Executive function and genetic predisposition to schizophrenia--the Maudsley family study.

Executive cognitive impairment has been found in families affected by schizophrenia and is a putative endophenotype. We wished to explore its genetic basis further by studying the association between impairment and genetic loading for schizophrenia. We studied 30 schizophrenia patients with a family history of schizophrenia, 53 of their nonpsychotic first-degree relatives (familial), 32 patients with schizophrenia but no known family history of psychosis, 52 of their first-degree relatives (nonfamilial), and 47 normal controls.

Reaction time and sustained attention in schizophrenia and its genetic predisposition.

Sustained attention is affected by schizophrenia. The simplest form of Continuous Performance Test (CPT-X) is a purer test of vigilance than more demanding variants but widely thought too insensitive to detect abnormalities in those with genetic predisposition to schizophrenia. We used a 7-minute CPT to compare 61 patients diagnosed with schizophrenia, 45 of their never-psychotic relatives, and 47 control subjects.

Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.

Background: Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders.

Methods: A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis.

Minor physical anomalies in familial and sporadic schizophrenia: the Maudsley family study.

Objectives: (1) To test the hypothesis that minor physical anomalies are increased in patients with schizophrenia and (2) to investigate differences in the prevalence of minor physical anomalies in patients with familial and sporadic schizophrenia and their first degree relatives.

Methods: A weighted Waldrop assessment was carried out on 214 subjects in five groups: schizophrenic patients from multiply affected families; first degree relatives of these familial schizophrenic patients; sporadic schizophrenic patients; first degree relatives of these sporadic schizophrenic patients, and normal controls. Broad and narrow criteria for abnormality were defined based on the distribution of minor physical anomalies in the control group.

White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal, community-living elderly.

We determined the prevalence and anatomical location of areas of white matter hyperintensity visualized by magnetic resonance imaging in the brains of 38 late paraphrenic patients with an onset of psychotic illness after the age of 60 and 31 healthy aged community volunteers. All degrees of white matter signal hyperintensity were very common in both groups, and there was no excess of such changes in the brain of patients. Periventricular white matter and subcortical grey matter hyperintensities were significantly associated with both measured diastolic and systolic blood pressure in patients and control subjects.

Effect of clozapine on d-fenfluramine-evoked neuroendocrine responses in schizophrenia and its relationship to clinical improvement.

Background: Clozapine is an effective antipsychotic that has high affinity for serotonin type 2 (5-HT2) receptors. The importance of 5-HT antagonism in the overall clinical efficacy of clozapine is unclear. Using a neuroendocrine strategy we tested the hypothesis that clinical response to clozapine is related to alteration in 5-HT function.

A twin study of psychosis and criminality.

Lifetime criminal and psychiatric histories were examined in a consecutive series of 280 individuals of twin birth with a diagnosis of major functional psychosis who were seen and followed up at the Maudsley Hospital between 1948 and 1988. Their 210 co-twins, 35% of whom had a similar diagnosis, were ascertained and followed up over the same period. In the absence of reliable general-population estimates for lifetime conviction rates, co-twins were used as case controls.

Ventricular size and regional cerebral blood flow in schizophrenia: an attempted replication.

We attempted to replicate the finding of Berman et al. (1987) that frontal cortical blood flow correlated inversely with ventricular size in schizophrenia. Computed tomography and high-resolution 99m-Tc-HMPAO single photon emission computed tomography were performed in 25 right-handed chronic schizophrenic men engaged in a word-fluency task.

The association between triple X and psychosis.

Two cases of psychotic illness in association with the karyotype triple X showed specific diagnostic and management problems as well as obstetric complications, EEG abnormalities, and lack of a family history of psychiatric disorder. Routine karyotyping during the investigation of psychosis is becoming relevant to psychiatric practice as research reports increasingly feature genetic and chromosome anomalies in association with schizophrenic psychoses.

A controlled study of 99mTc-HMPAO single-photon emission imaging in chronic schizophrenia.

Regional cerebral blood flow (rCBF) during a word fluency task was compared in twenty-five male, right-handed, medicated schizophrenic patients and twenty-five age-matched male, right-handed healthy volunteers, using 99mtechnetium-HMPAO multidetector single-photon emission tomography. Increased rCBF in caudate and thalamus was found in patients, probably secondary to neuroleptic medication. Patients showed decreased rCBF in left frontal cortical regions and increased rCBF in left posterior cortical regions, compared to controls.

Obsessive-compulsive disorder and schizophrenia in three identical twin pairs.

Three monozygotic twin pairs are described who are concordant for DSM-III-R obsessive-compulsive disorder while being discordant for schizophrenia or schizoaffective disorder. Follow-up interview showed the non-psychotic co-twins to have schizotypal personality disorder. It is concluded that obsessive-compulsive and schizophrenia-spectrum disorders can truly co-exist, thus supporting diagnostic changes introduced into DSM-III-R, and may in some cases be inherited together.

Can brain damage protect against schizophrenia? A case report of twins.

In a pair of male monozygotic twins discordant for schizophrenia, MRI revealed no abnormality in the ill proband, but extensive white-matter damage of likely congenital origin in the psychiatrically normal twin. These findings are difficult to reconcile with multifactorial models of schizophrenia, and raise the possibility that some forms of brain damage may preclude expression of the schizophrenia genotype.

Hand preference in psychotic twins.

In an attempt to replicate the influential study of Boklage (1977), hand preference for writing was examined in a new series of 30 monozygotic (MZ) and 30 dizygotic (DZ) twin pairs in whom the proband had suffered a functional psychosis. In contrast to the original report, no increased rate of left-handedness was found in MZ compared to DZ twins, or psychotic compared with nonpsychotic twins. In particular, no relationship between within-pair left-handedness and discordance for psychosis emerged.

Schizophreniform psychosis associated with the menstrual cycle.

The premenstrual and menstrual periods are associated with increased psychiatric disturbances, both of a psychotic and neurotic nature. Pre-existing psychosis can worsen in the premenstrual period, or, as we describe in the following case report, a psychosis can occur in the premenstrual period with complete remission once the bleeding has ceased.

Twin birth and adult psychiatric disorder. An examination of the case records of the Maudsley Hospital.

We compared the general distribution of diagnoses in 20,895 patients at the Maudsley Hospital with that of 504 patients born twins, including 117 twins where the co-twin had died before the age of 15. Significant differences in diagnostic distribution were found in the co-twin-dead compared with the co-twin-alive group; the former received diagnoses of schizophrenia, personality disorder, or substance abuse more often than the latter. While there were no overall differences between twins and non-twins, there were relatively more twins in the above three diagnostic groups.

The familial/sporadic distinction as a strategy in schizophrenia research.

The rationale and limitations of discriminating between cases of schizophrenia with and without a family history are reviewed. It is concluded from the evidence available that, by identifying subgroups of greater aetiological homogeneity, the strategy can be a useful starting point for research into likely causes.

Left cerebral hemisphere hypodensity in discordant schizophrenic twins. A controlled study.

Eleven identical (monozygotic) twin pairs discordant for schizophrenia and 18 unselected control monozygotic twin pairs received a computed tomographic scan. Brain absorption density was determined on quadrants at five slice levels using a fully automatic program that eliminated cerebrospinal fluid spaces from analysis. There was no difference in brain density among schizophrenics, co-twins, and controls.

The relationship of twinning to the familial-sporadic distinction in schizophrenia.

Cerebral ventricular enlargement in schizophrenia may occur more often in the absence of a family history of the disorder, suggesting that it is related to some non-genetic component of aetiology. This paper shows the finding to be much more apparent in a group of twins than in a similar group of singletons. Previous studies have shown twins in general to have larger cerebral ventricles than non-twins; we suggest that it is the greater susceptibility of twins to obstetric complications that is responsible for both the larger cerebral ventricles found in normal twins, and the very marked increase in ventricular size found in family history negative schizophrenic twins.

Family history and birthweight in monozygotic twins concordant and discordant for psychosis.

In a sample of monozygotic twins, intrapair differences in reported birthweight were larger in those pairs discordant for later psychosis, compared to pairs concordant for psychosis. A trend towards less family history of psychiatric disorder was also found in the discordant pairs.

Genetic vulnerability to schizophrenia.

The genetic contribution to schizophrenia is the most clearly established etiologic factor. This article briefly reviews the evidence for a genetic influence as well as recent challenges to that evidence. It discusses the possible modes of transmission and outlines current efforts to identify more precisely the genetic and environmental factors contributing to schizophrenia and the nature of the gene-environment interaction.

Genetic counselling for schizophrenia.

It is possible that genes contributing to the development of schizophrenia may be identified within the next decade. Genetic methods are improving rapidly, and are surrounded by great public interest. Requests for genetic counselling are keeping pace with this increased attention, but the problems faced by psychiatric genetic counsellors are complex, and the experience of offering such counselling and the issues involved are rarely discussed.