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Biomedical subjects

L Rifkin

Publications and source records attributed to L Rifkin.

At least 19 recordsLinked to original sources
PubMed2006

Neurological abnormalities in young adults born preterm.

OBJECTIVE: Individuals born before 33 weeks' gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. METHOD: We assessed 153 VPT individuals and 71 term-born controls at 17-18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. RESULTS: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. CONCLUSIONS: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

Adolescent↗
PubMed2004

Lateralisation of language function in young adults born very preterm.

OBJECTIVE: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm. SUBJECTS: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls. METHOD: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance. RESULTS: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area. CONCLUSIONS: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Adolescent↗
PubMed2004

The neurodevelopmental progress of infants less than 33 weeks into adolescence.

BACKGROUND: Several studies have shown an increased incidence of neurodevelopmental impairment in very preterm survivors at school age compared with controls. AIM: To compare findings in the same cohort at 8 years and 15 years. METHODS: A total of 151 of the 224 eligible infants born before 33 weeks of gestation from 1979 to 1982, and who were living in the UK, were assessed at 8 and 15 years. Items common to both assessments were compared to evaluate changes in neurodevelopmental function. The assessment included a structured neurological examination, psychometric tests using the WISC-R (in subjects born in 1981-82), a test of visuomotor integration (Beery), and a school questionnaire. RESULTS: There was a significant increase in the proportion of subjects classified as impaired with disability from 11% at 8 to 22% at 14-15 years of age. The proportion of subjects classified as impaired without disability increased from 16% at 8 to 26% at 14-15 years of age. Full scale IQ decreased from 104 to 95 from childhood to adolescence, and more adolescents (24%) were requiring extra educational provision than they had at the age of 8 years (15%). CONCLUSION: Results indicate that between the ages of 8 and 15 years in this cohort of very preterm survivors there is an apparent deterioration in neurodevelopmental outcome category, cognitive function, and extra educational support. It is not clear whether this represents a genuine deterioration in neurocognitive function or whether it represents the expression of pre-existing cerebral pathology in an increasingly complex environment.

Adolescent↗
PubMed2004

Diabetic keto-acidotic (DKA) coma following olanzapine initiation in a previously euglycaemic woman and successful continued therapy with olanzapine.

We report the case of a euglycaemic woman whose glucose control rapidly decompensated following olanzapine initiation leading to diabetic coma. Hyperglycaemia has been associated with chronic psychotic disorders and antipsychotics for many years. However, it is unusual to see such rapid and life-threatening changes associated with treatment. The case highlights that changes in antipsychotic treatment may be associated with large changes in glucose tolerance, and that it is possible to continue antipsychotic treatment with appropriate diabetic care.

Adult↗
PubMed2002

The functional significance of perinatal corpus callosum damage: an fMRI study in young adults.

We used functional MRI (fMRI) to establish the functional significance of corpus callosum damage in young adults who had been born very preterm. Seven subjects from a cohort of individuals who had been born at <33 weeks gestation and who had sustained callosal damage visualized on structural MRI were compared while they carried out auditory and visual tasks requiring callosal transfer with nine very preterm subjects with corpora callosa of normal appearance on structural MRI, and with seven full-term controls. The very preterm subjects with damaged corpora callosa had significantly different activation patterns compared with the two control groups. In the visual task, additional activity was seen in the right dorsolateral prefrontal cortex of the damaged callosum group, possibly because the task was accomplished by storing information in working memory. On the auditory task, a deficit of activity was seen in the right temporal lobe of the callosum group. The findings reveal a plasticity of function compensating for early damage to the corpus callosum.

Adolescent↗
PubMed2002

Functional imaging of the mechanisms underlying the bilateral field advantage.

Visual stimulus comparisons across the vertical meridian are faster and more accurate than those restricted to a single hemifield (the bilateral field advantage). We set out to investigate the cerebral mechanisms underlying this effect using functional magnetic resonance imaging. Seven normal volunteers were presented pairs of shape stimuli bilaterally across the vertical meridian and unilaterally within a single hemifield. We found a network of additional areas activated in the unilateral condition over the bilateral condition which have been related to working memory in previous studies. The results suggest different processing strategies with different temporal characteristics in the bilateral and unilateral conditions, providing a novel explanation for the bilateral field advantage.

Adolescent↗
PubMed2001

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14-15 years of age in very preterm infants.

BACKGROUND: Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN: Prospective cohort study. SUBJECTS: 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES: Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS: A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS: Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.

Adolescent↗
PubMed2001

Neuropsychological outcome at adolescence of very preterm birth and its relation to brain structure.

Neuropsychological outcome at 14 to 15 years of age of a cohort of 75 participants (39 male, 36 female) born at <33 weeks' gestation was investigated. Research was conducted parallel to a recent MRI study by Stewart and colleagues which reported that 55% of this cohort had evidence of brain abnormality. One aim of the study was to compare neuropsychological function in those very preterm children with and without MRI abnormality. Compared to a control sample of term adolescents, very preterm participants had impairment only on a measure of word production. On measures of attention, memory, perceptual skill, and visuomotor and executive function, the adolescents born very preterm performed in the normal range, whether or not they had evidence of MRI abnormality. Our findings are encouraging as the neuropsychological consequences of damage to the very preterm brain, still evident on MRI at 14 to 15 years of age, appear to be minor.

Adolescent↗
PubMed2001

Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term.

Individuals born before 33 weeks' gestation are at risk of brain lesions, which have the potential to disrupt subsequent neurodevelopment. As a result they manifest an increased incidence of neuromotor signs and cognitive deficits, which can still be detected in adolescence. The cerebellum is known to be involved in both the co-ordination of movement and in cognitive processes. We therefore set out to establish whether cognitive and motor impairments in adolescents born very pre-term are associated with abnormalities of the cerebellum as revealed by volumetric analysis of brain MRI scans. The volume of the whole cerebellum was determined manually using a PC-based Cavalieri procedure in 67 adolescents born very pre-term and 50 age-matched, full-term born controls. Cognitive and neurological assessments were performed at 1, 4, 8 and 14-15 years of age as part of the long-term follow-up of the pre-term subjects. The pre-term-born subjects had significantly reduced cerebellar volume compared with term-born controls (P<0.001). This difference was still present after controlling for potential confounders. There was no association between cerebellar volume and motor neurological signs. However, there were significant associations between cerebellar volume and several cognitive test scores, in particular the Wechsler Intelligence Scale for Children-Revised, the Kaufman Assessment Battery for Children and the Schonnel reading age. This provides further evidence implicating the cerebellum in cognition and suggests that cerebellar abnormalities may underlie some of the cognitive deficits found in individuals born very pre-term.

Adolescent↗
PubMed1999

Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm.

BACKGROUND: Infants born very preterm (<33 weeks) are at increased risk of neurocognitive deficits. Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography, but little is known of their later function. We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence. METHODS: A cohort of 105 infants born before 33 weeks of gestation in 1979-80 had ultrasonographic scans at University College Hospital, London, and were prospectively examined at 1, 4, and 8 years. At age 14-15 years, 72 of those who remained in UK (cases) and 21 age-matched full-term controls underwent brain magnetic resonance imaging (MRI), as well as neurological, cognitive, and behavioural assessment. MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status. FINDINGS: Of the 72 cases, 40 had unequivocally abnormal MRI and 15 had equivocal scans. Of the 21 controls, one had abnormal and five equivocal MRI. Abnormalities of ventricles, corpus callosum, and white matter were especially common in cases. More brain lesions were identified by MRI than by neonatal ultrasonography. The cases had significantly more reading, adjustment, and neurological impairments than controls, but their behaviour was significantly related to MRI abnormality. INTERPRETATION: Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence, and more than half have abnormal MRI brain scans.

Adolescent↗
PubMed1997

Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22.

Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 (theta = 0.01, alpha = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at theta = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding.

Bipolar Disorder↗
PubMed1997

Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences.

OBJECTIVE: This research examined social functioning in childhood and adolescence among patients with schizophrenia and patients with bipolar disorder compared with healthy subjects and investigated the relation between premorbid adjustment and risk factors for psychosis. METHOD: Maternal recall was used to assess the premorbid adjustment of patients with schizophrenia (N = 70) and patients with bipolar disorder (N = 28) recruited from a survey of consecutive hospital admissions for psychosis and of healthy comparison subjects (N = 100) drawn from the same catchment area. RESULTS: The patients with schizophrenia had significantly poorer premorbid adjustment in childhood and adolescence than the comparison subjects and were impaired in both sociability and school adjustment. The patients with bipolar disorder exhibited poorer social impairment in adolescence than the comparison subjects, though to a lesser degree than the schizophrenic subjects, but functioned well at school. There were significant linear trends in the risk of psychosis with worsening premorbid functioning, which was most marked in the schizophrenic group, and a specific linear relation between low birth weight and poor premorbid adjustment among the schizophrenic patients. CONCLUSIONS: Impaired premorbid social functioning is not specific to schizophrenia and is seen also in bipolar disorder. The data support the view that poor premorbid social adjustment is one manifestation of vulnerability to adult psychotic disorders. These results are consistent with other findings pointing to early developmental deficits in patients who subsequently develop psychosis.

Adolescent↗
PubMed1997

Test of Xq26.3-28 linkage in bipolar and unipolar affective disorder in families selected for absence of male to male transmission.

BACKGROUND: There have been several reports of linkage between genetic markers on the X chromosome at Xq26.3-28 and bipolar affective disorder in family samples obtained from distinct ethnic and geographical origins. As part of a genome search in a series of 23 UK and Icelandic families, specifically selected for their large size and power to resolve the issue of linkage heterogeneity, we have tested the hypothesis that there is a locus for a genetic subtype of bipolar affective disorder which is linked to this region. METHOD: In families selected on the basis of absent male to male transmission for affective disorder, we performed two-point and FASTMAP multipoint linkage analyses with markers spanning the region between the genetic loci DXS102 and F8. RESULTS: We found negative lod scores for several models of affection status in families selected under stringent and relaxed criteria for the absence of male to male transmission. CONCLUSIONS: In the family sample we have obtained, our study provides no support for the presence of a locus increasing genetic susceptibility to bipolar affective disorder in this region of the X chromosome. It is likely that our finding reflects heterogeneity of linkage for bipolar and genetically related unipolar disorder that exists in specific ethnic populations. Alternatively the X-linked subtype of the disorder may have been present only in a few of our small families resulting in loss of power to detect the Xq26.3-28 linked subtype.

Genetic Linkage↗
PubMed1996

Do obstetric complications cause the earlier age at onset in male than female schizophrenics?

We compared the age at onset of 184 patients with functional psychoses with and without a history of obstetric complications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in male compared to female schizophrenics.

Black or African American↗
PubMed1996

Generation and analysis of 280,000 human expressed sequence tags.

We report the generation of 319,311 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' and 3' ends of 194,031 human cDNA clones. Our goal has been to obtain tag sequences from many different genes and to deposit these in the publicly accessible Data Base for Expressed Sequence Tags. Highly efficient automatic screening of the data allows deposition of the annotated sequences without delay. Sequences have been generated from 26 oligo(dT) primed directionally cloned libraries, of which 18 were normalized. The libraries were constructed using mRNA isolated from 17 different tissues representing three developmental states. Comparisons of a subset of our data with nonredundant human mRNA and protein data bases show that the ESTs represent many known sequences and contain many that are novel. Analysis of protein families using Hidden Markov Models confirms this observation and supports the contention that although normalization reduces significantly the relative abundance of redundant cDNA clones, it does not result in the complete removal of members of gene families.

Adult↗
PubMed1996

Further tests for linkage of bipolar affective disorder to the tyrosine hydroxylase gene locus on chromosome 11p15 in a new series of multiplex British affective disorder pedigrees.

OBJECTIVE: This study was undertaken to confirm or refute previous reports that link bipolar affective disorder to polymorphic DNA markers at or near the gene for tyrosine hydroxylase. METHOD: A previous linkage analysis, which used a tetranucleotide repeat polymorphism at the tyrosine hydroxylase locus, of six Icelandic families was extended to include a new series of 17 multiply affected British families. RESULTS: Overall lod scores under the assumption of locus heterogeneity were between 1.20 and 1.40 at zero recombination with tyrosine hydroxylase, and these scores persisted across three affective disorder models. CONCLUSIONS: These results provide some support for linking affective disorder to this genetic region and suggest that additional linkage and association studies should be conducted to determine whether tyrosine hydroxylase or a nearby locus contributes to susceptibility to bipolar affective disorder in some families.

Alleles↗
PubMed1996

Mixed-handedness in patients with functional psychosis.

BACKGROUND: An excess of non-right-handedness has been shown among patients with schizophrenia. However it is not clear whether this finding can be accounted for by an increase in left-handedness, mixed-handedness or both. It is not known whether atypical patterns of hand preferences occur in other functional psychotic illnesses. METHOD: The Annett hand preference questionnaire was administered to patients with schizophrenia (n = 120); affective psychosis (n = 55); schizoaffective psychosis (n = 41), and control subjects (n = 86). Handedness was classified into three categories: right, mixed and left-handedness. RESULTS: The hand preference patterns of patients with functional psychotic illnesses were not significantly different from controls. Patients with schizophrenia showed a non-significant excess of mixed-handedness compared with controls. Patients with schizophrenia and affective psychosis showed a non-significant decrease in left-handedness compared with controls. CONCLUSIONS: Although our results showed a trend in the hypothesised direction, we failed to demonstrate that patients with psychotic illness differed from controls on self-reported hand preference patterns.

Adult↗