Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: Preliminary studies

Keshavan, Matcheri S.; Montrose, Debra M.; Pierri, Joseph N.; Dick, Elizabeth L.; Rosenberg, David; Talagala, Lalith; Sweeney, John A.

doi:10.1016/s0278-5846(97)00164-4

Cited by 135 publications

(69 citation statements)

References 25 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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“…Several studies using proton ( 1 H) MRS have shown reductions in N-acetylaspartate, an in vivo marker of neuronal integrity, in prefrontal and temporal brain regions in schizophrenia (see [45] for a review). Cross-sectional data from the authors' studies in Pittsburgh suggest reductions in the ratio of N-acetyl-aspartate to choline in offspring at risk for schizophrenia [46]. Similar observations have been reported in adult relatives of patients with schizophrenia [47], suggesting that MRS can potentially shed light on neurochemical underpinnings of the heritable diathesis in this illness.…”

Section: Magnetic Resonance Spectroscopy Studiessupporting

confidence: 54%

Approaches for adolescents with an affected family member with schizophrenia

Diwadkar

Prasad²,

Keshavan

2004

Curr Psychiatry Rep

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Prospective studies of adolescents at risk for schizophrenia (high-risk studies) can shed light on the possible premorbid precursors of schizophrenia. Recent studies have provided evidence of neurobehavioral, brain structural, physiologic, and neurochemical deficits in adolescent nonpsychotic high-risk relatives that may date back to childhood or earlier. These results are collectively providing a critical window into the inter-relationships between genetic predisposition, neurodevelopment, and premorbid indicators of risk in schizophrenia. Convergent approaches are inherently powerful in mutually informing each other in enriching the knowledge of the risk factors that predict the eventual onset of schizophrenia. Defining such reliable predictors of the onset of schizophrenia may provide us with the tools to better understand the etiology and pathophysiology of the illness, and may pave the way for innovative methods of treatment and possibly prevention. The authors review the relevant literature in this promising field of inquiry and summarize recent findings from high-risk studies.

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“…People at high risk of psychosis show qualitatively similar volumetric abnormalities to patients with schizophrenia. Cortical brain abnormalities have been found in genetically defined high-risk populations such as first-degree relatives and co-twins of patients with schizophrenia, as well in people with ARMS [13,[68][69][70][71][72][73][74][75][76][77][78][79][80]. Previous longitudinal MRI studies in this group found that the subset of patients who developed psychosis showed a longitudinal reduction in GM in the orbito-frontal, temporal lobe, parietal lobe and cerebellum [79,81,82].…”

Section: Effects Of Antipsychotic Medication On Structural Neuroimagimentioning

confidence: 82%

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

Smieskova

Fusar‐Poli²,

Allen³

et al. 2009

CPD

186

131

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Abstract:Despite a large number of neuroimaging studies in schizophrenia reporting subtle brain abnormalities, we do not know to what extent such abnormalities reflect the effects of antipsychotic treatment on brain structure. We therefore systematically reviewed cross-sectional and follow-up structural brain imaging studies of patients with schizophrenia treated with antipsychotics. 30 magnetic resonance imaging (MRI) studies were identified, 24 of them being longitudinal and six cross-sectional structural imaging studies. In patients with schizophrenia treated with antipsychotics, reduced gray matter volume was described, particularly in the frontal and temporal lobes. Structural neuroimaging studies indicate that treatment with typical as well as atypical antipsychotics may affect regional gray matter (GM) volume. In particular, typical antipsychotics led to increased gray matter volume of the basal ganglia, while atypical antipsychotics reversed this effect after switching. Atypical antipsychotics, however, seem to have no effect on basal ganglia structure.

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Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: Preliminary studies

Cited by 135 publications

References 25 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

Approaches for adolescents with an affected family member with schizophrenia

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

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