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Comments and Controversies

Schizophrenia is psychotic bipolar disorder? What a polarizing idea!

Vol. 5, No. 3 / March 2006

A hundred years ago, KraepelinDrs. Lake and Hurwitz for highlighting the diagnostic and treatment errors in a bipolar patient with severe psychotic features who was misdiagnosed as having schizophrenia. Errors such as this were common with DSM I and II but declined with the more reliable diagnostic schemas of DSM III and IV. I am puzzled, however, by their leap to the radical conclusion that schizophrenia does not exist and that all patients diagnosed with schizophrenia have psychotic bipolar disorder. This is not as egregious as Szasz’ absurd proclamation 4 decades ago that schizophrenia is a “myth,” but it is a significant scientific “transgression,” given the evidence that distinguishes schizophrenia from bipolar disorder.

Symptoms. Beyond a doubt, these two brain diseases have overlapping clinical features, pharmacotherapies, and even outcomes in a subgroup of patients. However, these diseases have major differences, as outlined in the accompanying table.

Brain anomalies. Neuroimaging studies indicate that schizophrenia is associated with more-severe and pervasive morphologic brain anomalies (dysplasia and hypoplasia) than bipolar disorder, although some bipolar patients have reduced cerebral and frontal volumes and marked cognitive deficits.3 Progressive neuro tissue loss has been observed early in schizophrenia but not in bipolar disorder.

Recent genetic studies indicate that several genes are found exclusively in schizophrenia or in bipolar disorder cohorts,4 but some are shared by both disorders and may be related to delusional symptoms.5 Familial transmission appears to differ: transgenerational studies find an abundance of mood disorders in family members of bipolar probands but relatively sparse occurrence of psychosis in families of probands with schizophrenia.


Symptom differences between schizophrenia and bipolar disorder



Bipolar disorder


Auditory hallucinations and bizarre delusions are more common

Grandiosity is more common


Occurs in both, but more systematic in schizophrenia

Core psychopathology

Far more negative symptoms and cognition dysfunction

Far more mood lability and affective cyclicity

Thought disorder

Far more disorganized and derailed thoughts

More likely to have racing thoughts and flight of ideas

Between-episode interpersonal skills

Withdrawn, alogic, seclusive

Much more interactive and verbal

Treatment. There is no doubt that monotherapy with antipsychotics (old and new) has similar efficacy6 in schizophrenia and bipolar mania (and even in bipolar depression, with some atypicals7). However, there is minimal, if any, evidence that monotherapy mood stabilizers (lithium or anti-convulsants) have any tangible efficacy in schizophrenia. Electroconvulsive therapy is remarkably efficious in all phases of bipolar disorder but of dubious, if any, lasting benefit in schizophrenia.

Course. Both the premorbid history and post-treatment functional outcome tend to be more favorable in patients with bipolar disorder than schizophrenia. Most patients with schizophrenia experience significant clinical, social, and vocational deterioration, compared with a relative minority of bipolar patients.

In summary, schizophrenia and bipolar disorder are clearly distinct in their pure forms, although many patients have varying mixtures of both. Schizoaffective disorder is one of the most extensively investigated. Although many scholars have studied schizoaffective disorder, the evidence defies lumping it with either end of the continuum.

I agree with Drs. Lake and Hurwitz that most cases of schizoaffective disorder, especially the “schizomanic” type, are probably bipolar disorder with severe psychotic features. To assert, however, that schizophrenia does not exist at all and should be reclassified as bipolar disorder with psychotic features would contradict a massive body of clinical and biological evidence. It would cause Kraepelin to squirm in his grave.


1. Kraepelin E, Lange J. Psychiatrie. In: Klinische Psychiatrie, vol 3 (8th ed). Leipzig, Germany: Barth; 1923.

2. Nasrallah HA. The continuum of psychoses between schizophrenia and bipolar disorder. Neurol Psychiatry Brain Res 1994;2:206-9.

3. Coffman JA, Bornstein RA, Olson SC, et al. Cognitive impairment and cerebral structure by MRI in bipolar disorder. Biol Psychiatry 1990;27(11):1188-96.

4. Weinberger DR. Genetic mechanisms of psychosis: in vivo and postmortem genomics. Clin Ther 2005;27(suppl):8-15.

5. Schulze TG, Ohlfaun S, Czerski PM, et al. Genotype-phenotype studies in bipolar disorder showing association between the DAOA/G30 locus and persecutory delusions: a first step toward a molecular genetic classification of psychiatric phenotypes. Arch Gen Psychiatry 2005;162:2101-8.

6. Tandon R, Fleischhacker WW. Comparative efficacy of antipsy chotics in the treatment of schizophrenia: a critical assessment. Schizophr Res 2005;79:145-55.

7. Calabrese JR, Keck P, Jr, McFadden W, et al:. A randomized double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005;162:1351-60.

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