Showing papers by "Liv S. Clasen published in 2011"

How Does Your Cortex Grow

Abstract: Understanding human cortical maturation is a central goal for developmental neuroscience. Significant advances toward this goal have come from two recent strands of in vivo structural magnetic resonance imaging research: (1) longitudinal study designs have revealed that factors such as sex, cognitive ability, and disease are often better related to variations in the tempo of anatomical change than to variations in anatomy at any one time point; (2) largely cross-sectional applications of new surface-based morphometry (SBM) methods have shown how the traditional focus on cortical volume (CV) can obscure information about the two evolutionarily and genetically distinct determinants of CV: cortical thickness (CT) and surface area (SA). Here, by combining these two strategies for the first time and applying SBM in >1250 longitudinally acquired brain scans from 647 healthy individuals aged 3–30 years, we deconstruct cortical development to reveal that distinct trajectories of anatomical change are hidden within, and give rise to, a curvilinear pattern of CV maturation. Developmental changes in CV emerge through the sexually dimorphic and age-dependent interaction of changes in CT and SA. Moreover, SA change itself actually reflects complex interactions between brain size-related changes in exposed cortical convex hull area, and changes in the degree of cortical gyrification, which again vary by age and sex. Knowing of these developmental dissociations, and further specifying their timing and sex-biases, provides potent new research targets for basic and clinical neuroscience.

Childhood Onset Schizophrenia: High Rate of Visual Hallucinations

Abstract: Objective To document high rates and clinical correlates of nonauditory hallucinations in childhood onset schizophrenia (COS). Method Within a sample of 117 pediatric patients (mean age 13.6 years), diagnosed with COS, the presence of auditory, visual, somatic/tactile, and olfactory hallucinations was examined using the Scale for the Assessment of Positive Symptoms (SAPS). We also compared hallucination modality membership (presence/absence) groups on gender, socioeconomic status, ethnicity, age of onset (of psychosis), Full Scale IQ, Verbal IQ, and clinical severity (Children's Global Assessment Scale [CGAS) and Scale for the Assessment of Negative Symptoms [SANS]). Results A total of 111 COS patients (94.9%) had auditory and 94 patients (80.3%) had visual hallucinations. Somatic/tactile (60.7%) and olfactory (29.9%) hallucinations occurred almost exclusively in patients who also had visual hallucinations. Children who had visual hallucinations had lower IQ, earlier age of onset, and more severe illness relative to children who did not have visual hallucinations. Conclusions In this study, we observed that patients with COS have high rates of hallucinations across all modalities. An increased rate of visual hallucinations is associated with greater clinical impairment and greater compromise in overall brain functioning. Somatic and olfactory hallucinations reflect an additive rather than alternative symptom pattern.

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

Abstract: 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 ( 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

Executive function in young males with Klinefelter (XXY) syndrome with and without comorbid attention-deficit/hyperactivity disorder.

Abstract: Deficits in executive function (EF) are reported to occur in individuals with Klinefelter syndrome (XXY). The degree of impairment, if any, is variable and the nature of these deficits has not been clearly elucidated in young males. In this report, we (a) examine EF skills using multiple tasks in a non-clinic referred group of youth with XXY, (b) describe the extent of EF weaknesses in XXY when this group is compared with typical males of a similar SES or typical males with similar verbal abilities, and (c) evaluate the contribution of comorbid attention-deficit/hyperactivity disorder (ADHD) to EF skills. The sample included 27 males with XXY (ages 9-25), 27 typically developing age- and vocabulary-matched males, and 22 age- and socioeconomic status-matched males. EF tasks included Verbal Fluency, the Trail Making Test, and the CANTAB Spatial Working Memory and Stockings of Cambridge tasks. Mixed model analysis of variance was used to compare the groups on EF tasks and revealed a main effect of group but no group by task interaction. Overall, the XXY group performed less well than both control groups, but performance did not differ significantly as a function of task. ADHD comorbidity in males with XXY was related to poorer EF skills.

Common functional polymorphisms of DISC1 and cortical maturation in typically developing children and adolescents

Abstract: Disrupted-in-schizophrenia-1 (DISC1), contains two common non-synonymous single-nucleotide polymorphisms (SNPs)—Leu607Phe and Ser704Cys—that modulate (i) facets of DISC1 molecular functioning important for cortical development, (ii) fronto-temporal cortical anatomy in adults and (iii) risk for diverse psychiatric phenotypes that often emerge during childhood and adolescence, and are associated with altered fronto-temporal cortical development. It remains unknown, however, if Leu607Phe and Ser704Cys influence cortical maturation before adulthood, and whether each SNP shows unique or overlapping effects. Therefore, we related genotype at Leu607Phe and Ser704Cys to cortical thickness (CT) in 255 typically developing individuals aged 9–22 years on whom 598 magnetic resonance imaging brain scans had been acquired longitudinally. Rate of cortical thinning varied with DISC1 genotype. Specifically, the rate of cortical thinning was attenuated in Phe-carrier compared with Leu-homozygous groups (in bilateral superior frontal and left angular gyri) and accelerated in Ser-homozygous compared with Cys-carrier groups (in left anterior cingulate and temporal cortices). Both SNPs additively predicted fixed differences in right lateral temporal CT, which were maximal between Phe-carrier/Ser-homozygous (thinnest) vs Leu-homozygous/Cys-carrier (thickest) groups. Leu607Phe and Ser704Cys genotype interacted to predict the rate of cortical thinning in right orbitofrontal, middle temporal and superior parietal cortices, wherein a significantly reduced rate of CT loss was observed in Phe-carrier/Cys-carrier participants only. Our findings argue for further examination of Leu607Phe and Ser704Cys interactions at a molecular level, and suggest that these SNPs might operate (in concert with other genetic and environmental factors) to shape risk for diverse phenotypes by impacting on the early maturation of fronto-temporal cortices.