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Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms.

Jalbrzikowski M, Jonas R, Senturk D, Patel A, Chow C, Green MF, Bearden CE - Neuroimage Clin (2013)

Bottom Line: Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices.Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of California, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA ; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, Los Angeles, CA 90095, USA.

ABSTRACT

Introduction: 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins.

Methods: High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10-25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed.

Results: Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.

Conclusion: Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

No MeSH data available.


Related in: MedlinePlus

Relationship between increased cortical thickness in the right medial orbitofrontal cortex and positive symptom severity in 22q11DS. Medial orbitofrontal cortical thickness and positive symptoms are residuals, with effects of age and sex regressed out.
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f0020: Relationship between increased cortical thickness in the right medial orbitofrontal cortex and positive symptom severity in 22q11DS. Medial orbitofrontal cortical thickness and positive symptoms are residuals, with effects of age and sex regressed out.

Mentions: Correlations were conducted for each of the CT and SA MRI indices. After FDR correction was applied, there was a significant positive correlation between right medial orbitofrontal CT and positive symptoms in 22q11DS participants (r = .46, q = .04). Increased CT in the right medial orbitofrontal cortex was associated with increased positive symptoms in 22q11DS (Fig. 4). Additional trend-level associations observed in this analysis are reported in Supplementary Table 4. Of note, trend-level associations were detected between positive symptoms and SA measures in multiple temporal regions: the left (r = − .38, q = .14) and right middle temporal (r = − .34, q = .19), right inferior temporal (r = − .36, q = .15), and temporal pole regions (r = − .34, q = .19). In all four regions, as SA decreased, positive symptoms increased in severity in those with 22q11DS.


Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms.

Jalbrzikowski M, Jonas R, Senturk D, Patel A, Chow C, Green MF, Bearden CE - Neuroimage Clin (2013)

Relationship between increased cortical thickness in the right medial orbitofrontal cortex and positive symptom severity in 22q11DS. Medial orbitofrontal cortical thickness and positive symptoms are residuals, with effects of age and sex regressed out.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814944&req=5

f0020: Relationship between increased cortical thickness in the right medial orbitofrontal cortex and positive symptom severity in 22q11DS. Medial orbitofrontal cortical thickness and positive symptoms are residuals, with effects of age and sex regressed out.
Mentions: Correlations were conducted for each of the CT and SA MRI indices. After FDR correction was applied, there was a significant positive correlation between right medial orbitofrontal CT and positive symptoms in 22q11DS participants (r = .46, q = .04). Increased CT in the right medial orbitofrontal cortex was associated with increased positive symptoms in 22q11DS (Fig. 4). Additional trend-level associations observed in this analysis are reported in Supplementary Table 4. Of note, trend-level associations were detected between positive symptoms and SA measures in multiple temporal regions: the left (r = − .38, q = .14) and right middle temporal (r = − .34, q = .19), right inferior temporal (r = − .36, q = .15), and temporal pole regions (r = − .34, q = .19). In all four regions, as SA decreased, positive symptoms increased in severity in those with 22q11DS.

Bottom Line: Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices.Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of California, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA ; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, Los Angeles, CA 90095, USA.

ABSTRACT

Introduction: 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins.

Methods: High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10-25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed.

Results: Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.

Conclusion: Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

No MeSH data available.


Related in: MedlinePlus