Lawrence Sharpe

The Comprehensive Assessment and Referral Evaluation (CARE)--Rationale, Development and Reliability.

The Comprehensive Assessment and Referral Evaluation (CARE) is a new assessment technique which is intended to reliably elicit, record, grade and classify information on the health and social problems of the older person. The CARE is basically a semi-structured interview guide and an inventory of defined ratings. It is designated comprehensive because it covers psychiatric, medical, nutritional, economic and social problems rather than the interests of only one professional discipline. The style, scope and scoring of the CARE makes it suitable for use with both patients and non-patients, and a potentially useful aid in determining whether an elderly person should be referred, and to whom, for a health or social service. The CARE can also be employed in evaluating the effectiveness of that service if given.

Second Stage of a Genome Scan of Schizophrenia: Study of Five Positive Regions in an Expanded Sample

In a previous genome scan of 43 schizophrenia pedigrees, nonparametric linkage (NPL) scores with empirically derived pointwise P-values less than 0.01 were observed in two regions (chromosomes 2q12-13 and 10q23) and less than 0.05 in three regions (4q22-23, 9q22, and 11q21). Markers with a mean spacing of about 5 cM were typed in these regions in an expanded sample of 71 pedigrees, and NPL analyses carried out. No region produced significant genomewide evidence for linkage. On chromosome 10q, the empirical P-value remained at less than 0.01 for the entire sample (D10S168), evidence in the original 43 pedigrees was slightly increased, and a broad peak of positive results was observed. P-values less than 0.05 were observed on chromosomes 2q (D2S436) and 4q (D4S2623), but not on chromosomes 9q or 11q. It is concluded that this sample is most supportive of linkage on chromosome 10q, with less consistent support on chromosomes 2q and 4q. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:864-869, 2000.

Reliability and relationship of various ages of onset criteria for major affective disorder

This paper presents data on six different clinical definitions (indices) of age of onset for major affective disorders. The inter-rater reliability for each index and the relationships among these indices are discussed. Age of onset for impairment with affective symptoms was found to be a reliable and useful index of early onset. It discriminated between unipolar depressed subjects and both bipolar I and bipolar II subjects.

The assessment of sexual function and marital interaction.

The increasing need expressed by clinicians and researchers alike for valid and reliable psychological measures of sexual behavior and adjustment contrast with the limited available information on the assessment of human sexual functioning. The aim of this article is to present relevant data on the psychometric characteristics of scales designed to measure one or more aspects of human sexual activity and marital interaction. This list is by no means exhaustive but covers most assessments of either individuals or dyads, mainly in a heterosexual context. Under the title of the scales, which have been arranged by alphabetical order according to the first authors name, the information provided may permit a preliminary judgment concerning the potential applicability of the instrument to the readers need.

A pedigree series for mapping disease genes in bipolar affective disorder: sampling, assessment, and analytic considerations.

A series of 57 extended pedigrees with high density of bipolar affective disorder is described. Ascertainment and diagnostic procedures are documented and simulation studies to assess statistical power are carried out. The pedigrees, obtained in the US and Israel, are comprised of 1508 adult individuals with best estimate consensus diagnoses (12-71 relatives per pedigree), 490 of whom (including 401 sib pairs) meet criteria for a conservative disease definition (bipolar disorder or recurrent major depression). Cell lines have been established on 1324 of these individuals. Statistical power to detect linkage with lod score analysis, assuming autosomal dominant transmission and highly polymorphic DNA markers, is nearly 100% for alpha (proportion of linked families) = 30%, and 75% for alpha = 20%. This is the largest bipolar pedigree series reported to date; its unique features make it amenable to various gene detection techniques.

Treatment of prementstrual symptoms

The etiology of premenstrual syndrome is unknown. A wide variety of etiological explanations has been suggested, but controlled studies based on these theories have generally failed to provide confirmation. This article reviews the literature on treatment of premenstrual symptoms and provides some practical suggestions for clinical management.

The treatment of anorgasmia: long-term effectiveness of a short-term behavioral group therapy.

A long-term follow-up of 19 women who participated in short-term group therapy for anorgasmia using masturbation and assertiveness training showed that the majority of women maintained treatment gains and progressed further in orgasm response and other aspects of sexual functioning, including assertiveness and liberalness of sexual attitudes. However, several women regressed, and four additional women who dropped out of treatment also improved dramatically in orgasm response, suggesting that other patient characteristics and factors affect apparent treatment outcome. Independent evaluations, standardized assessment scales, long-term, in-person follow-ups and multidimensional assessment are useful in evaluating treatment effectiveness.

Penetrance of schizophrenia‐related disorders in multiplex families after correction for ascertainment

Penetrance of schizophrenia and related disorders was calculated in 27 multiplex pedigrees ascertained by a consistent set of screening and selection criteria. The rationale for the study was that single major locus linkage models are frequently used on a pragmatic basis to analyze data for schizophrenia which is most likely to have a polygenic mechanism. Penetrance estimates assuming Mendelian inheritance represent maximum values and thus can provide guidance for construction of appropriate linkage models. Four diagnostic models were considered: narrow (schizophrenia and chronic schizoaffective disorder), intermediate (including other non‐affective psychoses), broad (including schizotypal and paranoid personality disorders), and broad + suspected (including suspected schizophrenia spectrum disorders). Penetrance was calculated in the youngest affected adult sibship, under both dominant and recessive inheritance assumptions, either without correction, or with a correction that excluded individuals necessary to meet pedigree selection criteria. Without correction, penetrance values ranged from 0.70 to 0.90 assuming dominant and 1.0 to > 1.0 assuming recessive inheritance. After correction, the ranges were 0.30–0.51 for dominant and 0.47–0.59 for recessive models. The corrected values are likely to be overestimates given that the penetrance of any one locus in a multilocus model must be lower. It is suggested that lod score analyses of schizophrenia should attempt to derive information primarily from affected diagnoses, because information derived from unaffecteds under high penetrance models is likely to be spurious.

The geriatric mental status interview (GMS).

The Geriatric Mental Status interview (GMS) is a semi-structured interview technique for assessing psychopathology in elderly patients. It is administered by a trained interviewer in a session of less than one hour. Between 100 and 200 question are asked and almost 500 items are rated. Twenty-one factor scores have been identified and the reliability of the ratings has been established. The interview is acceptable to the patient and is useful for making diagnostic distinctions and evaluation progress

No support for linkage to the bipolar regions on chromosomes 4p, 18p, or 18q in 43 schizophrenia pedigrees

Following the distinction proposed by Kraepelin[1919], who built on the work of Morel [1860], Hecker[1871] and Kahlbaum [1863], bipolar affective disorder(BPAD) and schizophrenia are generally thought of asseparate disorders. Modern epidemiological studiessupport this view since these disorders generally do notaggregate in the same families [Kendler et al., 1993;Maier et al., 1993]. An alternative view, originally putforward by Griesinger in 1861, is that schizophreniaand affective psychoses may be different expressions ofthe same disorder [Crow, 1986; Griesinger, 1861, asreferenced by Maier et al., 1993]. In support of thisview, cross prevalence studies have demonstrated asignificantly higher rate of unipolar affective illnessamongst the relatives of schizophrenia probands, com-pared with that observed amongst the relatives of con-trol probands [Kendler et al., 1993; Maier et al., 1993;Taylor et al., 1993]. Furthermore, commonality insymptomatology (with both schizophrenic and bipolarpatients experiencing Schneiderian first rank symp-toms), in illness course (deterioration in some severebipolar cases is more typical of the pattern seen inschizophrenia), and in effective treatments (neurolep-tics, lithium) raise the possibility of overlapping caus-ative factors, both genetic and nongenetic.Patients with schizoaffective disorder exhibit bothschizophrenic and affective symptoms in varying pat-terns over time, and in describing this group Kendelland Brockington [1980] raised four possible explana-tions: “that most are really schizophrenic illnesses,that most are really affective illnesses, that they are amixture of schizophrenic and affective illnesses, andthat they constitute a third independent type of psy-chosis” [Kendell and Brockington, 1980, p326]. Geneticstudies have forced the need for pragmatic distinctionsto be made within this group of patients for inclusion/exclusion in either schizophrenia or BPAD linkagestudies. For example, RDC [Endicott and Spitzer,1978] “schizoaffective, mainly schizophrenic” caseshave been included in schizophrenia linkage studies(including the present author’s study), while RDC“schizoaffective, mainly affective” cases have been in-cluded in BPAD linkage studies [Gershon et al., 1988].Taken together, these factors suggest that, whetherclassified as separate disorders or as a continuum,overlap exists between affective and schizophrenic ill-nesses, and that the existence of this clinical and fa-milial overlap raises the possibility of overlapping ae-tiologies, and perhaps shared susceptibility genes.Blackwood and co-workers [Blackwood et al., 1996]reported a peak lod score of 4.1 coincident with D4S394(a40.35) on chromosome 4p16.1 in a cohort of 12 Scot-tish BPAD pedigrees. More recent genome screen re-sults provide additional support for a bipolar predispo-sition gene in this region, particularly withinCaucasian populations [Detera-Wadleigh et al., 1997;Ewald et al., 1998; McInnis, 1997; Nothen, 1997;Philibert et al., 1997]. As with most psychiatric genet-ics findings, there are also negative reports of linkageto bipolar disorder in this region [Raeymaekers, 1997;Rice, 1997; Schofield, 1997].There is one report (an abstract) of a family withcases of schizophrenia and schizoaffective disorder thatgave a positive linkage score (lod 1.96) to markerD4S403, near DRD5, although analysis in an addi-tional 23 pedigrees collected by the same group failedto provide supportive evidence for this finding. [Asher-son et al., 1998].On chromosome 18 there are two distinct regions ofinterest for affective psychoses. Berrettini and co-workers [Berrettini et al., 1994, 1997, 1998] reported asuggestive finding in the analysis of five chromosome18 pericentromeric marker loci (APM,