Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms

Lawrie, Stephen M.; Whalley, Heather; Abukmeil, Suheib S.; Kestelman, Julia N; Miller, Patrick; Best, J. J. K.; Owens, David C.; Johnstone, Eve C.

doi:10.1017/s0007125000161860

Cited by 88 publications

(37 citation statements)

References 24 publications

(1 reference statement)

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“…Contrary to results obtained from highrisk or prodromal non-22q11.2DS subjects (Keshavan et al, 2005;Lawrie et al, 2002;Pantelis et al, 2003), we did not find accelerated decrease in cortical GM in adolescents with 22q11.2DS. The only cortical GM ROI that showed a longitudinal change significantly different from controls was STG GM, which in 22q11.2DS, in contrast to controls, did not show the normal significant decrease in volume.…”

Section: Discussioncontrasting

confidence: 99%

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: A longitudinal study

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Penniman

et al. 2007

Schizophrenia Research

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The 22q11.2 deletion syndrome (22q11.2DS) is associated with very high rates of schizophrenialike psychosis and cognitive deficits. Here we report the results of the first longitudinal study assessing brain development in individuals with 22q11.2DS. Twenty-nine children with 22q11.2DS and 29 age and gender matched controls were first assessed during childhood or early adolescence; Nineteen subjects with 22q11.2DS and 18 controls underwent follow-up during late adolescenceearly adulthood. The 22q11.2DS subjects showed greater longitudinal increase in cranial and cerebellar white matter, superior temporal gyrus, and caudate nucleus volumes. They also had a more robust decrease in amygdala volume. Verbal IQ (VIQ) scores of the 22q11.2DS group that developed psychotic disorders declined significantly between assessments. Decline in VIQ in 22q11.2DS was associated with more robust reduction of left cortical grey matter volume. No volumetric differences were detected between psychotic and nonpsychotic subjects with 22q11.2DS. Brain maturation associated with verbal cognitive development in 22q11.2DS varies from that observed in healthy controls. Further longitudinal studies are likely to elucidate brain developmental trajectories in 22q11.2DS and their association to psychotic disorders and cognitive deficits in this population.

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Section: Discussioncontrasting

confidence: 99%

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: A longitudinal study

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Penniman

et al. 2007

Schizophrenia Research

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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%

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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“…Recent studies of the first-degree relative studies appear to point against such evidence and fail to show any focal cortical GM deficits in siblings/relatives/cotwins, thus arguing against the trait status of the deficits. 14,33,34 In addition, studies of ultra-high risk subjects support the idea that cortical volume loss in schizophrenia is illness related, 35,36 as brain deficits were not found in subjects who did not convert to psychosis. Furthermore, reductions in GM volume have been related to duration of untreated psychosis 37 and duration of psychotic illness, 38 bolstering support for GM loss being reflective of disease state.…”

Section: Discussionmentioning

confidence: 75%

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

Mattai

Weisinger

Greenstein

et al. 2011

Journal of the American Academy of Child & Adolescent Psych

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Objective Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to “normalize” by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. Method Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval–matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. Results As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. Conclusions Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings.

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Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms

Abstract: BackgroundMagnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. These are thought to be neurodevelopmental in origin, but when they become evident is unknown.

Cited by 88 publications

References 24 publications

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: A longitudinal study

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: A longitudinal study

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

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

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