A follow-up MRI study of the superior temporal subregions in schizotypal disorder and first-episode schizophrenia

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Abstract

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains unknown whether patients with schizotypal features exhibit similar STG changes. In this study, longitudinal MRI data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7 years) scans and were compared across groups. At the baseline, both the schizophrenia and schizotypal patients had smaller left PT and left caudal STG than the controls. In a longitudinal comparison, the schizophrenia patients showed significant gray matter reduction of the STG over time (left: − 2.8%/year; right: − 1.5%/year) compared with the schizotypal patients (left: − 0.6%/year; right: − 0.3%/year) and controls (left: 0.0%/year; right: − 0.1%/year) without a prominent effect of subregion or type of antipsychotic (typical/atypical). In the schizophrenia patients, greater annual volume reductions of the left PP and right PT were correlated with less improvement of positive psychotic symptoms. A higher cumulative dose of antipsychotics during follow-up in schizophrenia was significantly correlated with less severe gray matter reductions in the left PT and bilateral caudal STG. Our findings suggest that the left posterior STG subregions are commonly reduced in diseases of the schizophrenia spectrum; whereas, schizophrenia patients exhibit further progressive STG changes associated with overt psychosis in the early years of the illness.

Introduction

Gray matter reductions of the superior temporal gyrus (STG) and its functionally relevant subregions [e.g., the primary auditory cortex (Heschl gyrus, HG), a neocortical language region (planum temporale, PT), and the lateral portion related to social cognition (Gallagher and Frith, 2003)] have been repeatedly described in previous magnetic resonance imaging (MRI) studies of schizophrenia (reviewed by Shenton et al., 2001, Sun et al., 2009). These morphologic changes, which have been implicated in various psychotic symptoms such as auditory hallucinations and thought disorders (Barta et al., 1997, Rajarethinam et al., 2000, Shenton et al., 1992, Sumich et al., 2005, Takahashi et al., 2006) appear to already be present at the onset of the first episode of schizophrenia (Hirayasu et al., 1998, Hirayasu et al., 2000, Kasai et al., 2003a, Kasai et al., 2003b, Keshavan et al., 1998, Kim et al., 2003, Takahashi et al., 2009b). These observations support a neurodevelopmental pathology (Weinberger, 1987); whereas, recent longitudinal MRI studies have demonstrated marked progressive gray matter reduction of the STG during the early phases of schizophrenia (Kasai et al., 2003a, Kasai et al., 2003b, Mané et al., 2009, Takahashi et al., 2009a, Whitford et al., 2006), suggesting a further ongoing pathological process associated with psychosis in this region.

Schizotypal (personality) disorder is a prototypic disorder within the schizophrenia spectrum, which is characterized by odd behavior and attenuated forms of schizophrenic features without manifestation of overt and sustained psychosis (World Health Organization, 1992, American Psychiatric Association, 1994). Such subjects with schizotypal features share genetic, biological, and psychological commonalities with schizophrenia patients and are thought to include individuals with the prodromal phase of schizophrenia (Siever and Davis, 2004). Based on previous studies concerning brain morphologic changes and cognitive characteristics in schizotypal and schizophrenia patients, it is hypothesized that abnormalities in the temporal regions are common to both groups as a neurobiological basis of schizophrenia susceptibility (Dickey et al., 2002a, Kurachi, 2003a, Kurachi, 2003b, Siever & Davis, 2004). In particular, although it has not been consistently replicated (e.g., Dickey et al., 2003), previous cross-sectional MRI studies from our (Kawasaki et al., 2004, Takahashi et al., 2006) and other (Dickey et al., 1999, Dickey et al., 2002b, Koo et al., 2006, Goldstein et al., 2009) groups have demonstrated gray matter reduction of the STG in schizotypal subjects to the same degree as that seen in schizophrenia patients. On the other hand, given the evidence of progressive STG changes associated with overt psychosis during the early phases of schizophrenia (Kasai et al., 2003a, Kasai et al., 2003b, Takahashi et al., 2009a), it is possible that the absence of such active pathological processes in this region underlies the sparing of schizotypal patients from the development of schizophrenic psychosis. To our knowledge, however, no volumetric MRI studies have examined longitudinal morphologic changes of the STG in subjects with schizotypal features.

This longitudinal MRI study aimed to examine the progressive gray matter changes of the STG and its subregions in schizotypal disorder and first-episode schizophrenia patients compared with healthy controls. On the basis of the differing phenomenology between schizophrenia and schizotypal disorder (World Health Organization, 1992) as well as the potential role of active STG pathological processes in the development of overt psychosis (Kasai et al., 2003b, Takahashi et al., 2009b), we predicted that only the schizophrenia patients would show progressive gray matter loss of this region and that its degree would be related to the severity of positive psychotic symptoms. We also explored the potential ameliorating effect of antipsychotic medication (Scherk and Falkai, 2006) on longitudinal STG changes.

Section snippets

Subjects

Schizotypal disorder patients (n = 13) who met the ICD-10 research criteria (World Health Organization, 1993) were recruited from among patients who visited the clinics of the Department of Neuropsychiatry of Toyama University Hospital. This patient group exhibited at least four of the schizotypal features (inappropriate affect, odd behavior, social withdrawal, magical thinking, suspiciousness, ruminations without inner resistance, unusual perceptual experiences, stereotyped thinking, and

Sample characteristics

The three groups were matched for age, gender, height, parental education, and inter-scan interval, but the control subjects had attained a higher mean level of education than the patients with either disorder (Table 1). While the baseline SAPS score for the schizophrenia patients was significantly higher than that for the schizotypal patients, no significant group difference was found at follow-up potentially due to relatively good response of positive symptoms to medication in our

Discussion

To the best of our knowledge, this is the first volumetric MRI study to examine progressive gray matter changes of the STG subregions in schizotypal disorder patients compared with first-episode schizophrenia patients and healthy controls. In a baseline comparison, both patient groups had smaller left PT and left caudal STG volumes than the controls, indicating that the left posterior STG subregions are commonly reduced in the schizophrenia spectrum as a neurobiological basis of schizophrenia

Role of funding source

This study was supported, in part, by a Grant-in-Aid for Scientific Research (No. 19591346) from the Japanese Society for the Promotion of Science and a Research Grant (17-2, 18-6) for Nervous and Mental Disorders from the Ministry of Health and Welfare of Japan.

Contibutors

MS and MK conceived the idea and methodology of the study. TT conducted the statistical analyses and wrote the manuscript. TT, MS, RT, KN, YK, and MK recruited the subjects, were involved in clinical and diagnostic assessments and for MRI scanning. TT, SYZ, and RT analyzed the MRI data. HS provided technical support for the MRI scanning and data processing. All authors contributed to the writing of the manuscript and have approved the final draft.

Conflict of interest

There are no conflicts of interest for any of the authors.

Acknowledgement

The authors are grateful to Drs. Mikio Kido and Tomohiro Miyanishi for their assistance in collecting the clinical data of the study participants.

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