Reduced Superior Temporal Gyrus Volume in Young Offspring of Patients With Schizophrenia

Rajarethinam, Rajaprabhakaran; Sahni, Sarah D.; Rosenberg, David; Keshavan, M.S.

doi:10.1176/appi.ajp.161.6.1121

Cited by 74 publications

(63 citation statements)

References 28 publications

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“…In general, our findings are consistent with previous MRI studies from five independent samples (Pittsburgh, Edinburgh, Ulm, Bethesda and Orangeburg/New York) of genetic highrisk individuals still within the age range for developing schizophrenia (DeLisi et al 2006;Gogtay et al 2003;Job et al 2003;Job et al 2005b;Job et al 2006;Keshavan et al 1997;Keshavan et al 2002b ;Lawrie et al 1999;Lawrie et al 2001;Lawrie et al 2002;Rajarethinam et al 2004;Schreiber et al 1999). Even though these young relatives do not have psychotic disorders, they have volume deficits in similar brain regions as schizophrenia patients -albeit less severe.…”

Section: Discussionsupporting

confidence: 91%

“…The most consistently reported abnormalities in young relatives of schizophrenia probands have been smaller hippocampus, amygdala and parahippocampus gyrus when compared to healthy volunteers with no family history. Additionally, larger third ventricles (Keshavan et al 1997;Lawrie et al 2001), smaller thalamus (Lawrie et al 1999), smaller anterior cingulate (Job et al 2003), smaller superior temporal gyrus (Rajarethinam et al 2004) have also been reported. In this study, relatives subjects did not differ significantly from healthy controls on temporal lobe GM volume even though these were intermediate between the other 2 comparison groups.…”

Section: Discussionmentioning

confidence: 94%

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MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

2007

Schizophrenia Research

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Schizophrenia is characterized by subtle but well-replicated total and regional (frontal and temporal) brain tissue volume deficits. Studies of individuals at-risk for developing schizophrenia suggest that the onset of brain volume decrement may closely pre-date overt manifestations of schizophrenia, making brain volume abnormalities potential predictors for early identification. In an ongoing longitudinal morphometric MRI study of young, nonpsychotic first-or second-degree relatives of schizophrenia probands, we compared brain volumes in 46 relatives who are still within age range for developing schizophrenia against comparison groups of 46 schizophrenia patients and 46 healthy volunteers without family history of schizophrenia. Relatives had similar brain volume abnormalities as schizophrenia patients albeit less severe. Relatives had significantly larger whole brain, frontal, temporal and parietal gray matter (GM) volumes than patients. Relatives also had significantly smaller frontal GM volumes than healthy volunteers. Both relatives and patients had significantly larger whole brain WM (specifically parietal WM) volumes compared to healthy volunteers. Abnormally greater WM volumes in relatives and patients are suggestive of genetically-mediated dysmaturation of the age-expected myelination during adolescence through mid adulthood. On prodromal symptoms assessed in relatives one year after MRI brain scans, initial GM deficits as well as larger WM volumes correlated significantly with greater severity of subsequent prodromal symptoms. Together with previous genetic high-risk studies of adolescent or young adult relatives, these findings indicate that premorbid MRI brain abnormalities may be of predictive value for the early identification of schizophrenia.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 94%

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

2007

Schizophrenia Research

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“…It is possible that a left-sided increase in gray matter loss would begin during this same period in schizophrenia. A recent MRI study in young offspring of patients with schizophrenia (mean age: 14.9 years) did not find a left sided asymmetry in the STG, even if general gray matter decrease was observed in these subjects at risk for schizophrenia compared to normal controls (Rajarethinam et al, 2004). Although gray matter reduction was shown to be progressive in the left STG in FEP patients (Kasai et al, 2003), no study to our knowledge investigated groups of patients with mean ages less than 25 years.…”

Section: Discussionmentioning

confidence: 84%

P300 asymmetry and positive symptom severity: A study in the early stage of a first episode of psychosis

Renoult

Prévost

Brodeur

et al. 2007

Schizophrenia Research

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The amplitude of the P300 event-related potential (ERP) has been reported to be reduced over left compared to right temporal sites in schizophrenia patients. This left temporal P300 reduction has been associated with positive symptom severity and gray matter reduction in the left superior temporal gyrus. We investigated a group of patients with a first episode of schizophrenia spectrum psychosis and a group of normal controls to verify if P300 amplitude asymmetry already exists around the time of presentation for treatment. Relative to normal control subjects, no P300 asymmetry was found in patients. Nevertheless, P300 asymmetry was correlated with the severity of positive symptoms and worse global functioning (GAF), a good predictor of poor outcome.

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“…For example, evaluations of studies using magnetic resonance imaging (MRI) have found that reduced gray matter volume of the STG is the most consistently reported change in cortical gray matter volume in subjects with schizophrenia (Honea et al, 2005;McCarley et al, 1999). STG gray matter volume reductions do not seem to be an artifact of illness duration or neuroleptic treatment because they are already present in subjects with schizophrenia at the time of their first psychotic episode (Hirayasu et al, 1998(Hirayasu et al, , 2000Kasai et al, 2003), and in some subjects at high risk for onset of schizophrenia (Rajarethinam et al, 2004). Furthermore, gray matter volume reductions in STG are not found in psychotic bipolar disorder subjects (Hirayasu et al, 1998(Hirayasu et al, , 2000 and are not prominent in subjects with alcohol dependence (Mathalon et al, 2003;Sullivan et al, 1998), suggesting that these reductions reflect the disease process of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia

Sweet

Henteleff

Zhang

et al. 2008

Neuropsychopharmacol

254

221

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We have previously identified reductions in mean pyramidal cell somal volume in deep layer 3 of BA 41 and 42 and reduced axon terminal density in deep layer 3 of BA 41. In other brain regions demonstrating similar deficits, reduced dendritic spine density has also been identified, leading us to hypothesize that dendritic spine density would also be reduced in BA 41 and 42. Because dendritic spines and their excitatory inputs are regulated in tandem, we further hypothesized that spine density would be correlated with axon terminal density. We used stereologic methods to quantify a marker of dendritic spines, spinophilin-immunoreactive (SP-IR) puncta, in deep layer 3 of BA 41 and 42 of 15 subjects with schizophrenia, each matched to a normal comparison subject. The effect of long-term haloperidol exposure on SP-IR puncta density was evaluated in nonhuman primates. SP-IR puncta density was significantly lower by 27.2% in deep layer 3 of BA 41 in the schizophrenia subjects, and by 22.2% in deep layer 3 of BA 42. In both BA 41 and 42, SP-IR puncta density was correlated with a marker of axon terminal density, but not with pyramidal cell somal volume. SP-IR puncta density did not differ between haloperidol-exposed and control monkeys. Lower SP-IR puncta density in deep layer 3 of BA 41 and 42 of subjects with schizophrenia may reflect concurrent reductions in excitatory afferent input. This may contribute to impairments in auditory sensory processing that are present in subjects with schizophrenia.

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Reduced Superior Temporal Gyrus Volume in Young Offspring of Patients With Schizophrenia

Cited by 74 publications

References 28 publications

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

P300 asymmetry and positive symptom severity: A study in the early stage of a first episode of psychosis

Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia

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