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ABSTRACT: Fibers connecting fronto-temporal and fronto-medial structures that pass through the anterior limb of the internal capsule (ALIC) subserve executive and psychomotor functioning. Both of these functions are adversely affected in schizophrenia, and may be abnormal at illness onset. In a study of first-episode psychosis, we used diffusion tensor imaging (DTI) and cognitive testing to examine ALIC integrity. Fourteen early psychosis patients and 29 healthy volunteers were included. Symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). All structural and diffusion scans were acquired on a GE Signa 1.5T scanner. A T1-weighted 3D FSPGR Inversion Recovery imaging series was acquired for manual seeding in structural space. Diffusion tensor imaging (DTI) was performed, and all DTI images were co-registered to structural space. Seeds were manually drawn bilaterally on the coronal plane at a specified location. Diffusion images were post-processed for subsequent Tract-based Spatial Statistics (TBSS) analysis. First-episode psychosis patients had significantly smaller fronto-medial and fronto-temporal AIC tract volumes compared to healthy volunteers on the left and the right (p-values<0.04). No differences in mean fractional anisotropy (FA) were seen within either left or right tracts (p-values>0.05), nor did TBSS reveal any other differences in FA values between groups in other regions. Relationships between tract volumes and symptom severity were not observed in this study.
Biological Psychiatry 08/2012; 141(1):29-34. · 8.28 Impact Factor
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ABSTRACT: The thalamus is the gateway for sensory and motor information en route to the cortex. Information is processed via thalamocortical and corticothalamic pathways coursing through the internal capsules. In this study, we investigated the relationship between the anterior limb of the internal capsule, posterior limb of the internal capsule, and thalamus in first-episode psychosis (FEP).
Twenty-nine FEP subjects (26 DSM-IV schizophrenia, 2 schizoaffective disorder, 1 psychosis not otherwise specified) and 22 healthy volunteers participated in this study. Anterior limb of the internal capsule (AIC), posterior limb of the internal capsule (PIC), and the thalamus volumes were manually determined from MRI scans.
FEP subjects had reduced AIC volumes (F(1,45)=6.18, p=0.017) and thalamic volumes (F(1,45)=8.00, p=0.007) compared to healthy volunteers. PIC volumes did not differ. Significant correlations between AIC volumes and thalamic volumes were observed in subjects with FEP, but not in healthy volunteers. Negative relationships between thalamic volumes and symptom severity were also observed.
The AIC and thalamic volumes were reduced in subjects with FEP compared to healthy volunteers. Abnormalities in thalamocortical and orticothalamic pathways may contribute to functional disruption of neural circuits in psychosis.
Schizophrenia Research 11/2006; 87(1-3):89-99. · 4.75 Impact Factor
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ABSTRACT: The risk for schizophrenia in immigrants to Europe is approximately three times that of native-born populations. Discrimination and marginalization may influence the risk for schizophrenia within migrant populations. The primary objective of the present study was to determine whether the risk associated with migration was also evident 100 years ago. A second objective was to determine whether changing social stresses are associated with changes to the incidence of schizophrenia.
During the first two decades of the twentieth century, the Provincial Mental Hospital was the sole provider of psychiatric services in British Columbia, Canada. Detailed clinical records have been preserved for 99.5% of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses were made after a detailed file review and 807 patients met DSM-IV criteria for first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified. Diagnoses had high inter-rater reliability. The incidence of schizophrenia in migrants from Britain or Continental Europe was compared with that in the Canadian-born population using indirect standardization and Poisson models.
Migration from Britain or Continental Europe to Canada in the early twentieth century was associated with an increased rate of schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in immigrants but not in the native-born population and this increase occurred during a period of economic recession.
Migration was a risk factor for schizophrenia a century ago as it is today. This risk occurred in white migrants from Europe and increased during a period of increased social stress.
Schizophrenia Research 11/2006; 87(1-3):205-11. · 4.75 Impact Factor
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ABSTRACT: The assessment of outcomes after treatment with antipsychotic medication is fundamental to clinical care and research. The Routine Assessment of Patient Progress (RAPP) is a reliable multidimensional scale that employs nurses' ratings of symptoms and functioning in psychiatric inpatients. The present study sought to extend validity evidence for the RAPP by examining its ability to reflect changes associated with treatment by antipsychotic medications. The use of a different sample in this study also provided the opportunity to replicate earlier validity data collected on the original set of patients. Ninety-seven separate trials were conducted, involving 65 consecutive admissions to a unit that specializes in the assessment and treatment of patients with long standing severe psychiatric disorders. The RAPP, along with the Positive and Negative Syndrome Scale and global measures of severity, were administered at baseline and at the end of each trial. Both factor scores and clinically-derived subscales were analysed for sensitivity to change. Patients were globally rated as improved, unchanged or worsened at the end of the medication trial. Results indicated that the RAPP factor, clinical scale and total scores compared favourably to other outcome measures in patients rated as improved or worse. In patients rated as unchanged, RAPP scores displayed significantly less change than did the PANSS scores. These findings support the validity of the RAPP as an outcome measure in treatment trials.
Journal of Psychopharmacology 01/2004; 17(4):425-9. · 3.04 Impact Factor
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S W Flynn,
D J Lang,
A L Mackay,
V Goghari,
I M Vavasour,
K P Whittall, G N Smith,
V Arango,
J J Mann,
A J Dwork,
P Falkai,
W G Honer
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ABSTRACT: Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2',3'-cyclic nucleotide 3'-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.
Molecular Psychiatry 10/2003; 8(9):811-20. · 13.67 Impact Factor
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ABSTRACT: This study sought to: a) ascertain the effect on rates of violence by varying its operational definition and b) compare characteristics of violent and nonviolent patients. Aggressive behavior was recorded daily for every patient (N = 78) during a 2-year period. Standardized rating scales were used to rate psychopathology and functioning. Almost two thirds of patients were aggressive to others, and 26% violently assaulted another person. Official incident reports underestimated rates of violence to others, self- harm, and property damage. Multivariate predictive models that greatly improved accuracy over base rates showed that violent patients tended to be female, schizophrenic (nonparanoid type), and abusive of alcohol before admission. Violence is more common in treatment resistant psychotic inpatients than suggested by incident reports. Standardized definitions of violence are urged in order to accurately study its prevalence and correlates. Models combining both historical/demographic and clinical data may enhance prediction of violence.
Journal of Nervous & Mental Disease 11/2001; 189(10):716-21. · 1.68 Impact Factor
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ABSTRACT: The basal ganglia may contribute to extrapyramidal movement disorders, affective disturbances, and cognitive deficits in schizophrenia. Basal ganglia volumes are putatively affected by antipsychotic medications. The purpose of this study was to determine the long-term effects of risperidone treatment in a cohort of first-episode patients with schizophrenia.
The subjects were 30 patients with first-episode schizophrenia, 12 patients chronically treated with typical antipsychotics, and 23 healthy comparison subjects. They were scanned by magnetic resonance imaging at baseline. The first-episode patients received 1 year of continuous risperidone treatment, after which they and the comparison subjects were rescanned. Caudate, putamen, and globus pallidus volumes were determined from coronal images.
The baseline caudate, putamen, and globus pallidus volumes were significantly larger in the chronically treated patients than in the untreated first-episode subjects and comparison subjects. These volumes did not differ between the first-episode patients and healthy comparison subjects. Basal ganglia volumes were unchanged after 1 year of exposure to risperidone in the first-episode subjects. Extrapyramidal movement disorders were present in the majority of chronically treated patients and more than one-third of the never-medicated first-episode patients at baseline.
This group of first-episode patients did not exhibit abnormalities of basal ganglia volumes, nor were basal ganglia volumes affected by exposure to risperidone. Movement disorders were observed in both first-episode and chronically treated patients, suggesting effects of both illness and medications.
American Journal of Psychiatry 05/2001; 158(4):625-31. · 12.54 Impact Factor
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ABSTRACT: In the general population, low birthweight (LBW) is associated with neurological and psychological problems during childhood and adolescence. LBW may result from premature birth or poor fetal growth, and the independent effects of these two events on childhood development are not fully understood. The rate of low weight births is increased in schizophrenia and is associated with social withdrawal during childhood and an early onset of illness. However, it is unclear whether this LBW reflects poor fetal growth or premature birth, or whether these two risk factors have distinct implications for childhood functioning and age at onset of schizophrenia. Subjects included 270 patients with schizophrenia for whom a detailed history of obstetric events could be obtained. The rate of low weight births was high and was associated with poorer premorbid functioning and an earlier age at illness onset. The rate of both premature births and poor fetal growth was high relative to the normal population. Prematurity, but not poor fetal growth, was associated with premorbid social withdrawal and an early age at illness onset. Poor fetal growth, but not prematurity, was associated with low educational achievement. These results suggest that poor fetal growth and prematurity are associated with distinct patterns of childhood maladjustment in individuals who develop schizophrenia.
Schizophrenia Research 04/2001; 47(2-3):177-84. · 4.75 Impact Factor
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ABSTRACT: Substantial variability in age at onset of illness and course of illness exists between patients with schizophrenia. Recent studies suggest that age at illness onset may be useful in defining biologically and clinically distinct subgroups of patients.
Two hundred and ten males with schizophrenia were classified as early-onset or adult-onset according to their age at first hospitalization. Birth history, clinical functioning and treatment response was assessed in a subgroup of patients. Brain anatomy was assessed from CT scans in all patients and in 32 non-psychiatric control subjects.
Patients with an early-onset were likely to have a history of obstetric complications, a poor response to neuroleptic treatment, and showed no relationship between ventricle size and duration of illness. Adult-onset patients were less likely to have obstetric complications, more likely to respond to treatment in the first years of illness, and showed an association between brain structure and duration of illness.
The distinction between early- and adult-onset patients may have important aetiological and treatment implications.
Psychological Medicine 06/1998; 28(3):645-53. · 6.16 Impact Factor
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ABSTRACT: Clozapine and risperidone are used in treatment-resistant schizophrenia. At present, there are few reported comparisons of these drugs in this population. We report on a consecutive series of treatment-resistant schizophrenics given either clozapine or risperidone in open clinical trials.
Subjects were treated with clozapine (n = 57) or risperidone (n = 29). Pretreatment GAF, CGI, and PANSS scores did not differ between the groups, nor did demographic variables including age, age at first hospitalization, years ill, number of previous hospitalizations, or gender. The mean treatment trial was 12.1 weeks, with mean doses of clozapine 420 mg, and risperidone 7.75 mg. The length of the trial did not differ significantly between the groups. Response was taken to be a 20% decrease in the PANSS score.
Using repeated measures ANOVA, PANSS total scores (F = 5.3, p = 0.02) and positive subscore (F = 7.4, p = 0.008) showed greater improvement in the clozapine group than the risperidone group, while other PANSS subscores showed a trend toward greater improvement with clozapine. The PANSS-derived factors of excitement (F = 6.7, p = 0.01), psychosocial withdrawal (F = 3.8, p = 0.05), and psychomotor retardation (F = 3.9, p = 0.05) improved more in the group treated with clozapine. The GAF (F = 10.9, p = 0.0014), CGI (F = 11.5, p = 0.0011), and CGI improvement (p = 0.0001) scores also improved more in the clozapine group. Of the clozapine group, 25 (44%) responded, while 8 (28%) of the risperidone group responded to treatment.
Clozapine had better efficacy in subjects with treatment-resistant schizophrenia compared to risperidone, although risperidone appears to yield better response rates than those previously reported for typical antipsychotics. Double-blind, controlled trials of risperidone are needed to establish its efficacy in treatment-resistant schizophrenia.
Pharmacopsychiatry 02/1998; 31(1):25-9. · 2.07 Impact Factor
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ABSTRACT: Morphological brain abnormalities are common in schizophrenia, although the aetiological and clinical significance of these findings is largely unknown. Substantial between-subject variability suggests that large samples are needed to study the full implications of brain pathomorphology. Computerized tomography (CT) is frequently used routinely in schizophrenia, and large numbers of scans are available for study. This article describes the development and statistical properties of a rapid and simple method of assessing CT scans. The CT Rating Scale for Schizophrenia (CTRSS) is minimally affected by variability in scanning procedures, is reliable, and accurately estimates area and volumetric measures of brain spaces. By promoting the comprehensive assessment of large numbers of routinely obtained scans, the CTRSS would allow the investigation of variables that may systematically affect results (e.g. gender and age) and variables with low prevalence. The CTRSS provides a useful adjunct to technologically more sophisticated methods of assessment such as magnetic resonance imaging (MRI).
Acta Psychiatrica Scandinavica 12/1997; 96(5):395-401. · 4.22 Impact Factor
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Biological Psychiatry 01/1997; 40(11):1173-5. · 8.28 Impact Factor
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ABSTRACT: Birth problems can lead to changes in brain morphology in the general population and an increased prevalence of both birth problems and altered brain morphology are found in patients with schizophrenia. The purpose of this study was to test the hypothesis that these two findings are related. Birth history and the size of ventricular and sulcal spaces from nine regions of the brain were assessed in 80 male subjects with schizophrenia. No differences were found between patients with and those without a history of birth problems for the size of any brain space; however, ventricular size increased significantly with age in patients who had no birth complications but not in patients with a history of birth problems. The size of cortical sulci increased with age in patients with and those without a history of birth problems. These results suggest that region-specific rates of change in size may identify clinically meaningful patients subgroups.
Biological Psychiatry 01/1997; 40(12):1200-8. · 8.28 Impact Factor
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ABSTRACT: Mechanisms determining temporal lobe structural asymmetries may be involved in the pathogenesis of schizophrenia. To investigate the temporal lobes in familial schizophrenia, computed tomographic scans were obtained from 51 subjects (seven families). Enlargement of sylvian fissures and temporal lobe sulcal spaces was observed in family members with schizophrenia. The posterior one-third of the sylvian fissure was larger on the left side in subjects with schizophrenia, and larger on the right side in unaffected individuals. This disturbed pattern of posterior sylvian fissure asymmetry suggests that adjacent language regions may be affected in schizophrenia. An intermediate degree of disturbance in subjects who had schizophrenia-related illnesses or were obligate carriers suggests that genetic factors may be important determinants of temporal lobe asymmetries in familial schizophrenia.
Neuroreport 01/1996; 7(1):221-4. · 1.66 Impact Factor
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ABSTRACT: Regional measures of cortical sulcal and ventricular enlargement on computed tomography scan were studied in a clinical sample of patients treated with clozapine. Cortical sulci were significantly enlarged in clozapine nonresponders compared to responders. The Clinical Global Impressions score at discharge was related to the size of the posterior frontal and lateral temporal sulci, with large sulci predicting a poorer response to clozapine treatment.
Neuropsychopharmacology 09/1995; 13(1):85-7. · 7.99 Impact Factor
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ABSTRACT: Neurodevelopmental abnormalities and cortical sulcal enlargement both occur in schizophrenia. To test the hypothesis that these abnormalities were related, CT scans from 164 psychotic patients (80 with schizophrenia) were reviewed. Neurodevelopmental abnormalities were observed in 11%. Abnormalities were equally prevalent in schizophrenia and other psychotic disorders. Cortical sulcal enlargement was observed in 39% of patients with schizophrenia, and was not associated with developmental abnormalities. Different mechanisms may contribute to distinct structural abnormalities.
Schizophrenia Research 09/1995; 16(2):121-5. · 4.75 Impact Factor
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ABSTRACT: To study the clinical response to clozapine in patients with refractory schizophrenia.
Open trial of clozapine in 61 consecutively-treated patients.
Following clozapine, the level of function of patients was improved relative to admission (p = 0.0001) and to the highest level in the previous year (p = 0.0001). Severity of illness was decreased (p = 0.0001). Overall, 31% of the patients were classified as responders to clozapine and the responders were all identified by 32 weeks of treatment. Poor functioning in the previous year was associated with less favourable response. At a mean interval of 26 months following discharge, 72% of the patients were continuing clozapine treatment.
This open trial of patients who were treated consecutively indicates a comparable degree of response to clozapine as observed in controlled clinical trials, and that level of functioning in the previous year was the best predictor of response.
Canadian journal of psychiatry. Revue canadienne de psychiatrie 06/1995; 40(4):208-11. · 2.42 Impact Factor
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ABSTRACT: A history of obstetric complications (OCs) is common in schizophrenia and may lead to a severe form of the disorder. In order to test this possibility, three questions were identified: (1) Is a history of OCs in schizophrenia common in patients with a severe form of illness? (2) Do patients with OCs have more impaired function, greater severity of illness, and poorer treatment outcome than those with no identified OCs? (3) Are OCs associated with an early age at onset of illness? Obstetric history, clinical indices of functioning, and illness severity were obtained for 83 severely ill patients with schizophrenia. The proportion of patients with a history of OCs was greater in this study than has been reported previously. Subjects with a history of OCs had better functioning than those with no OCs at the time of admission but no group differences were found at discharge. No difference in age at onset of illness was found between patients with and without an OC history.
Schizophrenia Research 02/1995; 14(2):113-20. · 4.75 Impact Factor
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ABSTRACT: Brain structure in familial schizophrenia was studied with computerized tomography in 42 individuals from six multigenerational families. Sulcal enlargement in the lateral temporal cortex, and ventricular and cisternal enlargement in the medial temporal region were observed in psychotic individuals compared to unaffected family members. Genetic factors in familial schizophrenia may exert part of their effect through determining or altering temporal lobe structure.
Biological Psychiatry 01/1995; 36(11):737-43. · 8.28 Impact Factor
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ABSTRACT: The reasons for poor treatment response in some patients with schizophrenia remain unclear. It is possible that misdiagnosis of nonschizophrenic disorders as schizophrenia could result in suboptimal pharmacotherapy in some patients.
To assess this possibility, 110 severely ill, chronic patients with a referral diagnosis of schizophrenia were comprehensively assessed and rediagnosed according to DSM-III-R criteria. Global Assessment of Function (GAF) and Clinical Global Impressions (CGI) ratings were made at admission and at discharge from the ward, after the implementation of individualized treatment plans.
The diagnosis of schizophrenia was confirmed in 80 patients (73%) and revised to another type of psychotic illness in 30 patients (27%). The GAF and CGI ratings were similar at admission in patients with confirmed and revised diagnoses. All patients improved by the time of discharge (p = .0001); however, patients with a revised diagnosis improved more than those with confirmed schizophrenia (p = .02). Patients with a revised diagnosis were less likely to require continued hospitalization on chronic care wards (p = .004). At admission, medication regimens were similar in the two groups of patients. At discharge, patients with a revised diagnosis were less likely to have received neuroleptics (p = .007) and more likely to have received antimanic drugs (p = .0002) or electroconvulsive therapy (p = .0004).
These findings from a clinical sample suggest that diagnostic reassessment is an important first step in the management of apparently refractory schizophrenia.
The Journal of Clinical Psychiatry 01/1995; 55(12):528-32. · 5.80 Impact Factor
