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
    Background: To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking.

    Methods: We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Read More

    Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial.
    Biol Psychiatry 2017 Dec 26. Epub 2017 Dec 26.
    Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan. Electronic address:
    Background: Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. Read More

    Altered Brain Network Dynamics in Schizophrenia: A Cognitive Electroencephalography Study.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 4;3(1):88-98. Epub 2017 Apr 4.
    Sagol Center for Brain and Mind, Baruch Ivcher School of Psychology, Interdisciplinary Center (IDC), Herzliya, Israel.
    Background: Alterations in the dynamic coordination of widespread brain networks are proposed to underlie cognitive symptoms of schizophrenia. However, there is limited understanding of the temporal evolution of these networks and how they relate to cognitive impairment. The current study was designed to explore dynamic patterns of network connectivity underlying cognitive features of schizophrenia. Read More

    When Proactivity Fails: An Electrophysiological Study of Establishing Reference in Schizophrenia.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 28;3(1):77-87. Epub 2017 Sep 28.
    Department of Psychology, Tufts University, Medford, Massachusetts.
    Background: Schizophrenia is characterized by abnormalities in referential communication, which may be linked to more general deficits in proactive cognitive control. We used event-related potentials to probe the timing and nature of the neural mechanisms engaged as people with schizophrenia linked pronouns to their preceding referents during word-by-word sentence comprehension.

    Methods: We measured event-related potentials to pronouns in two-clause sentences in 16 people with schizophrenia and 20 demographically matched control participants. Read More

    Phase-Amplitude Coupling of the Electroencephalogram in the Auditory Cortex in Schizophrenia.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 13;3(1):69-76. Epub 2017 Sep 13.
    Neural Dynamics Laboratory, Research Service, Veterans Affairs Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address:
    Background: Cross-frequency interactions may coordinate neural circuits operating at different frequencies. While neural oscillations associated with particular circuits in schizophrenia (SZ) are impaired, few studies have examined cross-frequency interactions. Here we examined phase-amplitude coupling (PAC) in the electroencephalograms of individuals with SZ and healthy control subjects (HCs). Read More

    Distinct Associations Between Low Positive Affect, Panic, and Neural Responses to Reward and Threat During Late Stages of Affective Picture Processing.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 12;3(1):59-68. Epub 2017 Oct 12.
    Department of Psychology, McGill University, Montreal, Quebec, Canada.
    Background: Abnormal patterns of attention to threat and reward have been proposed as potential mechanisms of dysfunction in anxiety and mood disorders. However, research on this topic has been inconsistent, perhaps because of both clinical heterogeneity in the samples assessed and measurement of attentional biases that is temporally imprecise.

    Methods: The present study measured transdiagnostic symptoms of anxiety and depression in 205 young adults and recorded affect-modulated event-related potentials in response to task-irrelevant pictures in a speeded response task. Read More

    Electroencephalography Source Functional Connectivity Reveals Abnormal High-Frequency Communication Among Large-Scale Functional Networks in Depression.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 13;3(1):50-58. Epub 2017 Jul 13.
    Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address:
    Background: Functional magnetic resonance imaging studies of resting-state functional connectivity have shown that major depressive disorder (MDD) is characterized by increased connectivity within the default mode network (DMN) and between the DMN and the frontoparietal network (FPN). However, much remains unknown about abnormalities in higher frequency (>1 Hz) synchronization. Findings of abnormal synchronization in specific frequencies would contribute to a better understanding of the potential neurophysiological origins of disrupted functional connectivity in MDD. Read More

    Time-Frequency Reward-Related Delta Prospectively Predicts the Development of Adolescent-Onset Depression.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 7;3(1):41-49. Epub 2017 Aug 7.
    Department of Biomedical Sciences and Psychology, Florida State University, Tallahassee, Florida. Electronic address:
    Background: A blunted reward positivity (RewP), an event-related potential elicited by feedback indicating monetary gain relative to loss, was recently shown to prospectively predict the development of adolescent-onset depression. Time-frequency-based representations of this activity (e.g. Read More

    Event-Related Potentials as Biomarkers of Behavior Change Mechanisms in Substance Use Disorder Treatment.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 23;3(1):30-40. Epub 2017 Sep 23.
    Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
    Substance use disorders (SUDs) are one of the most prevalent psychiatric conditions and represent a significant public health concern. Substantial research has identified key processes related to reinforcement and cognition for the development and maintenance of SUDs, and these processes represent viable treatment targets for psychosocial and pharmacological interventions. Research on SUD treatments has suggested that most approaches are comparable in effectiveness. Read More

    Aberrant Modulation of Brain Oscillatory Activity and Attentional Impairment in Attention-Deficit/Hyperactivity Disorder.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 6;3(1):19-29. Epub 2017 Oct 6.
    Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address:
    Electroencephalography and magnetoencephalography are noninvasive neuroimaging techniques that have been used extensively to study various resting-state and cognitive processes in the brain. The purpose of this review is to highlight a number of recent studies that have investigated the alpha band (8-12 Hz) oscillatory activity present in magnetoencephalography and electroencephalography, to provide new insights into the maladaptive network activity underlying attentional impairments in attention-deficit/hyperactivity disorder (ADHD). Studies reviewed demonstrate that event-related decrease in alpha is attenuated during visual selective attention, primarily in ADHD inattentive type, and is often significantly associated with accuracy and reaction time during task performance. Read More

    Using Event-Related Potentials and Startle to Evaluate Time Course in Anxiety and Depression.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2018 Jan 20;3(1):10-18. Epub 2017 Sep 20.
    Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois; Department of Psychology, University of Illinois at Chicago, Chicago, Illinois. Electronic address:
    The National Institute of Mental Health's Research Domain Criteria initiative is a research framework designed toward understanding psychopathology as abnormalities of dimensional neurobehavioral constructs rather than in terms of DSM-defined categories. Research Domain Criteria constructs within the negative valence domain are particularly relevant for understanding anxiety and depressive disorders, which are pervasive, debilitating, and characterized by negative processing bias. One important direction for Research Domain Criteria research is investigating processes and parameters related to the time course (or chronometry) of negative valenced constructs. Read More

    Calcium/Calmodulin-Dependent Protein Kinase II and Eukaryotic Elongation Factor 2 Kinase Pathways Mediate the Antidepressant Action of Ketamine.
    Biol Psychiatry 2017 Dec 5. Epub 2017 Dec 5.
    Sagol Department of Neurobiology, University of Haifa, Mount Carmel, Haifa, Israel; Center for Gene Manipulation in the Brain, University of Haifa, Mount Carmel, Haifa, Israel. Electronic address:
    Background: Ketamine is an N-methyl-D-aspartate receptor antagonist, which on administration produces fast-acting antidepressant responses in patients with major depressive disorder. Yet, the mechanism underlying the antidepressant action of ketamine remains unclear.

    Methods: To unravel the mechanism of action of ketamine, we treated wild-type C57BL/6 mice with calcium/calmodulin-dependent protein kinase II (CaMKII) specific inhibitor tatCN21 peptide. Read More

    Metabolic and Cardiovascular Complications in Obsessive-Compulsive Disorder: A Total Population, Sibling Comparison Study With Long-Term Follow-up.
    Biol Psychiatry 2017 Dec 21. Epub 2017 Dec 21.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Background: Obsessive-compulsive disorder (OCD) is associated with increased mortality, but the causes of this increase are poorly understood. This study examined whether OCD is associated with an increased risk of metabolic and cardiovascular complications.

    Methods: Individuals diagnosed with OCD (n = 25,415) were identified from a cohort of 12,497,002 individuals living in Sweden between 1973 and 2013. Read More

    Thalamic Control of Cognition and Social Behavior Via Regulation of Gamma-Aminobutyric Acidergic Signaling and Excitation/Inhibition Balance in the Medial Prefrontal Cortex.
    Biol Psychiatry 2017 Dec 7. Epub 2017 Dec 7.
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania. Electronic address:
    Background: The mediodorsal thalamus plays a critical role in cognition through its extensive innervation of the medial prefrontal cortex (mPFC), but how the two structures cooperate at the single-cell level to generate associated cognitive functions and other mPFC-dependent behaviors remains elusive. Maintaining the proper balance between excitation and inhibition (E/I balance) is of principal importance for organizing cortical activity. Furthermore, the PFC E/I balance has been implicated in successful execution of multiple PFC-dependent behaviors in both animal research and the context of human psychiatric disorders. Read More

    Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents.
    Biol Psychiatry 2017 Dec 15. Epub 2017 Dec 15.
    Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; The Jackson Laboratory, Bar Harbor, Maine. Electronic address:
    Sleep homeostasis and circadian function are important maintaining factors for optimal health and well-being. Conversely, sleep and circadian disruptions are implicated in a variety of adverse health outcomes, including substance use disorders. These risks are particularly salient during adolescence. Read More

    Nuclear Excluded Autism-Associated Phosphatase and Tensin Homolog Mutations Dysregulate Neuronal Growth.
    Biol Psychiatry 2017 Dec 2. Epub 2017 Dec 2.
    Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire. Electronic address:
    Background: Phosphatase and tensin homolog (PTEN) negatively regulates downstream protein kinase B signaling, resulting in decreased cellular growth and proliferation. PTEN is mutated in a subset of children with autism spectrum disorder (ASD); however, the mechanism by which specific point mutations alter PTEN function is largely unknown. Here, we assessed how ASD-associated single-nucleotide variations in PTEN (ASD-PTEN) affect function. Read More

    Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.
    Biol Psychiatry 2017 Dec 15. Epub 2017 Dec 15.
    Department of Stereotactic Neurosurgery, Cromwell Hospital, London, United Kingdom.
    Background: Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. Read More

    Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia.
    Biol Psychiatry 2017 Dec 7. Epub 2017 Dec 7.
    Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:
    Background: Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Read More

    Median and Dorsal Raphe Serotonergic Neurons Control Moderate Versus Compulsive Cocaine Intake.
    Biol Psychiatry 2017 Nov 20. Epub 2017 Nov 20.
    Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
    Background: Reduced expression of the serotonin transporter (SERT) promotes anxiety and cocaine intake in both humans and rats. We tested the hypothesis that median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) serotonergic projections differentially mediate these phenotypes.

    Methods: We used virally mediated RNA interference to locally downregulate SERT expression and compared the results with those of constitutive SERT knockout. Read More

    Executive Dysfunction in Autism Spectrum Disorder Is Associated With a Failure to Modulate Frontoparietal-insular Hub Architecture.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2017 Sep 18;2(6):537-545. Epub 2017 Mar 18.
    Department of Psychology, Children's National Medical Center, Washington, DC; Interdisciplinary Program in Neuroscience, Georgetown University, Children's National Medical Center, Washington, DC; Center for Neuroscience Children's Research Institute, Children's National Medical Center, Washington, DC.
    Background: Comorbid executive dysfunction in autism spectrum disorder (ASD) is a barrier to adaptive functioning, despite remittance of core social-communication symptoms. Network models of ASD address core symptoms but not comorbid executive dysfunction. Following recent demonstrations in healthy adults that, with increasing executive demands, hubs embedded within frontoparietal-insular control networks interact with a more diverse set of networks, we hypothesized that the capability of hubs to do so is perturbed in ASD and predicts executive behavior. Read More

    Negative Valence in Autism Spectrum Disorder: The Relationship Between Amygdala Activity, Selective Attention, and Co-occurring Anxiety.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2017 Sep 22;2(6):510-517. Epub 2017 Mar 22.
    Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:
    Background: A critical agenda of the National Institutes of Health Research Domain Criteria (RDoC) initiative is establishing whether domains within the RDoC matrix are truly transdiagnostic. Rates of anxiety disorders are elevated in autism spectrum disorder (ASD), but it is unclear whether the same mechanisms contribute to anxiety in individuals with and without ASD. As changes in selective attention are a hallmark of anxiety disorders in non-ASD samples, the identification of these changes in ASD would support the transdiagnostic nature of anxiety. Read More

    Face Processing Measures of Social Cognition: A Dimensional Approach to Developmental Psychopathology.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2017 Sep 22;2(6):502-509. Epub 2017 Mar 22.
    Brain Behavior Laboratory, Neuropsychiatry Division, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania; and the Lifespan Brain Institute, Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, Pennsylvania.
    Background: Social cognition impairments in neurodevelopmental disorders impact functioning. Face processing is the most extensively studied aspect of social cognition, commonly indexing this construct in neuropsychiatric disorders compared with typically developing youths. Applying social cognition measures as a Research Domain Criteria concept in the clinical arena requires establishing cutoffs for intervention and identifying vulnerability for psychopathology across disorders. Read More

    Children With Fragile X Syndrome Display Threat-Specific Biases Toward Emotion.
    Biol Psychiatry Cogn Neurosci Neuroimaging 2017 Sep 21;2(6):487-492. Epub 2017 Jun 21.
    Center for Mind and Brain, University of California, Davis, California; Department of Psychology, University of California, Davis, California; Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, California. Electronic address:
    Background: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. FXS is caused by a silencing of the FMR1 gene that results in a loss or absence of the gene's protein product, fragile X mental retardation protein. The phenotype of FXS is consistently associated with heightened anxiety, although no previous study has investigated attentional bias toward threat, a hallmark of anxiety disorders, in individuals with FXS. Read More

    Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.
    Biol Psychiatry 2017 Nov 20. Epub 2017 Nov 20.
    Department of Psychiatry, University of California San Diego, La Jolla, California; Center of Excellence for Stress and Mental Health, Veterans Affairs Hospital, La Jolla, California. Electronic address:
    Increasing predictability of animal models of posttraumatic stress disorder (PTSD) has required active collaboration between clinical and preclinical scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with ≥20 symptoms. Clinical research increasingly utilizes objective biological measures (e. Read More

    Identification of a Corticohabenular Circuit Regulating Socially Directed Behavior.
    Biol Psychiatry 2017 Dec 2. Epub 2017 Dec 2.
    Neuroscience Discovery, Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland. Electronic address:
    Background: The prefrontal cortex (PFC) has been implicated in the pathophysiology of social dysfunction, but the specific circuit partners mediating PFC function in health and disease are unclear.

    Methods: The excitatory designer receptor exclusively activated by designer drugs (DREADD) hM3Dq was used to induce PFC activation during social behavior measured in the three-chamber sociability assay (rats/mice). Functional magnetic resonance imaging was combined with hM3Dq-mediated PFC activation to identify novel nodes in the "social brain" in a hypothesis-free manner. Read More

    Specificity in Etiology of Subtypes of Bipolar Disorder: Evidence From a Swedish Population-Based Family Study.
    Biol Psychiatry 2017 Nov 20. Epub 2017 Nov 20.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Background: Uncertainty remains whether bipolar I disorder (BDI) and bipolar II disorder (BDII) differ etiologically. We used a population-based family sample to examine the etiological boundaries between BDI and BDII by assessing their familial aggregation/coaggregation and by assessing the coaggregation between them and schizophrenia, depression, attention-deficit/hyperactivity disorder, eating disorders, autism spectrum disorder, substance use disorders, anxiety disorders, and personality disorders.

    Methods: By linking Swedish national registers, we established a population-based cohort (N = 15,685,511) and identified relatives with different biological relationships. Read More

    Mechanisms of Sex Differences in Fear and Posttraumatic Stress Disorder.
    Biol Psychiatry 2017 Nov 21. Epub 2017 Nov 21.
    Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts.
    Following sexual maturity, females disproportionately have higher rates of posttraumatic stress disorder (PTSD) and experience greater symptom severity and chronicity as compared with males. This observation has led many to examine sex differences in PTSD risk factors. Though relatively few, these studies reveal that the root causes of PTSD sex differences are complex, and partly represent interactions between sex-specific nonbiological and biological risk factors, which differentially shape PTSD vulnerability. Read More

    Prion Protein as a Toxic Acceptor of Amyloid-β Oligomers.
    Biol Psychiatry 2018 Feb 21;83(4):358-368. Epub 2017 Nov 21.
    Medical Research Council Prion Unit, Institute of Prion Diseases, University College London (UCL), London, United Kingdom. Electronic address:
    The initial report that cellular prion protein (PrP) mediates toxicity of amyloid-β species linked to Alzheimer's disease was initially treated with scepticism, but growing evidence supports this claim. That there is a high-affinity interaction is now clear, and its molecular basis is being unraveled, while recent studies have identified possible downstream toxic mechanisms. Determination of the clinical significance of such interactions between PrPand disease-associated amyloid-β species will require experimental medicine studies in humans. Read More

    A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.
    Biol Psychiatry 2017 Dec 2. Epub 2017 Dec 2.
    Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.
    Background: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.

    Methods: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Read More

    Amphetamine-Induced Striatal Dopamine Release Measured With an Agonist Radiotracer in Schizophrenia.
    Biol Psychiatry 2017 Dec 7. Epub 2017 Dec 7.
    Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
    Background: Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with Dantagonist radiotracers, is the failure to provide information about Dreceptors configured in a state of high affinity for the agonists (i.e. Read More

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