Gray matter deficits in young onset schizophrenia are independent of age of onset
This study examined whether the degree of brain dysmorphology observable in adulthood was related to onset age of schizophrenic symptoms. Brain magnetic resonance imaging (MRI) scans were acquired in 57 men with schizophrenia, whose age at MRI was 19-53 years, and whose symptom onset ranged from age 7 to 29 years; all were inpatients in a state hospital. Volumes of intracranial space, cortical gray matter (GM) and white matter (WM), and cerebrospinal fluid (CSF) in lateral and third ventricles and cortical sulci were derived from MRI scans and corrected by regression analysis for variations attributable to age and head size, quantified in a control sample of healthy community volunteers. The schizophrenic patients had larger volumes of cortical and ventricular CSF and smaller volumes of cortical GM but not WM than age-matched controls, whether or not volumes were adjusted for head size and age norms. Age of onset did not correlate with any of the five age-adjusted brain measures. Neither current age, length of illness, nor symptom severity correlated with age-normalized volumes of cortical GM, sulcal CSF, or ventricular CSF. These observations are consistent with the theory that brain structure deficits 1) first develop prior to symptom onset (perhaps during the prenatal and/or early childhood process of GM development); 2) probably establish a vulnerability to subsequent dysfunctionality; but 3) are nonprogressive.
[Show abstract] [Hide abstract] ABSTRACT: Schizophrenia is a severe mental disorder affecting about 1% of the population worldwide. Although the dopamine (DA) hypothesis is still keeping a dominant position in schizophrenia research, new advances have been emerging in recent years, which suggest the implication of white matter abnormalities in schizophrenia. In this paper, we will briefly review some of recent human studies showing white matter abnormalities in schizophrenic brains and altered oligodendrocyte-(OL-) and myelin-related genes in patients with schizophrenia and will consider abnormal behaviors reported in patients with white matter diseases. Following these, we will selectively introduce some animal models examining a putative role of white matter abnormalities in schizophrenia. The emphasis will be put on the cuprizone (CPZ) model. CPZ-fed mice show demyelination and OLs loss, display schizophrenia-related behaviors, and have higher DA levels in the prefrontal cortex. These features suggest that the CPZ model is a novel animal model of schizophrenia.0Comments 7Citations
- "However, conventional MRI findings in earlier studies for cerebral white matter volume in schizophrenia have been mixed. Some of them found no differences in white matter volume between schizophrenic patients and normal subjects     , while some reported white matter reductions in schizophrenia   . "
[Show abstract] [Hide abstract] ABSTRACT: The present study examined, by means of Magnetic Resonance Imaging (MRI), the qualitative brain abnormalities in a group of 58 schizophrenic patients compared to a group of 58 matched control individuals. The possible relationships between these abnormalities and the demographic and clinical features of the participants in the study were also investigated. Schizophrenic patients presented a higher percentage of bland-moderate enlargement of the periencephalic-subarachnoid spaces (p=0.01) and a widespread cerebral atrophy, the latter below the threshold of significance (p=0.06). In the subset of patients with ventricular asymmetry (right larger than left) the age was significantly lower compared to the age of patients without this abnormality (p=0.04). In the subset of patients with cerebellar cisterns enlargement the age as well as the age of onset was higher in comparison to the one of patients without this abnormality (p=0.02; p=0.006). Taking together with previous studies, these findings underline the importance of qualitative assessment of brain morphology in research and clinical evaluation of patients with schizophrenia.0Comments 9Citations
- "These results seem to confirm those of previous MRI studies   , and they may be compatible with the hypothesis of a malformative origin of these alterations, connected to a developmental disorder of the cerebral structures. "
[Show abstract] [Hide abstract] ABSTRACT: A number of meta-analytic reviews of structural brain imaging studies have shown that multiple subtle brain abnormalities are consistently found in schizophrenia. However, quantitative reviews till now published have included mainly studies performed on chronic schizophrenic patients but have failed to provide clear information on specific, possibly different, findings in first-episode schizophrenia. We performed a systematic search for MRI studies that reported quantitative measurements of volumes of brain regions in first-episode schizophrenic patients and in healthy controls. Twelve meta-analyses were performed for 6 cerebral regions. Twenty-one studies were identified as suitable for analysis. Significant overall effect sizes were demonstrated for lateral and third ventricular volume increase, and for volume reduction of whole brain and hippocampus, but not for temporal lobe, amygdala and total intracranial volumes. The available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenic patients. However, unlike the results of published meta-analyses conducted primarily on samples of chronic schizophrenic patients, the present study did not confirm a significant reduction of temporal lobe or amygdala volumes in first-episode schizophrenia. These findings support the hypothesis of different patterns of involvement of various cerebral areas over the time course of schizophrenia.0Comments 266Citations
- "In the last years, a large number of MRI studies have examined different cortical and subcortical regions in first-episode schizophrenic patients. Some have demonstrated a similar pattern of brain abnormalities to that reported in samples of chronic patients, with reduction of gray matter volume (Lim et al., 1996; Zipursky et al., 1998; Fannon et al., 2000; Cahn et al., 2002a; Kasai et al., 2003), lateral and third ventricular enlargement (Degreef et al., 1992; Lieberman et al., 2001; Lawrie et al., 2001; Chua et al., 2003), frontal lobe volume reduction (Nopoulos et al., 1995; Ohnuma et al., 1997; Gur et al., 1998, Hirayasu et al., 2001; Hietala et al., 2003; Bachmann et al., 2004) and temporo-limbic abnormalities (Gur et al., 1998; Hirayasu et al., 1998, 2000; McCarley et al., 2002; Sumich et al., 2002; Joyal et al., 2003; Kasai et al., 2003; Hietala et al., 2003). The results of these studies, however, have been somehow contrasted by others, that reported nonsignificant changes of different brain structures such as cerebral ventricles (DeLisi et al., 1992; Puri et al., 2001; Salokangas et al., 2002), frontal lobe (DeLisi et al., 1991; Bilder et al., 1994; Lawrie et al., 2001; Cahn et al., 2002a; Molina et al., 2004), temporal lobe (DeLisi et al., 1991; Bilder et al., 1994; Nopoulos et al., 1995; Ohnuma et al., 1997; Niemann et al., 2000; Salokangas et al., 2002) and temporo-limbic structures (Razi et al., 1999; Matsumoto et al., 2001; Cahn et al., 2002a,b; Smith et al., 2003) in similar samples of first-episode patients. "