Innovations In Clinical Neuroscience

NOV-DEC 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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16 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE November-December 2017 • Volume 14 • Number 11–12 R E V I E W 1980s, Lewis Opler noticed changes in patient symptomatology that did not cohere entirely with the scholarly literature to date. Contrary to findings by Angrist, Rostrosen, and Gershon published in 1980, 27 Opler observed a marked improvement in negative symptoms after administering levodopa (L-DOPA) to counteract the motor side effects induced by neuroleptics in patients diagnosed with schizophrenia. 26 It had been thought that while negative symptoms were indicative of disorders such as schizophrenia, these symptoms were attributed to structural defect and therefore would not be responsive to drug therapy. Unfortunately, the "gold standard" psychometric instrument at the time, the BPRS, did not adequately cover the range of negative symptoms that Opler and his colleagues were observing and wished to measure. Opler was directed to Stanley Kay, who suggested the use of an experimental instrument, the Psychopathology Rating Schedule (PRS), alongside the BPRS. The PRS was the work of Kay, a psychologist, and Manmohan Singh, an Indian-born, British-trained psychiatrist. While working in a psychopharmacology unit at the Bronx State Hospital, Singh was asked to create, in partnership with Kay, a scale to assess typical and atypical schizophrenia and the efficacy of drug treatments. Drawing from his training and work in Britain, Singh approached his research with the goal of gaining insight into the disease process and embracing a wide range of foci including psychopathology, psychomotor skills, psychosocial cognition, and etiology. The widely available BPRS was designed around the occurrence of symptom changes due to treatment with first-generation antipsychotics. As such, Singh found that the BPRS lacked the means to gauge other dimensions that might be present beyond those known to change in response to first-generation neuroleptics but, per phone interview, Singh does not claim to attribute any of the so-called "negative symptoms" that have been added to the PANSS to any single or group of predecessor scales. Singh and Kay worked to modify and then append the instrument to suit their specific needs. Opler and Kay determined that many of the items from the PRS addressed negative symptoms, making it complimentary to the 18- item BPRS. The appeal of the PRS also stemmed from the presence of anchoring points ranging from absent (1) to extreme (9) to account for the severity of the symptoms, which improved reliability by defining criteria for each dimension through careful description. Kay and Opler decided to create a single measure that added 12 items from the PRS to the 18 BPRS items. They asserted a fundamentally different premise in the construction of their measure, in that there should be an equivalent number of positive and negative items. The positive subscale included six BPRS items and one PRS item, the negative subscale contained two BPRS items and five items from the PRS. The additional general pathology subscale contained 10 items from the BPRS and six from the PRS. Later joined by Abraham Fiszbein and others, Opler and Kay conducted preliminary studies to test and validate their instrument. 28 The three conceptually derived subscales—positive, negative, and general psychopathology—were determined to have high alpha coefficients, indicating that a new instrument with three internally consistent subscales had been born. 29 During the era in which the PANSS was developed, the DSM also experienced a transformation. For example, there were debates regarding "mood-congruent" versus "mood-incongruent" delusions and bizarre versus non-bizarre delusions and their relevance for treatment, prognosis, and possible subtyping. As a result, instead of using the "Unusual Thought Content" item from the BPRS for the anchoring point for delusions, Kay and Opler used the "Delusions" item from the PRS so that they could use "Unusual Thought Content" as a separate item to measure bizarreness. These debated subtleties led the way for researchers and clinicians to better interpret and rate psychotic symptoms among inpatient and outpatient populations around the world. To date, the PANSS has become the gold-standard for assessing psychotic symptoms through a semi-structured interview and has been translated into more than 40 different languages. 30 While this is currently a widely used and respected assessment, as previously mentioned, it too is a product of its time and context. Opler's interest in measuring negative symptoms in the 1980s preceded larger efforts in psychiatry to evaluate new treatments for schizophrenia. Clozapine was recognized to be an "atypical" antipsychotic agent not only for its improved motor side-effect profile but also for its increased efficacy in treating negative symptoms. The success of clozapine as an antipsychotic agent for otherwise treatment-refractory patients spurred a race to develop the next atypical agent. This necessitated a metric to monitor such efforts, thereby cementing the role of the PANSS in psychopharmacological and clinical assessment. Aided by the PANSS, the search for treatments that ameliorate negative symptoms, cognition, and functional impairments of schizophrenia continues as the focus of drug development efforts shifts away from the dopaminergic and toward glutamatergic and other neurotransmitter systems. CONCLUSION Since Moore's initial efforts and discovery of five highly correlated syndromes, there have been different assessments created to evaluate symptom profiles, target populations, and drug efficacy. All of the scales discussed here strive to appropriately assess an individual's symptoms and functioning. The advancements in assessments made by the discussed scientists, doctors, clinicians, and researchers discussed above paved the way for the future of understanding symptoms, treatment, and the overall state of knowledge for psychosis. Lorr contributed by stressing the importance of interrater reliability, and acknowledged that the use of scales could both assess the rater's ability to identify symptoms and assess the patient's symptoms themselves. Overall and Gorham developed a new scale to better assess the effects of medications on patients. Moore contributed factor analysis to assessing symptoms. These fathers of modern day measurement in psychiatry, like Kraeplin, contributed to our knowledge of the classification of symptoms. Each one of these individuals helped to establish building blocks to the gold-standard assessments used today, and the next generation of assessments will likely build upon these as well. As in the past, future generations of assessment tools will continue to be affected by the predominating philosophies and controversies of their day. REFERENCES 1. Engel J. American Therapy: The Rise of Psychotherapy in the United States. New York, NY:

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