Schizophrenia research: the problem of controls.
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Biomedical subjects
Publications and source records attributed to C Larkin.
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The nature of abnormalities of cerebral structure evident in schizophrenia on magnetic resonance imaging is considered in relation to the neurodevelopmental hypothesis of the disorder. While schizophrenic patients showed increased ventricular volume, the extent of increase with age was comparable with that evident in controls and was unrelated to duration of illness. Conversely, cortical atrophy was evident only in patients, and this increased markedly with age and duration of illness. Such findings could be suggestive of two distinct pathophysiological processes in schizophrenia, but a schema for their reconciliation with the neurodevelopmental hypothesis is elaborated.
Five billion normal myoblasts were injected into each of 21 Duchenne muscular dystrophy (DMD) boys aged 6-14 yr to assess the feasibility, safety, and efficacy of the Phase II myoblast transfer therapy (MTT). The Phase II study was designed to strengthen muscles of both lower limbs. Forty-eight intramuscular injections transferred the myoblasts into 22 major muscles at 55.6 x 10(6)/mL in 10 min under general anesthesia. Eleven boys had received 8 million myoblasts each 1 yr ago in the Phase I MTT. In the Phase II study, eight of them had their myoblasts subcultured from reserves frozen 1 yr ago. The donor myoblasts for each of the remaining boys were cultured from satellite cells derived from a 1-g muscle biopsy of a normal male who might or might not be histocompatible with the recipient. The immunosuppressant cyclosporine (Cy) is being administered to recipients for 6 mo after MTT to facilitate donor cell survival. There was no evidence of an adverse reaction to MTT or Cy as determined by serial laboratory evaluations including electrolytes, creatinine, and urea. Early objective functional tests using the KinCom Robotic Dynamometer were conducted on 13 subjects aged 6 to 13 before MTT and at 3 mo after MTT. Of the 69 muscle groups (knee extensors, knee flexors, plantar flexors) tested for isometric force generation in these subjects, 43% showed mean increase of 41.3% +/- 5.9 SEM, 38% showed no change, and 19% showed continuous force reduction of 23.4% +/- 3.1 SEM. The remaining subjects await the 3-mo post-MTT evaluation. The results indicate that 1) MTT is safe; 2) MTT increases muscle strength in DMD: 81% of the muscles tested showed either increase in strength or did not show continuous loss of strength; 3) more than 5 billion myoblasts can be cultured from 1 g normal muscle biopsy, providing unprecedented numbers of cells for MTT; 4) myoblasts, frozen over 1 yr, retain the ability to proliferate from 10 million to 5 billion, and to form normal myofibers; 5) injections of 5 billion myoblasts have not provoked any immunological rejection symptoms in the Phase II subjects, 11 of whom received 8 million myoblasts in the Phase I MTT a year ago; 6) it is safe to perform multiple injections of myoblasts into lower limb muscles without formation of emboli; and 7) donor cell rejection by the recipient can be prevented with Cy when properly managed.
The emergence of consultation psychiatry as an important psychiatric subspecialty is in part due to the siting of psychiatric units in general hospitals, the manifest advances in medical technology and the increasing elderly population needing specialist care. This paper describes an evaluation of all referrals to a liaison psychiatry unit in a 550 bed general hospital over a six month period. 205 requests for psychiatric consultation were received, which represented 2% of all admissions. There was considerable variation between departments with regard to the referral rate. Management most often consisted of advice, with over 50% of patients being subsequently referred for ongoing psychiatric care.
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OBJECTIVE: This study investigated possible antecedents of minor physical anomalies in schizophrenia, particularly in terms of obstetric and genetic factors, and demographic, clinical and cognitive correlates of such anomalies in schizophrenia. METHOD: Forty-one outpatients satisfying the DSM-III criteria for schizophrenia were examined for minor physical anomalies by using the Waldrop scale. These subjects were drawn from a group of 45 such patients whose cognitive function had been previously evaluated with Trail Making Tests A and B and whose biological mothers had been interviewed for any history of obstetric complications or family history of schizophrenia. RESULTS: Linear multiple regression analysis showed that higher scores for minor physical anomalies were associated with impaired cognitive flexibility on Trail Making Test B, family history of schizophrenia in a first-degree relative, maternal history of obstetric complications, smaller number of siblings, later position in the birth order, and male sex. A family history of schizophrenia was particularly associated with abnormalities of the mouth. The association between minor physical anomalies in the patients and obstetric complications in their mothers appeared to be confined to instances in which the mother had a history of bleeding in early pregnancy. CONCLUSIONS: Minor physical anomalies indicate early dysmorphogenesis in schizophrenia, particularly in males, which appears to be associated more reliably with genetic rather than obstetric factors and with cognitive impairment.
A susceptibility locus for schizophrenia in the 'pseudo-autosomal' region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia.
Although it is well recognised that schizophrenic patients are more often born in winter, the significance of this finding remains obscure. Data relating to season of birth and family history were analysed for 561 patients with an ICD-9 diagnosis of schizophrenia. Patients with no family history of any psychiatric disorder group were significantly more likely to be born in winter than patients with a first-degree relative affected by schizophrenia. In comparison with normal population controls, only those without a family history exhibited a significant excess of winter births, suggesting an environmental factor of greater aetiological significance in these patients.
The significance of the excess of obstetric complications which appears to characterize the histories of schizophrenic patients is critically dependent on the validity of the source of obstetric information, especially when this is obtained by maternal recall. Twenty-one biological mothers of 17 schizophrenic and four other patients were interviewed for their recollections of individual events characterizing the pregnancy and delivery relating to each patient. These were then compared with those events documented in maternity hospital records. Only in two of the 21 instances (9.5%) were inconsistencies of detail apparent which would have affected the designation of the relevant patient as having, or as not having, experienced major obstetric complication(s). It is concluded that maternal recall can be a surprisingly accurate source of obstetric information in relation to research on schizophrenia.
Obstetric complications were more common in the histories of those schizophrenic outpatients without a family history of psychiatric disorder, and were associated with an earlier onset of their illness. Those patients with tardive dyskinesia were more likely to have a family history of psychiatric disorder, less likely to have experienced obstetric complications, and showed greater cognitive deficit. Obstetric complications should be considered in juxtaposition with genetic factors in evaluating the putative familial-sporadic distinction in schizophrenia. Additionally, familial/genetic factors appears to contribute to vulnerability to tardive dyskinesia.
Anticholinergic psychosis was observed to follow ingestion of proprietary antidiarrhoeal preparations by a 63-year-old woman. Possible abuse or accidental overuse of such medicines in the acutely psychotic patient should always be considered.
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From 6,300 psychiatric admissions over a 37 month period, all 54 patient referrals for CT were identified and their charts reviewed. CT influenced diagnosis, management or prognosis in 11.7 percent of patients scanned. There was poor correlation between organicity on CT scan and findings on physical examination, laboratory testing, EEG and psychological testing. The mental state examination was the single significant correlate of CT abnormality. We suggest that the use of a formalised mental state examination such as the Mini Mental State, in addition to the usual clinical assessment of mental state, may improve the accuracy of prediction of abnormality on CT scan. The introduction of X-ray computed tomography (CT) is recognised to be one of the most important innovations in the recent history of clinical medicine. In neurology the value of a non-invasive technique for examining the intracranial contents was quickly realised in the areas of diagnosis, particularly in the detection of vascular accidents and tumours. CT has also attained a significant place in psychiatry. In research studies, it has provided important information on schizophrenia, alcoholism and chronic organic reactions. The place of CT in clinical psychiatry is less clear. As its availability has increased, such scans are being requested with increasing frequency in psychiatric patients. Cranial CT is a highly sensitive diagnostic procedure which, when used unselectively, may result in the discovery of incidental findings. Until recently, a function of the psychiatrist in relation to diagnosis was to first seek to distinguish symptoms produced by organic pathology from those produced by functional illness.(ABSTRACT TRUNCATED AT 250 WORDS)