Biomedical subjects

R C Mohs

Publications and source records attributed to R C Mohs.

At least 37 records · Page 2Linked to original sources

PubMed1999

Neuropeptide abnormalities in patients with early Alzheimer disease.

BACKGROUND: Deficits in somatostatin-like immunoreactivity (SLI) and corticotropin-releasing factor immunoreactivity (CRF-IR) are well recognized as prominent neurochemical deficits in Alzheimer disease (AD). The question of whether these profound neuropeptidergic deficits found in patients with end-stage disease extend into those with much earlier disease is relatively unanswered. To determine the relation between level of SLI and CRF-IR in different cerebrocortical regions to the earliest signs of cognitive deterioration in AD. METHODS: We examined SLI and CRF-IR levels in 9 neocortical brain regions of 66 elderly patients in a postmortem study of nursing home residents who had either no significant neuropathologic lesions or lesions associated only with AD. Patients were assessed by the Clinical Dementia Rating scale (CDR) to have no dementia or questionable, mild, or moderate dementia, and were compared with 15 patients with severe dementia. RESULTS: Both CRF-IR and SLI were significantly reduced in the cortices of patients with the most severe dementia, but only the levels of CRF-IR were reduced in those with mild (CDR = 1.0) and moderate dementia (CDR = 2.0). Levels of CRF-IR and SLI correlated significantly with CDR, but this correlation was more robust for CRF-IR and persisted even when severely cognitively impaired patients were eliminated from analysis. CONCLUSIONS: Although SLI and CRF-IR levels are significantly reduced in patients with severe dementia, only CRF-IR is reduced significantly in the cortices of those with mild dementia. Thus, CRF-IR can serve as a potential neurochemical marker of early dementia and possibly early AD.

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PubMed1999

The impact of behavioral impairment of functional ability in Alzheimer's disease.

This study sought to determine the relationship between behavioral disturbance and functional status in a longitudinally studied sample of patients with Alzheimer's disease (AD). One hundred and forty-nine patients meeting NINCDS-ADRDA criteria for probable AD were followed for an average of 37.3 months, with follow-up assessments every 6 months. Subjects were seen at the Alzheimer's Disease Research Center clinics at the Mt Sinai Medical Center, New York, and the Veterans Affairs Medical Center, Bronx, New York. Measures included the Physical and Self-Maintenance Scale (PSMS) and Instrumental Activities of Daily Living Scale (IADLS) of Lawton and Brody and the cognitive and non-cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS). For each patient the assessment at which they had their most severe non-cognitive symptoms as measured by the non-cognitive part of the ADAS (ADAS-NC) was determined. ADAS-NC scores at that assessment were correlated with IADLS and PSMS scores at the same assessment and at the next assessment 6 months later. While there was some modest association of ADAS-NC scores with functional impairment using pairwise correlation coefficients, none of the correlations remained significant when the severity of cognitive impairment was controlled statistically. Findings were not significantly changed when drug status was controlled. These results suggest that behavioral disturbance, while very troubling to caregivers and patients, does not substantially worsen functional ability beyond the contribution of cognitive impairment in AD. Together with previous results indicating that non-cognitive symptoms in AD are episodic and fluctuating rather than progressive, the present data suggest that interventions for non-cognitive disturbances in AD should be viewed as ways to increase patient comfort, safety and ease of care and not as ways to improve functional autonomy. The latter can be achieved only by improving the progressive cognitive deficits of AD.

Activities of Daily Living↗

PubMed1999

Identifying families with likely genetic protective factors against Alzheimer disease.

Elderly individuals who lived beyond the age of 90 years without dementia were hypothesized to have increased concentrations of genetic protective factors against Alzheimer disease (AD), conferring a reduced liability for this disease relative to less-aged nondemented elderly. However, testing this hypothesis is complicated by having to distinguish such a group from those who may lack genetic risk factors for AD, have had protective environmental exposures, or have escaped dementia for other reasons. Probands carrying genetic protective factors, however, should have relatives with lower illness rates not only for earlier-onset disease, when genetic risk factors are a strong contributing factor to the incidence of AD, but also for later-onset disease, when the role of these factors appears to be markedly diminished. AD dementia was assessed through family informants in 6,660 first-degree relatives of 1,049 nondemented probands aged 60-102 years. The probands were grouped by age (60-74, 75-89, and 90-102 years), and the cumulative survival from AD and 10-year-age-interval hazard rates of AD were calculated in their first-degree relatives. Cumulative survival from AD was significantly greater in the relatives of the oldest proband group (aged 90-102 years) than it was in the two younger groups. In addition, the reduction in the rate of illness for this group was relatively constant across the entire late life span. The results suggest that genetic factors conferring a lifelong reduced liability of AD may be more highly concentrated among nondemented probands aged >/=90 years and their relatives. Efforts to identify protective allele-bearing genes that are associated with very late-onset AD should target the families of nonagenarians and centenarians.

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PubMed1999

Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population.

The mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC) is deficient in Alzheimer's disease (AD). The DLST gene encodes the core, dihydrolipoyl succinyltransferase (DLST) component of KGDHC, and recent reports indicate an association between polymorphisms of DLST and AD in both white and Japanese patients. We therefore examined the relationship between AD and the DLST and apolipoprotein E (APOE) genes in elderly (89 +/- 7 years) AD patients, in whom the epsilon4 allele of APOE (APOE4) is a weak risk factor for AD. Polymorphisms of DLST (A19,117G and T19,183C), shown to be of interest in previous studies, were analyzed by restriction fragment length polymorphism analysis after polymerase chain reaction amplification. In a series of 429 white subjects from two Jewish nursing homes, an association of APOE4 with AD was found only in patients homozygous for the G,C allele of DLST. Similar relationships occurred in the "very elderly" (> or =85 years, n = 302) subgroup of this series, and also in an autopsy series (n = 225) that included white subjects from the Jewish nursing homes as well as other white subjects. These findings suggest a relationship between APOE4 and a DLST locus in the pathogenesis of AD in very elderly subjects.

Acyltransferases↗

PubMed1998

Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group.

BACKGROUND: Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer disease. This phase 3 study was 1 of 2 pivotal trials undertaken to establish the efficacy and safety of using donepezil in patients with mild to moderately severe Alzheimer disease. OBJECTIVES: To further examine the efficacy and safety of using donepezil in the treatment of patients with mild to moderately severe Alzheimer disease. To examine the relationships between plasma donepezil concentrations, inhibition of red blood cell acetylcholinesterase activity, and clinical response. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel-group trial with a 3-week single-blind washout. Outpatients at 23 centers in the United States were randomized to receive placebo, 5 mg of donepezil hydrochloride, or 10 mg of donepezil hydrochloride (5 mg/d during week 1 then 10 mg/d thereafter) administered once daily at bedtime. Primary efficacy was measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change including caregiver information (CIBIC plus). RESULTS: A total of 468 patients entered the study, more than 97% of whom were included in the intention-to-treat (end point) analyses. The use of donepezil produced statistically significant improvements in ADAS-cog, CIBIC plus, and Mini-Mental State Examination scores, relative to placebo. The mean drug-placebo differences, at end point, for the groups receiving 5 mg/d and 10 mg/d of donepezil hydrochloride were, respectively, 2.5 and 3.1 units for ADAS-cog (P<.001); 0.3 and 0.4 units for CIBIC plus (P< or =.008); and 1.0 and 1.3 units for Mini-Mental State Examination (P< or =.004). On the CIBIC plus scale, 32% and 38% of patients, respectively, treated with 5 mg/d and 10 mg/d of donepezil hydrochloride demonstrated clinical improvement (a score of 1, 2, or 3) compared with placebo (18%). The mean (+/-SEM) donepezil plasma concentrations at study end point were 25.9 +/- 0.7 ng/mL and 50.6 +/- 1.9 ng/mL in the groups receiving dosages of 5 mg/d and 10 mg/d, respectively. Corresponding mean (+/-SEM) percentages of inhibition of red blood cell acetylcholinesterase activity were 63.9% +/- 0.9% and 74.7% +/- 1.2% for these 2 dosages, respectively. There was a statistically significant positive correlation between plasma concentrations of donepezil and acetylcholinesterase inhibition; the EC50 (50% effect) was obtained at a concentration of 15.6 ng/mL. A plateau of inhibition (80%-90%) was reached at plasma donepezil concentrations higher than 50 ng/mL. The correlations between plasma drug concentrations and both ADAS-cog (P<.001) and CIBIC plus (P = .006) were also statistically significant, as were the correlations between red blood cell acetylcholinesterase inhibition and change in ADAS-cog (P<.001) and CIBIC plus (P = .005). The incidence of treatment-emergent adverse events with both dosages of donepezil (68%-78%) was comparable with that observed with placebo (69%). The use of 10 mg/d of donepezil hydrochloride was associated with transient mild nausea, insomnia, and diarrhea. There were no treatment-emergent clinically significant changes in vital signs or clinical laboratory test results. More important, the use of donepezil was not associated with the hepatotoxic effects observed with acridine-based cholinesterase inhibitors. CONCLUSION: Donepezil hydrochloride (5 and 10 mg) administered once daily is a well-tolerated and efficacious agent for treating the symptoms of mild to moderately severe Alzheimer disease.

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PubMed1998

A study of the efficacy of a comprehensive memory enhancement program in healthy elderly persons.

Well educated, high functioning older adults (ages 60-90) were given a comprehensive memory enhancement training program to determine the effectiveness of the program in increasing cognitive performance and positively influencing self-assessments of memory efficacy. The 68 subjects who participated in the memory enhancement training were compared to 74 subjects who were enrolled in a video control group. Between subject differences were analyzed prior to the interventions and at three time points following the interventions (immediately post, 3 months and 6 months). Only one cognitive measure, assessing verbal memory, revealed a significant difference between the groups, with participants in the memory enhancement group showing less decline from baseline than the video control group immediately following the intervention but with no difference between groups at 6 months post-intervention. Several self-report measures showed that the memory enhancement training subjects experienced improved memory functioning and decreased memory concerns relative to the video control group. The self-reported effects of the training were sustained over the 6-month follow-up period.

Adult↗

PubMed1998

Lateral ventricular enlargement in schizophrenic probands and their siblings with schizophrenia-related disorders.

BACKGROUND: To investigate possible genetic determinants of ventricular enlargement in schizophrenia, we compared lateral ventricle/brain ratios (VBRs) in schizophrenic patients with their own siblings, some with and some without other schizophrenia-related disorders [e.g., schizotypal personality disorder (SPD)], as well as with a group of unrelated normal controls. METHODS: VBRs, measured by computed tomography, were compared in both groupwise and within-sibship analyses, the latter method providing a measure of control over familial/genetic factors related to VBR, but unrelated to schizophrenia. RESULTS: The VBRs were significantly different across the groups, but the only significant pairwise group comparison was between the schizophrenia and no-SRD family member groups. In the within-sibship analyses, however, the VBRs of those with SPD and schizophrenia were similar, and both groups had significantly larger VBRs than their own siblings without SRD. In addition, siblings with a negative family history for SRD had larger VBRs than family history positive siblings. CONCLUSIONS: The results suggest that specific schizophrenia-related genetic factors may help determine ventricular enlargement in familial schizophrenia. The larger VBRs in family history negative siblings might be attributable to genetic factors not specifically associated with schizophrenia, but which nevertheless increase its susceptibility.

Adult↗

PubMed1998

Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease.

BACKGROUND: Identification of the neuropathological lesions that are most closely associated with the earliest symptoms of Alzheimer disease (AD) is crucial to the understanding of the disease process and the development of treatment strategies to affect its progress. Do the classical neuropathological lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? DESIGN AND OUTCOME MEASURES: We examined the extent of neuritic plaque (NP) formation in 5 neocortical regions and the hippocampus, entorhinal cortex, and amygdala in 66 elderly subjects with no dementia, questionable dementia, or mild dementia as assessed using the Clinical Dementia Rating Scale (CDR). SETTING AND PATIENTS: Postmortem study of nursing home residents. RESULTS: Even questionable dementia (CDR, 0.5) was associated with a significant (P = .04) increase in neocortical NP density. The density of NPs increased further with increasing dementia severity in all brain regions examined. However, subjects with questionable dementia or definite but mild dementia did not differ significantly from each other. Density of NPs was nearly maximal in subjects with moderate dementia (CDR = 2.0), suggesting that other neuropathological changes may be responsible for cognitive deficits beyond this level. Dementia severity correlated significantly with the density of NPs in all brain regions examined (r range, 0.47-0.56; P < .001), even when subjects with a CDR of 0 were excluded. CONCLUSIONS: These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia.

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PubMed1998

The relationship between apolipoprotein E, dementia, and vascular illness.

The purpose of this study was to concurrently assess the relationship of Apolipoprotein E (APOE) with both dementias and vascular illnesses in the very old. Nine hundred and fifty nine subjects (mean age 85 years) in a long-term care facility were genotyped and cognitively tested with the Mini Mental State Exam. All subjects were studied for the relationship of APOE with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. Four hundred fifty individuals met criteria for inclusion into one of the following groups: Alzheimer's disease (n = 318), vascular dementia (n = 49), or not demented controls (n = 83) and were investigated for the relationship between APOE and these diagnostic categories. APOE epsilon4 was not associated with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. The APOE epsilon3 allele was more common in men with atherosclerotic heart disease. In contrast, the APOE epsilon4 allele was more common in patients with Alzheimer's disease (22%) and vascular dementia (26%) than in not demented controls (7%). APOE epsilon4 is associated with dementias in the very old, whereas its relationship with either peripheral or central nervous system vascular disease without dementia is not as robust.

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PubMed1998

Verbal learning and memory in schizotypal personality disorder.

The investigation of cognitive deficits in patients with schizotypal personality disorder (SPD) is important both to establish commonalities between SPD and schizophrenia and to clarify the significance of these cognitive deficits for schizophrenic disorders. The purpose of this study was to examine verbal learning and memory with the California Verbal Learning Test (CVLT) in a group of patients with SPD (n=24) and a group of patients with personality disorders other than SPD (OPD; n=25). The results indicated that SPD patients learned significantly fewer words with practice on the CVLT than OPD patients (F=4.32, df=1,47, p < 0.05), and their rate of learning was reduced relative to normative standards. These findings suggest that SPD patients have a deficit in verbal learning that is similar to, although not as severe as, the impairments seen in schizophrenia.

Adult↗

PubMed1998

Relationship of disease severity to decline on specific cognitive and functional measures in Alzheimer disease.

Previous studies have shown that the sensitivity of global cognitive and functional measures to change in Alzheimer disease is related to overall disease severity. The present study assessed the sensitivity to decline, over a 12-month interval, for individual items of the cognitive portion of the Alzheimer Disease Assessment Scale (ADAS-Cog), the Instrumental Activities of Daily Living Scale (IADLS), and the Physical Self-Maintenance Scale (PSMS). This study was conducted in an effort to identify individual items likely to be sensitive at different stages of the disease. A total of 151 patients with Alzheimer disease were classified into four dementia categories by baseline scores on the Blessed Test of Information, Memory, and Concentration. The patients were retested after 12 months. For the individual items and for total scores on both the ADAS-Cog and the IADLS, rate of change was greater for patients in the moderate and severe categories than for mild or very severe patients. For individual items and for the total score on the PSMS, rate of change was greater for severe and very severe patients than for patients with mild or moderate disease.

Activities of Daily Living↗

PubMed1998

Association of elevated alpha 1-antichymotrypsin with cognitive impairment in a prospective study of the very old.

OBJECTIVE: The authors investigated the relationships between concentrations of two acute-phase proteins, alpha 1-antichymotrypsin (ACT) and alpha 2-macroglobulin (MAC), and cognitive impairment in the very old. METHOD: Concentrations of ACT and MAC were determined in a prospective study using sera from medically stable elderly nursing home residents. Cognitive impairment was assessed with the Mini-Mental State. RESULTS: Concentrations of ACT were associated with greater cognitive impairment, as reflected by lower Mini-Mental State scores. This relationship did not exist for MAC. CONCLUSIONS: These data extend previous reports that patients with Alzheimer's disease have greater concentrations of ACT in their blood by demonstrating in a diagnostically diverse nursing home population a relationship between serum ACT and mental status. Elevated serum ACT in patients with compromised mental status may reflect a cerebral acute-phase response.

Acute-Phase Proteins↗

PubMed1998

Genome scan of schizophrenia.

OBJECTIVE: The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHOD: A genomewide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals--126 of them with schizophrenia-related psychoses--from 43 pedigrees. Nonparametric linkage analysis was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirically derived p values reached nominal levels of significance at eight marker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002). CONCLUSIONS: The results do not support the hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychiatric disorders) has limited power to detect genes of small effect or those that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely to contain schizophrenia susceptibility genes.

Chromosome Mapping↗

PubMed1998

Symptoms, cognitive functioning, and adaptive skills in geriatric patients with lifelong schizophrenia: a comparison across treatment sites.

OBJECTIVE: Although many geriatric patients with schizophrenia have been referred to nursing home care, little is known about their characteristics. Across nursing home and chronic hospital settings, the authors directly assessed poor outcome geriatric patients with schizophrenia and contrasted their cognitive, symptomatic, and adaptive functioning to that of acutely admitted patients with a better outcome over the lifetime course of the illness. METHOD: The subjects were 97 chronically hospitalized patients with schizophrenia, 37 patients with chronic schizophrenia who lived in nursing homes, and 31 acutely admitted geriatric patients with schizophrenia. These patients were rated with the Positive and Negative Syndrome Scale, tested with a neuropsychological battery, evaluated with the Mini-Mental State examination, and rated on a scale of social and adaptive deficits, the Social Adaptive Functioning Evaluation scale. RESULTS: Each group of patients proved discriminable from the other two: nursing home patients displayed the most severe adaptive deficits, and acutely admitted patients were the least cognitively impaired. Cognitive impairment was the strongest predictor of adaptive deficits for all three groups, and negative symptom differences among the groups were smaller than differences in cognitive impairment. Nursing home patients had the least severe positive symptoms, and the acutely ill and chronic hospital patients did not differ on positive symptoms. CONCLUSIONS: Cognitive impairment is a predictor of both overall outcome and specific adaptive deficits. These data suggest that interventions aimed at cognitive impairment may have an impact on overall functional status. In comparison, positive symptom severity is less strongly correlated with overall adaptive outcome and is uncorrelated with specific deficits in adaptive skills.

Age Factors↗

PubMed1998

Cerebral infarcts in patients with autopsy-proven Alzheimer's disease: CERAD, part XVIII. Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: To study the relation between cerebral infarction and clinical and neuropsychologic manifestations in patients with autopsy-proven Alzheimer's disease (AD) enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). BACKGROUND: Prior studies report that subjects with neuropathologic evidence of AD and concomitant brain infarcts had poorer cognitive function and higher frequency of dementia than those with AD alone. METHODS: Clinical and neuropsychologic manifestations of dementia were studied in 74 subjects with neuropathologic findings of AD alone and 32 with AD and concomitant cerebral infarcts or lacunar lesions. RESULTS: The 32 patients with both AD and vascular lesions were significantly older at time of death (median age, 81 years) than the 74 patients with AD alone (76 years; p = 0.02). At the final follow-up visit, the severity of the dementia was greater in AD patients with vascular lesions (median Clinical Dementia Rating [CDR] = 3) than in those with AD alone (CDR = 2; p = 0.03). Patients with AD and vascular lesions performed significantly worse on verbal fluency, Boston Naming, and Mini-Mental State Examination (MMSE) tests. No differences between the groups were observed, however, in the semiquantitative measures of frequency of neuritic plaques or neurofibrillary tangles. CONCLUSIONS: The clinical-neuropathologic correlations in CERAD patients generally confirm those in prior studies, indicating that the presence of cerebral infarction in patients with AD is associated with greater overall severity of clinical dementia and poorer performance on specific tests of language and cognitive function.

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PubMed1997

Attentional and eye tracking deficits correlate with negative symptoms in schizophrenia.

Thirty patients with a DSM-III-R diagnosis of schizophrenia were assessed for severity of schizophrenic symptoms using the Brief Psychiatric Rating Scale (BPRS) and were tested on a Continuous Performance Test (CPT) and a smooth pursuit eye tracking task. Negative symptoms were significantly correlated with eye tracking impairment (r = 0.43, p < 0.01) and CPT deficits (r = 0.67, p < 0.001), but performance on neither task was correlated with positive symptoms. CPT performance and eye tracking performance were modestly correlated with each other (r = 0.39, p < 0.01) and CPT performance was found to be a stronger predictor of negative symptoms than eye tracking performance. These data indicate that neurocognitive markers of vulnerability to schizophrenia are associated with negative rather than positive symptoms.

Adult↗

PubMed1997

A linkage study of schizophrenia to markers within Xp11 near the MAOB gene.

A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular genetic studies produced weak evidence for linkage of schizophrenia to the proximal short arm of the X-chromosome, while some other regions were not ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a maternal pattern of inheritance (Study I), and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheritance at a theta of 0.20) for locus DXS7, with scores below 0.50 for other markers in this region (MAOB, DXS228, and ARAF1). Significant allele sharing among affected sibling pairs was present at DXS7. In the second study, positive lod scores were observed at MAOB (highest of 2.16 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for recessive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-chromosome have been investigated without evidence for linkage being found, a locus predisposing to schizophrenia in the proximal short arm of the X-chromosome is not excluded.

Chromosome Mapping↗

PubMed1997

Validity of the family history method for identifying schizophrenia-related disorders.

We examined the family history method's validity for identifying schizophrenia related disorders (SRD) by comparing family history and family study derived diagnoses. First degree relatives (n = 284) of 48 psychiatrically disordered probands, predominantly with schizophrenia, were diagnosed using the Family History RDC (FH-RDC) which include three psychotic schizophrenia related disorders (P-SRD): schizophrenia, chronic SAD and chronic unspecified functional psychosis (CUFP). Supplementary criteria for schizophrenia related personality disorders (SRP), derived to identify schizotypal and paranoid personality disorders (PD), were also assessed. About two thirds of these relatives (n = 196; 69.0%) were independently diagnosed by RDC and DSM-III-R on both axis I and axis II in a family study. The specificity was 1.0 (178/178) and the sensitivity of the family history derived diagnosis for P-SRD was 0.72 (13/18). Sensitivity for P-SRD was improved, however, by inclusion of SRP which captured three of the five false negative relatives. The sensitivity of SRP for schizotypal or paranoid PD was 0.39 (15/38) and the specificity was 0.92 (127/138). The FH-RDC have moderately good sensitivity and excellent specificity for the psychotic schizophrenia related disorders. While family history criteria for SRP are not a good proxy for schizotypal or paranoid PD, they can enhance the family history method's sensitivity for SRD.

Adult↗