Hostname: page-component-7c8c6479df-94d59 Total loading time: 0 Render date: 2024-03-27T12:58:58.827Z Has data issue: false hasContentIssue false

Superior temporal gyrus volume in antipsychotic-naive people at risk of psychosis

Published online by Cambridge University Press:  02 January 2018

Tsutomu Takahashi*
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Australia, Department of Neuropsychiatry, University of Toyama, Japan, and CREST, JST, Japan
Stephen J. Wood
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, Univeristy of Melbourne
Alison R. Yung
Affiliation:
ORYGEN Research Centre, PACE Clinic and Department of Psychiatry, University of Melbourne
Mark Walterfang
Affiliation:
ORYGEN Research Centre, PACE Clinic and Department of Psychiatry, University of Melbourne
Lisa J. Phillips
Affiliation:
Department of Psychology, University of Melbourne
Bridget Soulsby
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne
Yasuhiro Kawasaki
Affiliation:
Department of Neuropsychiatry, University of Toyama and CREST, JST
Patrick D. McGorry
Affiliation:
ORYGEN Research Centre, PACE Clinic and Department of Psychiatry, University of Melbourne
Michio Suzuki
Affiliation:
Department of Neuropsychiatry, University of Toyama and CREST, JST
Dennis Velakoulis
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne
Christos Pantelis
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne
*
Dr Tsutomu Takahashi, Melbourne Neuropsychiatry Centre, c/o National Neuroscience Facility, 161 Barry Street, Carlton South, Victoria 3053, Australia. E-mail: tsutomu@med.u-toyama.ac.jp
Rights & Permissions [Opens in a new window]

Abstract

Background

Morphological abnormalities of the superior temporal gyrus have been consistently reported in schizophrenia, but the timing of their occurrence remains unclear.

Aims

To determine whether individuals exhibit superior temporal gyral changes before the onset of psychosis.

Method

We used magnetic resonance imaging to examine grey matter volumes of the superior temporal gyrus and its subregions (planum polare, Heschl's gyrus, planum temporale, and rostral and caudal regions) in 97 antipsychotic-naive individuals at ultra-high risk of psychosis, of whom 31 subsequently developed psychosis and 66 did not, and 42 controls.

Results

Those at risk of psychosis had significantly smaller superior temporal gyri at baseline compared with controls bilaterally, without any prominent subregional effect; however, there was no difference between those who did and did not subsequently develop psychosis.

Conclusions

Our findings indicate that grey matter reductions of the superior temporal gyrus are present before psychosis onset, and are not due to medication, but these baseline changes are not predictive of transition to psychosis.

Type
Papers
Copyright
Copyright © Royal College of Psychiatrists, 2010 

Morphological abnormalities of the superior temporal gyrus, Reference Hirayasu, Shenton, Salisbury, Dickey, Fischer and Mazzoni1Reference Kim, Crespo-Facorro, Andreasen, O'Leary, Magnotta and Nopoulos3 and its functionally relevant subregions such as Heschl's gyrus and planum temporale, Reference Hirayasu, McCarley, Salisbury, Tanaka, Kwon and Frumin4,Reference Kasai, Shenton, Salisbury, Hirayasu, Onitsuka and Spencer5 in schizophrenia appear to be already present at onset of overt psychosis, but the time course of their occurrence remains unclear. Magnetic resonance imaging (MRI) studies have demonstrated that among participants at ultra-high risk of psychosis, Reference Yung, Phillips, Yuen, Francey, McFarlane and Hallgren6,Reference Yung, Phillips, Yuen and McGorry7 those who subsequently developed psychosis had less grey matter than those who did not in frontotemporolimbic–paralimbic regions, including the right anterior part of the superior temporal gyrus, prior to psychosis onset. Reference Pantelis, Velakoulis, McGorry, Wood, Suckling and Phillips8,Reference Borgwardt, Riecher-Rössler, Dazzan, Chitnis, Aston and Drewe9 However, the conclusions that can be drawn from these analyses are limited by the potential methodological problems of voxel-based morphometry (VBM), Reference Crum, Griffin, Hill and Hawkes10 and the inclusion of people taking medication such as antipsychotics or antidepressants. One MRI study investigating regions of interest in individuals at high genetic risk demonstrated smaller superior temporal gyral volumes bilaterally compared with controls, Reference Rajarethinam, Sahni, Rosenberg and Keshavan11 but this study did not examine diagnostic outcome (i.e. later transition) and subregional specificity of the superior temporal gyrus. Our longitudinal region-of-interest study did not detect baseline superior temporal gyrus changes in the individuals who went on to develop psychosis, Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 but was limited by a small sample size. We sought to address these limitations by conducting a region-of-interest analysis of the superior temporal gyrus subregions in a relatively large sample of antipsychotic-naive individuals at ultra-high risk who did and did not later develop a psychotic disorder, and healthy controls. Based on previous work, Reference Pantelis, Velakoulis, McGorry, Wood, Suckling and Phillips8,Reference Borgwardt, Riecher-Rössler, Dazzan, Chitnis, Aston and Drewe9 we predicted that the high-risk group who developed psychosis would have a smaller superior temporal gyrus at baseline compared with controls.

Method

Participants

Antipsychotic-naive individuals at ultra-high risk of psychosis (n=97) were recruited between 1995 and 2001 from admissions to the Personal Assessment and Crisis Evaluation clinic, Melbourne, Australia, which was established to identify young people at clinical risk of developing a first psychotic episode within a short follow-up period. Reference Yung, Phillips, Yuen and McGorry7 Those recruited were aged 14–30 years, had not experienced a previous psychotic episode, had never received antipsychotic medication (antipsychotics, antidepressants, mood stabilisers or benzodiazepines) and had an IQ score above 70, assessed with the National Adult Reading Test. Reference Nelson and O'Connell13 At intake, the Comprehensive Assessment of At Risk Mental States (CAARMS), Reference Yung, Phillips and McGorry14 a structured clinical interview designed to assess prodromal symptoms and risk of psychosis, was administered. General psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS), Reference Rhoades and Overall15 negative symptoms were rated with the Scale for the Assessment of Negative Symptoms (SANS), Reference Andreasen16 and family history of psychosis in a first- or second-degree relative was assessed using the Family Interview for Genetic Studies, Reference Maxwell17 as well as interviews with a family member. The CAARMS-defined risk identification criteria and their rationale have been fully described elsewhere. Reference Yung, Yuen, McGorry, Phillips, Kelly and Dell'Olio18 Briefly, individuals considered to be at ultra-high risk are characterised by one or more of the following:

  1. (a) attenuated psychotic symptoms, defined by subthreshold intensity or frequency;

  2. (b) brief limited intermittent psychotic symptoms with spontaneous resolution within 1 week;

  3. (c) family history of psychosis (first-degree relative) or a personal history of schizotypal personality disorder, accompanied by a decline in general functioning.

The group at risk were monitored regularly over a minimum 12-month period (mean 1.1 years, maximum 3.7 years) for the onset of full-blown psychosis and were then divided into subgroups based on operationalised criteria for psychosis onset using CAARMS and the Structured Clinical Interview for DSM–IV Axis I disorders. Reference First, Spitzer, Gibbon and Williams19 In total, 31 (32%) of this ultra-high risk group developed a psychotic illness (UHR–P) and 66 (68%) did not (UHR–NP) during follow-up. Of those who developed psychosis, 19 developed schizophrenia-spectrum disorder (17 schizophrenia, 2 schizoaffective disorder), 10 an affective psychosis (5 major depressive disorder with psychotic features, 5 bipolar disorder with psychotic features) and 2 other psychoses (1 psychosis not otherwise specified, 1 brief psychosis). Fifty of the at-risk sample had a positive family history of psychosis.

Healthy volunteers (n = 42) with sociodemographic characteristics similar to the high-risk group were recruited by approaching ancillary hospital staff and through advertisements; those with a personal or family history of psychiatric illness were excluded. All participants were screened for comorbid medical and psychiatric conditions by clinical assessment and by physical and neurological examination. Exclusion criteria were a history of significant head injury, seizures, neurological disease, impaired thyroid function, diabetes, corticosteroid use, or alcohol or substance misuse or dependence meeting DSM–IV criteria. 20 Of the 97 at-risk participants in this study, 64 (22 UHR–P and 42 UHR–NP) had taken part in our earlier VBM study, Reference Pantelis, Velakoulis, McGorry, Wood, Suckling and Phillips8 and 31 (11 UHR–P and 20 UHR–NP) had taken part in our longitudinal superior temporal gyrus study. Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 The study reported here was approved by local research and ethics committees, and written informed consent was obtained from the participants or their parents/guardians where appropriate.

Imaging procedure

Magnetic resonance scans were acquired with a 1.5 T GE Signa scanner (General Electric Medical Systems, Milwaukee, Wisconsin, USA). A three-dimensional volumetric spoiled gradient recalled echo sequence generated 124 contiguous 1.5 mm coronal slices (repetition time (TR) = 14.3 ms, time to echo (TE) = 3.3 ms, flip angle = 30°, field of view = 24 cm × 24 cm, matrix = 256 × 256, voxel dimensions = 0.938 mm × 0.938 mm × 1.5 mm). The scanner was calibrated fortnightly with the same phantom to ensure stability of measurements.

On a Unix workstation the image data were coded randomly and analysed with the software package Dr View version 5 (AJS, Tokyo, Japan). Brain images were realigned in three dimensions and reconstructed into contiguous coronal images, with a 0.938 mm thickness, perpendicular to the anterior–posterior commissural line. The whole cerebrum was manually separated from the brain stem and cerebellum. The signal-intensity histogram distributions from the T 1-weighted images across the whole cerebrum were used to segment the voxels semi-automatically into grey matter, white matter and cerebrospinal fluid. The intracranial volume was measured to correct for differences in head size as previously described. Reference Eritaia, Wood, Stuart, Bridle, Dudgeon and Maruff21

Volumetric analyses of superior temporal subregions

The grey matter of the superior temporal gyrus subregions (planum polare, Heschl's gyrus, planum temporale, rostral and caudal superior temporal gyrus; online Fig. DS1) was manually traced on 0.938 mm consecutive coronal slices as described in detail elsewhere. Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12,Reference Takahashi, Suzuki, Zhou, Tanino, Hagino and Kawasaki22 Briefly, the first coronal plane showing the temporofrontal junction and the coronal plane containing the posterior end of the posterior horizontal limb of the sylvian fissure were chosen as the anterior and posterior boundaries respectively of the whole superior temporal gyrus. On each coronal slice the whole superior temporal gyrus was bounded superiorly by the sylvian fissure and inferiorly by the superior temporal sulcus. The gyrus was then segmented into supratemporal and lateral portions by the lateral limb of the supratemporal plane. Heschl's gyrus was traced from posterior to anterior, beginning with the first slice containing Heschl's sulcus and ending anteriorly with the slice containing the most anterior point of Heschl's sulcus or the sulcus intermedius if it existed. On each coronal slice, Heschl's gyrus was bounded medially by the sylvian fissure, inferior circular insular sulcus or the first transverse sulcus and laterally by Heschl's sulcus. After tracing the Heschl's gyrus that takes a diagonal course on the supratemporal plane, the regions lying anteromedial and posterolateral to the gyrus within the remaining grey matter of the supratemporal plane were regarded as planum polare and planum temporale respectively. The lateral superior temporal gyrus was divided into rostral and caudal portions by the plane including the anterior tip of Heschl's gyrus.

All volumetric data reported here were measured by one rater (T.T.) masked to the participants' identities. Intra-rater (T.T.) and interrater (T.T., Y.K.) intraclass correlation coefficients in eight randomly selected brains exceeded 0.88 for all subregions.

Statistical analysis

Clinical and demographic differences between groups were examined with one-way analysis of variance (ANOVA) or chi-squared tests. The relative volume of the superior temporal gyrus, calculated as (absolute volume/intracranial volume) × 100, was assessed using a repeated-measures analysis of covariance (ANCOVA) with age as a covariate, with group (control, UHR–NP and UHR–P) and gender as between-participant factors, and subregion (planum polare, Heschl's gyrus, planum temporale, rostral superior temporal gyrus, caudal superior temporal gyrus) and side (left, right) as within-participant variables. For the at-risk group, the effects of family history (n = 50 with history v. n = 47 without history) and type of psychosis developed (schizophrenia-spectrum disorder n = 19 v. affective psychosis n = 10) on relative superior temporal gyrus volume were also examined by ANCOVA. The post hoc Tukey's test was employed to follow up the significant main effects or interactions. We performed a Cox regression analysis to examine whether superior temporal gyrus volume would predict later transition, using transition to psychosis as the status variable, time to onset (UHR–P) or follow-up period (UHR–NP) as the time variable, and relative superior temporal gyrus volume and intake BPRS and SANS scores as covariates. The relationships between the relative superior temporal gyrus volumes and demographic or clinical variables were examined with Pearson's r (time between scan and psychosis onset was log-transformed because of skewed distributions). Owing to the lack of prominent subregional effects, we used the whole superior temporal gyrus volume for the regression and correlational analyses. Statistical significance was defined as P<0.05 (two-tailed).

Results

Comparison of the control, UHR–P and UHR–NP groups revealed no significant difference in age, gender, handedness or IQ score (Table 1). Participants in the control group were taller than those in the UHR–NP group, but the groups did not differ significantly in their intracranial volume. Baseline SANS score, but not BPRS score, was higher in the UHR–P group.

Table 1 Demographic characteristics of the participants

Controls (n = 42) UHR—NP (n = 66) UHR—P (n = 31) Group comparisons
Age, years: mean (s.d.) 20.0 (2.8) 20.2 (3.3) 19.1 (3.6) F(2,136) = 1.34, P = 0.265
Male/female, n/n 28/14 39/27 20/11 χ2 = 0.69, P = 0.71
Handedness, n (right/mixed/left)a 38/1/2 54/2/9 28/0/3 P = 0.52, Fisher's exact test
Height, cm: mean (s.d.)a 175.7 (9.7) 171.2 (8.5) 172.3 (8.9) F(2,132) = 3.20, P = 0.044; controls > UHR—NP
Premorbid IQ, mean (s.d.)a 97.9 (8.9) 95.7 (13.5) 93.9 (13.6) F(2,118) = 0.77, P = 0.464
Time between scan and onset, days
    Mean (s.d.) - - 199 (199) -
    Median - - 104 -
BPRS score at intake, mean (s.d.) - 17.9 (7.1) 18.9 (7.2) F(1,95) = 0.36, P = 0.551
SANS score at intake, mean (s.d.) - 19.7 (14.2) 29.0 (15.7) F(1,95) = 8.37, P = 0.005; UHR—P > UHR—NP
Intracranial volume, cm3: mean (s.d.) 1453 (152) 1416 (146) 1470 (129) F(2,144) = 1.86, P = 0.160b

Superior temporal gyrus volumes

Analysis of covariance of the relative superior temporal gyral volumes revealed significant main effects for group (F (2,132) = 3.36, P = 0.038), side (F (1,133) = 99.13, P<0.001) and subregion (F (4,532) = 599.56, P<0.001), and a significant side × subregion interaction (F (4,532) = 14.54, P<0.001). There was no group × subregion (F (8,532) = 1.07, P = 0.384) or group × side × subregion (F (8,532) = 0.54, P = 0.821) interaction, implying that group difference in superior temporal gyrus volume was not highly localised to a particular subregion. These ANCOVA results remained the same when we analysed the absolute superior temporal gyrus volume with intracranial volume and age as covariates.

Post hoc tests showed that the superior temporal gyral volume was significantly smaller in the UHR–P group compared with the control group (P = 0.031), but there was no difference between the UHR–NP and control groups (P = 0.133), or the UHR–NP and UHR–P groups (P = 0.576). Heschl's gyrus (P<0.001) and planum temporale (P<0.001) had a significant asymmetrical pattern (left>right) for all groups. No group difference was found for any superior temporal gyrus subregion (Table 2, Fig. 1). When the UHR–P and UHR–NP groups were categorised together, the group as a whole had a significantly smaller whole superior temporal gyrus compared with controls bilaterally (group effect, F (1,134) = 5.48, P = 0.021; post hoc test, P = 0.014).

Fig. 1 Effect sizes (Cohen's d) based on relative superior temporal gyrus (STG) volumes for ultra-high risk participants who did (UHR–P) and did not (UHR–NP) develop psychosis relative to healthy controls. HG, Heschl's gyrus; PP, planum polare; PT, planum temporale.

Table 2 Absolute grey matter volume of the superior temporal subregions

Analysis of covariancea,b
Grey matter volume, mm3: mean (s.d.) Group Side Group × side
Controls (n=42) UHR—NP (n=66) UHR—P (n=31) F(2, 135) P F(1, 136) P F(2, 136) P
Whole STG 3.87 0.023 118.65 <0.001 3.11 0.048
    Left 15053 (2582) 13903 (2599) 13573c (1875)
    Right 12746 (1959) 12183 (2181) 12417c (1776)
Planum polare 0.63 0.533 18.05 <0.001 0.13 0.883
    Left 1984 (466) 1969 (615) 1912 (428)
    Right 1804 (508) 1754 (573) 1721 (445)
Heschl's gyrus 1.12 0.331 99.86 <0.001 2.82 0.063
    Left 2609 (842) 2282 (624) 2293 (806)
    Right 1846 (474) 1759 (490) 1921 (534)
Planum temporale 2.20 0.115 103.70 <0.001 2.34 0.100
    Left 3772 (837) 3393 (864) 3351 (818)
    Right 2875 (671) 2756 (712) 2851 (667)
Rostral STG 2.13 0.122 7.39 0.007 0.40 0.669
    Left 1598 (636) 1718 (781) 1446 (480)
    Right 1421 (632) 1490 (700) 1349 (591)
Caudal STG 3.34 0.038 1.26 0.264 0.798 0.452
    Left 5054 (1124) 4507 (1061) 4523 (976)
    Right 4760 (1050) 4394 (1001) 4601 (1027)

No difference in superior temporal gyral volume was found between the at-risk participants with and without a family history of psychosis (F (1,94) = 1.00, P = 0.319), or between those in the UHR–P group who later developed schizophrenia-spectrum disorder (n = 19) and those who developed affective psychosis (n = 10; F (1,26) = 0.61, P = 0.443).

Regression and correlational analyses

The SANS ratings predicted time to transition (Wald test = 5.784, β = 1.034, 95% CI 1.01–1.06, P = 0.016), but the superior temporal gyrus volume (left, P = 0.123; right, P = 0.658) and BPRS score (P = 0.819) were not predictive of later transition. The relative whole superior temporal gyrus volumes were not correlated with height and IQ score for all groups. There was a negative correlation between age and right superior temporal gyral volume only for the UHR–P group (r = –0.574, P<0.001); this correlation was significantly different from that in the other groups (v. UHR–NP, P = 0.010; v. controls, P = 0.020) (Fig. 2). Correlational analyses did not reveal any significant correlation between the superior temporal gyral volumes and intake BPRS and SANS scores in either UHR group (r values –0.033 to 0.109, all P>0.388) or time to the psychosis onset (log) in the UHR–P group.

Fig. 2 Correlations between age and relative volumes of the right whole superior temporal gyrus (STG) in a healthy control group (a) and in individuals at ultra-high risk who did not (b) and did (c) later develop psychosis.

Discussion

Compared with healthy controls, the ultra-high risk cohort, especially the UHR–P group, showed diffuse (not highly localised to a particular subregion) grey-matter reductions of bilateral superior temporal gyrus, whereas there was no difference in superior temporal gyral volumes between the UHR–NP and control or UHR–P groups. We also demonstrated that the superior temporal gyral volume did not predict who would develop psychosis.

Changes in superior temporal gyrus as a vulnerability marker

Consistent with previous VBM studies, Reference Pantelis, Velakoulis, McGorry, Wood, Suckling and Phillips8,Reference Borgwardt, Riecher-Rössler, Dazzan, Chitnis, Aston and Drewe9 our results suggest that the superior temporal gyrus changes in individuals at ultra-high risk of psychosis who subsequently develop full-blown psychosis are present before illness onset. Our findings indicate that these changes are not due to the effect of medication. The UHR–NP group also exhibited non-significant but mild grey matter reductions relative to the control group (effect size >0.2), especially in left posterior regions (Heschl's gyrus, planum temporale and caudal superior temporal gyrus). Furthermore, the ultra-high risk group as a whole (regardless of later transition) demonstrated significant grey matter reduction of the bilateral superior temporal gyrus compared with controls, consistent with previous MRI studies in clinically or genetically predisposed high-risk individuals. Reference Borgwardt, Riecher-Rössler, Dazzan, Chitnis, Aston and Drewe9,Reference Rajarethinam, Sahni, Rosenberg and Keshavan11,Reference Meisenzahl, Koutsouleris, Bottlender, Scheuerecker, Jäger and Teipel23 These findings are in line with the fact that those in the at-risk group who did not progress to psychosis were not asymptomatic, as evidenced by the range of non-psychotic diagnoses, Reference Yung, Phillips, Yuen, Francey, McFarlane and Hallgren6,Reference Yung, Phillips, Yuen and McGorry7 and also had experienced subthreshold psychotic symptoms, supporting the hypothesis that such superior temporal gyrus changes represent a vulnerability marker. Reference Borgwardt, Riecher-Rössler, Dazzan, Chitnis, Aston and Drewe9 However, given the issue of region-of-interest definition in this study (e.g. an external landmark for the anterior boundary of the superior temporal gyrus), Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 the possibility also exists that anterior reductions in the superior temporal gyrus are more prominent in the individuals with future transition. Reference Pantelis, Velakoulis, McGorry, Wood, Suckling and Phillips8,Reference Borgwardt, Riecher-Rössler, Dazzan, Chitnis, Aston and Drewe9

Onset-related superior temporal gyrus change

These cross-sectional findings are in line with our recent longitudinal region of interest analysis in a small ultra-high risk sample, Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 which demonstrated progressive grey matter reduction of the superior temporal gyrus in the UHR–P group during the transition phase (left –5.0% per year, right –3.9% per year). The current UHR–P cohort exhibited lesser reductions in superior temporal gyral grey matter (left –9.8%, right –2.6%) relative to controls compared with those in our previous region-of-interest study in first-episode schizophrenia (left –16.4%, right –15.5%). Reference Takahashi, Wood, Soulsby, Kawasaki, McGorry and Suzuki24 The results of a cross-sectional VBM study by Borgwardt et al were similar to ours: the superior temporal gyrus in high-risk participants with later transition was significantly larger than that in first-episode psychosis, but was smaller (at a less stringent statistical threshold) in the right hemisphere than in controls. Reference Borgwardt, McGuire, Aston, Berger, Dazzan and Gschwandtner25 Taken together, these superior temporal gyrus observations support the model of psychosis that morphological abnormalities seen in patients reflect a combination of pre-existing vulnerability and changes associated with the first expression of psychotic symptoms. Reference Pantelis, Yucel, Wood, Velakoulis, Sun and Berger26

We found no effect of family history of psychosis on superior temporal gyrus volume in our at-risk sample, consistent with a previous negative finding for this region in a large genetically high-risk sample (n = 146). Reference Job, Whalley, McConnell, Glabus, Johnstone and Lawrie27 These findings suggest that the superior temporal gyral volume changes related to psychosis are more likely to be acquired, e.g. due to environmental influences later in development, Reference Pantelis, Yucel, Wood, Velakoulis, Sun and Berger26,Reference Pantelis, Velakoulis, Wood, Yücel, Yung and Phillips28 than genetic in origin. A significant effect of age on superior temporal gyrus volume only in the UHR–P group may be consistent with the notion that the transition to psychosis is associated with an acceleration of normal brain maturational processes. Reference Job, Whalley, McConnell, Glabus, Johnstone and Lawrie27,Reference Pantelis, Velakoulis, Wood, Yücel, Yung and Phillips28

Clinical implications

Given the role of the superior temporal gyrus in manifesting psychotic symptoms such as hallucinations or thought disorder, Reference Barta, Pearlson, Powers, Richards and Tune29,Reference Shenton, Kikinis, Jolesz, Pollak, LeMay and Wible30 as well as relevance to social cognitive function, Reference Gallagher and Frith31 pre-onset superior temporal gyral changes might at least partly underpin prodromal symptoms such as subthreshold psychotic symptoms or increasing social withdrawal, Reference Yung, Phillips, Yuen and McGorry7 although we found no correlation between superior temporal gyrus volumes and symptom measures in our ultra-high risk group. However, our own work has demonstrated a significant relationship between ongoing superior temporal gyrus reduction and subsequent positive symptoms in people with first-episode psychosis. Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 These findings suggest that it is the progressive superior temporal gyrus changes during early phases of the illness that are relevant to clinical manifestations of psychosis.

One major aim of high-risk group studies has been to identify neurobiological and clinical predictors of future transition to psychosis, such as high level of depression, poor functioning and negative symptoms, Reference Yung, Phillips, Yuen and McGorry7 which would allow specific and targeted preventive strategies. Reference McGorry, Hickie, Yung, Pantelis and Jackson32 A series of our MRI studies has identified such predictive markers, including pituitary volume, thickness of the anterior cingulate cortex and corpus callosum shape. Reference Garner, Pariante, Wood, Velakoulis, Phillips and Soulsby33Reference Walterfang, Yung, Wood, Reutens, Phillips and Wood35 The study reported here replicated the predictive validity of the SANS score, Reference Yung, Phillips, Yuen and McGorry7 but did not support the role of pre-existing superior temporal gyrus volume reduction as a significant predictor of future transition. However, the onset-related ongoing superior temporal gyral changes, which could affect subsequent course of the illness, Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 and potential ameliorating effects of antipsychotics, Reference Scherk and Falkai36 may implicate the potential role of the superior temporal gyrus changes as a therapeutic target during the early phases or an outcome marker after the onset of psychosis.

Limitations

Some limitations of this study should be taken into account. First, although all participants tested were antipsychotic-naive at the time of scanning, 11 individuals (UHR–P n = 3, UHR–NP n = 6, control n = 2) had records of a significant degree of cannabis use, which could affect brain morphology. Reference Yücel, Solowij, Respondek, Whittle, Fornito and Pantelis37 However, exclusion of these participants did not change the statistical conclusions. Second, the superior temporal gyrus findings in the ultra-high risk group are partly inconsistent with our previous investigations despite considerable sample overlap. Our VBM study found smaller superior temporal gyral volumes in the UHR–P group only for the right hemisphere, Reference Pantelis, Velakoulis, McGorry, Wood, Suckling and Phillips8 but it should be noted that this VBM study used T 2-weighted and proton density images in 3 mm thick slices that might hinder detection of subtle changes, and that the use of VBM has been criticised because of its inadequacy in dealing with problems of brain registration. Reference Crum, Griffin, Hill and Hawkes10 Although our longitudinal region-based analysis failed to detect baseline superior temporal gyrus changes in the at-risk group, Reference Takahashi, Wood, Yung, Soulsby, McGorry and Suzuki12 this could be explained by limited statistical power due to small sample size (UHR–P n = 12, UHR–NP n = 23). The study reported here thus complements and extends our previous findings in suggesting that those at ultra-high risk of psychosis exhibit bilateral superior temporal gyrus reductions. Finally, our cohort included a rather diverse population with psychotic symptoms, and the findings could be relevant to psychoses in general. Neurobiological similarities and differences between schizophrenia and other psychoses such as bipolar disorder remain controversial. Reference Maier, Zobel and Wagner38 Although no difference in superior temporal gyrus volume was found between participants who later developed schizophrenia-spectrum disorders (n = 19) and those who developed affective psychosis (n = 10), further work will be required to clarify the diagnostic specificity of our findings in a larger sample.

Future research

Although we have demonstrated that superior temporal gyral changes are already present in people at ultra-high risk of psychosis, the most active and marked abnormalities of this brain region occur predominantly during the transition phase to active psychosis. This implies that this is a time of dynamic or even accelerated brain changes, which could be a target for intervention and preventive strategies.

Acknowledgements

Neuroimaging analysis was facilitated by the Neuropsychiatry Imaging Laboratory, managed by Ms Bridget Soulsby at the Melbourne Neuropsychiatry Centre, Australia, and supported by Neurosciences Victoria.

Footnotes

The study was supported by project grants from the National Health and Medical Research Council (NHMRC) (grants 145627, 145737, 970598, 981112, 970391), NHMRC programme grant 350241 and the Colonial Foundation. D.V. and S.J.W. were supported as research officers with funding from the NHMRC. M.W. was supported by a Stanley Research Centre grant. P.D.M. was supported by an NARSAD Distinguished Investigator Award. S.J.W. is currently supported by a Clinical Career Development Award from the NHMRC (359223) and an NARSAD Young Investigator Award. T.T. was supported to undertake this work by a grant-in-aid for scientific research (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, Japan.

Declaration of interest

None.

References

1 Hirayasu, Y, Shenton, ME, Salisbury, DF, Dickey, CC, Fischer, IA, Mazzoni, P, et al. 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 1998; 155: 1384–91.Google Scholar
2 Keshavan, MS, Haas, GL, Kahn, CE, Aguilar, E, Dick, EL, Schooler, NR, et al. Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? J Psychiatr Res 1998; 32: 161–7.CrossRefGoogle ScholarPubMed
3 Kim, JJ, Crespo-Facorro, B, Andreasen, NC, O'Leary, DS, Magnotta, V, Nopoulos, P. Morphology of the lateral superior temporal gyrus in neuroleptic naive patients with schizophrenia: relationship to symptoms. Schizophr Res 2003; 60: 173–81.CrossRefGoogle Scholar
4 Hirayasu, Y, McCarley, RW, Salisbury, DF, Tanaka, S, Kwon, JS, Frumin, M, et al. Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients. Arch Gen Psychiatry 2000; 57: 692–9.Google Scholar
5 Kasai, K, Shenton, ME, Salisbury, DF, Hirayasu, Y, Onitsuka, T, Spencer, MH, et al. Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 2003; 60: 766–75.CrossRefGoogle ScholarPubMed
6 Yung, AR, Phillips, LJ, Yuen, HP, Francey, SM, McFarlane, CA, Hallgren, M, et al. Psychosis prediction: 12-month follow up of a high-risk (‘prodromal’) group. Schizophr Res 2003; 60: 2132.Google Scholar
7 Yung, AR, Phillips, LJ, Yuen, HP, McGorry, PD. Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophr Res 2004; 67: 131–42.Google Scholar
8 Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Phillips, LJ, et al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 2003; 361: 281–8.CrossRefGoogle ScholarPubMed
9 Borgwardt, SJ, Riecher-Rössler, A, Dazzan, P, Chitnis, X, Aston, J, Drewe, M, et al. Regional gray matter volume abnormalities in the at risk mental state. Biol Psychiatry 2007; 61: 1148–56.Google Scholar
10 Crum, WR, Griffin, LD, Hill, DL, Hawkes, DJ. Zen and the art of medical image registration: correspondence, homology, and quality. Neuroimage 2003; 20: 1425–37.Google Scholar
11 Rajarethinam, R, Sahni, S, Rosenberg, DR, Keshavan, MS. Reduced superior temporal gyrus volume in young offspring of patients with schizophrenia. Am J Psychiatry 2004; 161: 1121–4.CrossRefGoogle ScholarPubMed
12 Takahashi, T, Wood, SJ, Yung, A, Soulsby, B, McGorry, PD, Suzuki, M, et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry 2009; 66: 366–76.CrossRefGoogle ScholarPubMed
13 Nelson, HE, O'Connell, A. Dementia: the estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex 1978; 14: 234–44.Google Scholar
14 Yung, AR, Phillips, LJ, McGorry, PD. Treating Schizophrenia in the Prodromal Phase. Taylor & Francis, 2004.CrossRefGoogle Scholar
15 Rhoades, HM, Overall, JE. The semistructured BPRS interview and rating guide. Psychopharmacol Bull 1988; 24: 101–4.Google Scholar
16 Andreasen, NC. The Scale for the Assessment of Negative Symptoms (SANS). University of Iowa, 1983.Google Scholar
17 Maxwell, ME. Family Interview for Genetic Studies (FIGS): A Manual for FIGS. Clinical Neurogentics Branch, Intramural Research Program, National Institute of Mental Health, 1992.Google Scholar
18 Yung, AR, Yuen, HP, McGorry, PD, Phillips, LJ, Kelly, D, Dell'Olio, M, et al. Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States. Aust N Z J Psychiatry 2005; 39: 964–71.Google Scholar
19 First, MB, Spitzer, RL, Gibbon, M, Williams, JB. Structured Clinical Interview for DSM–IV Axis I Disorders. American Psychiatric Press, 1997.Google Scholar
20 American Psychiatric Association. Quick Reference to the Diagnostic Criteria From DSM–IV. APA, 1994.Google Scholar
21 Eritaia, J, Wood, SJ, Stuart, GW, Bridle, N, Dudgeon, P, Maruff, P, et al. An optimized method for estimating intracranial volume from magnetic resonance images. Magn Reson Med 2000; 44: 973–7.Google Scholar
22 Takahashi, T, Suzuki, M, Zhou, SY, Tanino, R, Hagino, H, Kawasaki, Y, et al. Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum. Schizophr Res 2006; 83: 131–43.Google Scholar
23 Meisenzahl, EM, Koutsouleris, N, Bottlender, R, Scheuerecker, J, Jäger, M, Teipel, SJ, et al. Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study. Schizophr Res 2008; 102: 150–62.Google Scholar
24 Takahashi, T, Wood, SJ, Soulsby, B, Kawasaki, Y, McGorry, PD, Suzuki, M, et al. An MRI study of the superior temporal subregions in first-episode patients with various psychotic disorders. Schizophr Res 2009; 113: 158–66.CrossRefGoogle ScholarPubMed
25 Borgwardt, SJ, McGuire, PK, Aston, J, Berger, G, Dazzan, P, Gschwandtner, U, et al. Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis. Br J Psychiatry 2007; 191 (suppl 51): s6975.Google Scholar
26 Pantelis, C, Yucel, M, Wood, SJ, Velakoulis, D, Sun, D, Berger, G, et al. Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. Schizophr Bull 2005; 31: 672–96.Google Scholar
27 Job, DE, Whalley, HC, McConnell, S, Glabus, M, Johnstone, EC, Lawrie, SM. Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia. Schizophr Res 2003; 64: 113.Google Scholar
28 Pantelis, C, Velakoulis, D, Wood, SJ, Yücel, M, Yung, AR, Phillips, LJ, et al. Neuroimaging and emerging psychotic disorders: the Melbourne ultra-high risk studies. Int Rev Psychiatry 2007; 19: 371–81.Google Scholar
29 Barta, PE, Pearlson, GD, Powers, RE, Richards, SS, Tune, LE. Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am J Psychiatry 1990; 147: 1457–62.Google Scholar
30 Shenton, ME, Kikinis, R, Jolesz, FA, Pollak, SD, LeMay, M, Wible, CG, et al. Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. N Engl J Med 1992; 327: 604–12.Google Scholar
31 Gallagher, HL, Frith, CD. Functional imaging of ‘theory of mind’. Trends Cogn Sci 2003; 7: 7783.Google Scholar
32 McGorry, PD, Hickie, IB, Yung, AR, Pantelis, C, Jackson, HJ. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry 2006; 40: 616–22.Google Scholar
33 Garner, B, Pariante, CM, Wood, SJ, Velakoulis, D, Phillips, L, Soulsby, B, et al. Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis. Biol Psychiatry 2005; 58: 417–23.Google Scholar
34 Fornito, A, Yung, AR, Wood, SJ, Phillips, LJ, Nelson, B, Cotton, S, et al. Anatomic abnormalities of the anterior cingulate cortex before psychosis onset: an MRI study of ultra-high-risk individuals. Biol Psychiatry 2008; 64: 758–65.Google Scholar
35 Walterfang, M, Yung, A, Wood, AG, Reutens, DC, Phillips, L, Wood, SJ, et al. Corpus callosum shape alterations in individuals prior to the onset of psychosis. Schizophr Res 2008; 103: 110.Google Scholar
36 Scherk, H, Falkai, P. Effects of antipsychotics on brain structure. Curr Opin Psychiatry 2006; 19: 145–50.Google Scholar
37 Yücel, M, Solowij, N, Respondek, C, Whittle, S, Fornito, A, Pantelis, C, et al. Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry 2008; 65: 694701.CrossRefGoogle ScholarPubMed
38 Maier, W, Zobel, A, Wagner, M. Schizophrenia and bipolar disorder: differences and overlaps. Curr Opin Psychiatry 2006; 19: 165–70.Google Scholar
Figure 0

Table 1 Demographic characteristics of the participants

Figure 1

Fig. 1 Effect sizes (Cohen's d) based on relative superior temporal gyrus (STG) volumes for ultra-high risk participants who did (UHR–P) and did not (UHR–NP) develop psychosis relative to healthy controls. HG, Heschl's gyrus; PP, planum polare; PT, planum temporale.

Figure 2

Table 2 Absolute grey matter volume of the superior temporal subregions

Figure 3

Fig. 2 Correlations between age and relative volumes of the right whole superior temporal gyrus (STG) in a healthy control group (a) and in individuals at ultra-high risk who did not (b) and did (c) later develop psychosis.

Supplementary material: PDF

Takahashi et al. supplementary material

Supplementary Figure S1

Download Takahashi et al. supplementary material(PDF)
PDF 94.3 KB
Submit a response

eLetters

No eLetters have been published for this article.