Iris A. Fischer's research while affiliated with Harvard University and other places

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Publications (31)


A quantitative MR measure of the fornix in schizophrenia
  • Article

February 2001

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58 Reads

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32 Citations

Schizophrenia Research

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Chandlee C. Dickey

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Robert W. McCarley

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[...]

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Some cognitive disturbances accompanying schizophrenia may be due to abnormalities in the thalamus and components of the limbic system. The fornix is an important white-matter relay pathway connecting these structures and is likely to be affected in schizophrenia as well.Magnetic resonance images of the fornix were analyzed in 15 schizophrenic patients and 15 matched comparison group subjects. Fornix volume was compared between the two groups and was also correlated with the volumes of other neuroanatomical structures, as well as with illness presentation, clinical status, and cognitive/psychological measures. There was no significant difference in fornix volume between the two groups. Of note, fornix volume correlated significantly with the volumes of the hippocampus, parahippocampus, and the superior temporal gyrus in the schizophrenic subjects, but not in the controls. Moreover, the correlation between fornix and parahippocampal gyrus volumes differed significantly between the two groups. No association was found between fornix volume and illness presentation or between fornix and cognitive/clinical measures.Results suggest that there are no marked changes in fornix volume in schizophrenia by MRI. The fornix, however, may be part of a network of structures affected in schizophrenia, as indicated by correlated volumetric changes.

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Large CSF Volume Not Attributable to Ventricular Volume in Schizotypal Personality Disorder

April 2000

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10 Reads

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6 Citations

enia spectrum. For example, data indicate that schizotypal personality disorder has the same genetic diathesis as schizophrenia; the risks of schizophrenia in a sibling of a proband with schizotypal personality disorder and a sibling of a proband with schizophrenia are the same (1--4). Schizotypal personality disorder is thus an ideal spectrum disorder to study because subjects with this disorder often have not been treated with neuroleptics. In addition, persons with schizotypal personality disorder have not experienced the possible complicating effects of a chronic illness, including hospitalization, nor the stress of a long-term illness, which may result in glucocorticoidinduced cell morphological changes (5, 6). Environmental richness and nutrition, which may be different in the chronically ill, have also been demonstrated to affect cellular morphology (5, 6). There is also the further possibility that, by examining similarities and differences of neuroanatomical abnormaliti




Large CSF Volume Not Attributable to Ventricular Volume in Schizotypal Personality Disorder

January 2000

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28 Reads

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65 Citations

American Journal of Psychiatry

The purpose of this study was to determine whether schizotypal personality disorder, which has the same genetic diathesis as schizophrenia, manifests abnormalities in whole-brain and CSF volumes. Sixteen right-handed and neuroleptic-naive men with schizotypal personality disorder were recruited from the community and were age-matched to 14 healthy comparison subjects. Magnetic resonance images were obtained from the subjects and automatically parcellated into CSF, gray matter, and white matter. Subsequent manual editing separated cortical from noncortical gray matter. Lateral ventricles and temporal horns were also delineated. The men with schizotypal personality disorder had larger CSF volumes than the comparison subjects; the difference was not attributable to larger lateral ventricles. The cortical gray matter was somewhat smaller in the men with schizotypal personality disorder, but the difference was not statistically significant. Consistent with many studies of schizophrenia, this examination of schizotypal personality disorder indicated abnormalities in brain CSF volumes.


Subgenual Cingulate Cortex Volume in First-Episode Psychosis

August 1999

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38 Reads

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302 Citations

American Journal of Psychiatry

Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings. Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.


Schizotypal Personality Disorder and MRI Abnormalities of Temporal Lobe Gray Matter

July 1999

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64 Reads

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140 Citations

Biological Psychiatry

Background: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. Methods: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. Results: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. Conclusions: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.




Citations (18)


... Since the 1980s, when a resurgence of interest in initiating neurobiological studies in Schizophrenia took place, Kraepelin's viewpoint has been challenged and radically altered by advances from several levels of inquiry that point to a prenatal-perinatal origin of at least some of the brain abnormalities found in individuals with Schizophrenia (Cannon, 1998;Keshavan & Hogarty, 1999;Mednick, Cannon, Barr, & Lyon, 1991;Walker & DiForio, 1997;Weinberger, 1987). During the early 1980s, a number of investigations converged and all found evidence for increased ventricle size in persons with schizophrenic illness (Shenton et al., 2001). These enlarged ventricles were present at the onset of the illness and did not protract in size as the illness proceeded over time, even in prospective longitudinal studies. ...

Reference:

The Developing Brain and Neural Plasticity: Implications for Normality, Psychopathology, and Resilience
Morphometric magnetic resonance imaging studies: Findings in schizophrenia
  • Citing Article
  • January 2001

... Auditory sensory processing has been found to be impaired in schizophrenia (Salisbury et al., 1998; Javitt et al., 2000) and correlate with clinical features, particularly negative symptoms (Javitt et al., 2000), (Kasai et al., 2002) (Leitman et al., 2005) and cognitive impairment (Baldeweg et al., 2004). Abnormalities in the superior temporal gyrus (STG) have been implicated in the processing of pure tones, a fundamental element of complex sounds and language, using fMRI (Wible et al., 2001) and event-related potentials (Salisbury et al., 1998). ...

Mismatch negativity is reduced in chronic but not first episode schizophrenia
  • Citing Article
  • April 1999

Biological Psychiatry

... One issue raised by these studies in patients affected by chronic schizophrenia is whether factors such as chronic morbidity, long-term neuroleptic treatment, or other effects associated with chronic mental illness may contribute to the relationship between left-lateralized P300 and STG abnormalities. To determine if temporal lobe P300 and MRI abnormalities are present at the onset of the illness, we evaluated the auditory P300 component and STG volumes in first-episode patients with schizophrenia or affective psychosis and in age-matched controls (Hirayasu et al., 1997; Salisbury et al., 1998). Quantitative MRI evaluation revealed that schizophrenic patients showed significantly reduced gray matter in the left STG compared to first-episode affective psychotic patients or control subjects. ...

MRI and ERP abnormalities in first episode schizophrenia and affective psychosis
  • Citing Article
  • March 1997

Schizophrenia Research

... There was no significant correlation between volume reduction and length of illness as measured by number of recurrences or age of onset ( RD Todd et al, unpublished data, 2000). This finding has been replicated in individuals with first-episode psychosis with affective disorder [84,85]. Together these findings suggest some continuity in structural anatomy between early-onset and adult-onset mood disorders. ...

323. Subgenual prefrontal cortex reduction in first episode affective psychosis
  • Citing Article
  • April 1998

Biological Psychiatry

... [40][41][42][43] Moreover, progressive reduction of the superior temporal gyrus volume has been reported. 44 One would expect that a subtle active process of altered brain cellular growth and repair may be continuing through the course of the illness in some patients. ...

387. Superior temporal gyrus changes over time in first episode schizophrenia
  • Citing Article
  • April 1998

Biological Psychiatry

... We have also tried to predict the plasma u and CSF kinetics of methotrexate in healthy dogs by systems-based scaling of our rat (Abbott, 2004;Cserr et al., 1981) 10.5 ll/min (based on 0.11 ll/min/g brain (Cserr et al., 1981)) 50% of Q CSF (Kimelberg, 2004) (0.1 ml/min in 9 year old) 0.175 ml/min (Kimelberg, 2004) Q CSF 2.2 ll/min (Cserr, 1965) 63 ll/min (Bering, 1959) (8.798 * log(BW) À 1.365)/60 ml/min (Yasuda et al., 2002) (0.2 ml/min in 9 year old) 0.4 ml/min (Nilsson et al., 1992) V PL 10.6 ml (Lee and Blaufox, 1985) 1112 ml (Visser et al., 1982) Age-dependent (Linderkamp et al., 1977) (1600 ml for 9 year old) 2900 ml (Frank and Gray, 1953) (Cserr et al., 1981) 19 ml (based on 95.5 g brain) (Bering, 1959) 270 ml (Thorne et al., 2004) (based on 1350 g brain) (Dekaban and Sadowsky, 1978) 280 ml (Thorne et al., 2004) (based on 1400 g brain) (Dekaban and Sadowsky, 1978) V CSF,total 300 ll (Bass and Lundborg, 1973) 15.6 ml (Löfgren et al., 1973) 3 ml/kg (2-12 y) 1.75 ml/kh (>12 y) (Troncin and Dadure, 2009) (90 ml for 9 year old) 140 ml (Kimelberg, 2004) V LV 50 ll (Condon et al., 1986;Kohn et al., 1991) 3.8 ml (Vladić et al., 2009) (24% of total CSF volume) 17% of total CSF volume (Condon et al., 1986;Kohn et al., 1991) 22.5 ml (Condon et al., 1986;Dickey et al., 2000;Kohn et al., 1991) V TFV 50 ll (Levinger, 1971) 1.3 ml (Vladić et al., 2009) (8% of total CSF volume) 17% of total CSF volume (Condon et al., 1986;Kohn et al., 1991) 22.5 ml (Condon et al., 1986;Kohn et al., 1991) V CM 17 ll (Adam and Greenberg, 1978;Robertson, 1949) 0.9 ml (6% of total CSF volume (human value)) 6% of total CSF volume (Adam and Greenberg, 1978;Robertson, 1949) 7.5 ml (Adam and Greenberg, 1978;Robertson, 1949) V SAS 180 ll (Bass and Lundborg, 1973;Levinger, 1971) 9.0 ml (60% of total CSF volume (human value)) 60% of total CSF volume 90 ml (Pardridge, 2011) Parameter values in italic are derived from literature. F u,p is the fraction unbound in plasma, CL E is the elimination clearance from plasma. ...

Large CSF Volume Not Attributable to Ventricular Volume in Schizotypal Personality Disorder
  • Citing Article
  • January 2000

American Journal of Psychiatry

... Discrepancies in the selection of the eligible articles have been discussed in advance with the whole group and were resolved by discussion and consensus. PubMed (EEG OR electroencephalography OR "EEG microstate" OR "dipole source localization" OR sLORETA OR LORETA OR eLORETA OR ERP OR "event-related potential" OR "spectral analysis" OR "frequency domain analysis" OR "spectral band" OR "neural oscillations" OR "spectral power" OR N100 OR N1 OR MMN OR "mismatch negativity" OR P300 OR P3a OR P3b OR "event-related" OR "evoked potential" OR "evoked-response") AND ("ultra-high risk psychosis" OR "clinical high risk psychosis" OR "prodromal psychosis" OR "first episode schizophrenia" OR "first episode psychosis" OR "early onset schizophrenia") Filters: Languages, English Search in [All fields] No time limit 220 13.07.2020 ...

First-Episode Schizophrenic Psychosis Differs From First-Episode Affective Psychosis and Controls in P300 Amplitude Over Left Temporal Lobe
  • Citing Article
  • March 1998

Archives of General Psychiatry

... Of note, idiopathic and 22q11.2DS-associated schizophrenia present similar clinical paths [33,34] and clinical presentations [35] and high concordance of neuroanatomic correlates [36][37][38][39][40][41], which suggests that comparable neural changes could be explaining psychotic symptomatology in both populations. With approximately half of the adolescents with 22q11.2DS ...

MRI Study of Cavum Septi Pellucidi in Schizophrenia, Affective Disorder, and Schizotypal Personality Disorder
  • Citing Article
  • Full-text available
  • May 1998

American Journal of Psychiatry