Toward New Approaches to Psychotic Disorders: The NIMH Research Domain Criteria Project

National Institute of Mental Health, 6001 Executive Boulevard, MSC 9625, Bethesda, MD 20892.
Schizophrenia Bulletin (Impact Factor: 8.45). 10/2010; 36(6):1061-2. DOI: 10.1093/schbul/sbq108
Source: PubMed
Download full-text


Available from: Thomas R Insel, Jun 04, 2015
  • Source
    • "Recent emphasis on connecting neuropsychiatric disorders with brain networks (Research Doman Criteria-RDoCs initiative ) (Cuthbert and Insel, 2010; Singh and Feifel, 2013) has generated interest in studying the MNS in disorders with prominent social cognition and behavioral deficits. Under controlled conditions, the MNS modulates 8–13 Hz oscillations over sensorimotor cortex (Keuken et al., 2011), such that exposing a subject to motion generated by a biological agent desynchronizes these baseline rhythms. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dysregulation of the Mirror Neuron System (MNS) in schizophrenia (SCZ) may underlie the cognitive and behavioral manifestations of social dysfunction associated with that disorder. In healthy subjects intranasal (IN) oxytocin (OT) improves neural processing in the MNS and is associated with improved social cognition. OT׳s brain effects can be measured through its modulation of the MNS by suppressing EEG mu-band electrical activity (8-13Hz) in response to motion perception. Although IN OT׳s effects on social cognition have been tested in SCZ, OT׳s impact on the MNS has not been evaluated to date. Therefore, we designed a study to investigate the effects of two different OT doses on biological motion-induced mu suppression in SCZ and healthy subjects. EEG recordings were taken after each subject received a single IN administration of placebo, OT-24IU and OT-48IU in randomized order in a double-blind crossover design. The results provide support for OT׳s regulation of the MNS in both healthy and SCZ subjects, with the optimal dose dependent on diagnostic group and sex of subject. A statistically significant response was seen in SCZ males only, indicating a heightened sensitivity to those effects, although sex hormone related effects cannot be ruled out. In general, OT appears to have positive effects on neural circuitry that supports social cognition and socially adaptive behaviors.
    Full-text · Article · Jan 2016 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
  • Source
    • "The need for psychiatrists continues to grow. Second, important conceptual changes such as research domain criteria (RDoC) are gaining traction, raising hope for more valid approaches to organizing the translational body of knowledge central to psychiatric disorders (Cuthbert and Insel, 2010). Third, the neural circuits of behavioral domains such as attention, memory executive functions, thought processes, emotion perception and reward seeking have been increasingly well delineated using modern imaging techniques. "

    Full-text · Article · Nov 2015
  • Source
    • "Obsessive-compulsive disorder (OCD) is a chronic mental illness affecting 4–7 million people in the U.S. Patients are impaired in multiple Research Domain constructs (Cuthbert and Insel 2010, 2013) including Habit (perseverative compulsive behaviors), Sustained Threat (anxiety in response to obsessional thoughts that they know are untrue), and Reward Learning (inability to learn to resist obsessions/compulsions despite negative consequences). Medication and behavioral therapies yield inadequate symptom relief in 50–70 % (Greist et al. 1995; Koran et al. 2007; Pallanti et al. 2002; Pittenger and Bloch 2014) of patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.
    Full-text · Article · Oct 2015 · Brain Imaging and Behavior
Show more