Biomedical subjects

Nancy C Andreasen

Publications and source records attributed to Nancy C Andreasen.

At least 19 recordsLinked to original sources

PubMed2003

Initial magnetic resonance imaging volumetric brain measurements and outcome in schizophrenia: a prospective longitudinal study with 5-year follow-up.

BACKGROUND: Several demographic and phenomenological variables have been identified as predictors of outcome in schizophrenia. Far fewer studies have examined the relationships between brain morphology assessed at illness onset and subsequent outcome, and their results have been contradictory. METHODS: The relationships between magnetic resonance imaging (MRI) regional brain volumes at illness onset and outcome five years later were studied in 123 schizophrenia patients using regression and correlation analysis. Outcome measures included psychosocial functioning, weeks per year receiving inpatient treatment, and persistence of severe psychotic, disorganized and negative symptoms. RESULTS: Temporal lobe tissue volume at onset was predictive of outcome. Smaller temporal lobe gray matter volume (both left and right) was associated with persistence of hallucinations during follow-up. There were no significant associations between hallucinations and temporal white matter, or between delusions and temporal white or gray matter volumes. None of the other volumetric brain measures were predictive of outcome. CONCLUSIONS: The association between initial temporal lobe gray matter volume and subsequent persistent hallucinations may help identify individuals who are at higher risk for poor outcome and help guide their treatment planning. However, regional brain volumes assessed near illness onset, in general, do not appear to be indicative of subsequent outcome in schizophrenia.

Age of Onset↗

PubMed2003

Gyrification abnormalities in childhood- and adolescent-onset schizophrenia.

BACKGROUND: Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls. METHODS: Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes. RESULTS: There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri. CONCLUSIONS: This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.

Adolescent↗

PubMed2003

Marijuana alters the human cerebellar clock.

The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

Adult↗

PubMed2003

NOTCH4 and the frontal lobe in schizophrenia.

NOTCH4 is a developmentally expressed gene recently reported to be in linkage disequilibrium (LD) with schizophrenia. We investigated this finding in our sample of subjects, focusing on an exonic (CTG)(n) polymorphism, examining not only the association of this polymorphism with the disease phenotype, but also its effect on frontal lobe brain morphology and cognitive function in both affected individuals and a psychiatrically normal comparison group. While we did not find any association or LD with schizophrenia, we identified striking effects of NOTCH4 variability on the trait measures. Within the respective schizophrenia and comparison groups, NOTCH4 allelic variability was correlated with differences in measures of frontal lobe cognitive performance and frontal lobe brain tissue volumes that were intuitively congruent. These within-group effects, however, were in opposite directions across groups. These findings may reflect the interaction of NOTCH4 with the underlying genetic and phenotypic complexity that characterizes both schizophrenia and normal cognition and brain development.

Adult↗

PubMed2003

Morphology of the lateral superior temporal gyrus in neuroleptic nai;ve patients with schizophrenia: relationship to symptoms.

OBJECTIVE: The superior temporal gyrus (STG) is a large structure in the temporal lobe with multiple sub-regions that are structurally and functionally distinct. This study evaluates the structural morphology of a specific sub-region of the STG, the anterior and posterior portions of the lateral aspect of the STG. Furthermore, relationships between the morphology of these regions and symptoms of the illness were explored. METHOD: Regions of cortex were consecutively traced on a set of serial coronal slices in 25 male neuroleptic nai;ve patients with first episode schizophrenia and 25 age-matched healthy volunteers. Regional gray matter volumes were calculated and compared, and their correlations with three symptom dimensions were explored. RESULTS: The left anterior STG had a significant inverse correlation with psychotic symptoms, whereas the right posterior STG had a significant positive correlation with negative symptoms. These findings were confirmed by a follow-up analysis using extreme groups. There was no significant correlation between any region and disorganized symptoms. CONCLUSIONS: These findings suggest that abnormalities in the lateral side of the STG may be associated with both psychotic and negative symptoms through different pathophysiological mechanisms.

Adult↗

PubMed2003

Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia.

BACKGROUND: Many studies have shown that structural brain abnormalities in schizophrenia are already present by the time of index evaluation of first-episode patients. However, whether these abnormalities progressively worsen during the subsequent course of the disorder remains unresolved. METHODS: To study the longitudinal progression of structural brain abnormalities, high-resolution multispectral magnetic resonance images obtained on 73 recent-onset schizophrenic patients and 23 controls were analyzed using state-of-the-art, well-validated, and highly reliable neuroimaging tools. The mean duration between initial and follow-up MRIs was 3 years. Repeated-measures analysis of covariance was carried out to determine (1) whether brain volume changes differed between patients and controls and (2) the significance of regional brain changes on functional outcome in schizophrenia. RESULTS: We found accelerated enlargement in cortical sulcal cerebrospinal fluid spaces early in the course of schizophrenia. Instead of the usual trajectory of volume enlargement, patients showed progressive reduction in frontal lobe white matter volume. A reciprocal increase in frontal lobe cerebrospinal fluid volume also occurred at a more rapid rate in patients than in controls. In keeping with most of our a priori hypotheses, patients with poor outcome had greater lateral ventricular enlargement over time than patients with good outcome. Progressive decrement in frontal lobe white matter volume and enlargement in frontal lobe cerebrospinal fluid volume were associated with greater negative symptom severity. Reductions in frontal lobe gray and white matter volumes correlated with poorer executive functioning. CONCLUSIONS: There are ongoing changes in the brains of schizophrenic patients during the initial years after diagnosis despite ongoing antipsychotic drug treatment. These progressive changes seem to be most evident in the frontal lobes and to correlate with functional impairment. Disruptions in neurodevelopment or neural plasticity may act alone or in combination to bring about these progressive brain deficits in schizophrenia.

Adult↗

PubMed2003

Brain tissue volume segmentation in patients with anorexia nervosa before and after weight normalization.

OBJECTIVE: To examine whether gray and white matter volumes are preferentially reduced and cerebral spinal fluid (CSF) increased with starvation in patients with anorexia nervosa compared with healthy controls and to determine what changes occur with weight normalization. METHOD: Whole intracranial volumes of patients and controls were segmented into gray matter, white matter, and CSF volumes and results compared. A subgroup of patients were rescanned after weight normalization. RESULTS: Total white matter and several regional white matter volumes were significantly reduced and total and regional CSF volumes were significantly increased in patients versus controls whereas gray matter was not significantly reduced. Total and regional CSF volumes were significantly decreased in patients upon weight normalization whereas white and gray matter volumes increased. DISCUSSION: These changes in brain tissue may be related to a variety of pathophysiologic mechanisms. We hypothesize that insulin-like growth factor-1 may be involved.

Adult↗

PubMed2003

Subcortical, cerebellar, and magnetic resonance based consistent brain image registration.

A new landmark-initialized segmentation and intensity-based (LI-SI) inverse-consistent linear elastic image registration algorithm is presented. This method uses manually identified landmarks, segmented volumetric (anatomical) structures, and normalized image signal intensity information to coregister datasets. The features used for image registration and evaluation include 35 cortical, cerebellar, and commissure landmarks manually identified by experts, subcortical and cerebellar regions defined semi-automatically by an artificial neural network and manually trimmed for validity by experts, and tissue classified images that were generated using a discriminant analysis of three magnetic resonance image sets representing T1, T2, and PD modalities. Four groups of results were computed for coregistering 16 datasets with the following registration techniques: rigid registration, extended Talairach registration, intensity-only inverse-consistent linear elastic registration, and the new LI-SI registration. Results are presented showing that relative overlap measurements increased as the dimensionality of the registration algorithm and amount of anatomical information increased. The average relative overlap improved from 0.53 for the rigid registration to 0.55 for the Talairach registration to 0.74 for the intensity-only and to 0.85 for the LI-SI algorithm. We showed a statistically significant improvement for all but one structure using the intensity-only algorithm compared to the Talairach registration. Furthermore, statistically significant improvements for all structures were achieved using the LI-SI algorithm compared to the intensity-only algorithm.

Adult↗

PubMed2003

Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia.

OBJECTIVE: Studies of patients experiencing their first episode of psychosis have demonstrated that they typically remain undiagnosed and untreated for 1-2 years. It has been postulated that prolonged untreated psychosis may have serious effects: poor response to neuroleptic medications, poor clinical outcomes, and direct neurotoxicity. This study investigated the relationships between duration of untreated initial psychosis and neurocognitive functioning and high-resolution imaging brain measurements. METHOD: A total of 156 subjects with DSM-IV schizophrenia, schizophreniform disorder, or schizoaffective disorder were evaluated during their first episode of psychosis. Measurements included nine domains of neurocognitive functioning, volumetric measures of total brain tissue, gray and white matter, and CSF, and measures of brain surface anatomy. RESULTS: The mean duration of untreated initial psychosis was 74.3 weeks. Correlations between neurocognitive functioning, brain volumetric measurements, and surface anatomy measurements with duration of untreated initial psychosis were weak; none reached statistical significance. When the group was divided on the basis of median duration of untreated initial psychosis, there were again no significant differences between the groups with long and short duration of untreated initial psychosis except on two measures (verbal memory and cortical sulcal depth). CONCLUSIONS: The absence of strong correlations suggests that untreated initial psychosis has no direct toxic neural effects. These results suggest that large-scale initiatives designed to prevent neural injury through early intervention in the prepsychotic or early psychosis phase may be based on incorrect assumptions that neurotoxicity or cognitive deterioration may be avoided. Nevertheless, early treatment is justified because it reduces suffering.

Adult↗

PubMed2002

The effects of neuroleptic medications on basal ganglia blood flow in schizophreniform disorders: a comparison between the neuroleptic-naïve and medicated states.

BACKGROUND: Previous studies indicate that basal ganglia volumes of first-episode neuroleptic-naïve patients with schizophrenia are smaller than those of normal control subjects. Subsequent exposure to neuroleptic medication appears to induce volumetric change. Possible reasons for this include differences in blood flow and metabolism between the neuroleptic-naïve and medicated states. METHODS: We used positron emission tomography (PET) to measure blood flow to the caudate and putamen, in a sample of 29 neuroleptic-naïve patients with schizophreniform disorders and 29 matched control subjects. We also studied a subset of the patient sample (n = 13), comparing their "before" versus "on" medication PET scans. RESULTS: We did not find a significant difference in blood flow to the caudate and putamen between neuroleptic-naïve patients and control subjects even after controlling for whole brain blood flow; however, in the subset of 13 patients compared in the "on" versus "off" medication states, there was a statistically significant increase in blood flow to both the caudate and putamen. CONCLUSIONS: Before treatment, there appears to be no difference in striatal blood flow between first-episode neuroleptic-naïve patients and healthy volunteers, but there appears to be a significant increase in blood flow to the striatum after the treatment is initiated.

Adult↗

PubMed2002

Possible association of a cholecystokinin promoter variant to schizophrenia.

Several lines of research indicate a cholecystokinin (CCK) deficit in schizophrenia patients. A C to T substitution was found in the promoter region of the CCK gene. We investigated this promoter variant in patients with schizophrenia and geographically-matchedcontrols. The T allele was detected in 24% of the 85 schizophrenics and 16% of the 247 controls. No significant difference in the T allele frequency was found between patients and controls (chi(2) = 2.77, P > 0.1). The schizophrenia sample was analyzed further along the dimensions of positive and negative symptoms. The patients with prominent negative symptoms presented a statistically significant association to the T allele (chi(2) = 4.13, P < 0.04). However, the significance disappeared after the Bonferroni correction (P > 0.15). Since the case-control analysis may present incorrect ethnic match between cases and controls, we applied the family-based tests to verify the above findings. Both transmission disequilibrium test (TDT; chi(2) = 5.33, P < 0.025 in 12 trios) and haplotype relative risk (HRR; chi(2) = 3.844, P < 0.05 in 60 trios) indicated a significantly high transmission of T allele to schizophrenia offspring probands from their parents. While our family-based tests seem to support the CCK involvement in schizophrenia, no definite conclusion can be drawn based on such a small sample size. This preliminary finding is subjected to future investigations.

Alleles↗

PubMed2002

Morphology of the ventral frontal cortex in schizophrenia: relationship with social dysfunction.

BACKGROUND: Studies have reported premorbid as well as postonset social dysfunction in schizophrenia. This impairment has also been observed to emerge after lesions in the ventral aspect of the frontal cortex (i.e., straight gyrus and orbitofrontal cortex). METHODS: Magnetic resonance imaging scans were obtained from 45 male patients with schizophrenia and 45 matched control subjects. Cortical gray matter volume and surface area were determined for the ventral frontal cortex (VFC), subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). RESULTS: The global measures of gray matter volume and surface area in the VFC was not significantly different between patients and control subjects; however, there was a regional difference, with the right SG volume and surface area being smaller in patients compared with control subjects. Volume of the VFC had an inverse correlation with measurements of both premorbid and postdiagnosis social function. The smaller the gray matter in these regions, the greater the social dysfunction. There was no relationship between morphology of this brain region and any other clinical variable. CONCLUSIONS: Morphology of the VFC is directly related to abnormal social function in schizophrenia, including measures of social dysfunction that predate the onset of illness.

Adult↗

PubMed2002

Manual and semiautomated measurement of cerebellar subregions on MR images.

Previous structural and functional imaging studies suggest that the corticocerebellar-thalamic-cortical circuit is dysfunctional in schizophrenia. Accurate identification and volumetric measurement of cerebellar subregions are essential to the assessment of the cerebellum's role in healthy and disease states. Manual parcellation of the cerebellum on MR images was performed with the use of guide traces. Guide traces identified relevant fissures and borders in several planes, and their intersections with the primary tracing plane were used to maintain consistency and accuracy during the parcellation. The cerebellum was parcellated into right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. A systematic review of the final traces ensured their accuracy. An artificial neural network was trained using a novel landmark-warped method to help account for wide variability in structure size and location. Overlaps of the manually traced lobes (intersection/union) ranged from 0.78 to 0.85 and intraclass correlations (r2) ranged from 0.82 to 0.94. In a comparison of the semiautomated method with the manual method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.92 to 0.97. For two raters using the semiautomated method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.97 to 0.99. The semiautomated method was built on the groundwork of the manual method to produce more reliable results in a fraction of the time, making valid measurements possible on a large number of subjects.

Cerebellar Nuclei↗

PubMed2002

Cognitive dysfunction in adult males with non-syndromic clefts of the lip and/or palate.

Cognitive deficits have been well-documented in children with non-syndromic clefts of the lip and/or palate. However, no study to date has formally assessed cognition in adults with oral clefts. This study was designed to evaluate neuropsychological functioning in adult males with non-syndromic clefts of the lip and/or palate (n=50) compared to age and sex-matched controls. Subjects with oral clefts were found to have significantly lower full scale IQ, performance IQ and verbal IQ scores compared to their matched controls. After controlling for IQ, patients showed specific deficits in verbal fluency. Adult males with oral clefts manifest a specific pattern of cognitive deficits. As the development of the face is highly interdependent with the development of the brain, it is theorized that the etiology of these cognitive deficits is a primary problem with abnormal brain development.

Cleft Lip↗

PubMed2002

Effects of frequent marijuana use on memory-related regional cerebral blood flow.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using positron emission tomography (PET), memory-related regional cerebral blood flow was compared in frequent marijuana users and nonusing control subjects after 26+ h of monitored abstention. Memory-related blood flow in marijuana users, relative to control subjects, showed decreases in prefrontal cortex, increases in memory-relevant regions of cerebellum, and altered lateralization in hippocampus. Marijuana users differed most in brain activity related to episodic memory encoding. In learning a word list to criterion over multiple trials, marijuana users, relative to control subjects, required means of 2.7 more presentations during initial learning and 3.1 more presentations during subsequent relearning. In single-trial recall, marijuana users appeared to rely more on short-term memory, recalling 23% more than control subjects from the end of a list, but 19% less from the middle. These findings indicate altered memory-related brain function in marijuana users.

Analysis of Variance↗

PubMed2002

Effects of smoking marijuana on brain perfusion and cognition.

The effects of smoking marijuana on regional cerebral blood flow (rCBF) and cognitive performance were assessed in 12 recreational users in a double-blinded, placebo-controlled study. PET with [(15)Oxygen]-labeled water ([(15)O]H(2)O) was used to measure rCBF before and after smoking of marijuana and placebo cigarettes, as subjects repeatedly performed an auditory attention task. Smoking marijuana resulted in intoxication, as assessed by a behavioral rating scale, but did not significantly alter mean behavioral performance on the attention task. Heart rate and blood pressure increased dramatically following smoking of marijuana but not placebo cigarettes. However, mean global CBF did not change significantly. Increased rCBF was observed in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, as well as in the cerebellum. The increases in rCBF in anterior brain regions were predominantly in "paralimbic" regions and may be related to marijuana's mood-related effects. Reduced rCBF was observed in temporal lobe auditory regions, in visual cortex, and in brain regions that may be part of an attentional network (parietal lobe, frontal lobe and thalamus). These rCBF decreases may be the neural basis of perceptual and cognitive alterations that occur with acute marijuana intoxication. There was no significant rCBF change in the nucleus accumbens or other reward-related brain regions, nor in basal ganglia or hippocampus, which have a high density of cannabinoid receptors.

Adult↗

PubMed2002

Brain volumes and surface morphology in monozygotic twins.

Because healthy monozygotic twins share an identical genetic complement, they provide a unique opportunity to explore the genetic and environmental determinants of brain development. The purpose of this study was to evaluate the similarities between measures of cerebral and subcortical volumes and surface morphology in monozygotic twins compared with a matched control sample. Combinations of automated and manual methods were used to evaluate total brain volume, gray matter, white matter, ventricles and volumes of the frontal, temporal, parietal and occipital lobes. An artificial neural network algorithm was used to measure the cerebellum, thalamus, caudate and putamen. Measures of surface morphology included an index of gyral and sulcal curvature, surface area and cortical depth. The cerebral volume regions, including the gray matter, white matter and lobar volumes, were highly correlated within monozygotic twin pairs, with nearly all correlation coefficients >0.90. The cerebellum was also highly correlated (r = 0.99). Reasonably high correlations were found for the cortical depth (r = 0.84), caudate (r = 0.84), thalamus (r = 0.75) and putamen (r = 0.75). The surface measures, however, demonstrated the least correlation within twin pairs and thus are more prone to environmental influences. The high to moderate correlations between MZ twins compared with the matched controls highlights the role of heredity in both prenatal and postnatal neurodevelopment.

Adolescent↗

PubMed2002

Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance.

OBJECTIVE: Studies suggest the presence of premorbid cognitive impairment in patients with schizophrenia, yet the onset and course of these deficits remain unclear. The purpose of this study was to investigate the longitudinal course of premorbid cognitive functioning in individuals with schizophrenia by using prospective data obtained from scholastic test results. METHOD: Scores from grades 4, 8, and 11 on the Iowa Tests of Basic Skills and the Iowa Tests of Educational Development were obtained for 70 subjects who later developed schizophrenia. The mean percentile rank of the subjects' scores in the areas of vocabulary, reading comprehension, language, mathematics, sources of information, and an overall composite category were compared with state norms. RESULTS: The subjects scored below the 50th percentile for each category in all three grades, but only language, reading, sources of information, and composite scores from grade 11 were significantly below state norms. With regard to longitudinal course, there was a significant linear decrease in language scores over time. Scores from grade 11 were positively correlated with WAIS-R IQ, verbal fluency, and Rey Auditory Verbal Learning scores at first illness episode. Scores from grade 11 were not significantly correlated with age at illness onset or ratings of disorganized, psychotic, or negative symptoms. CONCLUSIONS: Scholastic test scores at grades 4 and 8 were nonsignificantly below average in this group of children who later developed schizophrenia. However, test scores dropped significantly between grades 8 and 11. This corresponds to ages 13-16 years, or the onset of puberty. Poor or declining scholastic performance may be a precursor to the cognitive impairment seen during the first episode of illness.

Adolescent↗