bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective and objective dimensions of quality of life in psychiatric patients: A factor analytical approach
Authors: Ruggeri Mirella , Warner Richard , Bisoffi Giulia , Fontecedro Laura
Published: August 2002

Background

Both subjective and objective information is necessary to assess quality of life (QOL).

Aims

To explore the role of subjective and objective QOL dimensions and their cross-sectional and longitudinal predictors.

Method

The relationship between QOL, as measured by the Lancashire Quality of Life Profile (LQL), and demographic variables, diagnosis, psychopathology, disability, functioning, affect balance, self-esteem, service use and service satisfaction was investigated at two points in time, using factor analysis and multiple regression techniques.

Results

One subjective and two objective LQL factors with strong face validity were identified. Cross-sectional predictors of the subjective factor were primarily subjective measures; longitudinally, few predictors of this factor were identified. The cross-sectional and longitudinal predictors of the objective factors were primarily demographic and observer-rated measures.

Conclusions

Subjective and objective data are distinct types of information. Objective measures may be more suitable in detecting treatment effects. Subjective information is necessary to complete the QOL picture and to enhance the interpretation of objective data.
How antidepressants work: New perspectives on the pathophysiology of depressive disorder
Authors: Reid Ian C. , Stewart Caroline A.
Published: August 2002

Background

New research in animals is beginning to change radically our understanding of the biology of stress and the effects of antidepressant agents.

Aims

To relate recent findings from the basic neurosciences to the pathophysiology of depressive disorder.

Method

Drawing together findings from molecular and physiological studies in rats, social studies in primates and neuropsychological studies in humans, we review the neurotrophic and neuroplastic effects of antidepressants and stress.

Results

Stress and antidepressants have reciprocal actions on neuronal growth and vulnerability (mediated by the expression of neurotrophins) and synaptic plasticity (mediated by excitatory amino acid neurotransmission) in the hippocampus and other brain structures. Stressors have the capacity to progressively disrupt both the activities of individual cells and the operating characteristics of networks of neurons throughout the life cycle, while antidepressant treatments act to reverse such injurious effects.

Conclusions

We propose a central role for the regulation of synaptic connectivity in the pathophysiology of depressive disorder.
Prophylactic effect of citalopram in unipolar, recurrent depression
Authors: Hochstrasser B. , Isaksen P. M. , Koponen H. , Lauritzen L. , Mahnert F. A. , Rouillon F. , Wade A. G. , Andersen M. , Pedersen S. F. , De Swart J. C. G. , Nil R.
Published: August 2002

Background

Major depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression.

Aims

Comparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression.

Methods

Patients 18–65 years of age with recurrent unipolar major depression (DSM–IV), a Montgomery–åsberg Depression Rating Scale score of ≥ 22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20–60 mg) for 6–9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48–77 weeks.

Results

A total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P< 0.001). Prophylactic treatment was well tolerated.

Conclusions

Citalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.
Light therapy for seasonal affective disorder in primary care
Authors: Wileman Samantha M. , Eagles John M. , Andrew Jane E. , Howie Fiona L. , Cameron Isobel M. , McCormack Kirsty , Naji Simon A.
Published: August 2002

Background

Studies of light therapy have not been conducted previously in primary care.

Aims

To evaluate light therapy in primary care.

Method

Fifty-seven participants with seasonal affective disorder were randomly allocated to 4 weeks of bright white or dim red light. Baseline expectations for treatment were assessed. Outcome was assessed with the Structured Interview Guide for the Hamilton Depression Scale, Seasonal Affective Disorder Version.

Results

Both groups showed decreases in symptom scores of more than 40%. There were no differences in proportions of responders in either group, regardless of the remission criteria applied, with around 60% (74% white light, 57% red light) meeting broad criteria for response and 31% (30% white light, 33% red light) meeting strict criteria. There were no differences in treatment expectations.

Conclusions

Primary care patients with seasonal affective disorder improve after light therapy, but bright white light is not associated with greater improvements.
Chronic benzodiazepine use in general practice patients with depression: An evaluation of controlled treatment and taper-off
Authors: Zitman Frans G. , Couvée Jaap E.
Published: August 2002

Background

Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value.

Aims

To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor (SSRI) prescribing and to determine the long-term outcome after benzodiazepine withdrawal.

Method

Patients went through three phases – change to an equivalent dose of diazepam; subsequent randomisation to either 20 mg of paroxetine or placebo; and gradual reduction of diazepam in depression-free patients – with a follow-up after 2 or 3 years.

Results

A total of 230 patients were recruited and 75% in the paroxetine group and 61% in the placebo group were successfully treated after 6 weeks (P=0.067). After 2 or 3 years 13% of patients were still benzodiazepine free: 26% of those who had successfully tapered off benzodiazepine and 6% of the total group.

Conclusions

Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use. The addition of SSRI treatment is of limited value.
Efficacy and safety of sildenafil citrate in the treatment of men with mild to moderate erectile dysfunction
Authors: Eardley Ian , Morgan Robert , Dinsmore Wallace , Yates Paula , Boolell Mitradev
Published: August 2002

Background

Erectile dysfunction is a common, multi-factorial disorder.

Aims

To evaluate the efficacy, tolerability and frequency of use of sildenafil citrate in men with mild to moderate erectile dysfunction of no established organic cause.

Method

This double-blind, randomised, placebo-controlled, flexible-dose, two-way crossover study was conducted at four centres in the UK in 44 men with mild to moderate erectile dysfunction of no clinically obvious organic cause. The study included two 28-day treatment periods, during which time sildenafil or placebo (25–75 mg, based on efficacy) was taken as required.

Results

Compared with placebo, sildenafil was associated with increases in frequency of use, erections adequate for sexual intercourse and level of sexual satisfaction (P< 0.0001). More patients receiving sildenafil stated they would use the treatment again compared with those receiving placebo (P< 0.0001). There were no discontinuations due to sildenafil treatment.

Conclusions

Sildenafil is effective and well tolerated in men with mild to moderate erectile dysfunction of no clinically identifiable organic cause.
Self-exposure therapy for panic disorder with agoraphobia
Authors: Ito L. M. , De Araujo L. A. , Tess V. L. C. , De Barros-Neto T. P. , Asbahr F. R. , Marks I.
Published: August 2002

Background

Exposure to external phobic cues is an effective therapy for panic/agoraphobia but the value of exposure to interoceptive cues is unclear.

Aims

Randomised controlled comparison in panic/agoraphobia of the effects of (a) external, (b) interoceptive or (c) combined external and interoceptive self-exposure to (d) control subjects.

Method

Eighty out-patients were randomised to a control group or to one of three forms of self-exposure treatment (external, interoceptive, or combined). Each treatment included seven sessions over 10 weeks and daily self-exposure homework. Assessments were at pre- and post-treatment and up to 1 year post-entry. Assessors remained blind during treatment.

Results

The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year follow-up, and significantly more than did the control subjects. Rates of improvement on main outcome measures averaged 60% at post-treatment and 77% at follow-up.

Conclusions

The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term.
Schizophrenia and the frontal lobes
Authors: Highley J. Robin , Walker Mary A. , Esiri Margaret M. , McDonald Brendan , Harrison Paul J. , Crow Timothy J.
Published: August 2002

Background

It has been suggested that there is frontal lobe involvement in schizophrenia, and that it may be lateralised and gender-specific.

Aims

To clarify the structure of the frontal lobes in schizophrenia in a postmortem series.

Method

The volume of white matter and cortical components of the frontal lobes was measured in brains of controls and patients with schizophrenia using planimetry and the Cavalieri principle. The components measured were: superior frontal gyrus, middle frontal gyrus, a composite of inferior frontal gyrus and orbito-frontal cortex, as well as total frontal lobe cortex and white matter. In addition, the anterior cingulate gyrus was measured.

Results

No diagnosis, gender, diagnosis × side, diagnosis × gender or diagnosis × gender × side interactions were observed in the volume of any of the components, the grey matter as a whole or the white matter. No evidence for volumetric inter-group differences was found for the anterior cingulate gyrus.

Conclusions

Such structural abnormalities as are present in the frontal lobes are more subtle than straightforward alterations in tissue volume; they may include changes in shape and the pattern of gyral folding.
Handedness, language lateralisation and anatomical asymmetry in schizophrenia
Authors: Sommer Iris , Aleman André , Ramsey Nick , Bouma Anke , Kahn René
Published: August 2002

Background

Cerebral lateralisation appears to be decreased in schizophrenia. Results of studies investigating this, however, are equivocal.

Aims

To review quantitatively the literature on decreased lateralisation in schizophrenia.

Method

Meta-analyses were conducted on 19 studies on handedness, 10 dichotic listening studies and 39 studies investigating anatomical asymmetry in schizophrenia.

Results

The prevalence of mixed- and left-handedness (‘non-right-handedness’) was significantly higher in patients with schizophrenia as compared to healthy controls, and also as compared to psychiatric controls. The analysis of dichotic listening studies revealed no significant difference in lateralisation in schizophrenia. However, when analysis was restricted to studies using consonant-vowel or fused word tasks, significantly decreased lateralisation in schizophrenia emerged. Asymmetry of the planum temporale and the Sylvian fissure was significantly decreased in schizophrenia, while asymmetry of the temporal horn of the lateral ventricle was not.

Conclusion

Strong evidence is provided for decreased cerebral lateralisation in schizophrenia.
Relationship between 5-HT function and impulsivity and aggression in male offenders with personality disorders
Authors: Dolan M. , Anderson I. M. , Deakin J. F. W.
Published: August 2002

Background

Reduced serotonergic (5-HT) function and elevated testosterone have been reported in aggressive populations.

Aims

To investigate relationships between impulsivity, aggression, 5-HT function and testosterone in male offenders with personality disorders.

Method

Sixty male offenders with DSM–III–R personality disorders and 27 healthy staff controls were assessed using the Special Hospital Assessment of Personality and Socialisation (SHAPS), impulsivity and aggression ratings, d-fenfluramine challenge and plasma hormone concentrations.

Results

The SHAPS non-psychopaths and those with schizoid personality disorders had enhanced 5-HT function (prolactin response to d-fenfluramine). Reduced 5-HT function was found in offenders with DSM–III–R borderline personality disorders and those with a history of repeated self-harm or alcohol misuse. The 5-HT function was inversely correlated more strongly with impulsivity than with aggression. Plasma testosterone correlated positively with aggressive acts. The SHAPS primary psychopaths had lower initial cortisol and higher testosterone concentrations than controls.

Conclusions

Future studies are needed to investigate regional brain 5-HT function.
Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly
Authors: Ancelin Marie-Laure , De Roquefeuil Guilhem , Ledésert Bernard , Bonnel François , Cheminal Jean-Claude , Ritchie Karen
Published: August 2002

Background

Anaesthesia could provoke persistent alterations in specific cognitive domains in the elderly where ageing-related neuronal changes may exacerbate pharmacotoxic effects.

Aims

To evaluate anaesthesia effects on the incidence of cognitive dysfunction after orthopaedic surgery in elderly patients.

Method

A total of 140 patients over the age of 64 years completed a full range of computerised cognitive tests. The study takes into account effects of pre-operative cognitive dysfunction, depressive symptomatology and ability to perform activities of daily living.

Results

Postoperative cognitive decline persisted for up to 3 months in 56% of subjects. Dysfunction was limited to verbal, visuo-spatial and semantic abilities and secondary and implicit memory. Age, low educational level, pre-operative cognitive impairment or depression are risk factors.

Conclusions

Cognitive functions are not equally affected, type of impairment being determined by the risk factors described above and anaesthesia type.
Incidence of psychotic disorders in immigrant groups to the Netherlands
Authors: Selten J.-P. , Veen N. , Feller W. , Blom J. D. , Schols D. , Camoenië W. , Oolders J. , Van Der Velden M. , Hoek H. W. , Rivero V. M. Vladár , Van Der Graaf Y. , Kahn R.
Published: August 2002

Background

Previous reports on the incidence of schizophrenia in immigrant groups to The Netherlands were based on hospital data.

Aims

To compare the incidence of psychotic disorders in the immigrant groups to that in natives.

Method

Two-year first-contact incidence study in The Hague.

Results

The risks of schizophrenia, schizophreniform or schizoaffective disorder (DSM–IV criteria) were increased for subjects born in Morocco (gender and age-adjusted relative risk=4.5; 95% CI 1.4–8.5), Surinam (relative risk=3.2; 1.8–5.7), The Netherlands Antilles (relative risk=2.9; 0.9–9.5) and other non-Western countries (relative risk=2.4; 1.3–4.7). This risk was also increased for Moroccans (relative risk=8.0; 2.6–24.5) and Surinamese (relative risk=5.5; 2.5–11.9) of the second generation. The risks for Turkish immigrants, first or second generation, and for immigrants from Western countries were not significantly increased.

Conclusions

This study indicates that the incidence of schizophrenia is increased in several, but not all, immigrant groups to The Netherlands. It is possible that factors associated with a process of rapid westernisation precipitate schizophrenia in people who are genetically at risk.
The Truth and Reconciliation Commission in South Africa: relation to psychiatric status and forgiveness among survivors of human rights abuses
Authors: Kaminer Debra , Stein Dan J. , Mbanga Irene , Zungu-Dirwayi Nompumelelo
Published: August 2002

Background

The impact on individual survivors of human rights abuses of testifying before South Africa's Truth and Reconciliation Commission (TRC) has not been established.

Aims

To examine the degree to which participation in the TRC is related to current psychiatric status and forgiveness among survivors.

Method

Survivors (n=134) who gave public, closed or no testimony to the TRC completed instruments measuring exposure to human rights abuses, exposure to other traumatic events, current psychiatric status and forgiveness attitudes towards the perpetrator(s).

Results

There was no significant association between TRC participation and current psychiatric status or current forgiveness attitudes, and low forgiveness was associated with poorer psychiatric health.

Conclusions

Truth commissions should form part of, rather than be a substitute for, comprehensive therapeutic interventions for survivors of human rights abuses. Lack of forgiveness may be an important predictor of psychiatric risk in this population.
Focus on psychiatry in South Africa
Authors: Emsley Robin
Published: August 2002

South Africa is a country of great fascination to those interested in the origins, development and behaviour of humankind. For example, recent fossil discoveries appear to confirm Darwin's hunch that Africa – and perhaps southern Africa – was the cradle of humankind. Caves in the Sterkfontein Valley near Johannesburg have produced abundant scientific information on the evolution of modern man over the past 3.5 million years. This is of interest not only from a historical point of view but also in terms of modern science. With the significant advances in medical genetics in general, and psychiatric genetics in particular, there has been a growing interest in homogeneous populations with novel gene pools. South Africa is a rich source of homogeneous populations with an apparently common ancestry.
Understanding the roles of genome and envirome: methods in genetic epidemiology
Authors: Neiderhiser Jenae M.
Published: August 2002

Background

In order to understand studies of psychiatric epidemiology focusing on the ‘genome’ and ‘envirome’, basic knowledge of the logic and methods is necessary.

Aims

To provide a review of typical methods used in genetic epidemiology.

Method

Reviews of the research designs usually employed in quantitative and molecular genetic studies. Genotype-environment correlation and interaction are also discussed.

Results

Quantitative genetic studies indicate that genetic influences are important for both psychiatric disorders and behavioural traits. Specific gene loci can be tested for associations with both psychiatric risk and behavioural traits by means of molecular genetic techniques. There has been little examination of genotype-environment correlation and interaction, although the few reports that have appeared suggest that these complex relationships are important.

Conclusions

Advances in quantitative and molecular genetics now permit more careful examination of genotype-environment interaction and correlation. Studies combining molecular genetic strategies with measurement of the environment are still at an early stage, however, and their results must be awaited.
Genes, environment and schizophrenia
Authors: Tsuang Ming T. , Stone William S. , Faraone Stephen V.
Published: August 2002

Background

Data from family, twin and adoption studies show overwhelming evidence of a substantial genetic component in schizophrenia and although molecular genetic studies have been more difficult to replicate, recent improvements in technology have resulted in the implication of genes at several chromosomal loci. Nevertheless, it remains clear that environmental factors both add to and interact with genetic factors to produce the disorder.

Aims

To incorporate genetic and environmental risk factors into a neurodevelopmental model in order to conceptualise the liability to schizophrenia.

Method

A representative selection of the literature related to this issue is reviewed, together with a reformulation of Meehl's term ‘schizotaxia’ to describe the liability to the disorder.

Results

The literature supports a multi-factorial view of the liability to schizophrenia, which includes both genetic and environmental components.

Conclusions

Schizotaxia provides a useful way to conceptualise both the liability for schizophrenia, and also the development of treatment strategies aimed at the eventual prevention of the illness.
Obstetric complications and schizophrenia: prenatal underdevelopment and subsequent neurodevelopmental impairment
Authors: Kunugi H. , Nanko S. , Murray R. M.
Published: August 2002

Background

Many studies have shown an association between obstetric complications and schizophrenia.

Aims

To investigate the possible relationship between prenatal underdevelopment, neurodevelopmental abnormality and subsequent schizophrenia.

Method

The literature was reviewed. In particular, by pooling data from recently published reports, we examined whether low birthweight (<2500 g) is a risk factor for schizophrenia.

Results

Low birthweight was significantly more common for subjects with schizophrenia than for control subjects:P< 0.00001, odds ratio 2.6 (95% CI 2.0 to 3.3). Individuals born prematurely are at greater risk of perinatal brain damage and subsequent neurodevelopmental abnormalities, which may constitute vulnerability to the development of schizophrenia. Patients with schizophrenia who had low birthweights also tended to have poor premorbid psychosocial adjustment.

Conclusions

Low birthweight is a modest, but definite, risk factor for schizophrenia. Brain damage associated with prenatal underdevelopment has a role in the pathogenesis of poor premorbid functioning and subsequent neurodevelopmental impairment in some cases of schizophrenia.
Moving on from old dichotomies: beyond nature-nurture towards a lifeline perspective
Authors: Rose Steven
Published: August 2002

Background

Genetics is increasingly being used to explain human behaviours, with growing enthusiasm for what could be termed ‘genetic determinism’, which an ultra-Darwinist approach seeks to apply to all aspects of the human condition.

Aims

To consider the validity of the claims concerning the genetics of human behaviour and psychological distress.

Method

A critical review of the current assumptions about the relative contributions of genetics and the environment.

Results and conclusions

Organisms are in constant interaction with their environment: that is, organisms select environments just as environments select organisms. Like organisms, environments evolve and are homeodynamic rather than homeostatic; both ‘genome’ and ‘envirome’ are abstractions from this continuous dialectic.
Epidemiology in neurobiological research: exemplified by the influenza-schizophrenia theory
Authors: Munk-J⊘rgensen Povl , Ewald Henrik
Published: August 2002

Background

During recent years the strategy for aetiological research in schizophrenia has been to concentrate on two closely connected directions: the search for the genetic element and the search for environmental factors. Damage to the immature brain during pregnancy and delivery has given us the most interesting results from recent environmental research.

Aims

To examine the validity of the influenza-schizophrenia hypothesis.

Method

A review of register-based epidemiological studies in Denmark conducted over a 10-year period.

Results

The studies reviewed provided strong inferential evidence in favour of the hypothesis, but some methodological problems are unresolved and not all replication studies have been positive.

Conclusions

The brain-damage hypothesis points to possibilities for identifying high-risk individuals at an early stage of life and perhaps establishing specific preventive programmes. There is, however, a great need for closer international collaboration in future research.
Towards a molecular epidemiology of alcohol dependence: Analysing the interplay of genetic and environmental risk factors
Authors: Heath A. C. , Madden P. A. F. , Bucholz K. K. , Bierut L. J. , Whitfield J. B. , Dinwiddie S. H. , Slutske W. S. , Statham D. B. , Martin Nicholas G.
Published: August 2002

Background

Progress in identifying genetic factors protective against alcohol dependence (AIcD) requires a paradigm shift in psychiatric epidemiology.

Aims

To integrate analysis of research into the genetics of alcoholism.

Method

Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed.

Results

In men, effects of alcohol dehydrogenase ADH2∗1/∗2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AIcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AIcD symptoms. No protective effect of the ADH2∗1/∗2 genotype was observed in women.

Conclusions

The early onset and strong familial aggregation of AIcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.
Genetics, environment and cognitive abilities: review and work in progress towards a genome scan for quantitative trait locus associations using DNA pooling
Authors: Plomin Robert , Craig Ian
Published: August 2002

Background

Multivariate genetic research indicates that genetic effects on diverse cognitive abilities are general rather than specific or modular. General cognitive ability (g), a key factor in learning and memory, is among the most heritable behavioural traits.

Aims

To give a brief overview of quantitative genetic research on g and to describe initial results from a programme of research that aims to identify genes responsible for the substantial heritability of general cognitive ability.

Method

The research uses a new technique called DNA pooling, which combines DNA from individuals within a group and makes it feasible to screen thousands of DNA markers for a systematic scan of the genome for associations between DNA markers and g. Two independent samples of children with very high g scores and two control samples of children with average g scores were compared in a systematic scan of 147 markers on chromosome 4 and 66 markers on chromosome 22.

Results

Three replicated associations on chromosome 4 were identified using DNA pooling and confirmed using individual genotyping.

Conclusions

These first results of the application of DNA pooling in systematic analysis of allelic association are encouraging.
Effect of prenatal exposure to polychlorinated biphenyls on cognitive development in children: A longitudinal study in Taiwan
Authors: Lai T. J. , Guo Y. L. , Guo N. W. , Hsu C. C.
Published: August 2002

Background

From 1978 to 1979, a group of people in Taiwan were exposed to high levels of heat-degraded polychlorinated biphenyls (PCBs) owing to accidental ingestion of contaminated rice oil. Children born to mothers following the exposure (‘Yucheng’ children) were known to have hyperpigmented skin and other dysmorphology after birth.

Aims

To determine the effect of prenatal exposure to PCBs on cognitive development in Yucheng children.

Method

One hundred and eighteen Yucheng children prenatally exposed to PCBs and degradation products, and community-matched control children who were exposed to background levels only, were followed from 1985 to 1998. The Bayley Scale for Infant Development, Chinese version of the Stanford – Binet IQTest, Raven's Coloured Progressive Matrices and Raven's Standardised Progressive Matrices were used to assess the cognitive development of these children.

Results

The Yucheng children scored lower than control children on each of these methods of measurement between the ages of 2 and 12 years.

Conclusions

Prenatal exposure to PCBs and their derivatives has long-term adverse effects on cognitive development in humans.
Early-onset Alzheimer's disease in Scotland: environmental and familial factors
Authors: Whalley Lawrence J.
Published: August 2002

Background

Alzheimer's disease (AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important.

Aims

To integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model.

Method

Disease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD.

Results

Informative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life.

Conclusions

The studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (≥600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms.
Understanding the excess of psychosis among the African-Caribbean population in England
Authors: Sharpley Mandy , Hutchinson Gerard , Murray Robin M. , McKenzie Kwame
Published: August 2002

Background

Increased rates of schizophrenia continue to be reported among the African–Caribbean population in England.

Aims

To evaluate the competing biological, psychological and social explanations that have been proposed.

Method

Literature review.

Results

The African–Caribbean population in England is at increased risk of both schizophrenia and mania; the higher rates remain when operational diagnostic criteria are used. The excess of the two psychotic disorders are probably linked: African–Caribbean patients with schizophrenia show more affective symptoms, and a more relapsing course with greater social disruption but fewer chronic negative symptoms, than White patients. No simple hypothesis explains these findings.

Conclusions

More complex hypotheses are needed. One such links cultural variation in symptom reporting, the use of phenomenological constructs by psychiatrists and social disadvantage.
Vulnerability factors for common mental illnesses
Authors: Goldberg David
Published: August 2002

Background

Twin studies suggest that shared early family environment is of only minor importance in the aetiology of depression, most of the variance being attributable either to genetic or to individual ‘non-shared’ environmental factors.

Aims

To examine the respective roles of personality and social experiences on the risk for common mental disorders, with special reference to depression.

Method

Analysis of preliminary findings from two large-scale British population surveys: (a) a multi-centre study of general practice patients, and (b) a study of working-class women in Manchester.

Results

(a) Persons recently separated from their partners have raised mean scores for psychological distress, but the relative excess is due entirely to persons with high ratings for introversion; (b) while severe life events were associated with physiological responses characteristic of depression, the probability of experiencing such life events varied between 0.2 monthly for low scorers and 1.5 monthly for high scorers on a vulnerability measure.

Conclusions

Social factors do appear to influence the prevalence of depression, but this effect is not independent of genetically determined vulnerability.
Neuroticism, life events and mental health: evidence for person-environment correlation
Authors: Van Os Jim , Park S. B. G. , Jones Peter B.
Published: August 2002

Background

There is some evidence that genetic effects on the likelihood of experiencing stressful life events (SLEs) are mediated by heritable traits such as cognitive ability (CA) and neuroticism (N).

Aims

To examine whether the association between CA, N and mental ill-health is driven in part by a predisposition to experience depressogenic SLEs.

Method

Childhood measures of N and CA were available in a birth cohort of 5362 individuals. At ages 36 and 43 years, mental state and occurrence of SLEs in the previous year were assessed. Using a path-analytic approach, models with and without a hypothesised influence of N and CA on the occurrence of SLEs were compared.

Results

The fit of the model with childhood N having a direct influence on SLEs was good with χ2=5.72, d.f.=4,P=0.22 at age 36 years and χ2=3.50, d.f.=5,P=0.62 at age 43. The fit of the model was significantly worse without this path at both ages (36 years: χ2=42,5, d.f.=1,P<0.001; 43 years χ2=15.3 d.f.=1,P<0.001). No consistent differences were seen in comparisons of models with CA.

Conclusions

The results are congruent with the suggestion that genetic effects on SLEs are mediated by personal characteristics. Part of the well-established association between N and minor psychiatric disorder may be mediated by an indirect effect of N on the likelihood of experiencing SLEs.
Longitudinal study assessing the joint effects of socio-economic status and birth risks on adult emotional and nervous conditions
Authors: Fan Angela P. , Eaton William W.
Published: August 2002

Background

Previous investigations into the impact of birth complications and social environment have generally followed their subjects only at young ages.

Aims

To assess the long-range impact of socio-economic status (SES) and birth risks on the development of emotional and nervous conditions through adulthood.

Method

The Johns Hopkins Pathways Study interviewed 1824 subjects born between 1960 and 1965. The median household income of the children at age 7–8 years was used to divide the cohort into high and low income categories. Differences in lifetime prevalence of emotional and nervous conditions through adulthood between the two income groups were identified.

Results

Children in the lower income group were 1.86 times more likely to report an emotional or nervous condition in adult life. Boys in the lower income group at age 7–8 years were 3.2 times more likely to do so. The risks of difficult birth for adult mental disturbance were accentuated in the low-income group.

Conclusions

Children who experience birth complications are at increased risk of developing adult mental disturbances; this increase is mitigated by higher SES.
The promise of psychiatric enviromics
Authors: Anthony James C.
Published: August 2002

Background

The human genome dwells within environment, determines environment and its expression is shaped by environment.

Aims

To introduce ‘psychiatric enviromics’ as a complement to human genomics and proteomics as applied to mental health.

Method

Selective literature review and synthesis.

Results and conclusions

Psychiatric enviromics can be planned to sustain the search for specific environments or environmental processes and conditions that promote mental health and reduce the occurrence of psychiatric disturbances. Subsets of the psychiatric envirome will be discovered to have functional importance precisely because specific environmental conditions or processes will reduce, amplify or otherwise modulate the expression of specific genes or multiple gene interactions at identifiable periods of life-span development. Other salubrious environmental conditions and processes will have funtional importance but lack specificity of action with respect to gene expression. An international collaboration in the form of a review of evidence is proposed as a starting point for ‘psychatric enviromics’.
Inter-generational longitudinal study of social class and depression: A test of social causation and social selection models
Authors: Ritsher Jennifer E. B. , Warner Virginia , Johnson Jeffrey G. , Dohrenwend Bruce P.
Published: August 2002

Background

Generations of epidemiologists have documented an association between low socio-economic status (SES) and depression (variously defined), but debate continues as to which is the causative factor.

Aims

To test the extent to which social causation (low SES causing depression) and social selection (depression causing low SES) processes are in evidence in an inter-generational longitudinal study.

Method

Participants (n=756) were interviewed up to four times over 17 years using the Schedule for Affective Disorders and Schizophrenia (SADS).

Results

Low parental education was associated with increased risk for offspring depression, even after controlling for parental depression, offspring gender and offspring age. Neither parental nor offspring depression predicted later levels of offspring occupation, education or income.

Conclusion

There is evidence for an effect of parental SES on offspring depression (social causation) but not for an effect of either parental or offspring depression on offspring SES (social selection).
Nature, nurture and mental disorder: old concepts in the new millennium
Authors: Cooper Brian
Published: August 2002

Background

Evidence from twin and adoption studies has highlighted the importance of gene-environment interaction in the aetiology of mental disorders, and advances in molecular genetics have raised hopes of more rapid progress in this field of investigation.

Aims

To review epidemiological knowledge concerning genetic and environmental risk factors for a cross-section of psychiatric conditions, and evidence of interaction between the two types.

Method

Searches of the literature in genetic and psychiatric epidemiology, including contributions to this supplement.

Results

Overall, firm knowledge on both genetic and environmental causal factors is still fragmentary, although progress has varied among diagnostic categories. Environmental aspects have been dealt with only perfunctorily in most genetic epidemiological research.

Conclusions

Better definition and classification of environmental hazards, and closer inter-disciplinary cooperation, will be necessary in future. Specific gene-environment interaction effects seem likely to prove most important in neuropsychiatric syndromes, and a less specific genetic influence on susceptibility to environmental stress among the common mental disorders.
Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilisers
Authors: Manji Husseini K. , Moore Gregory J. , Chen Guang
Published: August 2002

Background

New research is dramatically altering our understanding of the molecular mechanisms underlying neuronal communication.

Aim

To elucidate the molecular mechanisms underlying the therapeutic effects of mood stabilisers.

Method

Results from integrated clinical and laboratory studies are reviewed.

Results

Chronic administration of lithium and valproate produced a striking reduction in protein kinase C (PKC) isozymes in rat frontal cortex and hippocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked antimanic efficacy. Both lithium and valproate regulate the DNA binding activity of the activator protein 1 family of transcription factors. Using mRNA differential display, it was also shown that chronic administration of lithium and valproate modulates expression of several genes. An exciting finding is that of a robust elevation in the levels of the cytoprotective protein, bcl-2.

Conclusions

The results suggest that regulation of signalling pathways may play a major part in the long-term actions of mood stabilisers. Additionally, mood stabilisers may exert underappreciated neuroprotective effects.
Neuropsychology of bipolar disorder
Authors: Murphy F. C. , Sahakian B. J.
Published: August 2002

Background

Although the presence of wide-ranging neuropsychological deficits in individuals with major depression is well established, few studies have investigated the nature of cognitive impairment in patients with bipolar disorder.

Aims

To review research of the neuropsychology of bipolar disorder, with special attention to the relationship between mood and cognitive functioning.

Method

Literature review.

Results

Findings generally demonstrate mania-related impairments on conventional neuropsychological tests, with direct comparisons of patients with mania and patients with depression failing to find group differences. More recent work has sought to differentiate these disorders by employing tasks with affective components. This research has demonstrated biases for processing positive and negative stimuli in patients with mania and depression, respectively.

Conclusions

Future studies, employing tasks that require cognitive and emotional processing, should improve our understanding of the deficits observed in depression and mania. Neuroimaging studies of the neural regions that underlie cognitive processing of affective meaning suggest that the medial and orbitofrontal prefrontal cortex may be particularly involved.
Molecular genetics of bipolar disorder
Authors: Craddock Nick , Jones Ian
Published: August 2002

Background

A robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.

Aims

To present an overview for clinical psychiatrists.

Method

Review of current molecular genetics approaches and emerging findings.

Results

Occasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.

Conclusion

It is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.
Genetic studies of bipolar affective disorder in large families
Authors: Blackwood Douglas H. R. , Muir Walter J. , Visscher Peter M.
Published: August 2002

Background

Genetic factors are known to be important in the aetiology of bipolar disorder.

Aims

To review linkage studies in extended families multiply affected with bipolar disorder.

Method

Selective review of linkage studies of bipolar disorder emphasising the gains and drawbacks of studying large multiply-affected families and comparing the statistical methods used for data analysis.

Results

Linkage of bipolar disorder to several chromosome regions including 4p, 4q, 10p, 12q, 16p, 18q, 21q and Xq has first been reported in extended families. In other families chromosomal rearrangements associated with affective illnesses provide signposts to the location of disease-related genes. Statistical analyses using variance component methods can be applied to extended families, require no prior knowledge of the disease inheritance, and can test multilocus models.

Conclusion

Studying single large pedigrees combined with variance component analysis is an efficient and effective strategy likely to lead to further insights into the genetic basis of bipolar disorders.
Serial analysis of gene expression in the frontal cortex of patients with bipolar disorder
Authors: Sun Yeping , Johnston Nancy L. , Yolken Robert H. , Zhang Lin , Fullertorrey E.
Published: August 2002

Background

Bipolar disorder is a serious brain disease affecting more than a million individuals living in the USA. Epidemiological studies indicate a role for both genetic and environmental factors in the pathogenesis of this disorder.

Aim

To identify RNA transcripts that are up- or down-regulated in the frontal cortex regions of individuals with bipolar disorder.

Method

Serial analysis of gene expression (SAGE) and reverse transcriptase-polymerase chain reaction were used to identify RNA transcripts which are differentially expressed in the frontal cortex of brains obtained postmortem from individuals with bipolar disorder compared with other psychiatric and control conditions.

Results

Levels of RNA transcripts encoding the serotonin transporter protein and components of the NF-κB transcription factor complex are significantly increased in individuals with bipolar disorder compared with unaffected controls. Increased levels of expression of these RNA transcripts were also detected in the brains of some individuals with schizophrenia and unipolar depression.

Conclusion

The SAGE technique offers promise for the characterisation of complex human brain diseases.
Neuroanatomical studies on bipolar disorder
Authors: Baumann Bruno , Bogerts Bernhard
Published: August 2002

Background

Neuroimaging data showing structural and functional brain abnormalities in mood disorders suggest that brain alterations at the neurohistological level may underlie the macropathology seen by imaging in vivo.

Aims

To summarise recent post-mortem studies on affective disorders, with a focus on bipolar disorder.

Method

Literature review and discussion of results from volumetric, cyto-architectural and immunohistochemical analyses.

Results

Basal ganglia are smaller in patients with depression irrespective of diagnostic polarity. In addition, higher neuron numbers have been reported in the locus caeruleus of patients with bipolar disorder compared with those with unipolar depression. Patients with bipolar as well as unipolar illness show subtle structural deficits in the dorsal raphe. Histological data are consistent with a regional reduction in the synthesis of noradrenalin and serotonin, which appears to be compensated by antidepressants.

Conclusion

Preliminary results suggest that, aside from functional dysregulation, subtle structural abnormalities in the brain may contribute to the pathogenesis of mood disorders.
Use of antipsychotic drugs and lithium in mania
Authors: Cookson John
Published: August 2002

Background

Studies highlighting the difficulties associated with lithium suggest that the role of antipsychotic drugs and mood stabilisers in bipolar disorder should be reconsidered.

Aims

To review the efficacy and mode of action of antipsychotic drugs in mania, and to consider the differences between official guidelines and routine clinical practice in the use of these agents for mania.

Method

Review of research, guideline- and practice-based literature.

Results

Guidelines recommend lithium or valproate as first-line treatments for mania, and antipsychotic agents only as ‘adjuncts’ for agitation, dangerous behaviour or psychosis. However, in routine practice, antipsychotic drugs are often prescribed. The effectiveness of these agents in mania has been established by several studies; newer atypical compounds demonstrate antimanic efficacy with a reduced incidence of neurological side-effects.

Conclusion

Antipsychotic drugs are important in the treatment of bipolar disorder and mania. Future studies should evaluate the long-term efficacy and safety of newer atypical antipsychotic agents, and the place of anticonvulsants in combination with antipsychotics in bipolar disorder.