Brain structure in schizophrenia
It is only relatively recently that we have been able to study the structure of the living brain, using techniques such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Using these methods, we are able to study the shape and volumes of brain structures, and how these structures communicate and connect with others. Prior to the development of these methods, research was limited to post-mortem studies, which obviously limited the range of clinical populations that could be studied, and also precluded any type of longitudinal study of, for example, the effects of long-term antipsychotic medication, or possible degenerative brain changes.
What are the structural brain changes in schizophrenia?
The literature on brain structure in schizophrenia is controversial and contradictory, with many regions reported to be structurally abnormal 1 and too extensive to be covered in detail here. However, there are a few key findings worthy of mention.
The most common finding in structural imaging in schizophrenia is of enlarged lateral ventricles (the fluid-filled spaces in the brain).
There is some evidence that the volume of the brain is reduced in people with schizophrenia, although this is controversial, 2 and of a smaller cerebral cortex (the surface of the brain containing neurons). 3
Frontal lobes
People with schizophrenia often show impaired performance on tests of frontal lobe function. Functional imaging studies have most commonly reported abnormal frontal lobe activity (LINK TO FUNCTIONAL IMAGING SECTION).
The evidence from structural imaging studies, however, is much less conclusive about the frontal lobes. Although there is evidence of reduced volume of some frontal lobe regions, 4, 5, 6 no consistent pattern of pathology has yet emerged.
Temporal Lobes
There is a great deal of evidence of smaller temporal lobe structures in schizophrenia:
- Some studies have found reduced volume of the hippocampus and amygdala, components of the limbic system, a network of structures involved in the control of mood and emotion 6, 8
- Regions of the Superior Temporal Gyrus (STG), which is heavily involved in language function, has been reported to be smaller in people with schizophrenia. For example, there are reports of reduced volume of Heschl's Gyrus (which contains the primary auditory cortex), and the Planum Temporale 9. The severity of positive symptoms such as auditory hallucinations has been found to be associated with the volumes of these language areas. 10
What is the time course of the brain changes - is it a degenerative disorder?
Changes in brain structure are present very early in the course of the disorder. Studies of people within their first psychotic episode have shown that they have enlarged ventricles, 11 reduced cortical volume 12, and smaller hippocampi and superior temporal regions, 9,8. This has implications for the origins of these changes (and hence the disorder), as it suggests that such changes may predate the onset of symptoms. Indeed, it has been proposed that schizophrenia is principally a disorder of abnormal brain development.
While some people believe that brain structure in schizophrenia is a relatively static phenomenon, others have suggested that there may be a progressive deterioration with illness duration. There have been a couple of longitudinal studies of people with schizophrenia from their first presentation, which have reported evidence of a subtle atrophic process. The clinical and cognitive correlates of such changes are as yet unclear, although it has been suggested that progressive brain change may only occur in subset of patients with a poor prognosis. This is not purely an academic question, as if progressive change occurs (even if only in a subset of patients), then it may be possible to prevent it.
Post-mortem studies of schizophrenia
Although post-mortem studies are limited in terms of the range of clinical populations that can be studied, the spatial resolution of post-mortem analysis is much better than for in vivo imaging. It is possible to investigate neuronal number and structure, which is beyond the limits of in vivo imaging techniques.
Post-mortem studies have reported evidence of abnormal numbers of neurons and/or abnormal cell density in various cortical and subcortical brain regions. It has been proposed that increased neuronal density in regions such as the dorsolateral prefrontal cortex, may be due to a loss of dendritic outprocesses, which would result in impaired interneuronal connectivity.
Schizophrenia as a disorder of abnormal cerebral connectivity?
The brain is highly interconnected, with most brain functions requiring the activity of a number of spatially distant structures. Increasingly, people are becoming interested in studying the "wiring" that connects neurons.
Stuctural imaging techniques such as Diffusion Tensor Imaging (DTI) and Magnetization Transfer Imaging (MTI), have recently been developed that allow us to study these connecting fibre bundles.
Already there is evidence of widespread abnormalities in structural connectivity. This is a rapidly expanding area of study that has implications for our understanding of normal as well as well as abnormal brain structure.
Brief Summary
- Brain structure is abnormal in people with schizophrenia
- People with schizophrenia have a smaller cortex, and may have a smaller brain
- Abnormal brain structure may reflect maldevelopment in utero
- There may be progressive brain degeneration in schizophrenia
- Brain wiring is likely to be abnormal in schizophrenia
References
1. Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET. (2000) Meta-analysis of regional brain volumes in schizophrenia Am J Psychiatry 157(1): 16-25.
2. McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, Fischer IA, Shenton ME. (1999) MRI anatomy of schizophrenia Biol Psychiatry 45(9):1099-119
3. Zipursky RB, Lim KO, Sullivan EV, Brown BW, Pfefferbaum A. (1992) Widespread cerebral gray matter volume deficits in schizophrenia. Arch Gen Psychiatry 49(3):195-205
4. Gur RE, Cowell PE, Latshaw A, Turetsky BI, Grossman RI, Arnold SE, Bilker WB, Gur RC. (2000) Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia Arch Gen Psychiatry 57(8):761-8
5. Sigmundsson T, Suckling J, Maier M, Williams SC, Bullmore ET, Greenwood KE, Fukuda R, Ron MA, Toone BK. (2001) Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms Am J Psychiatry 158(2): 234-243
6. Wright IC, Ellison ZR, Sharma T, Friston KJ, Murray RM, McGuire PK. (1999) Mapping of grey matter changes in schizophrenia Schizophr Res. 35(1): 1-14
8. Velakoulis D, Pantelis C, McGorry PD, Dudgeon P, Brewer W, Cook M, Desmond P, Bridle N, Tierney P, Murrie V, Singh B, Copolov D. (1999) Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study Arch Gen Psychiatry 56(2):133-41
9. Hirayasu Y, Shenton ME, Salisbury DF, Dickey CC, Fischer IA, Mazzoni P, Kisler T, Arakaki H, Kwon JS, Anderson JE, Yurgelun-Todd D, Tohen M, McCarley RW. (1998) Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects Am J Psychiatry 155(10): 1384-91
10. Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf D, Coleman M, et al. (1992) Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. N Engl J Med 327(9): 604-12
11. Fannon D, Chitnis X, Doku V, Tennakoon L, O'Ceallaigh S, Soni W, Sumich A, Lowe J, Santamaria M, Sharma T. (2000) Features of structural brain abnormality detected in first-episode psychosis Am J Psychiatry 157(11): 1829-34
12. Lim KO, Tew W, Kushner M, Chow K, Matsumoto B, DeLisi LE. (1996) Cortical gray matter volume deficit in patients with first-episode schizophrenia. Am J Psychiatry 153(12): 1548-53
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