The utility of non-psychiatric phenotype in diagnosing secondary psychosis, and of psychopathology in diagnosing primary psychosis

Blog post by Rudolf N. Cardinal, clinical research associate, Department of Psychiatry, University of Cambridge, and honorary specialist registrar, Cambridgeshire and Peterborough NHS Foundation Trust, and Edward T. Bullmore, professor of psychiatry, University of Cambridge.

Psychosis originally meant any kind of disordered mental state [1], and subsequently a severe mental disorder involving loss of contact with reality [2, 3]. Nowadays it may be defined (1) narrowly as the presence of delusions and/or hallucinations without insight, or (2) more broadly to include delusions and/or hallucinations with insight into their hallucinatory nature, or (3) more broadly still to include disordered thought or speech, or (4) yet more broadly to include severe behavioural abnormalities including behavioural disorganization, gross excitement and overactivity, or psychomotor retardation and catatonia [4, 5]. Different classificatory systems vary slightly in their definition [4, 5].

Psychosis may result from primary psychiatric diseases, such as schizophrenia and severe affective disorders, or occur secondary to other (e.g. neurological or general medical) conditions. Primary psychiatric diseases have diagnostic criteria based on psychopathology, but are diagnoses of exclusion [4, 5]. Sometimes, secondary psychoses may exhibit striking or characteristic psychopathological features [6, 7]; however, we prefer not to emphasize “typical” psychiatric presentations of secondary psychosis [6], since there is no evidence that most such conditions may be reliably excluded based on mental state, and there is very considerable overlap in phenomenology between primary and secondary psychoses [7-10]. This includes when Schneider’s first-rank symptoms [11, 12] are present [10, 13]. As Asher noted [14], commenting on the variety of mental changes in hypothyroid psychosis, “No physician would attempt to diagnose lobar pneumonia or typhoid by the delirium they may produce, and likewise in myxoedema it is the disease which is the characteristic feature, not its mental manifestations.” A clinician’s mind is most likely to pick a diagnosis that fits a familiar disease pattern [15, 16], and in the situation where two diagnostic schemes compete — the hunt for secondary causes of psychosis and the descriptive classification when none is found — the recognition of “typical” psychiatric patterns of disease may hinder the hunt for features in the history, examination, or initial investigations that give a clue to a secondary cause.

However, in the context of psychosis, recognition of features that are not characteristic of primary psychiatric disease (such as clouding of consciousness, focal neurological abnormality, evidence of an inflammatory response, or systemic disease) is clearly an important clue to the presence of secondary psychosis. Likewise, atypical age of onset (>35 years), lack of prior episodes of psychosis, lack of an expected family history, focal symptoms (e.g. unilateral hallucinations), non-auditory hallucinations, catatonia, coexisting deficit syndromes (delirium, dementia, aphasia, amnesia, etc.), and an atypical clinical course or atypical response to treatment should heighten suspicion [5, 10, 17]. Despite our lack of emphasis on psychopathology for the diagnosis of secondary psychosis, the pattern of psychiatric symptoms in psychosis (such as schizophreniform versus affective psychosis) is clearly salient and clinically relevant for symptomatic management.

Rudolf Cardinal and Ed Bullmore are the authors of The Diagnosis of Psychosis, published by Cambridge University Press.

In this book, the authors review the differential diagnosis of psychosis, seeking to describe all known causes, including primary psychiatric diseases and psychosis secondary to other conditions. Part A of the book is a review of the causes of psychosis, giving disease characteristics, the frequency of psychosis in patients with that disease where this is known, and key investigations or diagnostic criteria. Part B addresses the difficult question of how to approach the diagnosis of a patient with psychosis, covering clues from the history, physical and mental state examination, plus initial investigations (and clues that may result from them), and specialist investigations. It provides decision trees and summaries of diagnostic criteria from the ICD-10 and DSM-IV classificatory systems. 

1.         von Feuchtersleben, E. F. (1845). Lehrbuch der ärztlichen Seelenkunde [Principles of Medical Psychology], C. Gerold (Vienna); Sydenham Society (London, 1847, translated by H.E. Lloyd).

2.         Oxford University Press (1997). New Shorter Oxford English Dictionary, Oxford University Press, Oxford, UK.

3.         Berrios, G. E. (1987). Historical aspects of psychoses: 19th century issues. British Medical Bulletin 43: 484-498. PMID 3322481.

4.         World Health Organization (1992). The ICD-10 Classification of Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines (CDDG). URL: Accessed 7 December 2007.

5.         American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), American Psychiatric Association, Washington DC.

6.         Cardinal, R. N. & Bullmore, E. T. (2011). The Diagnosis of Psychosis, Cambridge University Press, Cambridge, UK.

7.         Sachdev, P. S. & Keshavan, M. S., Eds. (2010). Secondary Schizophrenia. Cambridge: Cambridge University Press.

8.         Johnstone, E. C., Cooling, N. J., Frith, C. D., Crow, T. J. & Owens, D. G. (1988). Phenomenology of organic and functional psychoses and the overlap between them. British Journal of Psychiatry 153: 770-776. PMID 3256376.

9.         Fujii, D. & Ahmed, I., Eds. (2007). The Spectrum of Psychotic Disorders: Neurobiology, Etiology, and Pathogenesis. Cambridge: Cambridge University Press.

10.       Cummings, J. L. (1988). Organic psychosis. Psychosomatics 29: 16-26. PMID 3277215.

11.       Schneider, K. (1957). Primäre und sekundäre Symptome bei der Schizophrenie. Fortschritte der Neurologie, Psychiatrie und Ihrer Grenzgebiete 25: 487-490.

12.       Mellor, C. S. (1970). First rank symptoms of schizophrenia. I. The frequency in schizophrenics on admission to hospital. II. Differences between individual first rank symptoms. British Journal of Psychiatry 117: 15-23. PMID 5479324.

13.       Moore, D. P. (2008). Textbook of Clinical Neuropsychiatry, Hodder Arnold, London.

14.       Asher, R. (1949). Myxoedematous madness. British Medical Journal 2: 555-562. PMID 18148089.

15.       Elstein, A. S. & Schwartz, A. (2002). Clinical problem solving and diagnostic decision making: selective review of the cognitive literature. British Medical Journal 324: 729-732. PMID 11909793.

16.       Bowen, J. L. (2006). Educational strategies to promote clinical diagnostic reasoning. New England Journal of Medicine 355: 2217-2225. PMID 17124019.

17.       Sadock, B. J. & Sadock, V. A., Eds. (2005). Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Eighth edition. Philadelphia, PA: Lippincott Williams & Wilkins.


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