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N C Andreasen

Publications and source records attributed to N C Andreasen.

At least 19 recordsLinked to original sources
PubMed2006

Structure and function of the superior temporal plane in adult males with cleft lip and palate: pathologic enlargement with no relationship to childhood hearing deficits.

BACKGROUND: In a previous study from our lab, adult males with non-syndromic cleft lip and/or palate (NSCLP) were shown to have significantly lower temporal lobe gray matter volume than matched controls. The current study was designed to begin a regional analysis of specific subregions of the temporal lobe. The superior temporal plane (STP) is a brain region involved in the governance of auditory processing and aspects of language. The cognitive deficit of subjects with NSCLP is characterized by specific deficits in language; therefore this region of the temporal lobe is particularly important to investigate in this population. The STP has been found to be structurally abnormal in subjects with dyslexia, another developmental disorder involving language deficit. The hypothesis for the current study was that the STP in subjects with NSCLP would be structurally abnormal and that the abnormality would be related to cognitive deficit, but not to developmental hearing deficit. METHODS: Manual tracing of the STP in NSCLP males and matched controls was performed on magnetic resonance imaging (MRI) scans. Ratios of STP to total temporal lobe gray matter volume were calculated and compared across groups. In addition, the morphology of the STP was correlated to cognitive function as well as measures of hearing deficit during infancy and childhood. RESULTS: Despite overall deficit in temporal lobe gray matter, the STP is disproportionately large in subjects with NSCLP compared to controls. Further, gray matter volume of the STP was inversely correlated with IQ and language test scores in CLP subjects. Hearing loss throughout childhood and adulthood was not significantly correlated with brain morphology. CONCLUSIONS: The structure of the superior temporal plane in adult males with NSCLP was disproportionately large. This abnormally increased volume was directly related to IQ, with greater STP volume being associated with lower cognitive functioning, thus characterizing the finding as 'pathologic enlargement'. Moreover, there was no relationship between the structure of the STP and measures of childhood hearing impairment, supporting the notion that the language deficits of this population are more likely due to abnormal brain development than to the effects of hearing deficit during childhood.

Adolescent↗
PubMed2005

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow.

The catechol-O-methyl transferase (COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. V(158)M COMT genotype was obtained on 159 schizophrenia patients and 84 healthy controls. The effects of COMT genotype on four measures of working memory/executive functions (Wisconsin Card Sorting, digit span backward, Trail Making and N-back tests) and on MRI frontal brain volumes were examined. Genotype distributions were not significantly different between patients and controls. There were no significant genotype or genotype-by-group effects on any working memory/executive function measures. No genotype or genotype-by-diagnosis interaction effects were found with MRI frontal lobe volumes. Randomization analyses using [(15)O]H(2)O positron emission tomography (PET) cerebral blood flow data found Val/Val patients had higher frontal lobe activation than Met/Met patients while performing the one-back task. Overall, these findings do not support a major role for COMT in increasing susceptibility for schizophrenia or in mediating frontal lobe function. Age-related changes and phenotypic heterogeneity of schizophrenia may influence the complex relationships between COMT genotype and cognition.

Adult↗
PubMed2001

Neural mechanisms of anhedonia in schizophrenia: a PET study of response to unpleasant and pleasant odors.

CONTEXT: Loss of the capacity to experience pleasure (anhedonia) is a core clinical feature of schizophrenia. Although functional imaging techniques have been successful in identifying the neural basis of cognitive impairments in schizophrenia, no attempts to date have been made to investigate neural systems underlying emotional disturbances. OBJECTIVE: To study the neural basis of emotional processing in schizophrenia by exploring the pattern of brain responses to olfactory stimuli in patients and healthy volunteers. DESIGN: Positron emission tomographic study of patients with schizophrenia and healthy volunteers. Positron emission tomographic data were collected between July 21, 1995, and September 11, 1997, and data analyses were conducted in 1999-2001. SETTING: The Mental Health Clinical Research Center at the University of Iowa, Iowa City. PARTICIPANTS: Sixteen healthy volunteers with a mean age of 29.5 years and 18 patients with schizophrenia and a mean age of 30.0 years. MAIN OUTCOME MEASURE: Areas of relative increase or decrease in regional cerebral blood flow, measured using positron emission tomography and the [(15)O]water method while participants performed an emotion-induction olfactory task to determine response to pleasant (vanillin) and unpleasant (4-methylvaleric acid) odors, compared between patients and healthy volunteers. RESULTS: Patients with schizophrenia subjectively experienced unpleasant odors in a manner similar to healthy volunteers but showed impairment in the experience of pleasant odors. The analysis of the regional cerebral blood flow revealed that patients failed to activate limbic/paralimbic regions (eg, insular cortex, nucleus accumbens, and parahippocampal gyrus) during the experience of unpleasant odors, recruiting a compensatory set of frontal cortical regions instead. CONCLUSION: Abnormalities in the complex functional interactions between mesolimbic and frontal regions may underlie emotional disturbances in schizophrenia.

Adult↗
PubMed2001

Comparison of the effects of risperidone and haloperidol on regional cerebral blood flow in schizophrenia.

BACKGROUND: Atypical antipsychotics, such as risperidone, have been shown to be more effective for the treatment of the symptoms of schizophrenia and have a greater beneficial effect on neurocognition compared to the conventional antipsychotics. The present study used [(15)O]H(2)O positron emission tomography imaging of regional cerebral blood flow to examine and compare the effects of haloperidol and risperidone on brain function. METHODS: Thirty-two subjects with schizophrenia participated in the study. Each subject was scanned in a medication-free state, and after being on a stable clinically assigned dose of either risperidone or haloperidol for 3 weeks. The off-medication scan was subtracted from the on-medication scan, using a within-subjects design. A randomization analysis was used to determine differences between the effects of haloperidol and risperidone on regional cerebral blood flow. RESULTS: Haloperidol was associated with a significantly greater increase in regional cerebral blood flow in the left putamen and posterior cingulate, and a significantly greater decrease in regional cerebral blood flow in frontal regions compared to risperidone. Risperidone was associated with a significantly greater decrease in regional cerebral blood flow in the cerebellum bilaterally compared to haloperidol. CONCLUSIONS: The results show that risperidone and haloperidol have significantly different effects on brain function, which may be related to their differences in efficacy and side effects. Further work is required to more precisely determine the mechanisms by which different antipsychotic medications exert their therapeutic effects on the clinical symptoms and cognition in schizophrenia. These findings emphasize the importance of controlling for both medication status and the individual antipsychotic in neuroimaging studies.

Adult↗
PubMed2001

Sex differences in the absence of massa intermedia in patients with schizophrenia versus healthy controls.

OBJECTIVE: To evaluate sexual dimorphism and incidence of absent massa intermedia (MI), a midline thalamic structure, in patients with schizophrenia and healthy controls. METHODS: Thin slice magnetic resonance images of the brain were obtained. The presence of MI was determined by viewing sagittal, coronal, and axial planes. RESULTS: In healthy controls, females had a significantly lower incidence of absent MI (13.56%) compared with males (32.08%). In patients with schizophrenia, there was a sex by diagnosis interaction. Female patients had significantly higher incidence of absent MI (32.76%) compared with their healthy controls (13.56%), whereas the male patients showed no difference in incidence of absent MI compared with their controls. CONCLUSION: The MI, a sexually dimorphic midline structure, is more commonly absent in female patients with schizophrenia. These results support the growing literature reporting structural aberration of the thalamus, as well as other midline structures in the brains of patients with schizophrenia.

Adult↗
PubMed2001

Population-based association analyses of the HOPA12bp polymorphism for schizophrenia and hypothyroidism.

HOPA is an Xq13 chromosome gene that codes for a RXR nuclear receptor co-activator. In a prior study of the genetic basis of schizophrenia, we showed that exonic polymorphisms in HOPA were associated with increased risk of schizophrenia and hypothyroidism in a large cohort of probands from New York. In an attempt to replicate these findings, we examined this relationship in a cohort of 173 schizophrenic probands (128 males and 45 females providing 218 alleles) from Iowa. Consistent with the prior findings, we found an increased rate of the HOPA12bP exonic polymorphism in schizophrenic probands compared with random newborn controls (9 of 218 alleles vs. 33 of 2,049 alleles, P < 0.02). Furthermore, retrospective review of the medical records showed that two of the nine probands possessing the HOPA12bp allele in whom thyroid function was assessed were hypothyroid compared with 6 of 164 probands possessing the normal HOPAwild allele(s) (P < 0.06). We conclude that the HOPA12bp polymorphism shows a nominally significant association with schizophrenia and a nominal trend for association with hypothyroidism in our study and that further studies are required to define the features of this syndrome and the molecular mechanisms of disease pathogenesis.

Amino Acid Sequence↗
PubMed2001

An MRI study of midbrain morphology in patients with schizophrenia: relationship to psychosis, neuroleptics, and cerebellar neural circuitry.

BACKGROUND: The midbrain contains the perikarya of all the dopamine neurons in the human brain. Although other neurochemicals may well be involved, dopamine dysregulation is central in the pathophysiology of psychosis. Despite this, few imaging studies have evaluated the morphology of the midbrain. METHODS: Using high-resolution magnetic resonance imaging, morphology of three posterior fossa and brain stem structures were measured: midbrain, pons, and medulla. The patient sample consisted of 50 men with schizophrenia, matched by gender and age to 50 healthy control subjects. RESULTS: Patients had significantly smaller midbrain measures compared with control subjects. There were no differences between groups in measures of pons or medulla. Furthermore, midbrain size was significantly and inversely correlated with positive symptoms and cumulative neuroleptic exposure, but not with negative or disorganized symptoms. After controlling for the effect of cumulative neuroleptic exposure, the relationship between midbrain morphology and positive symptoms remained significant. CONCLUSIONS: Midbrain morphology of patients with schizophrenia is abnormal, being smaller in patients compared with control subjects. Although this appears to be specifically related to psychotic symptoms, there is also a robust medication effect, with greater exposure to neuroleptics being associated with greater morphologic abnormality. We discuss the role of dopaminergic dysregulation and possible neural circuit involvement.

Adult↗
PubMed2001

Neural basis of novel and well-learned recognition memory in schizophrenia: a positron emission tomography study.

The level of familiarity of a given stimulus plays an important role in memory processing. Indeed, the novelty/familiarity of learned material has been proven to affect the pattern of activations during recognition memory tasks. We used visually presented words to investigate the neural basis of recognition memory for relatively novel and familiar stimuli in schizophrenia. Subjects were 34 healthy volunteers and 19 schizophrenia spectrum patients. Two experimental cognitive conditions were used: 1 week and again 1 day prior to the PET imaging subjects had to thoroughly learn a list of 18 words (well-learned memory). Subjects were also asked to learn another set of 18 words presented 1 min before the PET experiment (novel memory). During the PET session, subjects had to recognize the list of 18 words among 22 new (distractor) words. Subjects also performed a control task (reading words). A nonparametric randomization test and a statistical t-mapping method were used to determine between- and within-group differences. In patients the recognition of novel material produced relatively less flow in several frontal areas, superior temporal gyrus, insular cortex, and parahippocampal areas, and relatively higher activity in parietal areas, visual cortex, and cerebellum, compared to controls. No significant differences in flow were seen when comparing well-learned memory activations between groups. These results suggest that different neural pathways are engaged during novel recognition memory in patients with schizophrenia compared to healthy individuals. During recognition of novel material, patients failed to activate frontal/limbic regions, recruiting a set of posterior perceptual brain regions instead.

Adult↗
PubMed2001

Anatomic and functional variability: the effects of filter size in group fMRI data analysis.

In the analysis of group fMRI scans, an optimal spatial filter should be large enough to accurately blend functionally homologous anatomic regions, yet small enough not to blur the functionally distinct regions. Hanning filters varying from 0.0 to 18.0 mm were evaluated in a group analysis of six healthy controls performing a simple finger-tapping paradigm. Test-retest reliability and Talairach-based measurements of the sensorimotor region were used to explore the optimal filter size. Two distinct regions of functional activation were noted in the sensorimotor cortex in group images (n = 6) at both time 1 and time 2. These regions merge once the filter size exceeds approximately 6.0 mm. The original hypothesis that these represented a motor and sensory activation was rejected on the basis of structural and functional variability. A discussion of the inherent difficulties in choosing an appropriate filter size is presented.

Adult↗
PubMed2001

Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task.

BACKGROUND: According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses. RESULTS: The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.

Adult↗
PubMed2001

Effects of retroactive and proactive interference on word list recall in schizophrenia.

Schizophrenia spectrum patients (N = 143) and healthy controls (N = 160) were administered the Rey Auditory Verbal Learning Test (RAVLT) and tests of executive functioning to directly investigate the effects of proactive interference (PI) and retroactive interference (RI) on word list recall. It was hypothesized that by virtue of the predicted preferential association between executive functioning and RI (relative to PI), patients would demonstrate increased susceptibility to RI in their ability to recall word lists. Results indicated that patients show increased susceptibility to RI relative to PI. Furthermore, this difference appeared to be related to the frontally-mediated central executive functions that were preferentially associated with RI but not PI susceptibility.

Adult↗
PubMed2001

Increased incidence of a midline brain anomaly in patients with nonsyndromic clefts of the lip and/or palate.

BACKGROUND AND PURPOSE: Nonsyndromic clefts of the lip and palate (CLP) are developmental craniofacial abnormalities that are often associated with cognitive dysfunction. This study was designed to evaluate, in patients with CLP, the presence of a specific midline brain anomaly (enlarged cavum septi pellucidi [CSP]) that has been shown in other developmental syndromes to be related to poor cognitive function. METHODS: Brain images were obtained using magnetic resonance imaging on 49 adult men with CLP and 75 healthy controls. Size of CSP was measured using consecutive coronal images. RESULTS: The incidence of large CSP in the CLP group was 8% (4 of 49), significantly higher than that found in the control group. In 2 of these 4 subjects, the anomaly was complete nonfusion of the septal leaflets, known as a combined CSP and cavum vergae. Furthermore, there was a significant inverse relationship of IQ and CSP in CLP patients that was not present in controls. That is, in individuals with CLP, the larger the CSP, the lower the IQ. CONCLUSIONS: Adult men with CLP have an increased prevalence of enlarged CSP. Moreover, this anomaly is directly related to cognitive deficits. This study provides further evidence that the development of the face and the development of the brain are intimately related and that defects in craniofacial development are most likely associated with defects in brain development.

Adult↗
PubMed2001

The relationship of akathisia with suicidality and depersonalization among patients with schizophrenia.

An association of suicidality and depersonalization with akathisia has been reported, but it is not clear whether these phenomena are specific to akathisia or are nonspecific manifestations of distress. The authors used the Barnes Akathisia Rating Scale, Brief Psychiatric Rating Scale, and Hamilton Rating Scale for Depression (Ham-D) to examine the relationships between suicidality, depersonalization, dysphoria, and akathisia in 68 patients with schizophrenia or schizophreniform disorder. Akathisia was associated with higher scores on the Ham-D ratings of suicidality, depersonalization, and agitation. In a logistic regression model, depressive mood and subjective awareness of akathisia appeared to be the only predictors of suicidality and depersonalization, respectively. These findings support the association between akathisia and both suicidality and depersonalization. However, these symptoms appear to be nonspecific responses to accompanying depressive mood and the subjective awareness of the akathisia syndrome, respectively.

Adult↗
PubMed2000

Cerebral cortex: a topographic segmentation method using magnetic resonance imaging.

Remarkable developments in magnetic resonance imaging (MRI) technology provide a broad range of potential applications to explore in vivo morphological characteristics of the human cerebral cortex. MR-based parcellation methods of the cerebral cortex may clarify the structural anomalies in specific brain subregions that reflect underlying neuropathological processes in brain illnesses. The present study describes detailed guidelines for the parcellation of the cerebral cortex into 41 subregions. Our method conserves the topographic uniqueness of individual brains and is based on our ability to visualize the three orthogonal planes, the triangulated gray matter isosurface and the three-dimensional (3D) rendered brain simultaneously. Based upon topographic landmarks of individual sulci, every subregion was manually segmented on a set of serial coronal or transaxial slices consecutively. The reliability study indicated that the cerebral cortex could be parcelled reliably; intraclass correlation coefficients for each subregion ranged from 0.60 to 0.99. The validity of the method is supported by the fact that gyral subdivisions are similar to regions delineated in functional imaging studies conducted in our center. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in circumscribed cortical subregions. The description of a thorough map of regional structural and functional cortical abnormalities will provide further insight into the role that different subregions play in the pathophysiology of brain illnesses.

Cerebral Cortex↗
PubMed2000

Insular cortex abnormalities in schizophrenia: a structural magnetic resonance imaging study of first-episode patients.

The insular cortex is a limbic integration region that is engaged in emotional and cognitive functions. To investigate possible insular cortex abnormalities in schizophrenia, we measured insular gray matter volume and cortical surface size in drug-naive first-episode patients. Magnetic resonance images were used to explore the morphology of the insular cortex of 25 healthy male volunteers, and 25 male schizophrenic patients. Groups were matched for age, sex, height, and parental socio-economic status. Clinical dimension scores were correlated with insular gray matter volume and cortical surface area. Patients had a significant reduction in cortical surface area [patients=2020 (206); controls=2142 (204); F=5.83, df=1, 47; P=0.01] and gray matter volume [patients=8.12 (0.77); controls=8.57 (0.94); F=3.93, df=1,47; P=0.05] in the left insular cortex. Insular gray matter volume and cortical surface size correlated negatively and significantly with the psychotic symptom dimension. Schizophrenic patients show morphological abnormalities in the insular cortex at early stages of the illness. These abnormalities are related to the severity of psychotic symptoms. Further investigations are needed to evaluate the role of the insula in the pathophysiology of schizophrenia.

Adult↗
PubMed2000

Acute marijuana effects on rCBF and cognition: a PET study.

The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

Adult↗