Biomedical subjects

L K Jacobsen

Publications and source records attributed to L K Jacobsen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Brief report: association of sex chromosome anomalies with childhood-onset psychotic disorders.

OBJECTIVE: An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in patients with adult-onset schizophrenia and with unspecified psychoses. This study describes the results of cytogenetic screening carried out for pediatric patients meeting DMS-III-R criteria for childhood-onset schizophrenia (COS) and a subgroup of patients with childhood-onset psychotic disorder not otherwise specified, provisionally labeled by the authors as multidimensionally impaired (MDI). METHOD: From August 1990 to July 1997, karyotypes were determined for 66 neuroleptic-nonresponsive pediatric patients (28 MDI, 38 COS), referred to the National Institute of Mental Health for an inpatient treatment trial of clozapine. RESULTS: Four (6.1%) of 66 patients (3 MDI, 1 COS) were found to have sex chromosome anomalies (mosaic 47,XXY; 47,XXY; 47,XYY; mosaic 45,XO, respectively), which is higher than the expected rate of 1 per 426 children or 2.34 per 1,000 in the general population (4/66 versus 1/426, chi 2 = 19.2, df = 1, p = .00001). All cases had been previously undiagnosed. CONCLUSIONS: These findings lend support to a hypothesis that a loss of balance of gene products on the sex chromosomes may predispose affected individuals to susceptibility to additional genetic and environmental insults that result in childhood-onset psychotic disorders. Karyotyping of children with psychotic disorders should be routine.

Adolescent↗

PubMed1998

Childhood-onset schizophrenia: an open-label study of olanzapine in adolescents.

OBJECTIVE: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinity similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For comparison, data are included from 15 patients who had received 6-week open-label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting. METHOD: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by age 12 for whom at least two different typical neuroleptics had been ineffective participated in the two separate studies. Some of the patients were intolerant of clozapine, although it had been effective (n = 4). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement. RESULTS: For the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in the Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to "ideal" admission status on typical neuroleptics. In contrast, the magnitude of the effect sizes for each of the clinical ratings was larger at week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS total scores were significantly lower at week 6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03). CONCLUSION: These data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia, but they also suggest the need for a more rigorous double-blind comparison of these two atypical antipsychotics.

Adolescent↗

PubMed1998

Progressive reduction of temporal lobe structures in childhood-onset schizophrenia.

OBJECTIVE: A previous cross-sectional study of brain morphology in childhood-onset schizophrenia indicated sparing of the temporal lobes from processes reducing total cerebral volume in this population. In the present study, subjects with childhood-onset schizophrenia and healthy subjects were rescanned at 2-year follow-up to determine whether this pattern of temporal lobe sparing persists with ongoing illness. METHOD: Anatomic brain magnetic resonance imaging scans were acquired for 10 adolescent patients with average onset of schizophrenia at 10.4 years (SD = 1.7) and 17 healthy adolescents. Scans were obtained on initial admission and at 2-year follow-up by using identical equipment and measurement methodology. RESULTS: Schizophrenic subjects showed significantly greater decreases than healthy subjects in right temporal lobe, bilateral superior temporal gyrus and posterior superior temporal gyrus, right anterior superior temporal gyrus, and left hippocampal volumes during the follow-up interval. Decline in right posterior superior temporal gyrus was associated with high total scores on the Scale for the Assessment of Positive Symptoms at baseline and at follow-up. CONCLUSIONS: Progressive reduction of temporal lobe structures occurs with ongoing illness in childhood-onset schizophrenia.

Adolescent↗

PubMed1998

Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study.

Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies suggest a role for the cerebellum in cognitive functions, including attention. However, the cerebellum has not been systematically studied in attention-deficit hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes, and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed boys with ADHD and 47 matched healthy controls. Vermal volume was significantly less in the boys with ADHD. This reduction involved mainly the posterior inferior lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII). These results remained significant even after adjustment for brain volume and IQ. A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor control, inhibition, and executive function deficits encountered in ADHD.

Adolescent↗

PubMed1998

Research update: childhood-onset schizophrenia: implications of clinical and neurobiological research.

Childhood-onset schizophrenia is a rare, clinically severe form of schizophrenia, which is associated with disrupted cognitive, linguistic, and social development well before the appearance of frank psychotic symptoms. This disruption of multiple developmental domains signals the important opportunity these patients present for examining neurodevelopmental and other etiologic hypotheses of schizophrenia. The present research update reviews studies of the phenomenology and neurobiology of childhood-onset schizophrenia conducted since 1994. Findings from these studies indicate that children can be diagnosed with schizophrenia using unmodified DSM-III, -IIIR, and -IV criteria, and that the atypical neuroleptic clozapine is an effective medication for this treatment refractory group. Neuropsychologic and neurobiologic studies generally support continuity with adult-onset schizophrenia, with evidence of more severe premorbid impairment. Longitudinal studies show preliminary evidence of progressive ventricular enlargement and more prolonged deterioration in intellectual function than is seen in the adult-onset disorder. If replicated, these observations, together with the insidious onset of this disorder, would suggest that the pathologic underpinning of childhood-onset schizophrenia is not a single static lesion or event but may be a continuous or multi-event process.

Age of Onset↗

PubMed1997

Cerebral glucose metabolism in childhood onset schizophrenia.

Decreased frontal cortical glucose metabolism has been demonstrated in adult schizophrenics both at rest and while engaging in tasks that normally increase frontal metabolism, such as the Continuous Performance Test (CPT). The authors tested the hypothesis that adolescents with childhood onset schizophrenia would also demonstrate hypofrontality while performing the CPT. Cerebral glucose metabolism was examined in 16 adolescents (mean age 14.1 +/- 1.7) with onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.8) and 26 healthy adolescents selected to be similar in age, sex and handedness using positron emission tomography and 18F-fluorodeoxyglucose. Patients with childhood onset schizophrenia made fewer correct and more incorrect identifications on the CPT. Region of interest analysis revealed no significant group differences in global cerebral glucose metabolism, but increased metabolic rate in supramarginal gyrus (F = 6.74, P < 0.05) and inferior frontal gyrus/insula (F = 7.09, P < 0.05) and decreased metabolic rate in middle frontal gyrus (F = 6.72, P < 0.05) and superior frontal gyrus (t = 2.04, P < 0.05) in schizophrenics. Comparison of effect sizes with an identically designed study of adult schizophrenics did not indicate more severe hypofrontality in childhood onset schizophrenia. Pixel-based analyses indicated a more complex pattern of group differences in cerebral metabolism with bilaterally increased cerebellar metabolic rate in childhood onset schizophrenics. These findings suggest that childhood onset schizophrenia may be associated with a similar, but not more severe, degree of hypofrontality relative to that seen in adult onset schizophrenia.

Adolescent↗

PubMed1997

Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease.

This study examines cerebrospinal fluid from patients with three neuropsychiatric diseases of childhood for the presence and levels of several cytokines relevant to cell-mediated (type 1) and humoral (type 2) immunity. The patient groups include childhood-onset schizophrenia (n = 22), obsessive-compulsive disorder (OCD) (n = 24), and attention deficit hyperactivity disorder (n = 42). The cytokines examined include IL-2, IFN-gamma, TNF-beta/LT, IL-4, IL-5, IL-10, and TNF-alpha. Patients with OCD had a preponderance of type 1 cytokines. IL-4 was detectable only in samples from patients with schizophrenia. IL-10 was rarely detected and never in patients with OCD. Few patients with schizophrenia had detectable amounts of IFN-gamma in CSFL. We conclude that there is a relative skewing of CSFL profiles toward type 1 cytokines in patients with OCD, whereas in schizophrenia the relative preponderance is toward type 2 mediators. Patients with attention deficit hyperactivity disorder exhibited profiles intermediate between OCD and schizophrenia. We infer that cell-mediated immunity may be involved in the etiopathogenesis of OCD, whereas a relative lack of cell-mediated immunity and involvement of humoral immunity may be present in schizophrenia. These data provide a rationale for immune-based strategies of study and therapeutics in childhood neuropsychiatric disease.

Attention Deficit Disorder with Hyperactivity↗

PubMed1997

Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia.

Corpus callosum size has been found to be abnormal in adult schizophrenia, and other studies have implicated abnormal interhemispheric communication in this disorder. To assess continuity with brain abnormalities in the later onset disorder and to further localize brain maldevelopment, this structure was examined in a unique sample of childhood onset schizophrenics. Anatomic brain magnetic resonance imaging scans were acquired for 25 patients (mean age 13.9 +/- 2.1) who had onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.9) and 55 normal children. The midsagittal area of the corpus callosum was divided into seven sections. With no adjustment for brain volume, no diagnostic differences were observed. After adjustment for the smaller cerebral volume of the schizophrenics, larger total, anterior and posterior corpus callosum areas emerged for the schizophrenics. These findings provide further evidence for continuity between childhood onset and later onset schizophrenia and support other studies showing white matter sparing in the context of decreased cortical volume.

Adolescent↗

PubMed1997

Autonomic nervous system markers of psychopathology in childhood-onset schizophrenia.

BACKGROUND: Consistent abnormalities in peripheral indicators of autonomic activity, ie, skin conductance (SC) and heart rate (HR), have been reported in adult-onset schizophrenia. Herein, we use these markers to test the hypothesis of continuity between childhood-onset schizophrenia and adult-onset schizophrenia. METHODS: Skin conductance and HR were recorded from 21 severely ill children and adolescents (mean age, 14.1 years) with childhood-onset (< or = 12 years) schizophrenia (patient group) and from 54 age-matched controls (control group) during a rest period, a series of innocuous tones, reaction time instructions, and a simple warned reaction time task. RESULTS: During rest, patients had higher rates of spontaneous SC responses (SCRs) and HRs than controls, but their SC level was marginally lower and declined more slowly over time. Half of the patients, compared with 4% of the controls, failed to give SC-orienting responses to the first 2 tones. Patients who responded had impaired SCR magnitudes, and their habituation was more erratic than that of controls. The increase in SC level and SCR frequency at the onset of the task period was greatly attenuated in the patients, so that both variables were higher in controls. Patients had smaller SCRs and anticipatory HR responses to the reaction time stimuli. Skin conductance nonresponding was associated with negative and total symptoms, and spontaneous SCR frequency was associated with positive symptoms. CONCLUSIONS: The findings show similar abnormalities in autonomic nervous system activity in childhood-onset schizophrenia to those found in adult chronic schizophrenia, thus supporting the hypothesis of continuity of the childhood and adult forms of the illness. Comparisons with data from other childhood disorders suggest that the combination of low-elicited SC activity with high levels of spontaneous SC activity may be specific to schizophrenia.

Adolescent↗

PubMed1997

Case study: risperidone-induced hepatotoxicity in pediatric patients.

The purpose of this case study is to document hepatic adverse effects associated with long-term risperidone use in pediatric populations. Charts of all patients admitted to the National Institute of Mental Health (NIMH) from December 1993 to April 1996 who had been treated with risperidone were screened for hepatotoxicity and weight gain. From the medical records of 13 psychotic children admitted to the NIMH and treated with risperidone, 2 children (both male) who presented with obesity, liver enzyme abnormalities, and confirmatory evidence of fatty liver were identified. In each case liver damage was reversed after discontinuation of risperidone and/or associated weight loss. The observations suggest that long-term risperidone therapy is possibly associated with hepatotoxicity in male pediatric patients. It is recommended that pediatric patients treated with risperidone have baseline liver function tests, careful monitoring of weight, and periodic monitoring of liver function tests during the maintenance phase of therapy.

Adolescent↗

PubMed1997

Cerebrospinal fluid monoamine metabolites in childhood-onset schizophrenia.

OBJECTIVE: Pediatric studies of cerebrospinal fluid (CSF) monoamine metabolites in childhood-onset schizophrenia may help to elucidate both pathophysiology and treatment response in early-onset psychosis. METHOD: CSF homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum prolactin were measured during drug-free and antipsychotic medication conditions in 18 patients (mean age = 14.2 years, SD = 1.7) who had onset of schizophrenia by age 12 (mean age at onset = 9.9 years, SD = 1.8). Relationships between changes in CSF monoamines and serum prolactin and clinical outcome were examined, and the degree of change in CSF monoamines in response to clozapine treatment was compared with that for 16 patients with later-onset schizophrenia. RESULTS: Despite patients' significant clinical improvement with treatment, CSF monoamine concentrations and ratios of HVA/5-HIAA and HVA/MHPG did not significantly change with 6 weeks of either haloperidol or clozapine treatment. Serum prolactin levels increased during haloperidol treatment. Clozapine had similar effects on CSF monoamines in patients with childhood- and later-onset schizophrenia. CONCLUSIONS: While these data are compatible with continuity between childhood- and later-onset schizophrenia, they also highlight the complexity of the biochemical events mediating clinical changes in schizophrenia.

Adolescent↗

PubMed1997

Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia.

OBJECTIVE: Studies have suggested that the maldeveloped neural circuitry producing schizophrenic symptoms may include the cerebellum. The authors found further support for this hypothesis by examining cerebellar morphology in severely ill children and adolescents with childhood-onset schizophrenia. METHOD: Anatomic brain scans were acquired with a 1.5-T magnetic resonance imaging scanner for 24 patients (mean age = 14.1 years, SD = 2.2) with onset of schizophrenia by age 12 (mean age at onset = 10.0 years, SD = 1.9) and 52 healthy children. Volumes of the vermis, inferior posterior lobe, fourth ventricle, and total cerebellum and the midsagittal area of the vermis were measured manually. RESULTS: After adjustment for total cerebral volume, the volume of the vermis and the midsagittal area and volume of the inferior posterior lobe remained significantly smaller in the schizophrenic patients. There was no group difference in total cerebellar or fourth ventricle volume. CONCLUSIONS: These findings are consistent with observations of small vermal size in adult schizophrenia and provide further support for abnormal cerebellar function in childhood- and adult-onset schizophrenia.

Adolescent↗

PubMed1997

Three-dimensional cortical morphometry of the planum temporale in childhood-onset schizophrenia.

OBJECTIVE: Anomalous planum temporale asymmetry has been linked to both schizophrenia and dyslexia. The authors examined the planum temporale of adolescents with childhood-onset schizophrenia who had a high rate of prepsychotic language disorders. METHOD: Planum temporale area and asymmetry were measured in 16 right-handed adolescent patients with schizophrenia who had experienced onset of psychosis by age 12. The same measures were made in 16 healthy adolescents matched for age, sex, and handedness. RESULTS: No differences between the healthy adolescents and those with schizophrenia in planum temporale area or asymmetry were observed. Prepsychotic language disorder predicted abnormal planum temporale asymmetry in the adolescents with schizophrenia. CONCLUSIONS: These findings do not support anomalous planum temporale asymmetry as a basis for psychopathology in childhood-onset schizophrenia.

Adolescent↗

PubMed1996

Blink rate in childhood-onset schizophrenia: comparison with normal and attention-deficit hyperactivity disorder controls.

Several lines of evidence have implicated central dopaminergic pathways in the modulation of blink rate. In the present study, blink rate during smooth pursuit was examined in 17 children with childhood-onset schizophrenia, on and off of clozapine, and compared to that of age-matched normal children and unmedicated children with attention-deficit hyperactivity disorder (ADHD). As has been observed in adolescent and adult schizophrenics, blink rate was significantly higher in schizophrenic children relative to normal and ADHD controls. Within the schizophrenic group, blink rate did not significantly change with the introduction of clozapine and was not related to clinical variables. Blink rate was positively correlated with deterioration in smooth pursuit in normal subjects.

Adolescent↗

PubMed1996

Smooth pursuit eye movements in childhood-onset schizophrenia: comparison with attention-deficit hyperactivity disorder and normal controls.

Abnormalities of the smooth pursuit eye movements of adults with schizophrenia have been well described. We examined smooth pursuit eye movements in schizophrenic children, contrasting them with normal and attention-deficit hyperactivity disorder (ADHD) subjects, to determine whether there is continuity of eye movement dysfunction between childhood- and adult-onset forms of schizophrenia. Seventeen schizophrenic children with onset of illness by age 12, 18 ADHD children, and 22 normal children were studied while engaged in a smooth pursuit eye tracking task. Eye tracking variables were compared across the three groups. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects. Within the schizophrenic group, there were no significant relationships between eye tracking variables and clinical variables, or ventricular/brain ratio. Childhood-onset schizophrenia is associated with a similar pattern of smooth pursuit abnormalities to that seen in later-onset schizophrenia.

Adolescent↗

PubMed1996

Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia.

BACKGROUND: Early-onset schizophrenia (first psychotic symptoms by age 12 years) has been the subject of a small number of studies, and its biological continuity with later-onset disorder has not been established. In this study quantitative anatomic brain magnetic resonance images of children and adolescents with early-onset schizophrenia were compared with those of matched controls. Brain abnormalities in childhood-onset schizophrenia were examined in relation to those reported for later-onset schizophrenics. METHODS: Anatomic brain magnetic resonance imaging scans were obtained for 21 patients (mean +/- SD age, 14.6 +/- 2.1 years; range, 10 to 18 years) with childhood-onset schizophrenia (13 males, eight females) and 33 age-, sex-, height-, and weight-matched normal controls. Quantitative measurements were obtained for the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. RESULTS: Total cerebral volume and midsagittal thalamic area were smaller in the patients (analysis of variance, P = .002, and analysis of covariance, P = .03, respectively); the caudate, putamen, and globus pallidus were larger in the patients (analysis of covariance, P = .05, P = .007, and P < .001, respectively); and the lateral ventricles tended to be larger in the patients (analysis of covariance, P = .06). Globus pallidus enlargement correlated with neuroleptic exposure and with age of onset of psychosis. The magnitude of abnormalities compared with controls was similar to that reported in adult studies, although there was a trend toward relatively smaller cerebral volumes for the childhood-onset group compared with controls. CONCLUSION: Brain anatomic abnormalities in childhood-onset schizophrenia are similar to those reported for adult populations, indicating overall continuity between these rare childhood cases and the adult schizophrenia populations.

Adolescent↗

PubMed1996

Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison.

BACKGROUND: Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory. In this study, the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia. METHODS: Twenty-one patients (mean [+/-SD] age, 14.0 +/- 2.3 years) with onset of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study. Patients were randomized to a 6-week double-blind parallel comparison of clozapine (mean [+/-SD] final dose, 176 +/- 149 mg/d), or haloperidol, (16 +/- 8 mg/d). RESULTS: Clozapine was superior to haloperidol on all measures of psychosis (P = .04-.002). Positive and negative symptoms of schizophrenia improved. However, neutropenia and seizures were major concerns. To date, one third of the group has discontinued using clozapine. CONCLUSIONS: Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia. However, due to possibly increased toxic effects in this pediatric population, close monitoring for adverse events is essential.

Adolescent↗

PubMed1996

Temporal lobe morphology in childhood-onset schizophrenia.

OBJECTIVE: Neurodevelopmental models of schizophrenia imply that a more severe early brain lesion may produce earlier onset of psychotic symptoms. The medial temporal lobes have been proposed as possible locations for such a lesion. The authors tested this hypothesis in a group of children and adolescents with childhood-onset schizophrenia who had severe, chronic symptoms and who were refractory to treatment with typical neuroleptics. METHOD: Anatomic brain magnetic resonance imaging scans were acquired with a 1.5-T scanner for 21 patients (mean age=14.6 years, SD=2.1) who had onset of schizophrenia by age 12 (mean age at onset=10.2, SD=1.5) and 41 normal children. Volumes of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus were measured by manually outlining these structures on contiguous 2-mm thick coronal slices. RESULTS: Patients with childhood-onset schizophrenia had significantly smaller cerebral volumes. With no adjustment for brain volume, no diagnostic differences were observed for any temporal lobe structure. Unexpectedly, with adjustment for total cerebral volume, larger volumes of the superior temporal gyrus and its posterior segment and a trend toward larger temporal lobe volume emerged for the patients with schizophrenia. These patients lacked the normal (right-greater-than-left) hippocampal asymmetry. CONCLUSIONS: These findings do not indicate a more severe medial temporal lobe lesion as the basis of very early onset schizophrenia.

Adolescent↗