A continuum of psychosis, one human gene, and not much else — the case for homogeneity

Crow, T. J.

doi:10.1016/0920-9964(95)00059-u

Cited by 126 publications

(59 citation statements)

References 75 publications

(49 reference statements)

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“…Attempts to define the boundary between the two disorders on the basis of symptom and outcome variables have failed 33,34 and some authors have gone as far as to propose that there is a continuum of psychoses resulting from the same genetic mutations. 35,36 Data from family studies suggest that by and large the two disorders are genetically distinct. 37 However there may be rare genetic subtypes of psychosis, such as that in family 50, that can manifest in either form.…”

Section: Discussionmentioning

confidence: 99%

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder

et al. 1998

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There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity ( 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC) n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

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Section: Discussionmentioning

confidence: 99%

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder

et al. 1998

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“…Therefore, patients with distinct intellectual abilities differ in their cognitive capabilities because they have fundamentally distinct illnesses with differing underlying pathophysiologies and correspondingly distinct effects on brain structure and function. On the other hand, advocates for homogeneity argue that there are no disease entities in psychiatry; only continua of variation (Crow, 1995). Even when the etiology of a disorder is known and is unitary, the manifestation and outcome may be surprisingly varied (Jablensky, 2006).…”

Section: Limitationsmentioning

confidence: 99%

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

Ammari¹,

Heinrichs²,

Pinnock³

et al. 2014

Neuropsychology

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Objective: Although impaired general intellectual ability is a prevalent feature in schizophrenia, patterns suggesting preserved, deteriorated, and premorbidly impaired intellect have also been identified. The main purpose of this investigation was to examine the clinical, cognitive, and neuroanatomical characteristics of these intellectual subtypes, and to establish the value and validity of this approach for reducing the heterogeneity of schizophrenia. Methods: A total of 71 patients with a diagnosis of schizophrenia or schizoaffective disorder and 66 healthy controls were assessed. A 'preserved' performance pattern (n=29) was defined by average-range estimated premorbid and current IQ with no evidence of decline (premorbid-current IQ difference <10 points). A 'deteriorated' pattern (n=14) was defined by a difference between estimated premorbid and current IQ estimates of 10 points or more. A 'premorbidly impaired' pattern (n=14) was defined by below average estimated premorbid and current IQ and no evidence of decline greater than 10 points. The groups were compared on demographic,

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“…Manic or depressive episodes may be observed between or during psychotic episodes in a significant number of patients with SCH, whereas psychotic symptoms may be observed during manic or depressive episodes in patients with BAD (Bramon and Sham 2001 (Hägele C et al 2016, Cuthbert BN andInsel TR 2013). A dimensional approach has been proposed as an alternative to categorical differentiation, which suggests that SCH and BAD are pathologies without great variation that exhibit continuity with regard to a psychotic dimension (Crow 1995). Based on widespread clinical, epidemiological and genetic features, several researchers have claimed that SCH and BAD represent the same disorder within a broad spectrum (Carpenter & Buchanan 1994).…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia and Bipolar Affective Disorder: A Dimensional Approach

et al. 2017

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A continuum of psychosis, one human gene, and not much else — the case for homogeneity

Cited by 126 publications

References 75 publications

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

Schizophrenia and Bipolar Affective Disorder: A Dimensional Approach

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