Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia - PubMed (original) (raw)

Comparative Study

Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia

Dean F Salisbury et al. Arch Gen Psychiatry. 2007 May.

Abstract

Context: Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes.

Objective: To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally.

Design: Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up).

Setting: A private psychiatric hospital.

Participants: Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status.

Interventions: Electrophysiologic testing and high-resolution structural magnetic resonance imaging.

Main outcome measures: Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes.

Results: Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=-0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04).

Conclusions: At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention.

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Figures

Figure 1

Figure 1

Venn diagram of the patient sample overlap among the 3 studies. FE indicates first-episode; MMN, mismatch negativity; MRI, magnetic resonance imaging; and T1, time 1.

Figure 2

Figure 2

Magnetic resonance imaging–defined regions of interest and correlations with mismatch negativity (MMN) at first hospitalization. A and B, Three-dimensional magnetic resonance imaging constructions of major subdivisions of the superior temporal plane. Heschl gyri (dark blue and dark green) mainly contain the primary auditory cortex. The planum temporale (light blue and yellow-green) contains secondary and tertiary auditory association cortices. The left side of the figure is the left hemisphere. Note the larger left hemisphere planum temporale. C, At first hospitalization, despite mean MMN amplitudes within the normal range, subjects with schizophrenia showed an abnormal relationship between MMN and underlying left hemisphere primary auditory cortex volumes, consistent with some degree of prehospitalization cortical volume reductions in some subjects with schizophrenia. HG indicates Heschl gyrus; colored lines, regression line.

Figure 3

Figure 3

At longitudinal retesting, subjects with schizophrenia, who showed normal mean mismatch negativity (MMN) initially, now show significant reduction in MMN. Control subjects and subjects with bipolar disorder showed essentially no change in MMN amplitude.

Figure 4

Figure 4

Relationship of mismatch negativity (MMN) amplitude reduction and left hemisphere primary auditory cortex gray matter volume loss. Whereas the subjects with bipolar disorder and control subjects cluster around 0 in both MMN amplitude change and gray matter change, those with schizophrenia are almost exclusively contained in the negative quadrant defined by MMN reduction and gray matter loss. HG indicates Heschl gyrus; colored lines, regression line.

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