Psychiatric Comorbidities and Schizophrenia

Peter F. Buckley; Brian J. Miller; Douglas S. Lehrer; David J. Castle


Schizophr Bull. 2009;35(2):383-402. 

In This Article

Abstract and Introduction


Psychiatric comorbidities are common among patients with schizophrenia. Substance abuse comorbidity predominates. Anxiety and depressive symptoms are also very common throughout the course of illness, with an estimated prevalence of 15% for panic disorder, 29% for posttraumatic stress disorder, and 23% for obsessive-compulsive disorder. It is estimated that comorbid depression occurs in 50% of patients, and perhaps (conservatively) 47% of patients also have a lifetime diagnosis of comorbid substance abuse. This article chronicles these associations, examining whether these comorbidities are "more than chance" and might represent (distinct) phenotypes of schizophrenia. Among the anxiety disorders, the evidence at present is most abundant for an association with obsessive-compulsive disorder. Additional studies in newly diagnosed antipsychotic-naive patients and their first-degree relatives and searches for genetic and environmental risk factors are needed to replicate preliminary findings and further investigate these associations.


The clinical heterogeneity of schizophrenia is indisputable. Virtually no 2 patients present with the same constellation of symptoms. Moreover, even in the same patient, symptoms can show dramatic change over time, and there is significant interplay between different sets of symptoms: eg, "secondary" negative symptoms might be ameliorated with resolution of positive symptoms, while core "deficit" negative symptoms are more enduring but can worsen over the longitudinal course of illness. Such observations give way to considerations that these may even constitute groups of diseases of generally common phenotypic expression but of different underlying etiopathology.[1]

Further complicating the clinical picture of schizophrenia as well as understanding the boundaries and etiology of this condition is the substantial psychiatric comorbidity.[2] Depression, anxiety, and substance abuse are common accompaniments of the schizophrenia condition, and they in turn perturb the clinical picture.[3] For example, depression can cause secondary negative symptoms, panic attacks can drive paranoia, and cannabis abuse can worsen positive and disorganization symptoms. Conversely, depressive symptoms seen in the context of a florid psychotic relapse often resolve with treatment of the positive symptoms but may remerge in the "postpsychotic" state and in turn worsen the longitudinal course of the illness.[4,5]

Nosologists have great difficulty dealing with complex sets of symptoms.[3,6,7] Generally, an implicit or explicit hierarchy is embraced, such that schizophrenia "trumps," depression, and anxiety. Or, if no primacy can be determined, resort is made to labels such as "schizoaffective disorder" or even "schizoobsessive" subtype of schizophrenia.[3,8] An alternative approach, reified in Diagnostic and Statistical Manual of Mental Disorders, is to consider these symptoms as part of another axis I diagnosis that is occurring alongside schizophrenia.[9] Under this scenario, the patient has 2 major conditions, and these have co-occurred (perhaps for some etiological reason common to both disorders). This is very much the model considered -- and clinically endorsed -- when a patient with schizophrenia also has an alcohol dependence or drug addiction problem.[10] Additionally, recent work on the potential biological vulnerability to cannabis abuse that might explain some variance in the risk of later developing schizophrenia raises again the proposition that the clinical associations that we commonly observe in schizophrenia may also have biological and potentially etiopathological significance.[11]

Bermanzohn et al[12] provocatively proposed that we "stake out the midground"; they suggest that psychiatric comorbidities are so common that they might be integral to schizophrenia. To a large extent, our current research in clinical trials and neurobiological studies is increasingly coming in line with this proposition because now such studies support broad inclusion criteria of "all comers" ... the schizophrenia patients whom we see in everyday clinical practice, who have prominent anxiety symptoms, or may also have depressive symptoms, and also abuse drugs and alcohol.

The purpose of this article is to "take stock" of these (anxiety, depression, and substance abuse) comorbidities and their relationship to schizophrenia. Reviewing the relevant epidemiological, genetic/familial, neurobiological, and therapeutic literature, we ask whether comorbidities should be considered:

  • to have simply, by chance, co-occurred with schizophrenia;


  • to have manifested "secondary" to the core disorder, schizophrenia;


  • to have manifested because schizophrenia is more common in this core disorder; or


  • are a consequence of some underlying shared liability to both sets of disorders.


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