Search PubMed⌕ Search

Biomedical subjects

Lynn E DeLisi

Publications and source records attributed to Lynn E DeLisi.

At least 19 recordsLinked to original sources
PubMed2006

Early detection of schizophrenia by diffusion weighted imaging.

A novel magnetic resonance imaging method was used to determine whether it is feasible to detect early signs of cortical atrophy among individuals who are at high risk for developing schizophrenia. Fifteen individuals at high-risk for schizophrenia and 15 of their first degree relatives diagnosed with schizophrenia were compared with controls (n=25) who did not have a family history of psychiatric illness or psychiatric hospitalizations. On the basis of a voxelwise analysis of apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance imaging, these individuals showed evidence of deficits in four separate regions of the brain, all on the left side only: parahippocampal gyrus, lingual gyrus, superior frontal gyrus, and middle frontal gyrus. However, conventional volumetric quantification of ventricular space to detect atrophy failed to reveal differences between high-risk subjects and controls. It is concluded that ADC may be a more sensitive measure than ventricular volume assessments for use in future studies of early prediction of schizophrenia.

Adolescent↗
PubMed2006

When is a "positive" association truly a "positive" in psychiatric genetics? A commentary based on issues debated at the World Congress of Psychiatric Genetics, Boston, October 12-18, 2005.

The accumulated literature on candidate gene findings in psychiatric genetics is extensive. There is concern that many of the published findings to data are false positives. At the October 2005 World Congress of Psychiatric Genetics this issue was discussed by a panel of experts. This manuscript describes the panel discussion, its implications for the reporting of association studies of psychiatric disorders and suggestions for when to decide that a positive finding is truly positive.

Genetic Linkage↗
PubMed2006

A preliminary comparison of the hopes of researchers, clinicians, and families for the future ethical use of genetic findings on schizophrenia.

A written questionnaire about genetic testing was distributed to all registrants at The 2004 World Congress of Psychiatric Genetics, mailed to clinical psychiatrists obtained from a directory of clinicians practicing in New York City, and mailed to members of families who have multiple affected family members with schizophrenia. A total of 274 individuals responded (162 researchers, 64 clinicians, and 48 family members). This survey shows that the majority of family members who completed the questionnaire (83.3%) would want to be tested if a genetic test were to become available. Over half of the family members (56.2%) would want prenatal testing. Similarly, over half of the clinicians (56.3%) would recommend it, despite only 25% of the researchers reporting that it would be a future useful tool. All of the clinicians surveyed thought adoption agencies should inform families about a family history of schizophrenia, while only half of the researchers thought this should be done (51.9%). These differences in opinions between consumers, their clinicians, and researchers could be based on a lack of understanding of the amount of risk conferred to family members by reported gene variants. Providing public discussions for placing these risks in perspective should be the responsibility of researchers. Open public discussion of the ethical and social uses of the information gained from psychiatric genetic research and its limitations is encouraged.

Adult↗
PubMed2006

Understanding structural brain changes in schizophrenia.

Schizophrenia is a chronic progressive disorder that has at its origin structural brain changes in both white and gray matter. It is likely that these changes begin prior to the onset of clinical symptoms in cortical regions, particularly those concerned with language processing. Later, they can be detected by progressive ventricular enlargement. Current magnetic resonance imaging (MRI) technology can provide a valuable tool for detecting early changes in cortical atrophy and anomalous language processing, which may be predictive of who will develop schizophrenia.

Antipsychotic Agents↗
PubMed2005

Ten year longitudinal study of neuropsychological functioning subsequent to a first episode of schizophrenia.

We previously reported relative stability in neuropsychological functions over a 4- to 5-year period after the onset of a first episode of schizophrenia, with patients demonstrating less improvement than controls on some functions [Hoff, A.L., Sakuma, M., Wieneke, M., Horon, R., Kushner, M., DeLisi, L.E., 1999. A longitudinal follow-up study of neuropsychological functioning subsequent to a first-episode of schizophrenia. American Journal of Psychiatry 156, 1336-1341.]. The current study was conducted to extend follow-up evaluations through 10 years of illness to determine whether neuropsychological functions remain stable or deteriorate over a longer time period. Twenty-one first episode patients and 8 controls were re-evaluated 10 years after an initial evaluation on neuropsychological and clinical measures. Repeated measures analyses demonstrated no differences between patients and controls in degree of change over this time period nor was change in symptoms reliably associated with improvement or deterioration in cognitive abilities. However, baseline level of cognitive functioning was correlated with the degree of change. Thus, when the baseline level of functioning was controlled for in the analyses, less or lack of improvement was seen in the patients compared with controls in verbal intellectual functioning, delayed verbal and nonverbal recall, and cognitive inhibition (Stroop Color Word Test). In no test did patients deteriorate significantly more than controls. We conclude that most first episode patients have had considerable cognitive decline by the time of their first hospitalization and that it remains relatively stable through at least 10 years of illness. Most cognitive change takes place early in this illness, prior to the first hospitalization, but its exact timing still remains unknown.

Adult↗
PubMed2005

Klinefelter's syndrome (XXY) as a genetic model for psychotic disorders.

Males with an extra-X chromosome (Klinefelter's syndrome) frequently, although not always, have an increased prevalence of psychiatric disturbances that range from attention deficit disorder in childhood to schizophrenia or severe affective disorders during adulthood. In addition, they frequently have characteristic verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of these individuals may yield clues to the influence of X chromosome genes on brain structural variation corresponding to psychiatric and cognitive disorders. Eleven adult XXY and 11 age matched XY male controls were examined with a structured psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven of the XXY men had some form of psychiatric disturbance, four of whom had auditory hallucinations compared with none of the XY controls. Significantly smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical volumes were observed bilaterally in the XXY men. In addition, diffusion tensor imaging (DTI) of white matter integrity resulted in four regions of reduced fractional anisotropy (FA) in XXY men compared with controls, three in the left hemisphere, and one on the right. These correspond to the left posterior limb of the internal capsule, bilateral anterior cingulate, and left arcuate bundle. Specific cognitive deficits in executive functioning attributable to frontal lobe integrity and verbal comprehension were noted. Thus, excess expression of one or more X chromosome genes influences both gray and white matter development in frontal and temporal lobes, as well as white matter tracts leading to them, and may in this way contribute to the executive and language deficits observed in these adults. Future prospective studies are needed to determine which gene or genes are involved and whether their expression could be modified with appropriate treatments early in life. Brain expressed genes that are known to escape inactivation on extra-X chromosomes would be prime candidates.

Adult↗
PubMed2005

Failure to find progressive temporal lobe volume decreases 10 years subsequent to a first episode of schizophrenia.

The present study used magnetic resonance imaging to examine the volumes of the temporal lobe and the superior temporal gyrus in a 10-year follow-up study of 27 patients with schizophrenia and 10 controls. No change over time was observed in these structures when patients were compared with controls. These results do not support the notion that progressive temporal lobe deterioration occurs in schizophrenia.

Adult↗
PubMed2005

Familial cognitive deficits in schizophrenia.

Susceptibility to schizophrenia is considered familial, but the mechanism for transmission has not been found. Since widespread cognitive deficits have been found in patients with schizophrenia, several of these have been proposed as candidate familial endophenotypes that may or may not be predictive of who develops the illness. The current study examines these candidates in individuals from 32 families with at least 2 members having the diagnosis of chronic schizophrenia and normal comparison subjects using an extensive neuropsychological battery. Consistent with previous literature, family members with schizophrenia were significantly impaired on all measures compared with controls. Well relatives demonstrated significantly worse performance on a measure of verbal learning, delayed visual recall, perceptual-motor, and pure motor speed. Expressive and receptive language, but not other functions, were highly correlated within both concordant for schizophrenia and discordant sibling pairs, suggesting that they are familial vulnerability endophenotypes, but not predictive of whom becomes ill. On the other hand, some measures of perceptual-motor, pure motor speed, and frontal/executive functioning were significantly correlated in concordant, but not discordant pairs. These latter correlations suggest that some cognitive measures may be genetically related to the illness.

Adult↗
PubMed2004

Hospitalized psychiatric patients view the World Trade Center disaster.

There is conflicting literature describing how psychiatric patients, particularly those with schizophrenia, respond to overwhelming environmental disasters, with some reports describing marked improvement in their symptoms. This view is contrary to the notion that those individuals who are most vulnerable (i.e. people with serious psychiatric illness) are at high risk for further increase in psychiatric symptoms subsequent to stressful events. Since the terrorist attack of September 11, 2001, was such a catastrophic event, the following project was undertaken to examine its consequences on a population of hospitalized and thus severely ill psychiatric patients. Medical records for 156 New York City psychiatric inpatients were examined to evaluate their psychiatric condition during the time prior to and subsequent to the September 11, 2001, terrorist attacks on the World Trade Center in New York City. We failed to find any difference between the patients who had the opportunity to directly view the disaster through windows and those who did not. However, significantly more patients with a schizophrenia spectrum diagnosis showed evidence of worsening in their symptoms than those with affective disorder or other diagnoses in response to the events of September 11.

Anxiety↗
PubMed2004

ProtocadherinX/Y, a candidate gene-pair for schizophrenia and schizoaffective disorder: a DHPLC investigation of genomic sequence.

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warranted.

Base Sequence↗
PubMed2004

Correlates of cognitive deficits in first episode schizophrenia.

OBJECTIVE: The presence of cognitive dysfunction in schizophrenia has been well documented, but questions remain about whether there are relationships between this dysfunction and clinical symptomatology. If present, such relationships should be most clearly observable in patients with first episode schizophrenia; that is, before the effects of chronic illness, institutionalization, or treatment might confound them. METHOD: 307 schizophrenia subjects in their first episode of illness were recruited to participate in a clinical trial comparing the long-term efficacy of haloperidol and risperidone. The psychopathology, cognitive functioning, early treatment history, and duration of untreated psychosis of these subjects were assessed prior to their assignment to randomized, double-blind treatment. Approximately two-thirds of the subjects were receiving antipsychotic treatment at the time of assessment; however, the duration of treatment was limited to 12 weeks or less. RESULTS: The severity of negative symptoms at the time of assessment was associated with deficits in memory, verbal fluency, psychomotor speed and executive function. Positive symptoms were not associated with cognitive deficits. Also, the duration of untreated illness (DUI) prior to assessment was not significantly associated with cognitive impairment. CONCLUSIONS: The results of this study of first episode schizophrenia patients suggest that a relationship exists between negative symptoms and cognitive dysfunction. However, that relationship accounts for only a minor portion of the variance (i.e., 10-15%) in the severity of cognitive dysfunction after controlling for a number of potentially confounding factors. This finding provides support for the theory that the neurobiological processes that give rise to symptomatology and cognitive dysfunction in schizophrenia are partially overlapping.

Adolescent↗
PubMed2004

A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.

Animals↗
PubMed2004

Cerebral ventricular change over the first 10 years after the onset of schizophrenia.

Whether the brain structural abnormalities seen in schizophrenia are progressive is controversial. We previously reported on a longitudinal study of 50 first-episode patients with schizophrenia and 20 controls who had serial MRI scans during the first 5 years of illness. Greater enlargement of lateral ventricles and reduction of hemispheric volume was observed over time in the patients compared with controls. The present study obtained MRI scans from 26 of these patients and 10 controls at a follow-up 10 years subsequent to their first evaluations. The initial, 4-5th and 10th year scans were examined for the degree of change in ventricular and hemispheric volume. Significantly greater ventricular enlargement during the second 5 years was detected in the patient cohort compared with controls (P<0.05) with nine of the patients having ventricular enlargement (as measured by percent change) occurring at a rate exceeding that of any of the controls from years 1 through 10. The rate of ventricular change during the first 5 years was significantly correlated with age at first hospitalization, and ventricular enlargement in years 5-10 was correlated with the amount of time spent in hospital. Paradoxically, greater change in ventricles over time was correlated with better, not worse, outcome at the 10th year of follow-up with regard to the presence of symptoms. These data suggest heterogeneity in the course of brain change whereby some patients may exhibit active structural brain change only early in their illness or not at all after their first episode, while others continue to exhibit ventricular change spanning the decade subsequent to their first episode. Despite these differences among patients, the present study fails to detect any relationship of ventricular enlargement to poorer outcome as has been reported by other investigators.

Cerebral Ventricles↗
PubMed2003

Parent-of-origin effects on handedness and schizophrenia susceptibility on chromosome 2p12-q11.

Schizophrenia and non-right-handedness are moderately associated, and both traits are often accompanied by abnormalities of asymmetrical brain morphology or function. We have found linkage previously of chromosome 2p12-q11 to a quantitative measure of handedness, and we have also found linkage of schizophrenia/schizoaffective disorder to this same chromosomal region in a separate study. Now, we have found that in one of our samples (191 reading-disabled sibling pairs), the relative hand skill of siblings was correlated more strongly with paternal than maternal relative hand skill. This led us to re-analyse 2p12-q11 under parent-of-origin linkage models. We found linkage of relative hand skill in the RD siblings to 2p12-q11 with P=0.0000037 for paternal identity-by-descent sharing, whereas the maternally inherited locus was not linked to the trait (P>0.2). Similarly, in affected-sib-pair analysis of our schizophrenia dataset (241 sibling pairs), we found linkage to schizophrenia for paternal sharing with LOD=4.72, P=0.0000016, within 3 cM of the peak linkage to relative hand skill. Maternal linkage across the region was weak or non-significant. These similar paternal-specific linkages suggest that the causative genetic effects on 2p12-q11 are related. The linkages may be due to a single maternally imprinted influence on lateralized brain development that contains common functional polymorphisms.

Chromosome Mapping↗
PubMed2003

Sex-dependent effects of schizophrenia: an MRI study of gyral folding, and cortical and white matter volume.

Alterations, sometimes sex-dependent, in volumes and gyral structure of areas of cerebral cortex have been reported in schizophrenia. Such changes imply an anomaly of connectivity. The gyrification, percentage of tissue volume attributed to white matter, cortical volume and white matter volume were measured from magnetic resonance images in males and females with (n = 61) and without (n = 42) schizophrenia. The frontal, temporal and an amalgam of occipital and parietal lobes were examined in both hemispheres. There was no effect of schizophrenia on the gyrification of the brain. For the volume of occipito-parietal white matter, females with schizophrenia had bilaterally lower volumes, while males with schizophrenia had greater volumes than controls. It is concluded that the changes in connectivity underlying the pathogenesis of schizophrenia are sex-specific and expressed in occipito-parietal white matter.

Adult↗
PubMed2003

Application of a new image analysis technique to study brain asymmetry in schizophrenia.

The hypothesis that normal brain torque (i.e. rightward frontal and leftward occipital asymmetry) is anomalous in schizophrenia (Crow, 1997. Trends in Neuroscience, 20, 339-343) was tested by application of a novel image analysis technique on three-dimensional magnetic resonance images obtained in 26 adult patients with chronic schizophrenia (18 males, 8 females) and 24 controls (14 males, 10 females). Right and left cerebral hemisphere tissue was extracted via non-linear co-registration with a mask image, and maps were computed of inter-hemispheric differences in tissue volume in an array of columns of voxels orthogonal to the mid-plane (2D), and profiles of coronal slice volumes (1D). Furthermore, integration of two-dimensional column maps gave approximate lobar asymmetries, and occipital and frontal asymmetries were combined to give a volumetric measure of brain torque. Significant brain torque was revealed in male and female control and patient groups, and did not correlate with brain size. Frontal and occipital asymmetries were significantly correlated in all groups. Both frontal and occipital components of torque were significantly increased in males than females. Patients tended to have reduced torque, particularly the leftward occipital component. Furthermore, 3/26 patients (but no controls) had reversed torque (leftward frontal and rightward occipital asymmetry). Contrary to Crow's hypothesis, brain torque was not significantly reduced in patients with schizophrenia relative to controls, although reversal of torque was found in three cases. Future studies with larger sample sizes should consider sexual dimorphism and specific symptoms in relation to asymmetry.

Brain↗