Biomedical subjects

Philip R Szeszko

Publications and source records attributed to Philip R Szeszko.

At least 19 recordsLinked to original sources

PubMed2006

Asymmetries of cortical shape: Effects of handedness, sex and schizophrenia.

Some evidence suggests that sex, handedness and disease processes associated with schizophrenia affect the magnitude and/or direction of structural brain asymmetries. There are mixed findings, however, on how these factors influence cerebral torque, when torque is assessed with linear or volumetric measurements. We obtained MRI data from 67 healthy (30 males, 10 non-dextrals) and 84 schizophrenia subjects (60 males; 16 non-dextrals) and applied cortical pattern matching to spatially relate and compare differences in the surface morphology of the two cerebral hemispheres at high spatial resolution. Asymmetry indices, computed at thousands of matched hemispheric locations, were used to examine effects of sex, handedness and schizophrenia on hemispheric shape asymmetries while controlling for age and the other factors. Highly significant and discriminative right-frontal and left parietal-occipital surface expansions and protrusions (petalias) were mapped within groups. Although hemispheric shape asymmetries appeared less pronounced within female non-dextrals, asymmetry indices were not shown to differ significantly across sex, hand preference or diagnosis, or to reveal interactions of handedness with sex or diagnosis. Our 3D maps of spatially detailed anterior and posterior hemispheric shape asymmetries reflect subtle geometric distortions in hemispheric surface morphology that cannot be characterized with 2D or volumetric methods. Inter-individual variations in hemispheric torque appear minimally influenced by sex, dextrality or disease status. Biological factors driving language dominance or other lateralized brain functions dissociable from handedness, may more closely relate to hemispheric shape asymmetries, while the lateralization of other discrete brain regions may be more influenced by sexually dimorphic factors or by schizophrenia pathophysiology.

Cerebral Cortex↗

PubMed2006

Increased stress and smaller anterior hippocampal volume.

Animal studies indicate that stress negatively impacts hippocampal structure; little is known, however, regarding the relationship between stress and hippocampal morphology in healthy humans. Twenty-one healthy adults underwent structural magnetic resonance imaging examinations and completed the Derogatis Stress Profile. Greater psychological stress at the time of the scan correlated significantly and more strongly with anterior than posterior hippocampal volume. These findings suggest that psychological stress may be associated with structural alterations in the anterior hippocampal formation and that this relationship may differ along the rostrocaudal axis of the hippocampus. Our results may also have implications for neuropsychiatric disorders that have implicated stress and hippocampal abnormalities in their pathogenesis.

Adult↗

PubMed2006

Genetic variation in DTNBP1 influences general cognitive ability.

Human intelligence is a trait that is known to be significantly influenced by genetic factors, and recent linkage data provide positional evidence to suggest that a region on chromosome 6p, previously associated with schizophrenia, may be linked to variation in intelligence. The gene for dysbindin-1 (DTNBP1) is located at 6p and has also been implicated in schizophrenia, a neuropsychiatric disorder characterized by cognitive dysfunction. We report an association between DTNBP1 genotype and general cognitive ability (g) in two independent cohorts, including 213 patients with schizophrenia or schizo-affective disorder and 126 healthy volunteers. These data suggest that DTNBP1 genetic variation influences human intelligence.

Adult↗

PubMed2005

Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder.

The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly understood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects.

Adult↗

PubMed2005

Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia.

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia.

Adult↗

PubMed2005

DISC1 and neurocognitive function in schizophrenia.

We recently reported an association between DISC1 and schizophrenia, schizoaffective disorder, and bipolar disorder. Convergent evidence suggests that DISC1 has a direct effect on central nervous system functioning. However, there is a paucity of data investigating the effects of DISC1 on neurocognition. Thus, we analyzed the relationship between five single-nucleotide polymorphisms that influenced risk for schizophrenia in our previous study and neurocognition in 250 patients with schizophrenia. DISC1 genotype was related to neurocognitive performance on measures of rapid visual search and verbal working memory, when controlling for age and premorbid intellectual capacity, and explained 3%-4% of the variance. These data suggest that DISC1 is associated with neurocognitive functioning in schizophrenia.

Adult↗

PubMed2005

Olfactory functions and volumetric measures of orbitofrontal and limbic regions in schizophrenia.

OBJECTIVE: Olfactory deficits in schizophrenia patients have been suggested to reflect medial temporal and/or prefrontal brain abnormalities. In this study, we examined the relationship between different olfactory functions and volumes of the hippocampus-amygdala complex (HAC) and the orbitofrontal brain region using magnetic resonance imaging (MRI). METHODS: Thirty-three young men with schizophrenia (DSM-IV) and 40 healthy controls performed unirhinal olfactory assessment including the main olfactory functions (threshold, discrimination, and identification), and odor judgements (intensity, edibility, familiarity, and pleasantness). Volumes of regions in the medial temporal lobe (hippocampus and amygdala) and the prefrontal region (orbitofrontal gray and white matter) were measured on MRI scans. RESULTS: Compared with controls, patients showed bilaterally impaired thresholds, quality discrimination and identification, as well as edibility judgements. Olfactory deficits were not attributable to smoking, premorbid intelligence, or impaired thresholds. Relative to controls, patients had bilateral reduced hippocampus and amygdala volumes. In patients, smaller hippocampus volumes were associated with poorer olfactory discrimination ability. CONCLUSIONS: Olfactory deficits in schizophrenia appear to be associated with morphometric abnormalities in the medial temporal rather than the orbitofrontal region (OFR). These results indicate that olfactory quality discrimination deficits are related to structural hippocampus abnormalities. Future studies of genetic and behavioral high-risk samples seem warranted.

Adult↗

PubMed2005

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study.

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.

Adult↗

PubMed2005

White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study.

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.

Adolescent↗

PubMed2005

White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study.

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.

Adult↗

PubMed2004

Mapping cortical thickness and gray matter concentration in first episode schizophrenia.

We mapped regional changes in cortical thickness and intensity-based cortical gray matter concentration in first episode schizophrenia. High-resolution magnetic resonance images were obtained from 72 (51 male, 21 female) first episode patients and 78 (37 male, 41 female) healthy subjects similar in age. Cortical pattern matching methods allowed comparisons of cortical thickness and gray matter concentration at thousands of homologous cortical locations between subjects in three dimensions. Principal components analyses reduced measures obtained across the cortex to identify global differences in cortical thickness/gray matter concentration. First principal component factor scores showed significant effects of diagnosis, sex and age for both cortical measures. Diagnosis and age effects remained significant after brain size correction. Cortical thickness and gray matter concentration values were highly correlated. Statistical maps showed significant regional gray matter thinning in frontal, temporal and parietal heteromodal association cortices bilaterally in first episode patients. Regional reductions in cortical gray matter concentration were similar but pronounced in the superior temporal lobe. Regional reductions in cortical thickness and gray matter concentration are present at disease onset in brain regions linked with functional disturbances in schizophrenia. Cortical thickness and gray matter concentration mapping produce similar results, although the concentration metric may be influenced by diagnostic differences in extra-cortical cerebrospinal fluid and surface curvature/complexity.

Adult↗

PubMed2004

Investigation of unirhinal olfactory identification in antipsychotic-free patients experiencing a first-episode schizophrenia.

Although olfactory deficits have been reported in patients with schizophrenia, few studies have examined whether these deficits are lateralized or investigated their possible clinical correlates. In this study, we administered the University of Pennsylvania Smell Identification Test (UPSIT) unirhinally (one nostril at a time) to 15 patients experiencing a first-episode of schizophrenia and 17 healthy comparison subjects. Clinical and olfactory assessments were conducted on the same day in patients while they were antipsychotic drug-free. Patients performed more poorly compared to healthy volunteers in their ability to identify odors across both nostrils, but there were no group differences in right and left nostril impairment. Among patients, greater deficits in grooming and hygiene correlated significantly and more strongly with poorer ability in identifying odors presented to the left compared to the right nostril. Our findings suggest that deficits in grooming and hygiene, including poor body odor, observed in patients experiencing a first-episode of schizophrenia are associated with an impairment in left nostril, and possibly left hemisphere, olfactory processing.

Adolescent↗

PubMed2004

Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings.

The amygdala is believed to be highly relevant to the pathophysiology of obsessive-compulsive disorder (OCD) given its prominent role in fear conditioning and because it is an important target of the serotonin reuptake inhibitors (SRIs), the pharmacotherapy of choice for OCD. In the present study, we measured in vivo volumetric changes in the amygdala in pediatric patients with OCD following 16 weeks of monotherapy with the selective SRI, paroxetine hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to and then following treatment. Eleven healthy pediatric comparison subjects also had baseline and follow-up scans, but none of these subjects received medication. Patients demonstrated significant asymmetry of the amygdala (L>R) prior to pharmacologic intervention in contrast to healthy comparison subjects who showed no asymmetry at the time of their baseline scan. Mixed model analyses using age and total brain volume as time varying covariates indicated that left amygdala volume decreased significantly in patients following treatment. The reduction in left amygdala volume in patients correlated significantly with higher paroxetine dosage at the time of the follow-up scan and total cumulative paroxetine exposure between the scans. No significant changes in either right or left amygdala volume were evident among healthy comparison subjects from the baseline to the follow-up scan. These preliminary findings suggest that abnormal asymmetry of the amygdala may play a role in the pathogenesis of OCD and that paroxetine treatment may be associated with a reduction in amygdala volume.

Adolescent↗

PubMed2004

Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder.

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.

Adolescent↗

PubMed2003

Sex differences in frontal lobe white matter microstructure: a DTI study.

There is evidence that the brains of men and women are structurally different, but there are few data regarding possible sex differences in white matter microstructure. Using diffusion tensor imaging we assessed fractional anisotropy (FA) in the frontal lobe white matter on contiguous 5 mm slices in nine healthy male and 11 healthy female adults. Overall, women had higher FA in the left frontal lobe compared to men and a leftward asymmetry of FA in contrast to men, who showed no hemispheric asymmetry. Among women, greater leftward asymmetry of frontal lobe FA correlated significantly with better verbal comprehension and memory functioning. Our findings may be indicative of increased directional coherence and/or density of left hemisphere white matter fibers and a leftward asymmetry of this structural integrity among women compared to men.

Adult↗

PubMed2003

Reversed cerebellar asymmetry in men with first-episode schizophrenia.

BACKGROUND: Abnormalities in cerebellar structure and function have been implicated in the pathophysiology of schizophrenia. In this study, we investigated whether patients experiencing first-episode schizophrenia differed from healthy comparison subjects in regional cerebellar volumes or cerebellar asymmetry. METHODS: Volumes of four cerebellar regions (right, left; anterior, posterior) were measured from contiguous coronal magnetic resonance (MR) images in 69 (37 men, 32 women) patients experiencing first-episode schizophrenia and in 49 (27 men, 22 women) healthy comparison subjects. Patients were rated on the Scale for the Assessment of Negative Symptoms and the Schedule for Affective Disorders and Schizophrenia-Psychosis/Disorganization before the initiation of antipsychotic medication and at the time of the MR imaging exam. RESULTS: Patients and healthy comparison subjects did not differ in regional cerebellar volumes, but male patients demonstrated significantly reversed anterior and posterior asymmetry compared with healthy male subjects. Among male patients, greater reversals in a composite measure of cerebellar asymmetry (i.e., torque) correlated significantly with increased negative symptoms before the initiation of antipsychotic medication. CONCLUSIONS: These findings implicate an aberrant neurodevelopmental process involving the metencephalon in the pathophysiology of schizophrenia and are consistent with prior studies implicating abnormal asymmetry in schizophrenia at the neocortical level.

Adult↗

PubMed2003

Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression.

BACKGROUND: Neurobiologic abnormalities in the temporal lobe, particularly medial temporolimbic circuits, have been implicated in the pathogenesis of major depressive disorder (MDD). Although MDD commonly emerges during childhood and adolescence, to our knowledge, no prior study has examined temporal lobe anatomy in pediatric patients with MDD near the onset of illness before treatment. METHODS: Volumetric magnetic resonance imaging scans were conducted in 23 psychotropic drug-naïve pediatric patients with MDD, aged 8-17 years, and 23 case-matched healthy comparison subjects. RESULTS: Pediatric patients with MDD had significantly larger left (14%) and right (11%) amygdala:hippocampal volume ratios than controls. Increased left and right amygdala:hippocampal volume ratios were associated with increased severity of anxiety but not increased severity of depression or duration of illness. CONCLUSION: These results suggest that alterations in amygdala:hippocampal volume ratios in pediatric MDD may more reflect severity of associated anxiety than depression. These results underscore the importance of assessment for comorbidity in the study of MDD.

Adolescent↗

PubMed2003

Lack of normal association between cerebellar volume and neuropsychological functions in first-episode schizophrenia.

OBJECTIVE: Functional neuroimaging studies have identified a role for the cerebellum in the neuropsychology of schizophrenia. Few studies, however, have examined the relationship between cerebellar size and neuropsychological functioning in schizophrenia. The authors' goal was to examine this relationship in patients and healthy comparison subjects. METHOD: Total cerebellar volume was computed from magnetic resonance images in 48 male and 33 female patients experiencing a first episode of schizophrenia and in 14 male and nine female healthy comparison subjects. Patients and comparison subjects completed a comprehensive neuropsychological assessment encompassing six domains of functioning: executive, motor, language, visuospatial, memory, and attention. A global domain of functioning was computed as the mean of these six domains. RESULTS: Larger cerebellar volume correlated significantly with better global functioning in healthy subjects but not among patients with schizophrenia; this relationship was significantly stronger in healthy subjects than in patients. Additional analyses revealed significant associations between cerebellar volume and visuospatial, executive, and memory functions in healthy volunteers but not among patients. CONCLUSIONS: The cerebellum plays a role in higher cognitive functions in healthy individuals, and normal associations between cerebellar size and function are absent in patients experiencing a first episode of schizophrenia. These findings are consistent with neurobiological models implicating the cerebellum in the pathogenesis of schizophrenia.

Adult↗