0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Brief Report   |    
Magnetic Resonance Imaging of the Thalamus in First-Episode Psychosis
Ulrich Ettinger, M.Sc.; Xavier A. Chitnis, M.Sc.; Veena Kumari, Ph.D.; Dominic G. Fannon, M.R.C.Psych.; Alex L. Sumich, M.A.; Séamus O’Ceallaigh, M.R.C.Psych.; Victor C. Doku, M.R.C.Psych.; Tonmoy Sharma, M.R.C.Psych.
Am J Psychiatry 2001;158:116-118. doi:10.1176/appi.ajp.158.1.116

Abstract

OBJECTIVE: There is some evidence of thalamic abnormalities in schizophrenia. This study investigated thalamic volumes in patients experiencing their first episode of psychosis and nonpsychotic comparison subjects. METHOD: Magnetic resonance imaging scans were obtained for 38 patients and 29 comparison subjects. Patients’ symptoms were rated by research psychiatrists using the Positive and Negative Syndrome Scale. RESULTS: Thalamic volumes were smaller in patients than in comparison subjects. There were no significant correlations between thalamic volumes and symptom scores. CONCLUSIONS: Thalamic abnormalities are present close to the onset of psychosis.

Abstract Teaser
Figures in this Article

Magnetic resonance imaging (MRI) studies have identified many brain regions affected in schizophrenia (1). The thalamus has been a focus of interest (2) because of its role as a sensory filter and reports of schizophrenia as a disorder of deficient information filtering (3). Andreasen (2) proposed a model of schizophrenia placing the thalamus in the center of dysfunctional cortical-subcortical-cerebellar circuitry.

MRI studies of the thalamus in schizophrenia have not conclusively demonstrated abnormalities. Although some (48) have reported reduced volumes, others (911) have found no significant reductions. Postmortem studies (12, 13) have reported reductions in the volume and number of neurons in the mediodorsal thalamus.

Most MRI studies of the thalamus have studied chronically ill patients, and one study found an association between antipsychotic medication dose and thalamic volumes (7). Thus, little is known about thalamic abnormalities in the early stages of psychosis, when the possible confounding effects of disease chronicity and long-term medication exposure do not apply.

In this study we investigated thalamic volumes in a group of patients who were experiencing their first psychotic episode and who had no or minimal exposure to antipsychotic medication. Our hypothesis was that patients would have smaller thalamic volumes than nonpsychotic comparison subjects.

Cerebral scans of 29 healthy volunteers (mean age=25.4 years, SD=5.8) and 38 patients (mean age=24.2 years, SD=5.4) with a DSM-IV diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder (according to the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition [14]) were obtained with MRI. Twenty-eight of the patients were men, and 20 of the comparison subjects were men. The groups were matched in age (t=–0.87, df=65, p=0.39) and height (t=–0.49, df=65, p=0.63).

The mean duration of the patients’ illness was 30.8 weeks (SD=24.9). Thirteen patients had never taken an antipsychotic, 18 were treated with typical antipsychotics, and seven were treated with atypical antipsychotics. The mean duration of treatment for medicated patients was 4.6 weeks (SD=3.0). Research psychiatrists (D.G.F., S.O’C., V.C.D.) rated symptoms using the Positive and Negative Syndrome Scale (15) within 5 days of MRI scanning. Inter- and intrarater reliability (over a period of 1 year), obtained from videotaped patient interviews, was above r=0.90.

Patients were recruited as inpatients or outpatients from a catchment area including inner and outer London. Comparison subjects were recruited from the same area; these volunteers had no history of mental disorder themselves or of psychosis among first-degree relatives. Scanning of patients and comparison subjects was interleaved.

All participants provided written informed consent. The study was approved by the Ethics Committee of the Bethlem and Maudsley National Health Service Trust.

Brains were scanned with a 1.5-tesla GE Signa Advantage MRI scanner (Milwaukee). Three-dimensional T1-weighted spoiled gradient recalled scans were acquired in the axial plane with the following sequence: TE=2.2 msec, TI=300 msec, TR=11.3 msec, field of view=22 cm, flip angle=20°>, number of excitations=1, producing 124 1.5-mm slices. A phantom was scanned biweekly for quality control.

Thalamic boundaries were based on detailed guidelines described elsewhere (11). Volumetric measurements were obtained by using stereological assessment software (MEASURE [16]). Thalamic ratings were performed by one researcher (U.E.) who was blind to diagnostic status. Inter- and intrarater reliabilities (over a period of 1 month), computed in a random sample of 10 brains, were r=0.82 (p<0.001) and r=0.99 (p<0.001), respectively.

Total thalamic volume was analyzed by one-way analysis of covariance (ANCOVA) with height as the covariate. Repeated measures ANCOVAs were performed, with side (left or right) as within-subject factors and group (patients or comparison subjects) as between-subject factors covarying for height. Further ANCOVAs covarying for height were performed to investigate sex differences and to examine medication status, comparing patients receiving atypical antipsychotics, those receiving typical antipsychotics, and untreated patients. Height was used as a covariate because it has been shown to predict brain size and has been used in previous MRI studies of schizophrenia (17). Pearson correlations explored associations between thalamic volumes and Positive and Negative Syndrome Scale subscores, duration of treatment (in weeks), and duration of illness (in weeks).

Patients had smaller total thalamic volumes than comparison subjects (F=3.87, df=1, 64, p=0.05). There was no effect of side (F=1.09, df=1, 64, p=0.30) and no side-by-group interaction (F=0.47, df=1, 64, p=0.50). A significant effect of group, however, was found (F=4.34, df=1, 64, p=0.04), confirming the effect for total thalamus. Thalamic volumes (t1) were similar to values reported previously for patients with schizophrenia (11).

There was no effect of sex (F=1.59, df=1, 62, p=0.21) and no sex-by-group interaction (F=0.00, df=1, 62, p=0.98). In the comparison of patients receiving atypical antipsychotics, those receiving typical antipsychotics, and medication-naïve patients, no differences in thalamic volume were found (F=0.01, df=2, 34, p=0.99).

Thalamic volumes did not correlate significantly with the positive, negative, or global psychopathology scales or any of the subscales of the Positive and Negative Syndrome Scale (all p>0.11), duration of treatment (r=0.11, p=0.50), or duration of illness (r=0.01, p=0.96).

The main finding of this study is that patients experiencing their first episode of psychosis had smaller thalamic volumes than nonpsychotic comparison subjects. This finding is consistent with structural (2) and functional (18) imaging evidence of thalamic abnormalities in schizophrenia.

No association between thalamic volumes and symptom scores was found, unlike previous reports of chronic schizophrenia (6, 11), possibly reflecting the fluctuating nature of symptoms early in psychotic illness.

Because medication status and treatment duration did not affect thalamic volumes, the observed differences may represent early manifestations of the psychotic disease process, possibly reflecting a neurodevelopmental insult. The functional importance of thalamic volume reductions may lie in aberrant gating of information through cortical-subcortical circuits (2, 3).

Given the structural and functional heterogeneity of the thalamus, abnormalities may be localized to specific nuclei. Future studies should investigate thalamic subregions such as the anterior or mediodorsal nuclei (19), which have been found to be abnormal in schizophrenia (10, 13).

 

Received Dec. 27, 1999; revisions received May 24 and June 16, 2000; accepted June 30, 2000. From the Section of Cognitive Psychopharmacology, Division of Psychological Medicine, Institute of Psychiatry, University of London. Address reprint requests to Dr. Sharma, Section of Cognitive Psychopharmacology, Department of Psychiatry, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK; t.sharma@iop.kcl.ac.uk (e-mail). Supported in part by Eastwood Care Homes plc and Psychmed Ltd. The authors thank Jessica Sheringham, Katy Piper, Steven Williams, Andrew Simmons, and the staff of the Institute of Psychiatry and Maudsley Hospital Neuroimaging Research Group for their contributions.

McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, Fischer IA, Shenton ME: MRI anatomy of schizophrenia. Biol Psychiatry 1999; 45:1099–  1119
 
Andreasen NC: The role of the thalamus in schizophrenia. Can J Psychiatry  1997; 42:27–33
[PubMed]
 
Braff D: Information processing and attention dysfunctions in schizophrenia. Schizophr Bull  1993; 19:233–259
[PubMed]
 
Andreasen NC, Arndt S, Swayze V II, Cizadlo T, Flaum M, O’Leary D, Ehrhardt JC, Yuh WTC: Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science  1994; 266:294–298
[PubMed]
[CrossRef]
 
Andreasen NC, Ehrhardt JC, Swayze VW II, Alliger RJ, Yuh WT, Cohen G, Ziebell S: Magnetic resonance imaging of the brain in schizophrenia: the pathophysiologic significance of structural abnormalities. Arch Gen Psychiatry  1990; 47:35–44
[PubMed]
 
Flaum M, Swayze VW II, O’Leary DS, Yuh WTC, Ehrhardt JC, Arndt SV, Andreasen NC: Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia. Am J Psychiatry  1995; 152:704–714
[PubMed]
 
Gur RE, Maany V, Mozley PD, Swanson C, Bilker W, Gur RC: Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. Am J Psychiatry 1998; 155:1711–  1717
 
Staal WG, Hulshoff Pol HE, Schnack H, van der Schot AC, Kahn RS: Partial volume decrease of the thalamus in relatives of patients with schizophrenia. Am J Psychiatry 1998; 155:1784–  1786
 
Buchsbaum MS, Someya T, Teng CY, Abel L, Chin S, Najafi A, Haier RJ, Wu J, Bunney WE Jr: PET and MRI of the thalamus in never-medicated patients with schizophrenia. Am J Psychiatry  1996; 153:191–199
[PubMed]
 
Hazlett EA, Buchsbaum MS, Byne W, Wei T-C, Spiegel-Cohen J, Geneve C, 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
 
Portas CM, Goldstein JM, Shenton ME, Hokama HH, Wible CG, Fischer I, Kikinis R, Donnino R, Jolesz FAA, McCarley RW: Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging. Biol Psychiatry  1998; 43:649–659
[PubMed]
[CrossRef]
 
Pakkenberg B: Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 1990; 47:1023–  1028
 
Pakkenberg B: The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics. Schizophr Res  1992; 7:95–100
[PubMed]
[CrossRef]
 
First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-P), version 2. New York, New York State Psychiatric Institute, Biometrics Research, 1995
 
Kay SR, Fiszbein A, Opler LA: The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull  1987; 13:261–276
[PubMed]
 
Sharma T, Lancaster E, Sigmundsson T, Lewis S, Takei N, Gurling H, Barta P, Pearlson G, Murray R: Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives—the Maudsley Family Study. Schizophr Res  1999; 40:111–120
[PubMed]
[CrossRef]
 
Andreasen NC, Flashman L, Flaum M, Arndt S, Swayze V II, O’Leary DS, Ehrhardt JC, Yuh WTC: Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. JAMA 1994; 272:1763–  1769
 
Crespo-Facorro B, Paradiso S, Andreasen NC, O’Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD: Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron emission tomography study. Am J Psychiatry  1999; 156:386–392
[PubMed]
 
Magnotta VA, Gold S, Andreasen NC, Ehrhardt JC, Yuh WT: Visualization of subthalamic nuclei with cortex attenuated inversion recovery MR imaging. Neuroimage  2000; 11:341–346
[PubMed]
[CrossRef]
 
+

References

McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, Fischer IA, Shenton ME: MRI anatomy of schizophrenia. Biol Psychiatry 1999; 45:1099–  1119
 
Andreasen NC: The role of the thalamus in schizophrenia. Can J Psychiatry  1997; 42:27–33
[PubMed]
 
Braff D: Information processing and attention dysfunctions in schizophrenia. Schizophr Bull  1993; 19:233–259
[PubMed]
 
Andreasen NC, Arndt S, Swayze V II, Cizadlo T, Flaum M, O’Leary D, Ehrhardt JC, Yuh WTC: Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science  1994; 266:294–298
[PubMed]
[CrossRef]
 
Andreasen NC, Ehrhardt JC, Swayze VW II, Alliger RJ, Yuh WT, Cohen G, Ziebell S: Magnetic resonance imaging of the brain in schizophrenia: the pathophysiologic significance of structural abnormalities. Arch Gen Psychiatry  1990; 47:35–44
[PubMed]
 
Flaum M, Swayze VW II, O’Leary DS, Yuh WTC, Ehrhardt JC, Arndt SV, Andreasen NC: Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia. Am J Psychiatry  1995; 152:704–714
[PubMed]
 
Gur RE, Maany V, Mozley PD, Swanson C, Bilker W, Gur RC: Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. Am J Psychiatry 1998; 155:1711–  1717
 
Staal WG, Hulshoff Pol HE, Schnack H, van der Schot AC, Kahn RS: Partial volume decrease of the thalamus in relatives of patients with schizophrenia. Am J Psychiatry 1998; 155:1784–  1786
 
Buchsbaum MS, Someya T, Teng CY, Abel L, Chin S, Najafi A, Haier RJ, Wu J, Bunney WE Jr: PET and MRI of the thalamus in never-medicated patients with schizophrenia. Am J Psychiatry  1996; 153:191–199
[PubMed]
 
Hazlett EA, Buchsbaum MS, Byne W, Wei T-C, Spiegel-Cohen J, Geneve C, 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
 
Portas CM, Goldstein JM, Shenton ME, Hokama HH, Wible CG, Fischer I, Kikinis R, Donnino R, Jolesz FAA, McCarley RW: Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging. Biol Psychiatry  1998; 43:649–659
[PubMed]
[CrossRef]
 
Pakkenberg B: Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 1990; 47:1023–  1028
 
Pakkenberg B: The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics. Schizophr Res  1992; 7:95–100
[PubMed]
[CrossRef]
 
First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-P), version 2. New York, New York State Psychiatric Institute, Biometrics Research, 1995
 
Kay SR, Fiszbein A, Opler LA: The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull  1987; 13:261–276
[PubMed]
 
Sharma T, Lancaster E, Sigmundsson T, Lewis S, Takei N, Gurling H, Barta P, Pearlson G, Murray R: Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives—the Maudsley Family Study. Schizophr Res  1999; 40:111–120
[PubMed]
[CrossRef]
 
Andreasen NC, Flashman L, Flaum M, Arndt S, Swayze V II, O’Leary DS, Ehrhardt JC, Yuh WTC: Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. JAMA 1994; 272:1763–  1769
 
Crespo-Facorro B, Paradiso S, Andreasen NC, O’Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD: Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron emission tomography study. Am J Psychiatry  1999; 156:386–392
[PubMed]
 
Magnotta VA, Gold S, Andreasen NC, Ehrhardt JC, Yuh WT: Visualization of subthalamic nuclei with cortex attenuated inversion recovery MR imaging. Neuroimage  2000; 11:341–346
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 59

Related Content
Articles
Books
Textbook of Psychotherapeutic Treatments > Chapter 6.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 17.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 24.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 20.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 46.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles