Reimagining psychoses: An agnostic approach to diagnosis

Beth Israel Deaconess Hospital, Harvard Medical School, Boston MA, United States. Electronic address: .
Schizophrenia Research (Impact Factor: 3.92). 03/2013; 146(1-3). DOI: 10.1016/j.schres.2013.02.022
Source: PubMed


Current approaches to defining and classifying psychotic disorders are compromised by substantive heterogeneity within, blurred boundaries between, as well as overlaps across the various disorders in outcome, treatment response, emerging evidence regarding pathophysiology and presumed etiology.

We herein review the evolution, current status and the constraints posed by classic symptom-based diagnostic approaches. We compare the continuing constructs that underlie the current classification of psychoses, and contrast those to evolving new thinking in other areas of medicine.

An important limitation in current psychiatric nosology may stem from the fact that symptom-based diagnoses do not "carve nature at its joints"; while symptom-based classifications have improved our reliability, they may lack validity. Next steps in developing a more valid scientific nosology for psychoses include a) agnostic deconstruction of disease dimensions, identifying disease markers and endophenotypes; b) mapping such markers across translational domains from behaviors to molecules, c) reclustering cross-cutting bio-behavioral data using modern phenotypic and biometric approaches, and finally d) validating such entities using etio-pathology, outcome and treatment-response measures.

The proposed steps of deconstruction and "bottom-up" disease definition, as elsewhere in medicine, may well provide a better foundation for developing a nosology for psychotic disorders that may have better utility in predicting outcome, treatment response and etiology, and identifying novel treatment approaches.

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Available from: John A Sweeney, Jan 20, 2015
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    • "As conceptual models of schizophrenia have developed during the last several decades, such fundamental alterations in consciousness have been deemphasized as core processes in favor of a focus on more discrete and observable symptoms and related neurocognitive and psychobiological processes (Keshavan et al., 2013; Nemeroff et al., 2013). One potential reason for the loss of interest in Bleuler's central observations is that it is difficult to measure the capacity to integrate and synthesize representations of self and others. "
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    ABSTRACT: Research has suggested that many with schizophrenia experience decrements in synthetic metacognition, or the abilities to form integrated representations of oneself and others and then utilize that knowledge to respond to problems. Although such deficits have been linked with functional impairments even after controlling for symptoms and neurocognition, it is unclear to what extent these deficits can distinguish persons with schizophrenia from others experiencing significant life adversity but without psychosis. To explore this issue we conducted logistic regression analysis to determine whether assessment of metacognition could distinguish between 166 participants with schizophrenia and 51 adults with HIV after controlling for social cognition and education. Metacognition was assessed with the Metacognitive Assessment Scale Abbreviated (MAS-A), and social cognition with the Bell Lysaker Emotion Recognition Test. We observed that the MAS-A total score was able to correctly classify 93.4% of the schizophrenia group, with higher levels of metacognition resulting in increased likelihood of accurate categorization. Additional exploratory analyses showed specific domains of metacognition measured by the MAS-A were equally able to predict membership in the schizophrenia group. Results support the assertion that deficits in the abilities to synthesize thoughts about oneself and others into larger representations are a unique feature of schizophrenia.
    Journal of Psychiatric Research 04/2014; 55(1). DOI:10.1016/j.jpsychires.2014.04.011 · 3.96 Impact Factor
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    • ") by distinguishing bipolar I disorder with psychosis (BDP) and schizophrenia (SZ) as categorical diseases despite substantial BDP-SZ overlap and nontrivial within-group heterogeneity on genetic disease risk (Craddock, O'Donovan, & Owen, 2009; Goes, Sanders, & Potash, 2008; Tamminga et al., 2013), clinical characteristics (Keshavan, Morris, et al., 2011; Tamminga et al., 2013), and biological profiles (Emsell & McDonald, 2009; Henry & Etain, 2010; Keshavan, Nasrallah, & Tandon, 2011; Nenadic, Gaser, & Sauer, 2012; Thaker, 2008). This distinction, therefore, may complicate understanding of etiology and disease processes underlying psychosis. "
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    ABSTRACT: Disrupted sensory processing is a core feature of psychotic disorders. Auditory paired stimuli (PS) evoke a complex neural response, but it is uncertain which aspects reflect shared and/or distinct liability for the most common severe psychoses, schizophrenia (SZ) and psychotic bipolar disorder (BDP). Evoked time-voltage/time-frequency domain responses quantified with EEG during a typical PS paradigm (S1-S2) were compared among proband groups (SZ [n = 232], BDP [181]), their relatives (SZrel [259], BDPrel [220]), and healthy participants (H [228]). Early S1-evoked responses were reduced in SZ and BDP, while later/S2 abnormalities showed SZ/SZrel and BDP/BDPrel specificity. Relatives' effects were absent/small despite significant familiality of the entire auditorineural response. This pattern suggests general and divergent biological pathways associated with psychosis, yet may reflect complications with conditioning solely on clinical phenomenology.
    Psychophysiology 04/2014; 51(4):348-57. DOI:10.1111/psyp.12185 · 3.18 Impact Factor
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    ABSTRACT: Background Psychotic disorders are characterized by aberrant neural connectivity. Alterations in gyrification, the pattern and degree of cortical folding, may be related to the early development of connectivity. Past gyrification studies have relatively small sample sizes, yield mixed results for schizophrenia (SZ), and are scant for psychotic bipolar (BP) and schizoaffective (SZA) disorders and for relatives of these conditions. Here we examine gyrification in psychotic disorder patients and their first-degree relatives as a possible endophenotype. Methods Regional Local Gyrification Index (LGI) values, as measured by FreeSurfer software, were compared between 243 controls, 388 psychotic disorder probands, and 300 of their first-degree relatives. For patients, LGI values were examined grouped across psychotic diagnoses and then separately for SZ, SZA, and BP. Familiality (heritability) values and correlations with clinical measures were also calculated for regional LGI values. Results Probands exhibited significant hypogyria compared to controls in three brain regions and relatives with axis II cluster A disorders showed nearly significant hypogyria in these same regions. LGI values in these locations were significantly heritable and uncorrelated with any clinical measure. Observations of significant hypogyria were most widespread in SZA. Conclusions Psychotic disorders appear to be characterized by significant regionally localized hypogyria, particularly in cingulate cortex. This abnormality may be a structural endophenotype marking risk for psychotic illness and it may help elucidate etiological underpinnings of psychotic disorders.
    Biological psychiatry 01/2013; 76(6). DOI:10.1016/j.biopsych.2013.11.018 · 10.26 Impact Factor
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