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Letter to the Editor   |    
Thalamic Alterations in Schizophrenia
JYRKI P. MÄKELÄ, M.D., PH.D.; MERVI KOTILA, M.D., PH.D.; MARKUS HENRIKSSON, M.D., PH.D.
Am J Psychiatry 2001;158:323-a-324. doi:10.1176/appi.ajp.158.2.323-a

To the Editor: Erin A. Hazlett, Ph.D., et al. (1) illustrated anatomic and metabolic alterations in the left anterior and mediodorsal thalamic nuclei in schizophrenic patients. Dorsal thalamic nuclei are smaller and contain fewer neurons in schizophrenic patients than in comparison subjects (2). Andreasen et al. (3) suggested that symptoms and signs of schizophrenia may derive from dysfunction in the thalamus and its circuitry. Infarctions in the anterior tuberothalamic artery region produce clear-cut thalamic lesions and memory impairments (4) resembling those observed in schizophrenic patients (5).

We studied seven patients with strokes in the left anterior thalamus by recording auditory-evoked fields and magnetic spontaneous brain activity (4). Two had delusions at disease onset. Auditory-evoked fields induced by tones delivered at a 2-second interstimulus interval were normal. However, an increase in the length of the interstimulus interval failed to enhance auditory-evoked fields in a fashion observed in comparison subjects. Mismatch fields, elicited by infrequent deviant tones among regular standard tones, were significantly smaller in patients than in comparison subjects. Parieto-occipital spontaneous brain activity was slowed. It is of interest that these electrophysiological alterations resembled those described previously in schizophrenic patients, who have lower mismatch responses (6) and a lower peak frequency of parieto-occipital spontaneous activity (7). A smaller interstimulus interval effect on auditory-evoked responses is implicated by an animal model (8).

Resemblances in findings among patients with thalamic infarctions and patients with schizophrenia support the hypothesis of thalamic alteration in schizophrenia. Further research on correlations of neuropsychological and electrophysiological findings and the severity of alterations in the left anterior thalamus among schizophrenic patients is clearly warranted.

Hazlett E, Buchsbaum MS, Byne W, Wei TC, Spiegel-Cohen J, Geneve G, Kinderlehrer R, Haznedar MM, Shihabuddin L, Siever LJ: Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum. Am J Psychiatry 1999: 156:1190–  1199
 
Harrison P: The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 1999: 122:593–624
 
Andreasen N, Arndt S, Swayze V, Cizadlo T, Flaum M, O’Leary D, Ehrhardt J, Yuh W: Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science 1994: 266:294–298
 
Mäkelä JP, Salmelin R, Kotila M, Salonen O, Laaksonen R, Hokkanen L, Hari R: Left thalamic infarctions modify neuromagnetic cortical signals. Electroencephalogr Clin Neurophysiol 1998: 106:433–443
 
Aleman A, Hijman R, de Haan EH, Kahn RS: Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry 1999: 156:1358–  1366
 
Javitt D, Doneshka P, Grochowski S, Ritter W: Impaired mismatch negativity generation reflects widespread dysfunction of working memory in schizophrenia. Arch Gen Psychiatry 1995: 52:550–558
 
Canive J, Lewine J, Roberts B, Edgar C, Davis J, Orrison WJ: Magnetoencephalographic assessment of spontaneous brain activity in schizophrenia. Psychopharmacol Bull 1996: 32:741–750
 
Jayachandra M, Schroeder C, Lindsley L, Javitt D: Auditory N1 refractoriness in a primate model of schizophrenia. Soc Neurosci Abstracts 1997: 23:557
 
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References

Hazlett E, Buchsbaum MS, Byne W, Wei TC, Spiegel-Cohen J, Geneve G, Kinderlehrer R, Haznedar MM, Shihabuddin L, Siever LJ: Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum. Am J Psychiatry 1999: 156:1190–  1199
 
Harrison P: The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 1999: 122:593–624
 
Andreasen N, Arndt S, Swayze V, Cizadlo T, Flaum M, O’Leary D, Ehrhardt J, Yuh W: Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science 1994: 266:294–298
 
Mäkelä JP, Salmelin R, Kotila M, Salonen O, Laaksonen R, Hokkanen L, Hari R: Left thalamic infarctions modify neuromagnetic cortical signals. Electroencephalogr Clin Neurophysiol 1998: 106:433–443
 
Aleman A, Hijman R, de Haan EH, Kahn RS: Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry 1999: 156:1358–  1366
 
Javitt D, Doneshka P, Grochowski S, Ritter W: Impaired mismatch negativity generation reflects widespread dysfunction of working memory in schizophrenia. Arch Gen Psychiatry 1995: 52:550–558
 
Canive J, Lewine J, Roberts B, Edgar C, Davis J, Orrison WJ: Magnetoencephalographic assessment of spontaneous brain activity in schizophrenia. Psychopharmacol Bull 1996: 32:741–750
 
Jayachandra M, Schroeder C, Lindsley L, Javitt D: Auditory N1 refractoriness in a primate model of schizophrenia. Soc Neurosci Abstracts 1997: 23:557
 
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