Superior temporal gyrus and the course of early schizophrenia: Progressive, static, or reversible?

https://doi.org/10.1016/S0022-3956(97)00038-1Get rights and content

Abstract

Accumulating evidence suggests alterations in brain structure, especially in the prefrontal and temporal cortex, in schizophrenia. Previous studies examining the progression of brain structural alterations in schizophrenia have led to conflicting results. Morphometric studies of the superior temporal gyrus (STG) volumes were conducted in a series of neuroleptic-naive first-episode schizophrenic patients, non-schizophrenic first-episode psychotic patients, and matched healthy controls. Three-dimensional MRI scans were carried out in these subjects before and after one year of treatment. Volume reductions were seen at baseline in the left superior temporal gyrus (adjusted for intracranial volume) in both of the patient groups. Pretreatment illness duration was inversely related to the volume of the left superior temporal gyrus; this relation was confined to males. One-year follow-up MRI investigations in a smaller subset of patients suggested that the STG volume reductions may be reversible. No significant changes were noted in the STG volumes in matched healthy controls who were also scanned at baseline as well as at one-year follow-up. These findings have implications for understanding the nature of the neuropathological processes in early schizophrenia, as well as the potential impact of early treatment.

Introduction

Compelling evidence for brain structural abnormalities in schizophrenia has accumulated over the last decade. Among the brain structures, the temporal cortex has attracted considerable attention, especially in view of the prominent involvement of the language functions in this disorder. The temporal lobe contains limbic and paralimbic (hippocampus, entorhinal cortex) as well as neocortical (i.e. superior temporal cortex) regions. Schizophrenia has been reported to be associated with volume reductions in the medial temporal lobe in the hippocampus and amygdala (Bogerts et al., 1990; Suddath et al., 1990; Shenton et al., 1992; Bogerts et al., 1993) as well as reductions in the superior temporal gyrus (STG) (Barta et al., 1990; Shenton et al., 1992). STG is a critically Barta, important brain region with important connections to other heteromodal association cortex regions as well as to temporal limbic brain regions; it plays a major role in the production, interpretation and self-monitoring of language (Ross and Pearlson, 1996). It has been hypothesized that pathology of this structure, by disrupting key cortical networks, leads to the cardinal positive symptoms of schizophrenia. Indeed, reductions in STG volume have been observed to correlate with hallucinations (Barta et al., 1990), thought disorder (Shenton et al., 1992), delusions (O'Donnell et al., 1993), and reduction in amplitude of the P300 Evoked Response Potentials (ERP) (McCarley et al., 1993). Impairments in verbal memory, abstraction, and categorization have also been correlated with reduced STG volume (Nestor et al., 1993). The questions of whether STG abnormalities are present at illness onset, and the impact of illness course and\or treatment on these alterations, remain unclear.

Since the evolution of the concept of schizophrenic illness, it has been argued that for at least some patients with this illness, a progressive disease process may underlie the functional decline over the course of illness. This view dates back to Kraepelin who suggested that a full recovery might bring the original diagnosis into question. Bleuler, who acknowledged that some patients recover, noted that the patient may never achieve a full restitutio ad integrum. On the contrary, the current neurodevelopmental model(s) of schizophrenia (reviewed by Weinberger, 1995) predict that cerebral structural alterations may occur at (or before) illness onset, and may not progress over time. Cross-sectional comparison of chronic and first-episode patients reveals more prominent abnormalities in smooth pursuit eye movements and neuropsychological test performance as compared to first-episode patients (Haas et al., 1991; Bilder et al., 1992; Sweeney et al., 1992). Ventricular enlargement and temporal lobe volume reductions have been observed cross-sectionally to be more prominent in chronic schizophrenic patients than in first-episode cases (Bogerts et al., 1990; DeLisi et al., 1991; Lieberman et al., 1992; Bogerts et al., 1993). It is, therefore, possible that temporal lobe structures show progressive abnormalities during the early active phase of the schizophrenic illness. Only a few studies have examined these brain structures in a prospective longitudinal design. Conflicting reports have appeared in the literature pertaining to the course of brain structural alterations in schizophrenia, with reports of both progressive atrophy (DeLisi et al., 1995) and no change (Jaskiw et al., 1994).

This paper presents preliminary data on the following questions from our ongoing investigations of neuroleptic naive psychotic patients. First, are there alterations in the volume of the superior temporal gyrus in previously untreated schizophrenic patients? Second, do these alterations progress during the untreated, early phase of the schizophrenic illness? This question is best addressed by examining the relation between untreated illness duration and the observed structural changes prior to treatment initiation. Finally, do the morphological abnormalities change during the early phase of the illness after treatment is begun? Data from our preliminary prospective follow-up studies of schizophrenic patients from early in treatment are provided to examine questions relating to the impact of illness course and\or treatment on the neurobiological and clinical characteristics of this disorder.

Section snippets

Subjects

A series of seventeen first-episode, treatment-naive patients with schizophrenia and related psychotic disorders [schizophrenia (n=13), schizoaffective (n=2), and schizophreniform (n=2)], eight patients with non-schizophrenic psychotic disorders [bipolar disorder with psychotic features (n=3), major depression with psychotic features (n=2) psychosis, not otherwise specified (n=3)], and seventeen normal controls were studied. All subjects provided informed, written consent after complete

Study 1: relation between pre-treatment illness duration and STG volume in schizophrenia

The clinical and demographic characteristics of our study sample are provided in Table 1. Group comparisons (ANOVA with intracranial volume as a covariate) revealed a significant diagnosis effect, with schizophrenia and other psychotic patients having lower volume of left STG compared to the non-schizophrenia psychotic and healthy control groups (F=5.3; p=0.009). No significant differences were seen in right STG or cerebellar volume not including CSF in the fourth ventricle (Table 2). A

Discussion

Consistent with previous studies (Barta et al., 1990; Shenton et al., 1992), we observed a significant reduction in left STG volume at baseline. An inverse relation was seen between illness duration (as determined from the time of onset of prodromal as well as psychotic symptoms) and the volume of the left STG. These correlations were confined to male schizophrenic patients. Previous studies examining the relation between brain structure and illness duration have led to inconsistent results.

Acknowledgements

This work was supported in part by NIMH grants MH45156-01A1 (JWP), MH01372 (DRR), MH46614-01 (JWP), MH42969 (JAS), MH45156 (NRS), MH48492 (GLH) and a Scottish Rite Schizophrenia Foundation Grant (MSK and the Center for Neurosciences in Mental Disorders). Werner W. Bagwell provided valuable support for the morphometric aspects of the study.

References (50)

  • K.O. Lim et al.

    Gray matter deficits in young onset schizophrenia are independent of age of onset

    Biological Psychiatry

    (1996)
  • L. Marsh et al.

    Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness

    Schizophrenia Research

    (1994)
  • S. Mukherjee et al.

    A new paradigm for schizophrenia? (review)

    Schizophrenia Bulletin

    (1994)
  • P. Nopoulos et al.

    Stability of cognitive functioning early in the course of schizophrenia

    Schizophrenia Research

    (1994)
  • B.F. O'Donnell et al.

    The auditory N2 component in schizophrenia: relationship to MRI temporal lobe gray matter and to other ERP abnormalities

    Biological Psychiatry

    (1993)
  • C.A. Ross et al.

    Schizophrenia, the heteromodal association neocortex and development: potential for a neurogenetic approach

    Trends in Neurosciences

    (1996)
  • L.D. Selemon et al.

    Chronic neuroleptic drug treatment induces mild gliosis in the prefrontal cortex of rhesus monkeys (abstract)

    Schizophrenia Research

    (1997)
  • R. Simantov et al.

    Dopamine-induced apoptosis in human neuronal cells: inhibition by nucleic acides antisense to the dopamine transporter

    Neuroscience

    (1996)
  • D.R. Weinberger

    From enuropathology to neurodevelopment

    Lancet

    (1995)
  • American Psychiatric Association (1987). Diagnostic and statistical manual of mental disorders. Washington, DC:...
  • P.E. Barta et al.

    Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia

    American Journal of Psychiatry

    (1990)
  • M. Beiser et al.

    Establishing the onset of psychotic illness

    American Journal of Psychiatry

    (1993)
  • R.M. Bilder et al.

    Intellectual deficits in first-episode schizophrenia: evidence for progressive deterioration

    Schizophrenia Bulletin

    (1992)
  • M.H. Chakos et al.

    Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs

    American Journal of Psychiatry

    (1994)
  • G.L. Haas et al.

    Delay to first medication in schizophrenia: evidence for a possible negative impact of exposure to psychosis

    American College of Neuropharmacology, Annual Meeting

    (1994)
  • Cited by (0)

    View full text