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Letter to the Editor   |    
Is Multiple Cavernoma a Developmental Defect in Schizophrenia?
DAVID ISRAELI, M.D.; JOSEPH ZOHAR, M.D.
Am J Psychiatry 2004;161:924-924. doi:10.1176/appi.ajp.161.5.924

To the Editor: The neurodevelopmental hypothesis of schizophrenia suggests that the interaction between genetic and environmental events during critical periods of neuronal growth in utero may adversely affect neuronal architecture in adulthood (1). Multiple cavernoma (multiple cavernous hemangioma) is a developmental defect of small blood vessels that causes diffuse honeycombing of vascular spaces in the brain (2). This results in sedimentation, thrombosis, and calcification, which can be seen on magnetic resonance imaging (MRI). Here we present a case of schizophrenia with obsessive-compulsive symptoms in a woman with familial bilaterally diffuse cavernoma.

Ms. A, an 18-year-old unmarried woman, was admitted to our ward with psychosis and obsessive-compulsive symptoms. She had ego-dystonic mental obsessions (she reported having "ugly thoughts" about others) and an ego-syntonic delusion that others could read these thoughts. She reported an extensive family history. Her mother had a meningioma, and her brother and uncle suffered from cavernous hemangioma (cavernoma). Her brother also suffered from epilepsy. There was no family history of schizophrenia or obsessive-compulsive disorder. During high school, she was socially withdrawn and preferred to stay at home. One year before her admission, she developed paranoid delusions about her classmates but was not treated.

On admission, results of Ms. A’s neurological and dilated ophthalmoscopic examinations were normal. A computerized tomography scan showed two suspected enhancements. Subsequent MRI demonstrated multiple cerebral cavernomas bilaterally, with typical "rings" visible on T2 imaging. Cavernomas were most abundant in the temporal and frontal regions. Her EEG was normal. An exacerbation of her paranoid thoughts during the first hospital week did not respond to 5 weeks of risperidone treatment (maximum dose=6 mg/day). At that time, she was switched to olanzapine, 20 mg/day, with a remission of her psychosis within 3 weeks. The addition of sertraline, 50 mg/day, relieved her obsessive-compulsive symptoms after an additional 4 weeks.

Familial cavernoma is an autosomal dominant disorder with incomplete penetrance (3). The 7q locus might harbor the causative gene (4). Common clinical signs of multiple cavernoma include neurological deficits, seizures, and hemorrhage (2), although these were not present in this patient. It is possible that this patient’s schizophrenia was causally linked to the developmental effects of her hereditary diffuse brain vessel malformation. Alternatively, this could represent an incidental and extremely rare comorbidity. (We found no such cases in the literature.)

Bloom FE: Advancing a neurodevelopmental origin for schizophrenia. Arch Gen Psychiatry  1993; 50:224–227
[PubMed]
 
Maraire J, Awad I: Intracranial cavernous malformation: lesion behavior and management strategies. Neurosurgery  1995; 37:591–605
[PubMed]
[CrossRef]
 
Labauge P, Laberge S, Brunereau L, Levy C, Tournier-Lasserve E (Societé Française de Neurochirurgie): Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Lancet  1998; 352:1892–1897
[PubMed]
[CrossRef]
 
Sarraf D, Payne AM, Kitchen ND, Sehmi KS, Downes SM, Bird AC: Familial cavernous hemangioma: an expanding ocular spectrum. Arch Ophthalmol  2000; 118:969–973
[PubMed]
 
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References

Bloom FE: Advancing a neurodevelopmental origin for schizophrenia. Arch Gen Psychiatry  1993; 50:224–227
[PubMed]
 
Maraire J, Awad I: Intracranial cavernous malformation: lesion behavior and management strategies. Neurosurgery  1995; 37:591–605
[PubMed]
[CrossRef]
 
Labauge P, Laberge S, Brunereau L, Levy C, Tournier-Lasserve E (Societé Française de Neurochirurgie): Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Lancet  1998; 352:1892–1897
[PubMed]
[CrossRef]
 
Sarraf D, Payne AM, Kitchen ND, Sehmi KS, Downes SM, Bird AC: Familial cavernous hemangioma: an expanding ocular spectrum. Arch Ophthalmol  2000; 118:969–973
[PubMed]
 
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