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Asami T, Whitford TJ, Bouix S, Dickey CC, Niznikiewicz M, Shenton ME, Voglmaier MM, McCarley RW. Globally and locally reduced MRI gray matter volumes in neuroleptic-naive men with schizotypal personality disorder: association with negative symptoms. JAMA Psychiatry. 2013 Apr 1 ; 70(4):361-72. Pubmed Abstract

Comments on News and Primary Papers

Primary Papers: Globally and locally reduced MRI gray matter volumes in neuroleptic-naive men with schizotypal personality disorder: association with negative symptoms.

Comment by:  Mark Lenzenweger
Submitted 22 February 2013
Posted 22 February 2013

This is a very good and important new study. As someone who has studied schizotypic psychopathology for nearly three decades, and long argued that schizotypic pathology (including SPD) is a cleaner window on schizophrenia liability, I think this is a very exciting study. It highlights the incredible utility of studying schizotypic pathology as a window on causal mechanisms in schizophrenia. Unclouded by medication, institutionalization, and deterioration effects, these findings in schizotypal personality disorder shed important new light on schizophrenia (see Lenzenweger, 2010, for extended discussion of these ideas).


Lenzenweger, MF. (2010). Schizotypy and schizophrenia: The view from experimental psychopathology. New York: Guilford.

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Primary Papers: Globally and locally reduced MRI gray matter volumes in neuroleptic-naive men with schizotypal personality disorder: association with negative symptoms.

Comment by:  Erin A. HazlettLarry Siever
Submitted 26 February 2013
Posted 26 February 2013

Frontal-Temporal Gray Matter Volume and Negative Symptoms in Schizophrenia-Spectrum Disorders
The paper by Asami et al. (2013) in the latest issue of JAMA Psychiatry highlights the strengths of studying schizotypal personality disorder (SPD), which is genetically related to and shares common phenomenological, biological, and neurocognitive abnormalities with schizophrenia, but without the overt psychosis. This MRI study has several noteworthy strengths, including a large, never-medicated sample which alleviates medication as a confound. The voxel-based morphometry (VBM) MRI findings indicate reduced gray matter volume in the left superior temporal gyrus and widespread frontal, frontolimbic, and parietal regions in a sample of men with SPD compared with healthy control participants (54 in each group). Consistent with the concept that SPD probably represents a milder form of disease along the schizophrenia continuum, reduced superior temporal gyrus volume has consistently been reported in SPD and schizophrenia (Dickey et al., 2002; Hazlett et al., 2012; McCloskey et al., 2005). Additionally, Asami et al. report that smaller gray matter volume in several frontal and temporal regions was associated with greater negative symptoms (summed across social isolation, introversion, restricted emotion, and sensitivity) in the subgroup of 21 individuals with SPD examined.

These findings are of clear interest; however, some cautionary comments are warranted. First, a large number of correlations between gray matter volume and negative symptoms were conducted in a relatively small sample without correction for multiple tests. Nevertheless, the pattern of correlational findings replicates and extends prior SPD work showing an association between superior temporal gyrus volume and clinical symptom severity (Hazlett et al., 2008). Second, while the sample is large and neuroleptic naive, no females were included, making it unclear how well the results generalize to the population as a whole. Lastly, the frontal lobe volume reductions reported in this paper are in contrast with some prior MRI work providing evidence of preserved volume of the prefrontal cortex in individuals with SPD compared with healthy controls and schizophrenia patients, (e.g., Hazlett et al., 2008; Siever and Davis, 2004; Suzuki et al., 2005). It is unclear whether the source of between-study differences is due to sample characteristics (e.g., prior work included females while Asami et al. excluded them, characteristics of the healthy control comparison groups), methodological approaches to the MRI analysis (VBM vs. region-of-interest), and/or other factors. In conclusion, this paper underscores the need for further examination of the relevance of prefrontal and temporal lobe pathology, negative symptoms, and psychosis in schizophrenia-spectrum disorders.


Dickey CC, McCarley RW, Shenton ME. The brain in schizotypal personality disorder: a review of structural MRI and CT findings. Harv Rev Psychiatry . 2002 Jan-Feb ; 10(1):1-15. Abstract

Hazlett EA, Buchsbaum MS, Haznedar MM, Newmark R, Goldstein KE, Zelmanova Y, Glanton CF, Torosjan Y, New AS, Lo JN, Mitropoulou V, Siever LJ. Cortical gray and white matter volume in unmedicated schizotypal and schizophrenia patients. Schizophr Res . 2008 Apr ; 101(1-3):111-23. Abstract

Hazlett EA, Goldstein KE, Kolaitis JC. A review of structural MRI and diffusion tensor imaging in schizotypal personality disorder. Curr Psychiatry Rep . 2012 Feb ; 14(1):70-8. Abstract

McCloskey MS, Phan KL, Coccaro EF. Neuroimaging and personality disorders. Curr Psychiatry Rep . 2005 Mar ; 7(1):65-72. Abstract

Siever LJ, Davis KL. The pathophysiology of schizophrenia disorders: perspectives from the spectrum. Am J Psychiatry . 2004 Mar ; 161(3):398-413. Abstract

Suzuki M, Zhou SY, Takahashi T, Hagino H, Kawasaki Y, Niu L, Matsui M, Seto H, Kurachi M. Differential contributions of prefrontal and temporolimbic pathology to mechanisms of psychosis. Brain . 2005 Sep ; 128(Pt 9):2109-22. Abstract

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