Background. We aimed to determine if an association exists between uncomplicated hepatitis C virus (HCV) infection and depression or fatigue.

Method. A review of the literature was undertaken.

Results. There is an association between HCV infection and either depression or fatigue in certain circumstances – those who are aware they are HCV positive, those with advanced liver disease and those seen in specialist referral centres. All these studies are subject to important biases. There are only a few studies in which knowledge of HCV status and assessment of fatigue or depression is independent. These studies do not suggest an association. There is no association between conventional markers of liver disease and depression or fatigue.

Conclusions. Despite anecdotal evidence to the contrary, at the moment there is no evidence that HCV infection per se is associated with fatigue or depression, and there is a suggestion that it is not. The same risk factors that exist for fatigue in other physical illnesses, such as metabolic disorder, mood disorder, demographics and lack of exercise, certainly exist for HCV. Although there are elegant theoretical mechanisms, there is no compelling epidemiological evidence for an additional HCV specific fatigue or depression factor.

Background. Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders.

Methods. Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors.

Results. The prevalence of suicidal ideation and suicide attempt were 16·1% and 2·4% respectively. In a multinomial regression model, co-twin’s suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin’s suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects.

Conclusions. There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.

Background. We aimed to explore the prevalence and factor structure of premenstrual symptoms in a sample of Australian twins; to investigate phenotypic associations between reported premenstrual symptoms, personality and reproductive dimensions; and to identify the relative contributions of genes and environment to premenstrual symptoms and the extent of genetic and environmental covariation with the personality trait Neuroticism and lifetime major depression.

Method. Seven hundred and twenty female twin pairs (454 monozygotic and 266 dizygotic) from the Australian National Health and Medical Research Council Twin Register reported on experience of 17 premenstrual symptoms during the previous 12 months. In the same questionnaire twins also responded to questions on symptom states, and personality dimensions including neuroticism. Interview data enabling diagnosis of lifetime history of DSM-IV major depression were also available. We fitted univariate and multivariate genetic models to the data.

Results. Most frequently reported symptoms were breast tenderness/pain and bloating/weight gain, followed by affective symptoms. Twelve-month prevalence was 2·4% for the combination of symptoms and functional interference meeting a very rough approximation of DSM-III-R criteria for late luteal dysphoric disorder. Principal factor analysis identified a single premenstrual (PMS) factor. Additive genetic influences (44% of total variance) were identified for PMS. Although we found genetic correlations of 0·62 between reported PMS and neuroticism, and 0·70 with lifetime major depression, 39% of the genetic variance of PMS was not explained by these factors.

Conclusions. Our findings support the existence of genetic influences on premenstrual symptoms, but we were unable to distinguish between liability to symptom experience and symptom reporting. Retrospective reporting may have contributed to our finding that PMS genes were shared in part with neuroticism and liability to lifetime major depression.

Background. Previous studies have shown that the presence of conduct disorder may contribute to the persistence of attention deficit-hyperactivity disorder (ADHD) symptomatology into adolescence; however, the aetiological relationship between the two phenotypes remains undetermined. Furthermore, studies utilizing multiple informants have indicated that teacher ratings of these phenotypes are more valid than maternal reports.

Methods. The genetic structure underlying the persistence of ADHD and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatologies as rated by mothers and teachers at two occasions of measurement was investigated on a sample of 494 male and 603 female same sex adolescent twin pairs participating in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD).

Results. Using structural modelling techniques, one common genetic factor was shown to govern the covariation between the phenotypes across informants and occasion of measurement with additional genetic factors specific to ODD/CD symptomatology and persistence of symptomatology at reassessment. Genetic structures underlying the phenotypes were, to some extent, informant dependent.

Conclusions. The findings indicate that it is unlikely that the co-morbidity between ADHD and ODD/CD is due to environmental influences that are independent of ADHD. Rather it is likely to be due to a shared genetic liability either operating directly, or indirectly through gene–environment correlations or interactions. The covariation between phenotypes across informants and time is governed by a common set of genes, but it seems that ODD/CD is also influenced by additional genetic factors. Developmentally, different forms of genetic liability control ADHD in males and inattention in females.

Background. As part of a collaborative linkage study, the authors obtained clinical and demographic data on 160 families in which more than one sibling was affected with a bipolar illness. The aim of the study was to identify clinical characteristics that had a high degree of familiality.

Method. Data on age at onset, gender, frequency of illness-episodes and proportion of manic to depressive episodes were examined to determine intra-pair correlations in affected sibling pairs. Dimension scales were developed measuring frequency and severity of lifetime mania, depression, psychosis and mood-incongruence of psychotic symptoms; degree of familial aggregation for scores on these dimensions was calculated.

Results. Sibling pairs correlated significantly for age at onset (ρ = 0·293, P<0·001); dimension scores for psychosis (ρ = 0·332, P < 0·001); and proportion of manic to depressive episodes (ρ = 0·184, P = 0·002). These findings remained significant when correcting for multiple testing. Of the other test variables; mania (ρ = 0·171, P = 0·019); incongruence dimensions (ρ = 0·242, P = 0·042); frequency of manic episodes (ρ = 0·152, P = 0·033); and frequency of depressive episodes (ρ = 0·155, P = 0·028) were associated with modest correlations but these were not significant after correction. Degree of familial aggregation was not significant for sex (κ = 0·084) or dimension scores for depression (ρ = 0·078, P = 0·300).

Conclusions. Significant but modest familial resemblance has been shown for some specific features of bipolar illness, particularly age at onset and degree of psychosis. Further research may establish the extent to which these findings are mediated by genetic and/or environmental factors.

Background. We examined the association between parental alcohol use disorders and patterns of alcohol consumption and DSM-IV alcohol use disorders in their offspring in a community-based sample of young adults.

Methods. Data are based on baseline and 4-year follow-up data of 2427 respondents aged 14–24 at baseline. Alcohol use and disorders in respondents were assessed using the Munich-Composite-International-Diagnostic-Interview with DSM-IV algorithms. Diagnostic information about parents was collected by family history information from the respondents, and by direct interview with one parent (cohort aged 14 to 17 years only).

Results. Although the association between maternal and paternal alcohol use disorders and non-problematical drinking in offspring was minimal, there was a strong effect for the transition to hazardous use and for alcohol abuse and dependence; the effect of parental concordance for transition into hazardous use was particularly striking. Maternal history was associated with a higher probability of progression from occasional to regular use, whereas paternal history was associated with progression from regular to hazardous use. Parental alcoholism increased the risk for first onset of hazardous use and alcohol dependence between the ages of 14–17, and for an earlier onset of the alcohol outcomes in offspring. The impact of parental alcohol use disorders was comparable for male and female offspring.

Conclusions. Parental alcoholism predicts escalation of alcohol use, development of alcohol use disorders and onset of alcohol outcomes in offspring.

Background. This study assessed the relationship of early adolescent marijuana use to performance of developmental tasks integral to the transition to young adulthood. The tasks concerned intimacy, education, and work and social conformity.

Methods. African American (N = 617) and Puerto Rican (N = 531) youths completed questionnaires in their classrooms. Five years later they were individually interviewed. Logistic regression analysis estimated the increased likelihood that early marijuana users would make an inadequate transition to young adult social roles.

Results. Analyses examining the association between early marijuana use and 20 outcome variables found significant relationships for 10 of them: (a) having lower educational and occupational expectations; (b) being suspended or expelled from school, fired from jobs, ‘high’ at school or work, collecting welfare; and (c) rebelliousness, not participating in productive activities, not attending church, and being an unmarried parent. Marijuana use was not related to any of the intimate relationship measures. These finding emerged with controls on gender, ethnicity, age and mother's education.

Conclusions. Among African Americans and Puerto Ricans, early marijuana use predicts less adequate performance on some developmental tasks integral to becoming an independent young adult. Marijuana is not a benign drug and is associated with future risks for the individual and society at large.

Background. Neurocircuits comprising limbic, striato–pallidal and thalamo–cortical brain areas are assumed to be involved in the pathophysiology of mood disorders. All these brain regions receive serotonergic afferents arising from the rostral raphe, mainly the dorsal raphe. Although serotonergic systems appear to be involved in the pathology of mood disorders, there is uncertainty as to whether structural alterations in raphe nuclei exist alongside a functional dysregulation of the serotonergic system.

Methods. In the brains of 12 patients with mood disorders (major depressive disorder N = 6, bipolar disorder N = 6) and 12 normal subjects we performed a morphometric post-mortem study on neuronal morphology in all subnuclei of the dorsal raphe nucleus using Nissl stained 20 μm axial serial sections of the brainstem.

Results. The number of neurones of the ventrolateral subnucleus of the dorsal raphe was reduced by 31% in patients with mood disorders compared with non-psychiatric control subjects. Ventrally located subnuclei of the rostral dorsal raphe (ventrolateral, ventral, interfascicular) taken together also showed a smaller number of neurones. Neurone numbers of the dorsal and the caudal subnucleus and volumes of all single subnuclei appeared to be unchanged. Analysis of morphological neuronal types revealed a smaller number of triangular neurones in the ventrolateral subnucleus. Numbers of ovoid and round neurones in the ventrolateral subnucleus also showed a trend to reduction. No correlation was found between neurone numbers in any subnucleus of the dorsal raphe and duration of illness. Neurone numbers did not differ in any subnucleus between patients with unipolar and those with bipolar affective disorder.

Conclusions. Results indicate that patients with primary mood disorders have a circumscribed numerical neuronal deficiency in the dorsal raphe. This structural deviation may contribute to impaired serotonergic innervation of brain regions which are involved in the pathology of mood disorders.

Background. Reduced serotonin (5-HT) function and deficits on neuropsychological tasks have been separately reported in antisocial populations. We investigated whether these impairments are independent or associated factors underlying impulsivity in aggressive personality disordered (PD) offenders and healthy controls and whether there are associated changes in quantitative brain measures.

Methods. This study reports on the findings from a sample of 51 PD offenders and 24 controls, recruited from maximum security psychiatric hospitals, who were characterized using the Special Hospital Assessment of Personality and Socialisation (SHAPS). Subjects underwent assessment of 5-HT function (prolactin response to D-fenfluramine challenge), neuropsychological testing and had a diagnostic MRI scan. Of this sample 19 controls and 24 patients also had quantitative measurement of frontal and temporal lobe volumes on magnetic resonance imaging (MRI).

Results. Non-psychopathic (low-impulsive) aggressive PDs had enhanced 5-HT function compared with controls and highly impulsive aggressive psychopaths. Primary and secondary psychopaths had poorer executive/frontal, but not memory/temporal neuropsychological function than controls and non-psychopaths. There were no significant group differences in frontal or temporal lobe brain volumes. Although impulsivity and aggression are correlated constructs impulsivity appeared to be related to both executive function and 5-HT function, while aggression only correlated inversely with executive/frontal and memory/temporal function. 5-HT did not directly correlate with frontal or temporal volume or function.

Conclusion. Impulsivity appears to be contributed to by both impaired neuropsychological function and 5-HT function. Impaired neuropsychological function alone makes a contribution to aggression. Treatment needs to take account of the neuropsychological and biochemical deficits in this challenging population.

Background. Despite an abundance of clinical research on premenstrual and menstrual symptoms, few epidemiological data provide estimates of the prevalence, incidence, co-morbidity, stability and correlates of premenstrual dysphoric disorder (PMDD) in the community.

Aims. To describe the prevalence, incidence, 12 co-morbidity factors and correlates of threshold and subthreshold PMDD in a community sample of young women.

Methods. Findings are based on prospective–longitudinal community survey of 1488 women aged 14–24, who were followed-up over a period of 48 months (follow-up, N = 1251) as part of the EDSP sample. Diagnostic assessments were based on the Composite International Diagnostic Interview (CIDI) and its 12-month PMDD diagnostic module administered by clinical interviewers. Diagnoses were calculated using DSM-IV algorithms, but daily ratings of symptoms, as required, were not available.

Results. The baseline 12-month prevalence of DSM-IV PMDD was 5·8%. Application of the diagnostic exclusion rules with regard to concurrent major depression and dysthymia decreased the rate only slightly (5·3%). An additional 18·6% were ‘near-threshold’ cases, mostly because they failed to meet the mandatory impairment criterion. Over the follow-up period only few new PMDD cases were observed: cumulative lifetime incidence was 7·4%. PMDD syndrome was stable across 48 months with <10% complete remissions among baseline PMDD cases. The 12-month and lifetime co-morbidity rates were high (anxiety disorders 47·4%, mood disorders 22·9%; somatoform 28·4%), only 26·5% had no other mental disorder. Particularly high odds ratios were found with nicotine dependence and PTSD. In terms of correlates increased rates of 4-weeks impairment days, high use of general health and mental health services, and increased rates of suicide attempts were found.

Conclusion. In this sample of adolescents and young adults, premenstrual symptoms were widespread. However, DSM-IV PMDD was considerably less prevalent. PMDD is a relatively stable and impairing condition, with high rates of health service utilization, increased suicidality and substantial co-morbidity.

Background. The relationships between acculturation and suicide were investigated in East Taiwan.

Methods. Psychological autopsy interviews were conducted for consecutive suicides from two native Taiwanese groups (Atayal and Ami) (N = 30 for each group); each of them was matched with two controls for age, sex and area of residence. The Taiwan Aboriginal Acculturation Scale was used to measure the extent of acculturation.

Results. A lower degree of social assimilation was significantly associated with a higher risk of suicide in the Atayal and the male groups. In multivariable regression analysis, a significant effect of low social assimilation on the risk of suicide was found in Atayal and in men, even after controlling for the effects of ICD-10 depressive episode and emotionally unstable personality disorder. Meanwhile, there was a significant trend across low, moderate and high social assimilation on suicide risk in Atayal and in men.

Conclusions. For the native Taiwanese, the stress from rapid acculturation into the main Chinese society is crucial to their mental health. It might be reduced through targeted social and educational programmes.

Background. This paper examines the association between exposure to the Chornobyl nuclear power plant explosion and the psychological and physical well-being of mothers with young children. The study also examines whether exposure to Chornobyl increased the vulnerability of mothers to subsequent economic and social stress, and thus represents a unique test of the stress–vulnerability model in a non-Western setting.

Method. The sample consisted of mothers evacuated from the contamination zone surrounding the plant (evacuees) and mothers who had never lived in a radiation-contaminated area (controls). In addition to exposure status, the interview obtained data on perceived economic stress, social stress and stress moderators. The dependent variables were measured by the SCL-90 global severity index (GSI), perceived physical health and number of days unable to work due to illness.

Results. Overall, evacuees reported fewer stressors and greater personal and social resources than control mothers. Nevertheless, evacuees scored higher on the GSI, reported lower perceived physical health and took more sick days relative to control mothers, even after controlling for demographic factors, stressors and stress moderators. Tests of interaction effects were not statistically significant.

Conclusions. The findings confirmed that married women with young children evacuated to Kyiv following the Chornobyl nuclear power plant explosion reported significantly poorer psychological and perceived physical health than controls 11 years later. Although perceived social and economic adversities also affected these outcomes, there was no evidence that exposure to the Chornobyl accident increased the vulnerability of mothers to these stressors, giving support to the additive burden model of stress.

Background. Few studies have shown that maladaptive beliefs relate to treatment outcome.

Method. In a randomized controlled study, 87 patients with post-traumatic stress disorder (PTSD) had exposure therapy alone or cognitive restructuring alone, or both combined, or relaxation. Independent blind assessors assessed patients at pre-, mid- and post-treatment and at follow-up; at those times patients rated cognitive, behavioural and emotional aspects of their disorder.

Results. Baseline beliefs about mistrust, helplessness, meaninglessness and unjustness of the world related to baseline PTSD symptoms but did not predict treatment outcome, though improvement in certain beliefs correlated with more symptom improvement. Several ‘key’ beliefs changed after, and none before, symptoms improved. At post-treatment, sense of control and attribution of gains to personal efforts predicted maintenance of gains at follow-up.

Conclusions. Baseline beliefs and improvement in beliefs did not predict outcome. Post-treatment sense of control/internal attribution predicted maintenance of gains at follow-up. How much sense of control is produced by or causes improvement deserves testing.

Background. Mood congruent memory bias predicts a more superior recall memory of learnt material congruent with the mood state at the time of learning. The present study is the first report of an experimental study in which a biological mood induction was used to test this hypothesis. The influence of acute tryptophan (TRP) depletion, inducing low serotonin neurotransmission and a depression of mood, on memory bias was evaluated in healthy volunteers (16 with and 11 without a family history of major affective disorder).

Methods. Twenty-seven subjects received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind, balanced, cross-over design. An affective memory test consisting of a 30-word list with words of positive, neutral, and negative affective valence and a mood questionnaire were assessed at 6 and 24 h following treatment administration.

Results. TRP depletion impaired delayed recall of neutral and positive words, but not of negative words. There was no interaction of family history and treatment and there was no post hoc association between the influence of TRP-depletion on mood and on affective memory bias.

Conclusion. Experimentally induced serotonergic depletion in normal individuals shifts affective memory bias towards negative affective valent verbal stimuli.

Background. Several studies suggest that many patients with schizophrenia have pre-morbid neurodevelopmental abnormalities. This study examines how behavioural abnormalities are associated with mild psychotic symptoms and later schizophrenic illness.

Methods. Maternal ratings on the Child Behavior Checklist (CBCL) of the early behaviour of 155 subjects were obtained at entry to the Edinburgh study of people at high risk of schizophrenia. These maternal ratings were compared in those with and without psychotic symptoms and used to predict the later onset of psychosis.

Results. The CBCL syndrome scores for the children prior to age 13 did not distinguish any of the study groups at entry to the study. In the ratings made for the subjects when aged from 13 to 16, delinquent behaviour and ‘other problems’ were weakly associated with these symptoms. However, with the exception of somatic symptoms and thought problems, the age 13–16 scales were significant predictors of later schizophrenic illness. This was true also for some of the ratings prior to age 13.

Conclusions. Various behaviours, in particular, withdrawn and delinquent–aggressive behaviour in adolescents at risk of schizophrenia may predict later onset of the illness. These behaviours, however, are far less predictive of isolated psychotic symptoms prior to psychosis onset.

We read with considerable interest the recent paper by Kéri et al. (31, 915–922) in which they observed that siblings of schizophrenia patients could be distinguished from siblings of bipolar patients on the basis of dysfunctions of visual backward masking and spatial working memory.