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

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Schizophrenia Bulletin (Impact Factor: 8.45). 10/2010; 36(6):1061-2. DOI: 10.1093/schbul/sbq108
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Available from: Thomas R Insel, Jun 04, 2015
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    • "While memory impairments in ADHD are likely more circumscribed (Castel et al., 2011), impairments in bipolar disorder may be closer to those found in schizophrenia, particularly among cases with psychotic symptoms (Glahn et al., 2006; Hill et al., 2013). Thus, it is important to assess the structure of cognitive dysfunction across diagnostic boundaries (Cuthbert and Insel, 2010). This study sought to clarify the distribution and covariation of impairments across domains of memory in patients with schizophrenia and to determine to the extent to which these impairments are shared with bipolar disorder and ADHD. "
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    ABSTRACT: Schizophrenia patients exhibit impaired working and episodic memory, but this may represent generalized impairment across memory modalities or performance deficits restricted to particular memory systems in subgroups of patients. Furthermore, it is unclear whether deficits are unique from those associated with other disorders. Healthy controls (n=1101) and patients with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit-hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and spatial episodic and working memory. Effect sizes for group contrasts were compared across tasks and the consistency of subjects' distributional positions across memory domains was measured. Schizophrenia patients performed poorly relative to the other groups on every test. While low to moderate correlation was found between memory domains (r=.320), supporting modularity of these systems, there was limited agreement between measures regarding each individual's task performance (ICC=.292) and in identifying those individuals falling into the lowest quintile (kappa=0.259). A general ability factor accounted for nearly all of the group differences in performance and agreement across measures in classifying low performers. Pathophysiological processes involved in schizophrenia appear to act primarily on general abilities required in all tasks rather than on specific abilities within different memory domains and modalities. These effects represent a general shift in the overall distribution of general ability (i.e., each case functioning at a lower level than they would have if not for the illness), rather than presence of a generally low-performing subgroup of patients. There is little evidence that memory impairments in schizophrenia are shared with bipolar disorder and ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 08/2015; DOI:10.1016/j.schres.2015.08.014 · 3.92 Impact Factor
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    • "It is increasingly recognized that there is overlap between certain psychiatric syndromes in terms of their genetic, neurobiological , cognitive, behavioral, and phenomenological characteristics (Guilmatre et al., 2009; Bellivier et al., 2013; Doherty and Owen, 2014; Monzani et al., 2014). The mounting evidence for this conclusion has led the National Institute of Mental Health (NIMH) to introduce the Research Domain Criteria (RDoC) initiative (Cuthbert and Insel, 2010; Insel et al., 2010). The rationale behind RDoC is that diagnosis and treatment of mental disorders should not be driven primarily by a focus on signs and symptoms (given their problems with reliability and various forms of validity ), but rather, by a focus on dimensions of functioning with known pathophysiological mechanisms. "
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    ABSTRACT: People with schizophrenia are impaired at organizing potentially ambiguous visual information into well-formed shape and object representations. This perceptual organization (PO) impairment has not been found in other psychiatric disorders. However, recent data on body dysmorphic disorder (BDD), suggest that BDD may also be characterized by reduced PO. Similarities between these groups could have implications for understanding the RDoC dimension of visual perception in psychopathology, and for modeling symptom formation across these two conditions. We compared patients with SCZ (n=24) to those with BDD (n=20), as well as control groups of obsessive-compulsive disorder (OCD) patients (n=20) and healthy controls (n=20), on two measures of PO that have been reliably associated with schizophrenia-related performance impairment. On both the contour integration and Ebbinghaus illusion tests, only the SCZ group demonstrated abnormal performance relative to controls; the BDD group performed similarly to the OCD and CON groups. In addition, on both tasks, the SCZ group performed more abnormally than the BDD group. Overall, these data suggest that PO reductions observed in SCZ are not present in BDD. Visual processing impairments in BDD may arise instead from other perceptual disturbances or attentional biases related to emotional factors. Copyright © 2015 Elsevier Ltd. All rights reserved.
    06/2015; 229(1-2). DOI:10.1016/j.psychres.2015.05.107
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    • "Seventh, future studies on mirror mechanisms should be supplemented with the investigation of the top-down regulatory mechanisms, which modulate mirror responses (Ganos et al., 2012; Hamilton, 2013). Lastly, in keeping with the proposed RDoC framework (Cuthbert and Insel, 2010; Maj, 2014), mirror neuron dysfunction and its potential cognitive parallels should be examined across diverse psychiatric disorders (e.g., autism, psychotic and affective disorders, and personality disorders ) that manifest with stark impairments in social cognition and social functioning. "
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    ABSTRACT: Dysfunctional mirror neuron activity (MNA) has been posited to underlie diverse symptoms of schizophrenia (e.g., ego-boundary disturbances, negative symptoms, social cognition impairments and catatonic symptoms). In this paper, we systematically review studies that have empirically compared putative MNA in schizophrenia patients and healthy subjects using different neurophysiological probes. Majority of the studies (n = 9) reported reduced MNA in patients. Two each reported either increased MNA or mixed (both increased and decreased) results, while only one study reported normal findings. Reduced MNA was associated with greater negative symptoms and theory of mind deficits. The neurophysiological technique, task paradigms used, specific brain regions studied and laterality did not influence these findings. Further, we propose an overarching model to understand the heterogeneous symptom dimensions of schizophrenia, in which an inherent mirror system deficit underlying persistent negative symptoms, social cognition impairments and self-monitoring deficits triggers a pathological metaplastic reorganization of this system resulting in aberrant excessive MNA and the phasic catatonic symptoms, affective instability and hallucinations. Despite being preliminary in nature, evidence of abnormal MNA in schizophrenia reported necessitates more detailed investigation. Future research directions of using this model within the Research Domain Criteria framework of the National Institute of Mental Health are discussed.
    Schizophrenia Research 11/2014; 160(1-3). DOI:10.1016/j.schres.2014.10.040 · 3.92 Impact Factor
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