Background. Lower serum high-density lipoprotein cholesterol and increased ratio of omega-6/omega-3 fatty acids have been reported in unipolar and bipolar depressed patients. Changes in cholesterol and fatty acids have been suggested to affect membrane viscosity and consequently serotonergic neurotransmitter expression.

The goal of this study was to investigate whether lower baseline cholesterol and increased omega-6 and lower omega-3 fatty acids are present in healthy first-degree relatives of bipolar patients compared with controls and whether these changes were associated with neuroendocrine responses to an i.v. tryptophan challenge or mood.

Method. Baseline cholesterol, fatty acids and mood were determined in healthy first-degree relatives of patients with bipolar disorders (N=30) and healthy matched controls (N=15) (parallel-group design). Prolactin and cortisol were measured following tryptophan infusion.

Results. First-degree relatives showed significantly lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids. Lower total omega-3 and higher total omega-6 fatty acids in phospholipids were positively correlated with peak prolactin response to tryptophan. Lower total omega-3 fatty acids in phospholipids and cholesteryl esters were associated with lower mood.

Conclusions. Abnormalities of lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids in these subjects are in agreement with findings in bipolar and major depressed patients. Changes in fatty acids show an association with central serotonergic parameters. It is suggested that these abnormalities in cholesterol and fatty acids may constitute a trait marker for bipolar disorders.

Background. Therapist competence may be an important factor in determining clinical outcome in psychological therapies. However, there are few published studies of therapist competence v. patient outcome from randomized controlled trials. We tested the hypothesis that higher levels of therapist competence would lead to better clinical outcomes in both patient- and observer-rated measures at 6- and 12-month follow-up.

Method. A random sample of 49 audiotapes of manual assisted cognitive therapy sessions delivered by 21 therapists involved in the Prevention of Parasuicide by Manual Assisted Cognitive Behaviour Therapy trial was rated to assess the level of therapist competence. Patient outcome was assessed using self and observer ratings of depressive and anxiety symptoms, social functioning, global functioning and number of episodes of deliberate self-harm.

Results. At 6-month follow-up, there was a statistically significant association between therapist level of competence and observer-rated depression only. At 12-month follow-up, significant associations were noted between therapist competence and all observer-rated clinical outcomes but not for self-rated outcome measures. However, there was no association between therapist competence and the number of self-harm episodes during follow-up.

Conclusions. When treated by therapists rated as more competent than other therapists who received equivalent brief training, patients with recurrent self-harm show significant clinical improvements. However, this benefit is not identified across all outcome measures and is not fully apparent until 12-month follow-up.

Background. In animals, early trauma can produce long-lasting changes in sensitivity to the pathogenic effects of stress. To explore whether similar processes occur in humans, we examine whether childhood sexual abuse (CSA) in women alters sensitivity in adulthood to the depressogenic effects of stressful life events (SLEs).

Method. A history of CSA was obtained from a population-based sample of 1404 female adult twins. Cox Proportional hazard models were used to predict onsets of episodes of DSM-III-R major depression (MD) in the past year from previously assessed levels of neuroticism (N), CSA and past-year SLEs scored on long-term contextual threat.

Results. In the best-fit model, onset of MD was predicted by CSA, SLEs and N. Individuals with CSA (and especially with severe CSA) had both an overall increased risk for MD and a substantially increased sensitivity to the depressogenic effects of SLEs. A ‘dose–response’ relationship between severity of CSA and sensitivity to SLEs was clearer in those with low to average levels of N than in those with high levels of N.

Conclusion. As documented with physiological responses to a standardized laboratory stressor, CSA increases stress sensitivity in women in a more naturalistic setting. Both genetic and early environmental risk factors can produce long-term increase in the sensitivity of individuals to depressogenic life experiences.

Background. Knowledge about factors that predict relapse in anorexia nervosa (AN) is needed for the development of effective relapse prevention treatments and may also advance understanding of the psychopathology of AN. The aim of the present study was to examine the rate, timing and prediction of relapse in AN following weight restoration in a specialized in-patient treatment programme.

Method. Fifty-one consecutive first-admission AN patients who were weight-restored following in-patient treatment participated in the study. Follow-up assessments were conducted a median of 15 months post-discharge. Relapse of AN was defined as a body mass index <17·5 for 3 consecutive months. Data were analysed using Kaplan–Meier survival analysis and Cox regression.

Results. The overall rate of relapse was 35% and the mean survival time was 18 months. The highest risk period was from 6 to 17 months after discharge. Several significant predictors of relapse were identified: a history of suicide attempt; previous specialized treatment for an eating disorder; severity of obsessive–compulsive symptoms at presentation; excessive exercise immediately after discharge; and residual concern about shape and weight at discharge.

Conclusions. There continues to be a significant risk of relapse among AN patients who remain well for the first year post-discharge. Several variables were shown to be associated with an elevated risk of relapse. These findings have implications for the development of initial treatments and relapse prevention strategies for AN.

Background. Evidence is increasing that amygdala and hippocampus show significant structural abnormalities in affective disorders. Two previous studies found enlarged amygdala size in subjects with recent-onset major depression.

Method. Amygdala and hippocampal volumes were assessed in 17 young women with major depressive disorder and 17 healthy matched control subjects by use of three-dimensional structural magnetic resonance imaging. The severity of depressive symptoms was assessed using the Hamilton Depression Scale and the Beck Depression Inventory.

Results. Compared with control subjects, depressive subjects had significantly larger (+13%) amygdala volumes and significantly smaller (−12%) hippocampal volumes. Amygdala and hippocampal volumes were not significantly correlated with disorder-related variables.

Conclusions. Our results are consistent with previous findings of structural abnormalities of amygdala and hippocampus in subjects with recent-onset major depression. It may be suggested that the size of the amygdala is enlarged in the first years of the disorder, and may decrease with prolonged disorder duration.

Background. The present study aimed to investigate the relative importance of genetic and environmental influences on depressive symptoms in the elderly.

Methods. Depressive symptoms were assessed through the Center for Epidemiological Studies – Depression (CES-D) scale. The CES-D scale was administered to 959 twin pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years). A dichotomous depressed state variable was constructed based on CES-D cut-offs and self-reported use of antidepressant medication. Structural equation models were fitted to the data to dissect genetic and environmental variance components.

Results. The sex-specific heritability estimates for depressive symptoms were 14% for males and 29% for females and 23% when constrained to be equal for men and women. The prevalence of clinically significant depressive symptoms was 16% for men and 24% for women. Heritability estimates for the dichotomous depressed state measure were 7% for males and 49% for females in the full model and 33% when constrained to be equal.

Conclusion. Our results suggest that depressive symptoms in the elderly are moderately heritable, with a higher heritability for women than men, although differences in heritability estimates were not statistically significant.

Background. Results of previous research examining long-term residual effects of marijuana use on cognition are conflicting. A major methodological limitation of prior studies is the inability to determine whether differences between users and non-users are due to differences in genetic vulnerability preceding drug use or due to the effects of the drug.

Method. Fifty-four monozygotic male twin pairs, discordant for regular marijuana use in which neither twin used any other illicit drug regularly, were recruited from the Vietnam Era Twin Registry. A minimum of 1 year had passed since the marijuana-using twins had last used the drug, and a mean of almost 20 years had passed since the last time marijuana had been used regularly. Twins were administered a comprehensive neuropsychological test battery to assess general intelligence, executive functioning, attention, memory and motor skills. Differences in performance between marijuana-using twins and their non-using co-twins were compared using a multivariate analysis of specific cognitive domains and univariate analyses of individual test scores. Dose–response relationships were explored within the marijuana-using group.

Results. Marijuana-using twins significantly differed from their non-using co-twins on the general intelligence domain; however, within that domain only the performance of the block design subtest of the Wechsler Adult Intelligence Scale – Revised reached a level of statistical significance.

Conclusions. Out of the numerous measures that were administered, only one significant difference was noted between marijuana-using twins and their non-using co-twins on cognitive functioning. The results indicate an absence of marked long-term residual effects of marijuana use on cognitive abilities.

Background. How insight, paranoia and depression evolve in relation to each other during and after the first episode of schizophrenia is poorly understood but of clinical importance.

Method. Serial assessments over 18 months were made using multiple instruments in a consecutive sample of 257 patients with first episode DSM-IV non-affective psychosis. Repeated measures of paranoia, insight, depression and self-esteem were analysed using structural equation modelling, to examine the direction of relationships over time after controlling for confounds.

Results. Depression was predicted directly by greater insight, particularly at baseline, and by greater paranoia at every stage of follow-up. Neither relationship was mediated by self-esteem, although there was a weak association of lower self-esteem with greater depression and better insight. Paranoia was not strongly associated with insight. Duration of untreated psychosis and substance use at baseline predicted depression at 18 months.

Conclusions. In first-episode psychosis, good insight predicts depression. Subsequently, paranoia is the strongest predictor. Neither effect is mediated by low self-esteem. Effective treatment of positive symptoms is important in preventing and treating low mood in early schizophrenia.

Background. Many people with symptoms of psychological distress do not seek professional help. Little is known about the actions taken by these people to reduce their symptoms. The present study aimed to assess, in a community sample, actions taken to cope with depression at different levels of psychological distress.

Method. A postal survey was carried out with 6618 adults living in Canberra and south-east New South Wales, Australia. Measures covered psychological distress and a checklist of actions taken to cope with depression in the previous 6 months.

Results. Actions taken to cope with depression could be classified as: intensification of everyday strategies, initiation of new self-help (including complementary therapies, non-prescription medication and dietary changes) and seeking professional help. Use of everyday strategies peaked with mild psychological distress, new self-help showed a peak in moderate distress, while professional help-seeking peaked in severe distress.

Conclusion. Self-help strategies are very commonly used, particularly in mild–moderate psychological distress. More evidence is needed to evaluate their effectiveness, so that optimal self-help can be encouraged.

Background. Several sources of heterogeneity in major depression have been identified. These include age of onset, presence of co-morbid disorders, and history of childhood sexual abuse. This study examined these factors in the context of the contrast between onset of depression in young women before and after age 16.

Method. Sampling was carried out in two phases. In the first, questionnaires were sent to women aged 25–36 in five primary care practices. Second-phase subjects for interview (n=197) were drawn from three strata defined on the basis of childhood adversities. Interviews conducted and rated independently assessed (1) recalled childhood experiences, psychopathology and parental psychiatric disorder, and (2) adult personality functioning and adult lifetime psychopathology. Frequencies of predictor and response variables, effect estimates and their confidence intervals were weighted back to the general population questionnaire sample.

Results. Compared with adult-onset depression, juvenile-onset adult depression was associated with co-morbid childhood psychopathology and peer problems, poor parental care, and childhood sexual abuse involving actual or attempted intercourse; in adult life there were higher levels of co-morbid psychiatric disorders, and personality dysfunction. The adult-onset depression group was characterized by a history of contact childhood sexual abuse without actual or attempted intercourse, and to a lesser extent, poor parental care.

Conclusions. The juvenile- versus adult-onset distinction appears to be important to heterogeneity in adult depression, implicating different individual and environmental factors during childhood, and different mechanisms in adult life.

Background. Whether current criteria used to define nicotine dependence are informative for genetic research is an important empirical question. The authors used items of the DSM-IV and of the Heaviness of Smoking Index to characterize the nicotine dependence phenotype and to identify salient symptoms in a genetically informative community sample of Australian young adult female and male twins.

Method. Phenotypic and genetic factor analyses were performed on nine dependence symptoms (the seven DSM-IV substance dependence criteria and the two Heaviness of Smoking Index (HSI) items derived from the Fagerström Tolerance Questionnaire, time to first cigarette in the morning and number of cigarettes smoked per day). Phenotypic and genetic analyses were restricted to ever smokers.

Results. Phenotypic nicotine dependence symptom covariation was best captured by two factors with a similar pattern of factor loadings for women and men. In genetic factor analysis item covariation was best captured by two genetic but one shared environmental factor for both women and men; however, item factor loadings differed by gender. All nicotine dependence symptoms were substantially heritable, except for the DSM-IV criterion of ‘giving up or reducing important activities in order to smoke’, which was weakly familial.

Conclusions. The salient behavioral indices of nicotine dependence are similar for women and men. DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men.

Background. Family members adopt key caregiving roles in the maintenance of transplant recipients' health. While the bulk of the caregiving literature suggests that rates of psychiatric disorder should be high in these caregivers, the potential benefits of transplantation may instead lead to less distress than in other caregiving situations. We examined prevalence and risk factors for depressive and anxiety-related disorders in caregivers throughout 3 years after their family member's heart transplant.

Method. A total of 190 caregivers (97% of eligible respondents) were enrolled. They received psychiatric and psychosocial evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis determined cumulative rates of psychiatric disorders and the impact of potential risk factors.

Results. Rates of depressive and anxiety-related disorders met or exceeded other caregiver populations' rates. By 3 years post-transplant, cumulative onset rates were: Major Depressive Disorder (MDD), 31·6%, Adjustment disorders, 35·4% (29·4% with anxious mood); Post-Traumatic Stress Disorder related to the transplant (PTSD-T), 22·5%, Generalized Anxiety Disorder, 7·3%, and any assessed disorder, 56·3%. PTSD-T occurred primarily during the first year post-transplant. Other disorders' rates increased over the entire study period. Risk for disorder was elevated by positive lifetime history of psychiatric disorder, greater post-transplant caregiving responsibilities, and a poorer relationship with the patient. Risk for MDD was further increased by caregiver unemployment, and risk for anxiety disorders was further increased by younger age, low sense of personal mastery, and high use of avoidance coping strategies.

Conclusions. Transplantation is associated with costs and benefits for not only patients but family caregivers. Caregivers' risk for psychiatric illness should be considered when developing interventions to promote families' long-term adjustment to the transplant process.

Background. Separate lines of research link lowered serotonin tone to interpersonal submissiveness and bulimia nervosa (BN). We explored the impact of co-morbid avoidant personality disorder (APD), as a proxy for submissiveness, on behavioural inhibition and serotonin function in women with BN.

Method. Participants included women with BN with co-morbid APD (BNA+, N=13); women with BN but without APD (BNA−, N=23), and control women with neither BN nor APD (N=23). The women were assessed for psychopathological tendencies and eating disorder symptoms, and participated in a computerized laboratory task that measured behavioural inhibition and disinhibition. Participants also provided blood samples for measurement of serial prolactin responses following oral administration of the partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP).

Results. The BNA+ group had higher scores than the other groups on self-report measures of submissiveness, social avoidance, restricted emotional expression, affective instability and self-harming behaviours. Compared with the other groups, the BNA+ group tended to be more inhibited under cues for punishment on the computerized task and to have blunted prolactin response following m-CPP. The bulimic groups did not differ from each other on current eating symptoms or on frequencies of other mental disorders.

Conclusions. Findings indicate that women with BN and co-morbid APD may be characterized by interpersonal submissiveness and avoidance, affective instability, self-harm, behavioural inhibition in response to threat and lower sensitivity to serotonergic activation. These findings may indicate common, serotonergic factors, associated with social submissiveness, behavioural inhibition to threat and BN.

Background. There is evidence that depression impairs natural killer cell activity (NKA); this could have implications for anti-tumour immunity. Our aim was to examine the role of the hypothalamic–pituitary–adrenal (HPA) axis in suppressing NKA in a population of patients with early breast cancer, screened for depression. Secondary aims were to study the relationship between psychological, endocrine and immune variables and baseline tumour characteristics.

Methods. A cross-sectional population of female patients (n=55) with early breast cancer was sampled prior to primary surgery. Structured interview and psychometric instruments measured psychological distress. Flow cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning saliva samples were collected to measure free cortisol levels. Tumour characteristics were obtained from hospital laboratory data.

Results. A high rate of psychological morbidity (40%) was observed in the population. NKA was reduced in those with past or current psychiatric illness compared to those without (344 v. 553 LU20 and 455 v. 569 LU20 respectively, p<0·05 for both). Cortisol was not related to psychological status but was modestly positively correlated to NKA. A positive correlation was observed between the Fighting Spirit subscale of the Mental Adjustment to Cancer Scale and tumour size (r=0·383, p=0·012)

Conclusions. Our data support the evidence that psychological morbidity is associated with immune dysfunction; however, the most obvious candidate mediator of this effect, the HPA axis, does not appear responsible for this effect. Possible reasons for this are discussed.

Background. Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary.

Method. We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry.

Results. The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80% of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75%, 80% and 60% respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females.

Conclusions. This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND.

Background. It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks.

Method. Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered.

Results. Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments.

Conclusions. The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.

Background. Depression affects outcome following myocardial infarction but the risk factors for such depression have been little studied. This study considered whether the causes of depression occurring before and after myocardial infarction were similar to those of depression in the general population.

Method. Consecutive patients admitted to hospital following their first myocardial infarction were interviewed with the Schedule for Clinical Assessment in Neuropsychiatry to detect psychiatric disorders and the Life Events and Difficulties Schedule to assess recent stress. Participants completed the Hospital Anxiety and Depression Scale (HADS) at entry to the study and 1 year later and the risk factors associated with a high score at both times were assessed.

Results. Of 314 (88% of eligible) patients who were recruited, 199 (63%) were male and 63 (20%) had depressive disorders. Logistic regression identified the following as independently associated with depressive disorder that had been present for at least 1 month before the myocardial infarction: younger age, female sex, past psychiatric history, social isolation, having marked non-health difficulties and lack of a close confidant. At follow-up 269/298 (90%) responded; of 189 participants not depressed at first assessment, 39 (21%) became depressed by the 1 year follow-up. Logistic regression identified frequent angina as the only significant predictor of raised HADS scores at 12 months.

Conclusions. Depression developing during the year following myocardial infarction does not have the same risk factors as that which precedes myocardial infarction. Further clarification of the mechanisms linking depression to poor outcome may require separation consideration of pre- and post-myocardial infarction depression, and its risk factors.

Background. Previous research has found that depression is a major cause of memory complaints. However, there is evidence that memory complaints also weakly predict cognitive decline and dementia. The present study examined a range of possible determinants of memory complaints, covering psychiatric and personality factors, medical history, cognitive test performance, and biological risk factors for dementia (APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities).

Method. A community survey was carried out with 2546 persons aged 60–64 years living in Canberra and Queanbeyan, Australia. Participants were asked about memory problems which interfered with daily life and whether medical help had been sought. A randomly selected subsample of 476 persons was given a brain MRI scan.

Results. Participants with memory complaints were found to have poorer memory test performance, more depression and anxiety symptoms, have higher scores on personality traits involving negative affect, and to have worse physical health. Multivariate analyses showed that measures of cognitive performance did not make a unique contribution to the prediction of memory complaints above that of the other categories of predictors. Those with memory complaints did not differ on any of the biological risk factors for dementia.

Conclusion. In a community sample aged 60–64 years, memory complaints were most closely related to psychiatric symptoms, personality characteristics and poor physical health. There was no evidence of brain changes indicating early dementia.

Background. An adoption study of alcoholism suggests that in women, the impact of genetic risk factors become greater in the presence of conflict in the family of origin. Is the same true for cigarette smoking (CS)?

Method. We obtained, in a sample of 1676 twins from female–female twin pairs from a population-based register, a measure of maximum lifetime CS (divided into six ordinal categories) and family dysfunction (FD) assessed as the mean report of up to four informants (twin, co-twin, mother, father). Statistical analysis was conducted by traditional regression analysis and a moderator structural equation twin model using the computer program Mx.

Results. With increasing levels of FD, maximum CS increased substantially while correlations for CS in monozygotic (MZ) and dizygotic (DZ) twins decreased modestly. Regression analyses demonstrated reduced twin-pair resemblance for CS with increasing levels of FD. The best-fit structural equation model found high levels of heritability for CS and no evidence for a role of shared environment. With increasing levels of FD, the proportion of variance in CS due to genetic factors (i.e. heritability) decreased while that due to unique environmental effects increased.

Conclusions. Several different statistical methods suggested that, contrary to prediction, heritability of CS decreased rather than increased with higher levels of dysfunction in the family of origin. The hypothesis that genetic effects for psychiatric and drug-use disorders become stronger in more adverse environments is not universally true.

Background. Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia.

Method. Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses.

Results. Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance.

Conclusion. The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.