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Nancy C Andreasen

Publications and source records attributed to Nancy C Andreasen.

At least 37 records · Page 2Linked to original sources
PubMed2005

Informed consent in medication-free schizophrenia research.

OBJECTIVE: The authors' goal was to determine whether people with schizophrenia experience changes in decisional capacity when their antipsychotic regimens are discontinued for research purposes. METHOD: Capacity for informed consent for research, neuropsychological performance, and psychiatric symptoms were assessed before and after discontinuation of antipsychotic medication in 10 individuals with schizophrenia. RESULTS: Overall, participants showed minimal change on most measures during the medication-free interval, although their reasoning ability declined significantly. All participants who demonstrated adequate understanding of study procedures at enrollment retained this capacity throughout the study. CONCLUSIONS: Participants in medication-free schizophrenia research do not show a major decline in decisional capacity. However, the apparent decline in reasoning ability found in this study is of concern and underscores the need for both additional research on this topic and the development of remediational interventions aimed at enhancing this aspect of decisional capacity.

Adult↗
PubMed2005

Hippocampus volume and treatment delays in first-episode schizophrenia.

OBJECTIVE: Many schizophrenia patients remain undiagnosed and untreated for long periods of time. It has been suggested that untreated psychosis may have deleterious neurotoxic effects. However, studies examining the correlates of untreated initial psychosis duration have been mixed. Previous MRI studies have reported no significant correlations between duration of untreated initial psychosis and brain volumes but have not examined specific brain regions that may be most susceptible to neuronal damage. METHOD: The authors investigated the relationship between duration of untreated initial psychosis and hippocampus morphology in 105 patients with first-episode DSM-IV schizophrenia spectrum disorders. High-resolution MRI-based hippocampal volume measurements were obtained by using a semiautomated artificial neural network method. RESULTS: There were no significant associations between hippocampal volumes and duration of untreated initial psychosis. When the patient group was split around the median duration of untreated initial psychosis (13 weeks), there were again no significant differences in left, right, or total hippocampal volume between groups. CONCLUSIONS: These findings do not support the hypothesis that psychosis is neurotoxic or that delaying antipsychotic drug treatment results in reduced hippocampal volumes.

Adult↗
PubMed2005

Subgenual prefrontal cortex volumes in major depressive disorder and schizophrenia: diagnostic specificity and prognostic implications.

OBJECTIVE: A variety of findings have implicated the portion of the anterior cingulate cortex ventral to the corpus callosum in the pathophysiology of familial depressive disorder. There are, as yet, few data to address the specificity of these abnormalities to depressive disorders or to characterize their stability over time. METHOD: The authors studied 10 subjects who were judged to have had major depressive disorder with psychotic features, who underwent magnetic resonance imaging (MRI) protocols, and who participated in a longitudinal study of recent-onset psychosis. These were group-matched to 10 subjects with schizophrenia and to 10 well comparison subjects. Volumetric measures were made of the posterior and anterior portions of the subgenual prefrontal cortex for these 30 subjects. Follow-up scans done an average of 4 years after intake were available for seven subjects with major depressive disorder, nine subjects with schizophrenia, and five well comparison subjects. RESULTS: Volumes of the left side of the posterior subgenual prefrontal cortex differed significantly by group and were smallest for the group with psychotic major depressive disorder. Volumes of the anterior subgenual prefrontal cortex did not differ significantly by group. Patients with major depressive disorder were more likely to show increases in posterior subgenual prefrontal cortex volume on follow-up than were comparison subjects or patients with schizophrenia. CONCLUSIONS: These findings add to the evidence that abnormalities in the subgenual region of the anterior cingulate play a role in at least some types of mood disorder.

Adult↗
PubMed2004

Temporal pole morphology and psychopathology in males with schizophrenia.

A dysfunction of the paralimbic system has been implicated in the pathophysiology of schizophrenia. The temporal pole (TP) is a relevant component of the paralimbic circuit. Functional and structural imaging studies have shown circumscribed abnormalities in the TP. Subjects were 30 controls and 30 schizophrenia patients. Cortical surface size and gray matter volume of the TP were accurately measured to explore the morphology of the TP cortex and the relationship of TP measures to clinical variables in patients with schizophrenia. Correlations between structural measures and clinical dimensions, duration of illness, and cumulative neuroleptic exposure were determined. Neither macroscopic abnormalities in the TP nor differences in the pattern of asymmetry were demonstrated. The TP volume was correlated negatively to the psychotic and disorganized dimension scores. No other significant correlations were found. No morphological abnormalities in the TP were found in patients with schizophrenia. Interestingly, a reduction in the TP volume, a higher-order multimodal association cortex, was associated with the severity of disorganized and psychotic symptoms.

Adult↗
PubMed2004

Symptoms and interference from memory in schizophrenia: evaluation of Frith's model of willed action.

The present study was undertaken to test Frith's [The Cognitive Neuropsychology of Schizophrenia, 1992. Erlbaum (UK) Taylor and Francis, East Sussex] model which states that certain symptoms of schizophrenia arise from diminished capacity to regulate willed (goal-directed) and stimulus-driven action systems. A total of 107 patients were administered the Rey Auditory Verbal Learning Test (RAVLT), a task that on interference trials requires individuals to recall target material while suppressing non-target distracting stimuli from memory. Symptom ratings were obtained using the SANS/SAPS [Andreasen, N.C., 1984. Scale for the Assessment of Negative Symptoms/Scale for the Assessment of Positive Symptoms [Manual] University of Iowa Press, Iowa City]. It was predicted that (1) negative symptoms would result in diminished recall, reflecting compromised activation of the willed action system, and (2) disorganized symptoms would be associated with heightened interference susceptibility resulting from diminished ability to suppress the stimulus-driven action system. Results revealed that diminished recall was related to negative, but not disorganized or positive symptoms. Symptom ratings were also evaluated in a subset of patients with intrusion error data (n=38). In this subset, it was found that patients who committed intrusion errors on the interference trials evidenced more disorganized, but not negative or positive symptoms, than individuals failing to commit such errors. These findings provide some support for Frith's hypothesis that impaired regulation of action systems may underlie some of the specific symptoms and cognitive impairments of this illness.

Adult↗
PubMed2004

Cerebellar dysfunction in neuroleptic naive schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs.

BACKGROUND: There is increasing evidence that, aside from motor coordination, the cerebellum also plays an important role in cognition and psychiatric disorders. Our previous studies support the hypothesis that cerebellar dysfunction may disrupt the cortico-cerebellar-thalamic-cortical circuit and, in turn, lead to cognitive dysmetria in schizophrenia. The goal of this study was to investigate cerebellar dysfunction in schizophrenia by examining the clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs in schizophrenia patients. METHODS: We compared the prevalence of cerebellar neurologic signs in 155 neuroleptic-naive schizophrenia patients against 155 age- and gender-matched healthy control subjects. Differences in clinical characteristics, standardized neuropsychologic performance, and magnetic resonance imaging brain volumes between patients with and without cerebellar signs were also examined. RESULTS: Patients had significantly higher rates of cerebellar signs than control subjects, with coordination of gait and stance being the most common abnormalities. Patients with lifetime alcohol abuse or dependence were no more likely than those without alcoholism to have cerebellar signs. Presence of cerebellar signs in patients was associated with poorer premorbid adjustment, more severe negative symptoms, poorer cognitive performance, and smaller cerebellar tissue volumes. CONCLUSIONS: These findings lend further support for cerebellar dysfunction in schizophrenia.

Adult↗
PubMed2004

Validity of symptom assessment in psychotic disorders: information variance across different sources of history.

BACKGROUND: Factors such as poor insight, amotivation, suspiciousness, disorganized speech and attentional problems may interfere with the ability of acutely ill individuals with psychotic disorders to provide a valid account of their symptoms. This study was designed to determine the degree to which history provided by such subjects is consistent with that obtained from other sources. METHOD: Fifty-five subjects presenting with psychotic disorders were multiply evaluated with a semi structured interview, the Comprehensive Assessment of Symptoms and History (CASH), which includes the Scales for the Assessment of Negative and Positive symptoms (SANS and SAPS). One interviewer assessed the severity of the patient's symptoms in the previous month based solely on information provided by the patient. A second rater made symptom ratings based on information obtained from a "best informant". Following this, a consensus rating was established based on an extensive evaluation and review of all sources of information. An item-by-item comparison of the three sets of symptom ratings was then quantified by paired t-tests, simple and multiple correlations. RESULTS: Positive and negative symptoms ratings based on the subjects' report were significantly lower than the corresponding consensus ratings. However, those based on the informants' report did not differ from consensus ratings for negative symptoms. Information obtained from subjects and from informants together accounted for a majority of the variance of the consensus ratings. CONCLUSIONS: These findings demonstrate that assessment limited to patients' own reports are likely to underestimate psychopathology in acutely ill patients with psychotic disorders. Obtaining corroborative history from a family member may substantially improve the validity of the assessment of negative symptoms.

Adult↗
PubMed2004

Association of the HOPA12bp allele with a large X-chromosome haplotype and positive symptom schizophrenia.

HOPA is a X-chromosome gene that encodes an essential nuclear receptor co-activator. Previously, we have demonstrated that an exonic polymorphism, termed HOPA(12bp), in the Opa (Opposite Paired) domain of this gene that is critical for neuronal growth and differentiation is associated with a low risk for schizophrenia. But curiously, we have also noted that all HOPA(12bp) probands have the same haplotype immediately surrounding the HOPA(12bp), and other investigators have found evidence of population stratification with the HOPA(12bp) allele. Since deleterious alleles are weeded from the population, and the HOPA(12bp) allele is not rare, these prior findings suggest the possibility that positive selection may be occurring with respect to the HOPA(12bp) allele and that unique phenotypic features may be associated with this allele. To test these hypotheses, we analyzed symptom data collected from schizophrenic probands and conducted haplotyping studies around the HOPA(12bp) polymorphism. Consistent with our hypotheses, genotyping studies of 43 unrelated HOPA(12bp) males and 137 HOPA(wild) males demonstrated that the HOPA(12bp) allele is associated with a large conserved DNA haplotype that extends over several genes known to be critical for human survival. Furthermore, ANOVA analysis of symptom data demonstrated that HOPA(12bp) schizophrenic probands (n = 14) have significantly lower severity of negative symptoms (P < 0.002) and better attention (P < 0.002) than matched controls (n = 30). Taken together, these findings further refine the behavioral endophenotype associated with the HOPA(12bp) allele and suggest that the sequence surrounding HOPA may need to be considered to fully understand the molecular basis of the phenotype associated with the HOPA(12bp) allele.

Adolescent↗
PubMed2004

Changes in caudate volume after exposure to atypical neuroleptics in patients with schizophrenia may be sex-dependent.

BACKGROUND: Changes in the volume of the caudate nucleus over time in patients with schizophrenia has been shown to be directly related to neuroleptic exposure. Few studies have evaluated caudate volume in subjects with schizophrenia who were neuroleptic naive at intake and treated exclusively with atypical neuroleptics. METHODS: Fourteen patients were matched by gender to 14 healthy controls and were evaluated over time using MRI. The patients were neuroleptic naïve at intake and at follow-up had been treated exclusively with atypical neuroleptics. Difference scores were calculated for caudate volumes. Neuroleptic exposure was quantified using a dose-years formula. RESULTS: There was no difference between patients and controls in the amount of change over time in the volume of the caudate. However, the female patients had a negative correlation (r= - 0.74) between drug exposure and volume change while the male patients had a positive correlation (r = 0.63). Therefore, there was a significant gender effect on the relationship between atypical neuroleptic exposure and changes in the structure of the caudate over time (test for difference in correlations: z = 2.39, p = 0.016). CONCLUSIONS: The change in caudate nucleus volume over time with exposure to atypical neuroleptics may be sex-dependent. Atypical neuroleptic expsoure was associated with volume increase over time in the males, while exposure in females was associated with volume decrement over time.

Adult↗
PubMed2004

Morphometry of the superior temporal plane in schizophrenia: relationship to clinical correlates.

A magnetic-resonance-imaging-based method of cortical parcellation was used to evaluate the morphology of the superior temporal plane and its subregions (Heschl's gyrus [HG], planum temporale [PT], and planum polare [PP]) in a group of 30 patients with schizophrenia versus a matched group of healthy subjects. Right HG volume was significantly reduced in patients compared with control subjects. Each subregion showed a unique set of structure/function relationships: reduced volumes of the HG were associated with greater duration of illness; reduced volumes of the PT were associated with positive symptoms; and in most contrast, elevated volumes of the PP were associated with cumulative neuroleptic exposure.

Adult↗
PubMed2003

The genetics of adult-onset neuropsychiatric disease: complexities and conundra?

Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.

Adult↗
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↗