Sex differences in the absence of massa intermedia in patients with schizophrenia versus healthy controls

Abstract

Objective. To evaluate sexual dimorphism and incidence of absent massa intermedia (MI), a midline thalamic structure, in patients with schizophrenia and healthy controls.

Methods. Thin slice magnetic resonance images of the brain were obtained. The presence of MI was determined by viewing sagittal, coronal, and axial planes.

Results. In healthy controls, females had a significantly lower incidence of absent MI (13.56%) compared with males (32.08%). In patients with schizophrenia, there was a sex by diagnosis interaction. Female patients had significantly higher incidence of absent MI (32.76%) compared with their healthy controls (13.56%), whereas the male patients showed no difference in incidence of absent MI compared with their controls.

Conclusion. The MI, a sexually dimorphic midline structure, is more commonly absent in female patients with schizophrenia. These results support the growing literature reporting structural aberration of the thalamus, as well as other midline structures in the brains of patients with schizophrenia.

Introduction

Many of the structural brain abnormalities reported in patients with schizophrenia have been located in the midline or medial region of the brain. In particular, midline abnormalities have been consistently identified in the corpus callosum (Tibbo et al., 1998, Woodruff et al., 1995), septum pellucidum (Kwon et al., 1998, Nopoulos et al., 1997a, Nopoulos et al., 1997b), and cerebellar vermis (Lippman et al., 1982, Nopoulos et al., 1999, Rossi et al., 1993, Sandyk et al., 1991, Weinberger et al., 1979). Median structures would include the ventricular system and the thalamus. In particular, the thalamus has become a region that has been identified as having a central role in the pathophysiology of the illness. Neuroimaging (Andreasen et al., 1994, Buchsbaum et al., 1996, Flaum et al., 1995, Gur et al., 1998, Staal et al., 1998) and neuropathologic (Baumer, 1954, Pakkenberg, 1990, Pakkenberg, 1992, Treff and Hempel, 1958) studies have found morphologic abnormalities of the thalamus in patients with schizophrenia.

The massa intermedia (MI) is a midline thalamic structure, connecting the two thalami through somewhat loosely organized axons. In mammals this region is composed of several nuclei; however, in humans it is much smaller and quite variable in its size. In fact, in post-mortem studies, the MI has been documented to be altogether absent in 20–30% of normal human brains (Barr and Kiernan, 1988, Carpenter, 1991). Furthermore, the variability in presence and size of MI is sexually dimorphic, with the MI being present more often in females compared with males (Allen and Gorski, 1991, Davie and Baldwin, 1967, Morel, 1948, Rabl, 1958, Samra and Cooper, 1968). In addition, the study by Allen and Gorski (1991) showed that, of those brains with an MI, the size of the MI was substantially larger in the women compared with men.

Only one other study has evaluated the presence or absence of the MI in patients with schizophrenia. In a magnetic resonance imaging (MRI) and post-mortem study of first-episode patients, Snyder et al. (1998) found that patients with schizophrenia were more likely to have an absent MI compared with healthy controls. However this study did not examine the sexual dimorphism of the MI either in the controls or the patients.

Gender differences in the severity of morphologic brain changes within schizophrenia have been well documented. Although male and female patients tend to have the same pattern of abnormal brain morphology, most of the studies indicate that male patients tend to have more severe brain changes [for review see Nopoulos et al., 1997a, Nopoulos et al., 1997b]. The current study was designed to evaluate the frequency in which the MI appears in a large sample of patients with schizophrenia and a comparison group of healthy controls using state of the art MRI. In addition, the sexual dimorphism of this structure, both among the controls and the patient population, was evaluated.