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Biomedical subjects

R Rawlings

Publications and source records attributed to R Rawlings.

34 records · Page 2Linked to original sources

Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism.

BACKGROUND: To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. METHODS: Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers. RESULTS: In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration. CONCLUSION: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

Adult↗

Neurochemical correlates of sympathetic activation during severe alcohol withdrawal.

Cerebrospinal fluid (CSF) was obtained from 17 patients during acute alcohol withdrawal. Eight of these 17 patients had a second lumbar puncture a mean of 11.9 +/- 8.1 (SD) days later, when the clinical signs of alcohol withdrawal had subsided. CSF 3-methoxy-4-hydroxyphenylglycol concentrations declined significantly (p < 0.05) during the course of alcohol withdrawal from 52.0 +/- 22.1 (SD) to 39.6 +/- 12.6 pM/ml. In early withdrawal, there was a significant positive correlation between CSF norepinephrine (NE) and corticotropin releasing hormone (CRH) concentrations (r = 0.95, p < 0.001). Both NE and CRH concentrations correlated positively with diastolic blood pressure (r = 0.88, p < 0.001 and r = 0.62, p < 0.05, respectively). In all samples, CSF 5-hydroxyindole acetic acid concentrations correlated positively with CSF-homovanillic acid concentrations (r = 0.83, p < 0.001). These findings indicate significant perturbations of the noradrenergic neuronal system and a change in CRH-NE interactions during acute alcohol withdrawal.

Adult↗

Obstetric complications in histories of monozygotic twins discordant and concordant for schizophrenia.

Histories of obstetric complications (OCs) during pregnancy, labor-delivery and the neonatal period were investigated by detailed maternal report for 23 monozygotic (MZ) twin pairs discordant for schizophrenia, 10 MZ twin pairs concordant for schizophrenia and 7 normal MZ control pairs. Statistically significant differences in OC rates were found across these 3 groups. OCs being most frequent in discordant pairs and least frequent in normal control pairs. Labor complications were significantly more frequent in discordant than concordant pairs. OC rates were equivalent in sick and well discordant twins. The results provide evidence for the role of OCs in the development of schizophrenia, complications at the time of birth being especially associated with the development of schizophrenia in discordant twins.

Adult↗

Link between pregnancy complications and minor physical anomalies in monozygotic twins discordant for schizophrenia.

OBJECTIVE: The aim of the current study was to explore the relevancy of early pregnancy complications for the development of minor physical anomalies in monozygotic twins discordant and concordant for schizophrenia. METHOD: Pregnancy complications and minor physical anomalies were independently assessed in 22 discordant, 10 concordant, and six normal comparison monozygotic twin pairs. RESULTS: Complications occurring during early pregnancy were associated with a higher frequency of minor physical anomalies in the total group and in the discordant twin pairs particularly. While no significant differences in anomaly rates were observed among the discordant, concordant, and normal comparison groups, the discordant ill twins showed a trend toward having more anomalies than their well co-twins. CONCLUSIONS: Complications occurring early in pregnancy are relevant for the development of minor physical anomalies and may be of particular importance for the development of these anomalies in twin pairs discordant for schizophrenia.

Adult↗

Are neurological abnormalities in well discordant monozygotic co-twins of schizophrenic subjects the result of perinatal trauma?

OBJECTIVE: Neurological abnormalities found in schizophrenic subjects and their healthy relatives have raised questions concerning etiology. The aim of the present study was to investigate the genetic and environmental antecedents of neurological impairment in monozygotic twins discordant for schizophrenia, with particular focus on the well discordant twins. The etiological factors of interest were history of obstetric complications, family history of psychosis, history of substance abuse, and history of postnatal cerebral trauma. METHOD: History of obstetric complications, including information from pregnancy through the neonatal period, and data on neurological "hard" and "soft" signs were obtained blindly and separately for each member of 22 monozygotic twin pairs discordant for schizophrenia and seven normal comparison monozygotic twin pairs. Clinical and family interviews provided information about background factors. RESULTS: Degree of neurological impairment in the well discordant monozygotic twins was significantly positively related to history of both neonatal and total obstetric complications. None of the three other background factors investigated was related to degree of neurological impairment in the ill or well co-twins. CONCLUSIONS: The contribution of obstetric complications to the current level of neurological impairment in well discordant co-twins suggests that the spectrum of neuroabnormality, ranging from neurological signs to schizophrenia, in monozygotic discordant twins may be the result of subtle gene-environment interaction.

Adult↗

Changes in semantic memory in early stage Alzheimer's disease patients.

The types and number of exemplars of categories that are retrieved from semantic memory differentiate elderly normal controls and early stage Alzheimer's disease (AD) patients. Elderly normal controls generated more uncommon exemplars from closed semantic categories (fruits and vegetables) than did AD patients 2 1/2 years prior to the presumed onset of AD. AD patients, however, were just as productive as elderly normal controls in generating associations to open categories (letters). The findings suggest that one of the early cognitive symptoms of AD is changes in availability of uncommon exemplars of semantic networks.

Aged↗

Seasonality of schizophrenia and stillbirths.

A study of the birth pattern of 30,467 patients with schizophrenia and 428,406 stillbirths in New York State showed a significant winter-month excess in both schizophrenia births (p = 0.0000) and stillbirths (p = 0.0000). Excess births of individuals with schizophrenia in November and December provided additional evidence to refute the age-incidence explanation for the observed seasonality. Time series spectral analysis showed coherence in the pattern of schizophrenia births and stillbirths of 0.898 (p < 0.003) with schizophrenia births preceding stillbirths by 13 days. These results suggest that a common etiological seasonal factor affects a subgroup of births of individuals who later develop schizophrenia and a subgroup of stillbirths. Nutritional factors, temperature, and infectious agents known to cause both central nervous system disease and stillbirths are possible candidates.

Adult↗

Relationship of diagnostic, demographic, and personality variables to self-reported stimuli for chemical use.

While extensive research has been conducted to determine internal and external stimuli for drinking by alcoholics, the topic of how demographic, diagnostic, and personality variables may relate to these precipitants is largely unexplored. This study suggests that stimuli to use alcohol or drugs differ partly as a function of diagnosis (alcohol dependence vs. concurrent alcohol and drug dependence). Age, education, and gender do not appear related to the stimuli in either diagnostic group. Personality characteristics of cognitive reflectiveness, impulse control, sociability, and intrapunitiveness, however, seem to be associated with certain classes of high risk stimuli.

Adult↗

Quantitative shape analysis of the temporal and prefrontal lobes of schizophrenic patients: a magnetic resonance image study.

In a recent quantitative neuroimaging study, the authors reported significant reduction in the gray matter volume of both temporal lobes of schizophrenic (SC) patients. In order to better elucidate the nature of this finding (i.e., diffuse vs. focal), we analyzed the shape of the temporal lobes of 17 SC patients and an equal number of age-sex matched controls. Our shape analysis was able to discriminate between a significant number of SC and control patients based on the Fourier harmonic amplitudes of both the middle and posterior levels of the temporal lobes. These results are consistent with bilateral focal or multifocal distortions of the temporal lobes of SC patients. A similar shape analysis of the prefrontal lobes showed no significant conformational differences between the groups. The basis of this quantitative shape analysis (the Fourier expansion series) and the method by which it can be applied are explained in detail.

Atrophy↗

Subtypes of substance abusers: personality differences associated with MacAndrew scores.

Several earlier studies have reported clinically relevant personality correlates of high vs low scores on the MacAndrew Scale (Mac) of the MMPI. Unfortunately, these projects have not adjusted for age or nature of abuse. Also, most have assumed that the personality correlates are the same for female patients as for male patients. This study attempts to address these deficiencies. Even after correcting for age and diagnosis, high Mac patients differ from low Mac patients on major scales of the MMPI. The pattern of such differences varies considerably between men and women. Substance abuse treatment implications of these differences are discussed.

Alcoholism↗

A quantitative investigation of hippocampal pyramidal cell size, shape, and variability of orientation in schizophrenia.

Hippocampal abnormalities have been described in patients with schizophrenia, with disarray of pyramidal cells being one of the more intriguing findings. Controversy exists regarding whether disarray is present in the brains from schizophrenics in the Yakovlev collection at the Armed Forces Institute of Pathology, Washington, DC. We examined for disarray the CA1 region of the midhippocampus of 17 schizophrenics and 32 controls from this collection using computerized determination of neuronal angle and directional statistical analysis of the variability of neuronal angle. Neuronal area and shape were also assessed. We found no differences between patients and controls in these measures. Possible methodological reasons for the discrepancy between our and others' findings are discussed, as well as directions for further research into possible pathological study of the hippocampus and related structures in schizophrenia.

Anthropometry↗

Laboratory test changes in young abstinent male alcoholics.

Data collected over time from an abstaining young alcoholic population were analyzed together with data from a nonalcoholic population, which served as a reference group. The laboratory tests of the abstaining alcoholics were measured at baseline (zero weeks), three weeks, and six weeks, while those of the nonalcoholic group were measured once, at baseline. The analysis attempts to reveal how abstinence from beverage alcohol consumption in an alcoholic population affects 25 commonly ordered laboratory tests over time and whether cigarette smoking mediates any observed effects. The primary findings of this detailed examination of clinical chemistries in abstaining alcoholics indicate that drinking and smoking have independent effects and that the effects of drinking persist even after six weeks of abstinence.

Adult↗

Pharmacogenetics of phenylethylamine: determination of heritability and genetic transmission of locomotor effects in recombinant inbred strains of mice.

beta-Phenylethylamine (PEA) is an amphetamine-like compound that is postulated to be a possible endogenous psychotogen. We studied locomotor response to PEA in two inbred progenitor strains of mice (C57BL/6 By and BALB/c By), their reciprocal F1 hybrids (B6CF1 and CB6F1), and seven recombinant inbred strains (CXBD, CXBE, CXBG, CXBH, CXBI, CXGJ, and CXBK). Univariate and multivariate statistical analyses were done. Heritability of the response to PEA was 82%. The strain distribution pattern was suggestive of the inheritance of the trait through a single major gene locus.

Animals↗

Auditory recovery function and P3 in boys at high risk for alcoholism.

We have previously reported P3 decrements in boys at risk for alcoholism in a complex visual rotation reaction time task. The present study investigated the generalizability of these observations by studying a new high risk sample of boys of Type 2 alcoholic fathers under different experimental conditions. The current experimental design consisted of an easy auditory oddball task (P3) which stressed accuracy over speed of responding, and which also included variable interstimulus intervals (0.5, 1.0 and 5.0 sec), allowing recovery functions to be derived from the evoked responses to frequent non-target stimuli. The results did not yield statistically significant differences between groups in the recovery function data. However the baseline-to-peak results to the target stimulus indicated significant decreases in both P2 and P3 amplitudes in the high risk boys. No differences in latency were obtained between groups. Furthermore frequency analysis of responses to the target stimulus using a multivariate time series model indicated between-group differences at 4 frequencies (1.43, 7.14, 8.6 and 11.43 Hz). These results replicate our previous findings of P3 decrements in boys at risk for alcoholism in a new sample of sons of Type 2 alcoholics. As we have now made these observations with different experimental conditions and sensory modalities, it is suggested that these findings are generalizable.

Adolescent↗

Schizophrenic births and viral diseases in two states.

In order to investigate a possible relationship between schizophrenic births and viral diseases, the birth month and year of all state hospital admissions for schizophrenia in Connecticut and Massachusetts from 1973-1974 were compared with the occurrence of reportable viral diseases for 1920-1955. Data was statistically examined by time series using spectral analysis. Statistically significant coherences were found between schizophrenic births and measles (both states), varicella-zoster (Connecticut) and polio (Connecticut). Influenza just missed statistical significance. No temporal relationship between schizophrenic births and rubella or mumps was found. The results are compared with similar studies in Minnesota and Finland. Definitive explanations for the observed relationships are precluded by the emerging complexity of virus-CNS interactions. A triggering of immune dysfunction by the infectious agents is proposed as the most reasonable explanation.

Connecticut↗

Seasonal birth patterns of neurological disorders.

Existing seasonal birth studies were reviewed for multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), epilepsy, cerebral palsy, congenital malformations of the central nervous system and mental retardation. Epilepsy appears to have the most consistent pattern, with an excess of births in winter and a deficit in September. MS, ALS and possibly Parkinson's disease appear to have an excess of spring births. Studies of cerebral palsy are not conclusive, although there are suggestions that there may be an excess of summer births. The findings for Alzheimer's disease, congenital malformations of the central nervous system, and mental retardation are contradictory and insufficient to draw any conclusions.

Central Nervous System Diseases↗