Biomedical subjects

Philip Szeszko

Publications and source records attributed to Philip Szeszko.

8 recordsLinked to original sources

PubMed2006

Cognitive development in schizophrenia: follow-back from the first episode.

Despite consensus that schizophrenia is a neurodevelopmental disorder characterized by cognitive deficits, objective data documenting the course of cognitive development remain sparse. We conducted a follow-back study of patients ascertained at the time of their initial episode of schizophrenia or schizoaffective disorder, and a group of demographically matched healthy volunteers. We obtained school records containing standardized achievement test scores from the 1st through 12th grades, and scholastic aptitude test results from the 11th and 12th grades, and examined the developmental trajectories of cognitive performance with respect to prospective examinations conducted following participants' enrollment in our study. We found significant differences in academic achievement tests as early as the first grade, with scores from participants who would later develop schizophrenia lagging behind their peers by 0.8 to 1.1 grade equivalents. This gap widened resulting in a difference between groups of 1.5 to 1.8 grade equivalents by the 12th grade. In the subset of patients for whom SAT scores were available, we found that WAIS-R Full Scale IQ was 11.5 points lower than predicted from earlier SAT scores, suggesting a substantial decline in cognitive ability accompanying the initial episode of illness. These findings suggest that schizophrenia is marked by substantial cognitive deficits in the first grade, that there may be additional subtle decline preceding the overt onset of psychotic symptoms, and that the initial episode of illness is marked by additional decline. These observations may help advance concepts of premorbid cognitive ability in the schizophrenia syndrome and constrain models of pathophysiology.

Adolescent↗

PubMed2005

Regional specificity of cerebrospinal fluid abnormalities in first episode schizophrenia.

The timing and regional specificity of cerebrospinal fluid (CSF) enlargements have not been well described in schizophrenia. High-resolution magnetic resonance images and computational image analysis methods were used to localize cross-sectional changes in lateral ventricle and sulcal and subarachnoid CSF in first episode schizophrenia patients (51 males/21 females) and healthy subjects (37 males/41 females). Volumes were obtained for each lateral ventricle horn and regional differences identified by comparing the distances from the ventricular surfaces to the central core at anatomically matched locations. Extra-cortical CSF differences were compared by measuring the proportion of CSF voxels sampled from spatially homologous cortical surface points. Significant extra-cortical CSF enlargements were observed in first episode patients, where regional differences surrounded the temporal, anterior frontal and parietal cortices. Volume and ventricular surface analyses failed to show significant effects of diagnosis. However, interactions indicated dorsal superior horn expansions in female patients compared with same-sex controls. Since ventricular enlargements are widely reported in chronic patients, our observations at first episode suggest ventricular enlargement may progress after disease onset with early changes occurring around the dorsal superior horn. In contrast, sulcal and subarachnoid CSF increases may be manifest near or before the first episode but after brain development is complete, reflecting pronounced reductions in proximal brain tissue.

Adult↗

PubMed2005

Cortical thinning in cingulate and occipital cortices in first episode schizophrenia.

BACKGROUND: Postmortem studies examining discrete regions show reduced cortical thickness in schizophrenia. Computational image analysis methods allow spatially detailed cortical thickness measurements across the entire cortex in 3D, but have not addressed thickness changes in cingulate or other cortices bordering the medial walls of the cerebral hemispheres in first episode schizophrenia. METHODS: Magnetic resonance images and cortical pattern matching methods were used to compare gray matter thickness, measured at sub-voxel resolution at thousands of spatially equivalent locations on the medial hemispheric surfaces, between 72 (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls similar in age. Group differences were mapped in 3D, and their overall significance was confirmed by permutation testing. RESULTS: Patients with little or no prior antipsychotic medication treatment showed significant cortical thinning within cingulate, occipital and frontopolar cortices with no significant increases in any cortical location. Regional sex differences were observed with pronounced thinning in the left paracentral lobule and right posterior cingulate in male and female patients respectively compared to same sex controls. CONCLUSIONS: Cortical thinning may correspond to cytoarchitectural and neurochemical abnormalities observed in similar anatomic locations and may underlie systems-wise disturbances that include heteromodal association cortices, where cortical thinning has been previously observed in first episode schizophrenia.

Adult↗

PubMed2005

Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study.

BACKGROUND: The purpose of this study was to explore whether there are white matter (WM) abnormalities in children with attention-deficit/hyperactivity disorder (ADHD) using diffusion tensor imaging. Based upon the literature, we predicted decreased fractional anisotropy (FA) findings in the frontal and cerebellar regions. METHODS: Eighteen patients with ADHD and 15 age- and gender-matched healthy volunteers received DTI assessments. Fractional anisotropy maps of WM were compared between groups with a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Children with ADHD had decreased FA in areas that have been implicated in the pathophysiology of ADHD: right premotor, right striatal, right cerebral peduncle, left middle cerebellar peduncle, left cerebellum, and left parieto-occipital areas. CONCLUSIONS: These preliminary data support the hypothesis that alterations in brain WM integrity in frontal and cerebellar regions occur in ADHD. The pattern of decreased FA might implicate the corticopontocerebellar circuit in the pathophysiology of ADHD.

Anisotropy↗

PubMed2004

Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study.

BACKGROUND: Research suggests that brain frontal white matter (WM) might be qualitatively altered in adolescents with early onset schizophrenia (EOS). Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of WM in vivo. METHODS: Diffusion tensor imaging was used to examine the WM integrity of frontal regions at seven levels from 25 mm above to 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. Three other regions were examined: the occipital region at the AC-PC plane and the genu and splenium of the corpus callosum. Fractional anisotropy was compared between 12 adolescents (nine male, 3 female) with EOS (onset of psychotic symptoms by age 18 years) and nine age-similar healthy comparison subjects (six male, 3 female). RESULTS: Adolescents with EOS had significantly reduced fractional anisotropy in the frontal WM at the AC-PC plane in both hemispheres and in the occipital WM at the AC-PC plane in the right hemisphere. CONCLUSIONS: These preliminary data support a hypothesis that alterations in brain WM integrity occur in adolescents with EOS. Abnormalities found in this study were similar to those reported in adults with chronic schizophrenia. Additional studies are needed to assess whether there is progression of WM abnormalities in schizophrenia.

Adolescent↗

PubMed2004

Abnormal gyral complexity in first-episode schizophrenia.

BACKGROUND: Abnormalities in the patterns and frequency of cortical folding might help identify temporal and regionally specific disturbances in normal neurodevelopmental processes that occur in association with schizophrenia. Few studies, however, have investigated gyral complexity in schizophrenia. METHODS: High-resolution magnetic resonance images were used to examine differences in gyral complexity, measured three-dimensionally in five separate hemispheric regions covering the entire cortical surface, in patients with first-episode schizophrenia (n = 50) compared with demographically matched healthy comparison subjects (n = 50). The modulating effects of gender and hemisphere were also examined. RESULTS: Significant increases in cortical folding were observed in the right superior frontal cortex in male schizophrenic patients compared with male control subjects, but not between female diagnostic groups. Significant main effects of hemisphere were found in frontal, parietal, and occipital regions in directions complementary to cerebral torques. CONCLUSIONS: Results support previous findings of right frontal hypergyria in male schizophrenic patients and suggest that these abnormalities predate illness onset and are of neurodevelopmental origin. Therefore, in schizophrenia, sexually dimorphic developmental processes and differences in hemispheric connectivity, which have been shown to influence the organization and/or frequency of cortical folding, seem to be disturbed during gyral formation in utero.

Adult↗

PubMed2004

Left middle temporal gyrus activation during a phonemic discrimination task.

There is considerable evidence that receptive language processing depends, at least in part, on cortical tissue in the temporal lobe. Few studies, however, have investigated the neural basis of phonemic discrimination while controlling for non-linguistic and attentional components. In this study nine healthy volunteers discriminated sets of phonemes and tones interspersed by rest periods in a block design paradigm while undergoing fMRI. A comparison of phonemic discrimination with tone discrimination revealed pure left lateralized superior and middle temporal gyrus activations. A comparison of phonemic discrimination with the rest blocks resulted in areas of activations encompassing the language and non-language components of the task. Our findings are consistent with prior reports demonstrating the involvement of the superior and middle temporal gyrus in phonemic discrimination and stronger left temporal lobe activation during speech compared to non-speech sounds. This study also demonstrates the advantage of tone discrimination control blocks as opposed to conventional rest periods to isolate the pure language component of phonemic discrimination.

Adult↗

PubMed2004

Regional specificity of hippocampal volume reductions in first-episode schizophrenia.

Hippocampal volume reductions are widely observed in schizophrenia. Some studies suggest anterior hippocampal regions are more susceptible and associated with frontal lobe dysfunctions, while others implicate posterior regions. Using high-resolution MR images and novel computational image analysis methods, we identified the hippocampal subregions most vulnerable to disease processes in 62 (45 m/17 f) first-episode schizophrenia patients compared to 60 (30 m/30 f) healthy controls, similar in age. The hippocampi were traced on coronal brain slices and hemispheric volumes were compared between diagnostic groups. Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups in 3D. CSF concentrations were also compared statistically at homologous hippocampal surface points to localize corresponding gray matter reductions. Significant bilateral hippocampal volume reductions were observed in schizophrenia irrespective of brain size corrections. Statistical mapping results, confirmed by permutation testing, showed pronounced left hemisphere shape differences in anterior and midbody CA1 and CA2 regions in patients. Significant CSF increases surrounding the hippocampus were observed in a similar spatial pattern in schizophrenia. Results confirm that hippocampal volume reductions are a robust neuroanatomical correlate of schizophrenia and are present by first episode. Mid- to antero-lateral hippocampal regions show pronounced volume changes and complementary increases in peri-hippocampal CSF, suggesting that these hippocampal regions are more susceptible to disease processes in schizophrenia. Targeting regional hippocampal abnormalities may help dissociate schizophrenia patients from other groups exhibiting global hippocampal volume changes, and better focus systems-level pathophysiological hypotheses.

Adolescent↗