This issue features groups of papers reporting controlled trials, depression assessment and biological aspects, and disorders in the elderly. The lead editorial reviews recent studies of the effects on cognition of tryptophan depletion, an important probe of serotonin function.

Serotonin (5-hydroxytryptamine, 5-HT) is known to play a role in a wide variety of functions including: mood, anxiety, sleep, aggression, sexual function and cognitive function. In the past decade, the sudden interest in acute amino acid depletion paradigms has stimulated the interest in studying the function of 5-HT in man in vivo. In particular, investigating the association of experimentally lowered 5-HT with cognition by measuring the influence of acute tryptophan depletion (ATD) on performance, and in some cases applying ATD as a challenge test using cognition as disease surrogate marker, have recently become popular. The crucial questions, ‘what can this method tell us about cognitive function in health and disease?’ and ‘what can ATD-induced cognitive changes tell us about health and disease?’ can only be answered after first considering basic assumptions about the method. These pertain to the derived questions, ‘is ATD a serotonergic manipulation?’, ‘is the placebo used in ATD an inactive treatment?’. Also, ‘are there specific cognitive markers of ATD?’. After a brief consideration of these issues, we will focus on the more clinical issues addressing the question whether ATD can be used as a challenge test, to indicate serotonergic vulnerability, using cognitive functions as surrogate measures of disease in particular.

Background. The demand for time-consuming psychotherapy of phobia/panic exceeds the supply of trained therapists. Delegating routine therapy aspects to a computer might ease this problem.

Method. Ninety-three out-patients with phobia or panic disorder were randomized in a 2[ratio ]2[ratio ]1 ratio to have self-exposure therapy guided either mainly by a stand-alone computer system (FearFighter) or entirely face-to-face by a clinician, or to have mainly computer-guided self-relaxation as a placebo. Both computer groups (FearFighter and relaxation) had brief back-up advice from a clinician. Primary outcome measures were self- and blind-assessor ratings of Main Problem and Goals, and Global Phobia.

Results. Drop-outs occurred significantly more often in the two self-exposure groups (43% if mainly computer-guided, 24% if entirely clinician-guided) than with self-relaxation (6%); the difference between the two self-exposure groups was not significant. Even with all drop-outs included, the mainly computer-guided exposure group and the relaxation group had 73% less clinician time per patient than did the entirely clinician-guided exposure group. The two self-exposure groups had comparable improvement and satisfaction at post-treatment and at 1-month follow-up, while relaxation was ineffective. Mean improvement on the primary outcome measures (self- and assessor-rated) was 46% computer, 49% clinician, 9% relaxation at post-treatment (week 10) and 58% computer, 53% clinician and −4% relaxation at 1-month follow-up (week 14). Mean effect sizes on the primary outcome measures were 2·9 computer, 3·5 clinician and 0·5 relaxation at post-treatment; and 3·7 computer, 3·5 clinician and 0·5 relaxation at 1-month follow-up. The assessor did not rate patients at follow-up.

Conclusions. Despite its (non-significantly) higher dropout rate, self-exposure therapy for panic/phobia cut clinician time per patient by 73% without losing efficacy when guided mainly by a computer rather than entirely by a clinician. The finding needs confirmation at a follow-up that is longer and includes a blind assessor. Self-relaxation had the highest rate of completers but was ineffective.

Background. The present paper describes a component of a large population cost-effectiveness study that aimed to identify the averted burden and economic efficiency of current and optimal treatment for the major mental disorders. This paper reports on the findings for the anxiety disorders (panic disorder/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder and obsessive–compulsive disorder).

Method. Outcome was calculated as averted ‘years lived with disability’ (YLD), a population summary measure of disability burden. Costs were the direct health care costs in 1997–8 Australian dollars. The cost per YLD averted (efficiency) was calculated for those already in contact with the health system for a mental health problem (current care) and for a hypothetical optimal care package of evidence-based treatment for this same group. Data sources included the Australian National Survey of Mental Health and Well-being and published treatment effects and unit costs.

Results. Current coverage was around 40% for most disorders with the exception of social phobia at 21%. Receipt of interventions consistent with evidence-based care ranged from 32% of those in contact with services for social phobia to 64% for post-traumatic stress disorder. The cost of this care was estimated at $400 million, resulting in a cost per YLD averted ranging from $7761 for generalized anxiety disorder to $34 389 for panic/agoraphobia. Under optimal care, costs remained similar but health gains were increased substantially, reducing the cost per YLD to <$20 000 for all disorders.

Conclusions. Evidence-based care for anxiety disorders would produce greater population health gain at a similar cost to that of current care, resulting in a substantial increase in the cost-effectiveness of treatment.

Background. Patients frequently present with unexplained fatigue in primary care, but there have been few treatment trials in this context. We aimed to test cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for patients presenting to their family doctor with fatigue. Secondly, we described the outcome for a cohort of patients who presented to the same doctors with fatigue, who received standard care, plus a booklet.

Method. This was a randomized trial, followed by a prospective cohort study. Twenty-two practices in SE England referred 144 patients aged 16 to 75 years with over 3 months of unexplained fatigue. Self-rated fatigue score, the hospital anxiety and depression rating scale, functional impairment, physical step-test performance and causal attributions were measured. In the trial six sessions of CBT or GET were randomly allocated.

Results. In the therapy groups the mean fatigue score decreased by 10 points (95% confidence interval (CI)=−25 to −15), with no significant difference between groups (mean difference=−1·3; CI=−3·9 to 1·3). Fewer patients attended for GET. At outcome one-half of patients had clinically important fatigue in both randomized groups, but patients in the group offered CBT were less anxious. Twenty-seven per cent of the patients met criteria for CFS at baseline. Only 25% of this subgroup recovered, compared to 60% of the subgroup that did not meet criteria for CFS.

Conclusions. Short courses of GET were not superior to CBT for patients consulting with fatigue of over 3 months in primary care. CBT was easier ‘to sell’. Low recovery in the CFS subgroup suggests that brief treatment is too short.

Background. Chronic fatigue greatly affects quality of life and is a common reason for consulting a physician. Since conventional therapy is often of limited help, fatigued patients may use herbal treatments. This randomized controlled trial evaluated the effectiveness of Siberian ginseng.

Method. Subjects were recruited from advertisements in Iowa (82%) and members of chronic fatigue syndrome support groups (18%). Potential subjects were required to have substantial fatigue [ges ]6 months with no identifiable cause. The mean change in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2 months. Comparisons were for all subjects and for subjects with characteristics previously identified in the literature as important for categorizing chronic fatigue.

Results. Ninety-six subjects were randomized to treatment groups, and 76 provided information at 2 months of follow-up. Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample. Fatigue severity and duration had a statistically significant interaction with response to Siberian ginseng at the P<0·05 level. Treatment was effective at 2 months for 45 subjects with less severe fatigue (P=0·04 unadjusted for multiple comparisons) and for 41 subjects with fatigue for [ges ]5 years (P=0·09 unadjusted for multiple comparisons).

Conclusion. Overall efficacy was not demonstrated. However, the findings of possible efficacy for patients with moderate fatigue suggests that further research may be of value.

Background. General practitioners (GPs) can be provided with effective training in the skills to manage depression. However, it remains uncertain whether such training achieves health gain for their patients.

Method. The study aimed to measure the health gain from training GPs in skills for the assessment and management of depression. The study design was a cluster randomized controlled trial. GP participants were assessed for recognition of psychological disorders, attitudes to depression, prescribing patterns and experience of psychiatry and communication skills training. They were then randomized to receive training at baseline or the end of the study. Patients selected by GPs were assessed at baseline, 3 and 12 months. The primary outcome was depression status, measured by HAM-D. Secondary outcomes were psychiatric symptoms (GHQ-12) quality of life (SF-36), satisfaction with consultations, and health service use and costs.

Results. Thirty-eight GPs were recruited and 36 (95%) completed the study. They selected 318 patients, of whom 189 (59%) were successfully recruited. At 3 months there were no significant differences between intervention and control patients on HAM-D, GHQ-12 or SF-36. At 12 months there was a positive training effect in two domains of the SF-36, but no differences in HAM-D, GHQ-12 or health care costs. Patients reported trained GPs as somewhat better at listening and understanding but not in the other aspects of satisfaction.

Conclusions. Although training programmes may improve GPs' skills in managing depression, this does not appear to translate into health gain for depressed patients or the health service.

Background. The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats.

Method. The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted.

Results. Internal consistencies (Cronbach's alpha) ranged from 0·81 to 0·94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c=0·83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c=0·82) and patients with BD (c=0·81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score.

Conclusion. The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression.

Background. Most of the available evidence on the effects of depression is based on in- and out-patient samples focusing on individuals suffering from major depression. The aims of this study were to examine cognitive functioning in population-based samples and to determine whether cognitive performance varies as a function of depression subgroup.

Method. Population-based samples (aged 20–64 years) with major depression (N=68), dysthymia (N=28), mixed anxiety-depressive disorder (N=25) and minor depression (N=66) were examined on a variety of cognitive tasks (i.e. episodic memory, verbal fluency, perceptual-motor speed and mental flexibility). One hundred and seventy-five non-depressed individuals served as controls.

Results. The total group of depressed individuals showed impairments in tasks tapping episodic memory and mental flexibility. Of more interest, however, was the observation that the pattern of impairments varied as a function of depression subgroup: the major depression and mixed anxiety-depressive disorder groups exhibited significant memory dysfunction, whereas individuals with dysthymia showed pronounced difficulties in mental flexibility. Minor depression did not affect cognitive performance. Verbal fluency and perceptual-motor speed were not affected by depression.

Conclusions. These results indicate that persons with depressive disorders in the population exhibit cognitive impairments in tasks tapping episodic memory and mental flexibility and that cognitive impairment varies as a function of depressive disorder.

Background. Neurocognitive functioning may be impaired in the luteal phase of the menstrual cycle due to associated changes in hypothalamic–pituitary–adrenal (HPA) axis function. This study examines the relationship between changes in neurocognition and HPA axis function in different phases of the menstrual cycle.

Method. Fifteen female volunteers, free from psychiatric history and hormonal medication were tested twice, during mid-follicular and late-luteal phases in a randomized, crossover design. Mood, neurocognitive function, and basal cortisol and dehydroepiandrosterone (DHEA) were profiled.

Results. Relative to the follicular phase, verbal fluency was impaired in the luteal phase and reaction times speeded on a continuous performance task, without affecting overall accuracy. ‘Hedonic’ scores on the UWIST-MACL scale were decreased in the luteal phase. There was also evidence of changes in the function of the HPA axis, with 24 h urinary cortisol concentrations and salivary DHEA levels being significantly lower during the luteal phase.

Conclusions. These data suggest that luteal phase HPA axis function is lower than in the follicular phase in premenopausal healthy women. This putative biological difference may be important for our understanding of the aetiopathogenesis of menstrually related mood change and neurocognitive disturbance.

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. 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. Late-onset depressive disorder is associated with white matter lesions and neuropsychological deficits that in some studies are linked to a poorer outcome for depression. Some white matter lesions may be vascular in origin. This study investigated the relationship between response or non-response to antidepressant monotherapy and neuropsychological function, structural brain measures and vascular factors.

Method. This was a case–control study. Fifty patients with late-onset major depressive disorder (29 who were responders to antidepressant monotherapy and 21 who were not) were compared with 35 non-depressed control subjects. Measures included assessment of vascular risk factors, neuropsychological testing and a magnetic resonance imaging (MRI) scan.

Results. After adjustment for depressed mood and medication at evaluation, both patient groups had significantly more impairment compared to control subjects on verbal learning tasks involving immediate or delayed recall. Patients who did not respond to antidepressant monotherapy had significantly poorer performance than controls on tests involving visuospatial ability, language, word recognition and tests of executive function, whereas there were no differences between control subjects and responders. On two tests of executive function (verbal fluency and the Stroop test) non-responders scored significantly worse than responders. There were no significant group differences on MRI measures of atrophy or of white matter lesions apart from a higher periventricular hyperintensity score in non-responders compared to controls. There were no group differences on measures of vascular disease.

Conclusion. The results lend support to the emerging evidence that resistance to treatment in late-onset depression may be associated with impaired executive function. Subtle cerebrovascular mechanisms may be involved.

Background. Mental disorders amplify suicide risk across the lifecourse, but most people with mental disorder do not take their own lives. Few controlled studies have examined the contribution of stressors to suicide risk.

Method. A case–control design was used to compare 86 suicides and 86 controls aged 50 years and older, matched on age, gender, race and county of residence. Structured interviews were conducted with proxy respondents for suicides and controls.

Results. Perceived physical illness, family discord and employment change amplified suicide risk after controlling for sociodemographic covariates and mental disorders that developed [ges ]1 year prior to death/interview. Only the effect of physical illness (OR 6·24, 95% CI 1·28–51·284) persisted after controlling for all active mental disorders.

Conclusions. Interventions to decrease the likelihood of financial stress and to help families manage discord and severe physical illness may effectively reduce suicides among middle-aged and older adults.

Background. Little is known about the factors associated with the receipt of care by older people. This study investigates the use, costs and factors associated with service usage among people aged 65 or older living in inner London.

Method. A community-based survey, using questionnaires, examined psychiatric and physical morbidity, formal and informal care. The relationships between demographic, pathological features and the costs of health and social care were explored using multivariate regression.

Results. A total of 1085 people were interviewed at home of these 18% did not receive any service at all. The total cost of services per week for people with dementia was £109, with activity limitation £14 and with depression £12. The greatest effect of physical limitation was on the receipt of social care. Dementia had the strongest effect on receipt of social care services. Depression increased health care costs to a much greater degree than social care costs. Despite presenting to services, black elders received significantly less health care than other people with the same needs. Older people living alone were more likely to receive social care support and appeared less likely to use health services.

Conclusions. Physical dependency significantly affects both health and social care costs. Increasing cognitive impairment mainly leads to increasing social care costs. Overall costs are increased by physical dependency, dementia, depression, subjective health problems, living alone and are negatively affected by being black.

Background. Telephone interviewing has economic and logistical advantages but has not been widely used in the UK. Most studies comparing face-to-face and telephone psychiatric assessment have been carried out in the US, often restricted to a population with known psychiatric disorder and involving comparisons between two separate sample groups rather than repeat interviews with the same group. The aim of the present study was to compare face-to-face and telephone administration of the 12-item General Health Questionnaire and the Revised Clinical Interview Schedule in a UK general practice sample.

Method. Ninety-eight consecutive attenders at two general practices were assessed twice within 48 h. The order of face-to-face and telephone interviews was alternated.

Results. There was no evidence that the mode of administration led to a bias in scores on the CIS-R. For the GHQ, those aged over 60 tended to score higher on the telephone. There was good agreement between face-to-face and telephone scores for both GHQ and CIS-R and good agreement for case definition. Participants had a strong preference for face-to-face interviews.

Conclusions. Telephone assessment of mental health using the GHQ and CIS-R is a reasonable method to be used in primary care research in the UK with the limitation that telephone responses from older people might be different from face-to-face assessments for the GHQ. However, telephone interviewing appeared less acceptable and should probably be used in the context of established or ongoing personal contact between researcher and subject.

Background. Recent research studies on the psychological processes underlying suicidal behaviour have highlighted deficits in social problem-solving ability, and suggest that suicide attempters may, in addition, be passive problem-solvers. The aim of this study was to examine problem-solving in suicide attempters (including passivity) and to see whether the deficits are mood-dependent.

Method. Two groups, a suicide attempter group and a non-suicidal psychiatric control group completed measures of depression, hopelessness, suicidal ideation and social problem-solving ability shortly after admission, and again 6 weeks later. In addition, a non-psychiatric control group provided baseline data at a single time point.

Results. The suicide attempter group displayed poorer problem-solving ability than matched psychiatric controls and this difference persisted despite change in mood. However, although suicidal patients were more passive in their problem-solving style than non-psychiatric controls, they were not significantly more passive than psychiatric controls. Problem-solving did not change with improving mood.

Conclusions. Although passivity is not unique to suicidal patients, in combination with the smaller number and less effective alternatives generated, it may increase vulnerability.

Background. In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic–pituitary–adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression.

Method. Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 μg was given intravenously and ACTH and cortisol release was monitored for 120 min.

Results. The mean±S.E.M. ACTH response in the depressives was 28·4±4·3 ng/l and in the healthy subjects was 18·8±4·9 ng/l (P=0·04). The mean±S.E.M. cortisol response in the depressives was 261·8±46·5 nmol/l and in the healthy subjects was 107·3±26·1 nmol/l (P<0·01).

Conclusions. Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.