Biomedical subjects

J G Csernansky

Publications and source records attributed to J G Csernansky.

At least 37 records · Page 2Linked to original sources

PubMed1998

Glucocorticoid interactions with memory function in schizophrenia.

Glucocorticoid (GC) exposure can affect brain function, including potential adverse effects on hippocampal physiology and on specific elements of cognitive performance. In a prior study of healthy adult humans, decreased verbal memory performance was detected during four days of double-blind, placebo-controlled dexamethasone (DEX) treatment. Using an identical experimental design and sample size (n = 19), the cognitive effect of DEX treatment was studied in 11 subjects with schizophrenia, compared with 8 receiving placebo. In contrast to the effect in healthy adults, GC treatment with DEX at this dose (cumulative 3.5 mg) and duration did not decrease verbal memory performance or other measures of cognitive function in the patients with schizophrenia. When data from this experiment was compared with data from the previous study of healthy adults, covarying differences in baseline memory performance, a significant 3-way interaction was detected between subject group, treatment condition, and the repeated measurements of verbal memory performance across baseline, treatment and washout (F[3,87] = 4.84, p = .0066), suggesting differential cognitive effects of DEX in the patients versus the previously studied healthy subjects. Baseline plasma cortisol concentrations (0800 h) prior to DEX treatment were inversely correlated with baseline delayed (rs = -0.536, p = .03) verbal recall performance, supporting a previous report. The current results await replication using a larger sample size but provide preliminary evidence for an altered behavioral response to acute GC exposure in schizophrenic versus healthy subjects, and further evidence for a relationship between chronic changes in circulating cortisol and the memory impairments found in this disorder.

Adult↗

PubMed1998

New models of the pathophysiology of schizophrenia: editors' introduction.

New models of the pathogenesis of schizophrenia are presented. These models represent hypotheses intended to stimulate discussion and new experimentation. Each of the contributions approach the pathophysiology of schizophrenia from a unique perspective. Yet, all of them emphasize the integration of new advances in basic neuroscience, the functional neuroanatomy of schizophrenia, and information drawn from new biotechnologies, such as neuroimaging and molecular genetics, to provide unique insights into schizophrenia. In each case, the novel hypotheses proposed also illustrate the continuing need for a better understanding of the dynamic interaction between synaptic plasticity and neural circuitry to further our understanding of the human brain in health and disease.

Humans↗

PubMed1998

Limbic-cortical neuronal damage and the pathophysiology of schizophrenia.

Neurobiological studies of patients with schizophrenia suggest that abnormalities of both anatomy and function occur in limbic-cortical structures. An anatomical circuit links the functioning of the ventral striatum (i.e., nucleus accumbens) with the hippocampus and other limbic-cortical structures where neurobiological abnormalities have been found. In animals, lesions of limbic-cortical neurons cause decreases in glutamatergic input to the nucleus accumbens and are also associated with decreases in presynaptic dopamine release, increases in the density of D2-like dopamine receptors, and insensitivity to the actions of dopamine antagonists such as haloperidol. These experiments suggest a plausible pathophysiology of schizophrenia, in that schizophrenic symptoms may be caused by an abnormal dopaminergic state brought about by a primary limbic-cortical lesion and deficits in glutamatergic inputs to the ventral striatum.

Animals↗

PubMed1998

Predicting length of stay in an acute psychiatric hospital.

OBJECTIVE: Multivariate statistical methods were used to identify patient-related variables that predicted length of stay in a single psychiatric facility. The study investigated whether these variables remained stable over time and could be used to provide individual physicians with data on length of stay adjusted for differences in clinical caseloads and to detect trends in the physicians' practice patterns. METHODS: Data on all patients discharged over two six-month periods were collected at an acute psychiatric inpatient facility. Stepwise multiple regression analyses were conducted on the two datasets. RESULTS: The results from both analyses revealed that five variables significantly predicted length of stay and were stable over time. They were a primary diagnosis of schizophrenia, the number of previous admissions, a primary diagnosis of a mood disorder, age, and a secondary diagnosis of an alcohol- or other drug-related disorder. For some physicians, the mean length of stay of their patients differed significantly from the length predicted by the regression model--generally, it was shorter. CONCLUSIONS: The results demonstrate that patient-related predictors of length of stay in a single psychiatric hospital can be identified using relatively simple statistical procedures and can be consistent across a large dataset and over time.

Adult↗

PubMed1998

Higher cerebrospinal fluid MHPG in subjects with dementia of the Alzheimer type. Relationship with cognitive dysfunction.

The authors sought to determine the relationships between cerebrospinal fluid (CSF) levels of three neurotransmitter monoamine metabolites and cognitive function. CSF was collected from subjects with dementia of the Alzheimer's type ([DAT] n = 28) and control subjects (n = 10) for determination of CSF 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxy-phenylglycol (MHPG), and homovanillic acid (HVA) levels. All subjects underwent systematic assessment to determine cognitive function. Subjects with DAT had higher concentrations of CSF MHPG. In the overall sample, cognitive function was inversely correlated with CSF levels of MHPG but not with 5-HIAA or HVA. Within the DAT sample, these correlations did not achieve significance.

Aged↗

PubMed1997

Structural magnetic resonance imaging abnormalities in men with severe chronic schizophrenia and an early age at clinical onset.

BACKGROUND: Early age at onset of schizophrenia often signifies a more severe form of the illness. However, the relationship between age at onset and brain abnormalities has not been established. We assessed temporal-limbic morphometry in severely ill men with chronic schizophrenia who had a relatively early onset of illness and examined the relationships among regional brain volumes, clinical symptoms, and age at illness onset. METHOD: Temporal lobe, superior temporal gyrus, hippocampus, temporal horn, lateral ventricles, third ventricle, and frontoparietal volumes were measured on magnetic resonance imaging data from 56 schizophrenic men (mean [SD] age at illness onset, 16.6 [4.2] years) recruited from a state hospital and 52 age- and range-matched healthy control men. RESULTS: Patients had significantly smaller gray matter volumes in the temporal lobe, superior temporal gyrus, and frontoparietal regions; smaller temporal lobe white matter volumes; and larger cerebrospinal fluid volumes for temporal lobe sulci and the 3 ventricular measures. There were no group differences in hippocampal volumes. Psychotic symptom subscores from the Brief Psychiatric Rating Scale were selectively correlated with smaller left posterior superior temporal gyrus gray matter volumes. None of the brain measurements were significantly correlated with age at illness onset. CONCLUSIONS: Data from this unique sample of severely ill schizophrenic men emphasize a pattern of structural abnormalities involving the cortex, but not the hippocampus, in schizophrenia. Furthermore, these data support theories suggesting that superior temporal gyrus abnormalities contribute selectively to psychotic symptoms and that the extent of structural abnormalities is unrelated to age of clinical symptom onset.

Adolescent↗

PubMed1997

The effects of kainic acid lesions on dopaminergic responses to haloperidol and clozapine.

The antipsychotic drugs haloperidol and clozapine have the common action of increasing dopamine metabolism in the striatum (nucleus accumbens, caudate-putamen) of the rat. Intracerebroventricular administration of kainic acid (KA) produces neuronal loss in limbic-cortical brain regions which project directly or indirectly to the striatum. In the present study, dopamine metabolism in subregions of the striatum was examined in rats with KA lesions after acute and chronic haloperidol or clozapine administration. The main findings was that the elevating effect of acute haloperidol treatment on the dopamine metabolite, DOPAC, was blocked in the nucleus accumbens shell and diminished in medial and laterodorsal caudate-putamen of the KA-lesioned rats. In addition, the elevating effects of both acute and chronic haloperidol treatment on dopamine turnover were attenuated in the laterodorsal caudate-putamen of KA-lesioned rats. The levels of dopamine, DOPAC, and HVA after chronic clozapine treatment were greater in KA-lesioned than control rats. These results indicate that dopaminergic responses to haloperidol may be diminished by limbic-cortical neuropathology, while such pathology does not significantly alter dopaminergic responses to clozapine.

Animals↗

PubMed1997

Kainic acid lesions enhance locomotor responses to novelty, saline, amphetamine, and MK-801.

Intracerebroventricular (i.c.v.) administration of kainic acid (KA) to rats produces neuronal loss in the hippocampus and other areas of the limbic system. The present study demonstrates that i.c.v. KA enhances the locomotor response to novelty and saline injection, as well as to amphetamine and MK-801. Sixteen to 18 days after i.c.v. administration of KA or vehicle, lesioned and control rats were placed in a novel cage, and locomotor activity and grooming were recorded for 30 min prior to and 60 min following a subcutaneous injection of saline, D-amphetamine, or MK-801. In response to the novel cage and after each injection, KA rats exhibited increased locomotor activity relative to controls. Grooming behavior was found to be elevated in the KA rats when compared to controls, but only in response to the novel cage and saline injection. The possibility that damage to the limbic system disrupts dopaminergic regulation of locomotor behavior is discussed, as well as implications for neuropathology in schizophrenia.

Animals↗

PubMed1997

Impulsive aggression in personality disorder correlates with platelet 5-HT2A receptor binding.

The purpose of this study was to examine the relationship between platelet 5-HT2A receptor binding and aggressive behavior. 125I-LSD Bmax and Kd values were measured for 22 subjects meeting DMS-III-R criteria for one or more personality disorders and 12 healthy volunteer subjects. Aggression and impulsivity were assessed using the Buss-Durkee Hostility Inventory (BDHI) Assault scale, Life History of Aggression (LHA) scale, and the Barratt-11 Impulsiveness scale (BIS-11). Bmax and Kd values did not differ between personality disordered subjects and healthy volunteers. However, both Bmax and Kd values correlated positively with BDHI Assault scores in personality-disordered subjects but not in healthy volunteer subjects. These results suggest that assaultiveness in personality-disordered subjects may covary with increasing numbers, but decreasing affinity, of platelet 5-HT2A receptor sites labeled by 125I-LSD.

Adult↗

PubMed1997

Correlated reductions in cerebrospinal fluid 5-HIAA and MHPG concentrations after treatment with selective serotonin reuptake inhibitors.

We sought to determine whether fluvoxamine and fluoxetine, two different antidepressants with in vitro selectivity for the serotonin uptake transporter also demonstrated similar selectivity in vivo. To accomplish this, we measured cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) before and after 6 weeks of treatment with these two drugs. Twenty-four subjects who had major depression according to DSM-III-R criteria gave written, informed consent for the collection of CSF during a double-blind comparative treatment trial of fluvoxamine (50-150 mg/day) and fluoxetine (20-80 mg/day). The symptoms of subjects were assessed clinically on a weekly basis throughout the treatment trial. CSF samples were obtained after a 7- to 14-day washout period before treatment and again at the end of treatment. CSF samples were analyzed for 5-HIAA, HVA, and MHPG using high-pressure liquid chromatography coupled to electrochemical detection. Fluvoxamine- and fluoxetine-treated patients did not differ in clinical outcome or in the CSF concentrations of monoamine metabolite levels before or after treatment. Therefore, the CSF data were pooled. Drug treatment, overall, was associated with significant decreases in 5-HIAA and MHPG and a trend toward a reduction in HVA levels. Levels of 5-HIAA, MHPG, and HVA were reduced by 57%, 48%, and 17%, respectively. In addition, the magnitude of the decreases in 5-HIAA and MHPG appeared to be correlated (r = 0.83) across the subjects, although a Spearman rank correlation indicated that outlying values had an undue effect on this relationship. These results suggest that treatment with selective serotonin reuptake inhibitors, which are selective for serotonin uptake in vitro, does not show a similarly selective effect on serotonin in vivo during treatment of patients.

Adult↗

PubMed1997

Three-dimensional hippocampal MR morphometry with high-dimensional transformation of a neuroanatomic atlas.

PURPOSE: To test automated three-dimensional magnetic resonance (MR) imaging morphometry of the human hippocampus, to determine the potential gain in precision compared with conventional manual morphometry. MATERIAL AND METHODS: A canonical three-dimensional MR image atlas was used as a deformable template and automatically matched to three-dimensional MR images of 10 individuals (five healthy and five schizophrenic subjects). A subvolume containing the hippocampus was defined by using 16 landmarks that constrained the automated search for hippocampal boundaries. Transformation of the hippocampus template was automatically performed by using global pattern matching through a sequence of low-then high-dimensional translations, rotations, and scalings. RESULTS: The average test-retest volume difference measured with the automatic method was 3.1%, compared with the manual test-retest difference of 7.1%. Correlation between automated and manually determined volumes demonstrated the validity of the automated technique (intraclass correlation coefficient = .86). CONCLUSION: The automated method estimates hippocampal volumes with less variability (ie, lower variance) than that of manual out-lining.

Adult↗

PubMed1996

Platelet serotonergic markers and Tridimensional Personality Questionnaire measures in a clinical sample.

A group of patients with major depressive disorder, with and without comorbid obsessive-compulsive disorder, completed the Tridimensional Personality Questionnaire (TPQ). Harm Avoidance scores were found to be high compared to published age-matched norms and to display a significant positive correlation with Hamilton Depression Rating Scale scores. Platelet 125I-lysergic acid diethylamide (125I-LSD) and 3H-paroxetine binding Bmax values were measured to test Cloninger's hypothesis that Harm Avoidance scores would correlate significantly with measures of serotonergic function. A significant inverse correlation was found between Harm Avoidance scores and 125I-LSD Bmax values. Correlations between 3H-paroxetine Bmax values and TPQ scale scores were not significant. These results suggest an alternative view of the literature relating platelet 5-hydroxytryptamine-2a receptors and mood disorders in that the temperament dimension, Harm Avoidance, may explain prior inconsistencies involving links with depression and suicidality.

Adult↗

PubMed1996

Gray matter deficits in young onset schizophrenia are independent of age of onset.

This study examined whether the degree of brain dysmorphology observable in adulthood was related to onset age of schizophrenic symptoms. Brain magnetic resonance imaging (MRI) scans were acquired in 57 men with schizophrenia, whose age at MRI was 19-53 years, and whose symptom onset ranged from age 7 to 29 years; all were inpatients in a state hospital. Volumes of intracranial space, cortical gray matter (GM) and white matter (WM), and cerebrospinal fluid (CSF) in lateral and third ventricles and cortical sulci were derived from MRI scans and corrected by regression analysis for variations attributable to age and head size, quantified in a control sample of healthy community volunteers. The schizophrenic patients had larger volumes of cortical and ventricular CSF and smaller volumes of cortical GM but not WM than age-matched controls, whether or not volumes were adjusted for head size and age norms. Age of onset did not correlate with any of the five age-adjusted brain measures. Neither current age, length of illness, nor symptom severity correlated with age-normalized volumes of cortical GM, sulcal CSF, or ventricular CSF. These observations are consistent with the theory that brain structure deficits 1) first develop prior to symptom onset (perhaps during the prenatal and/or early childhood process of GM development); 2) probably establish a vulnerability to subsequent dysfunctionality; but 3) are nonprogressive.

Adult↗

PubMed1996

Hippocampal atrophy in recurrent major depression.

Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity.

Aged↗

PubMed1996

Impulsive aggression in personality disorder correlates with tritiated paroxetine binding in the platelet.

BACKGROUND: To examine the relationship between binding parameters of the platelet central serotonergic (5-HT) transporter and measures of aggression and impulsivity in adult human subjects. METHODS: Maximal number of platelet tritiated paroxetine binding sites (Bmax) and dissociation constant (Kd) values were measured in patients with personality disorder (n = 24) and healthy volunteers (n = 12). Measures of aggression and impulsivity included the total score and aggression subscale of the Life History of Aggression, the Motor Aggression factor and the assault subscale of the Buss-Durkee Hostility Inventory, and the total score and motor impulsivity subscale of the Barratt Impulsiveness Scale. RESULTS: The Bmax, but not Kd, values of platelet tritiated paroxetine binding was inversely correlated with the Life History of Aggression total score and aggression score and with the Buss-Durkee Hostility Inventory assault score in patients with personality disorder but not in healthy volunteer subjects. This relationship was independent of influences of factors related to depression, global function, or history of alcoholism or drug abuse. CONCLUSIONS: Reduced numbers of platelet 5-HT transporter sites may covary with life history of aggressive behavior in patients with personality disorder. This may represent another abnormality in 5-HT function in individuals with personality disorder and aggressive behavior.

Adult↗

PubMed1996

The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients.

Thirty chronically hospitalized, refractory schizophrenic patients were evaluated while on typical neuroleptics and again after 12 weeks of clozapine treatment. Patients demonstrated small but statistically significant reductions in total Brief Psychiatric Rating Scale (BPRS) symptoms, need for seclusion and restraint, and PRN medications, and they frequently were transferred to a less restrictive treatment environment. Neuropsychological test data from a subset of patients suggested improvement on measures of verbal fluency and graphomotor speed, but deterioration on measures of visual memory and executive/frontal ability. Clozapine's different effects on multiple neurotransmitter systems may be responsible for its mixed effects on cognitive abilities. No significant relationships were found between symptom reduction, cognitive improvement, and transfer to a less restrictive environment.

Adult↗

PubMed1996

A neuropsychological study of early onset schizophrenia.

Characterizing a pattern of cognitive dysfunction in early onset schizophrenic patients may illuminate neurodevelopmental contributions to the illness. A cohort of chronically institutionalized schizophrenic patients with a variable range of age of onset (range 7-29 years) was administered a comprehensive battery of neuropsychological tests that included the Luria-Nebraska Neuropsychological Test Battery. After statistical control of age, parental socioeconomic class (SES) effects, and thorazine equivalents, age of illness onset was positively correlated with performance on measures of motor ability, perceptual motor and pure motor speed, receptive and expressive speech, and overall cognition function, and inversely related to severity of negative symptoms; that is, earlier age of onset was associated with worse cognitive performance and an increase in negative symptoms. This study demonstrates that an early age of onset in schizophrenic illness is associated with impairment on tasks which involve motor and language abilities, functions linked to the frontal, temporal, and subcortical regions of the brain. This association is not due to the effects of medication, negative symptoms, or duration of illness.

Adult↗

PubMed1996

Hippocampal MR imaging morphometry by means of general pattern matching.

PURPOSE: To determine the repeatability and validity of a pattern-matching method for the segmentation and measurement of hippocampi on magnetic resonance (MR) images. MATERIALS AND METHODS: Comparable two-dimensional MR images obtained in 18 subjects (nine healthy control subjects [six men, three women; aged 24-54 years] and nine patients with schizophrenia [six men, three women; aged 22-61 years]) were twice segmented manually and twice segmented by using pattern matching with digital atlas transformation. The atlas transformation was accomplished in two steps: global followed by local matching. Global matching was performed with use of landmarks; local matching was performed with use of a viscous fluid model. RESULTS: The mean percentage of difference between two atlas-based measurements was 1.33% +/- 1.23 (+/- standard deviation); that between two manual measurements was 4.67% +/- 4.71. The validity of the atlas transformation measurements was demonstrated by means of the high correlation (intraclass correlation coefficient = .96) with manual segmentation measurements. Schizophrenic hippocampal areas tended to be smaller; however, no differences in hippocampal shape were found between patients with schizophrenia and patients with control subjects. CONCLUSION: General pattern matching of a digital brain atlas to an individual MR image is a mathematically robust method of measurement that is reproducible and less variable than manual measurement.

Adult↗