Background. Disturbance of the HPA axis may be important in the pathophysiology of chronic fatigue syndrome (CFS) and fibromyalgia. Symptoms may be due to: (1) low circulating cortisol; (2) disturbance of central neurotransmitters; or (3) disturbance of the relationship between cortisol and central neurotransmitter function. Accumulating evidence of the complex relationship between cortisol and 5-HT function, make some form of hypothesis (3) most likely. We review the methodology and results of studies of the HPA and other neuroendocrine axes in CFS.

Method. Medline, Embase and Psychlit were searched using the Cochrane Collaboration strategy. A search was also performed on the King's College CFS database, which includes over 3000 relevant references, and a citation analysis was run on the key paper (Demitrack et al. 1991).

Results. One-third of the studies reporting baseline cortisol found it to be significantly low, usually in one-third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function, and enhanced 5-HT function on neuroendocrine challenge tests. The opioid system, and arginine vasopressin (AVP) may also be abnormal, though the growth hormone (GH) axis appears to be intact, in CFS.

Conclusions. The significance of these changes, remains unclear. We have little understanding of how neuroendocrine changes relate to the experience of symptoms, and it is unclear whether these changes are primary, or secondary to behavioural changes in sleep or exercise. Longitudinal studies of populations at risk for CFS will help to resolve these issues.

Background. There is still a relative paucity of information about the long-term course of depression.

Methods. Consecutive patients admitted to a teaching hospital psychiatry unit with symptoms of depression, previously assessed at 6 months and 2, 5 and 15 years after index admission, were reviewed at 25 years (N = 49, including eight informants of deceased probands, of an original 145 with major depression (DEPs)). Prospective psychiatric (N = 22) and retrospective surgical (N = 50) control groups assessed after 25 years were used for comparison.

Results. A further decade of follow-up confirmed the chronicity of depression. Of depressed patients (DEPs) followed for the full 25-year-period only 12% of the 49 original DEPs recovered and remained continuously well, 84% experienced recurrences, 2% experienced an unremitting course and another 2% died by suicide. Note that in the first 15-year-period 6% (9/145 DEPs) committed suicide, a further 38 died and 32 were lost to follow-up. They experienced an average of three episodes of depression over the 25 years. In the decade since the 15-year follow-up, 27% improved in clinical outcome (including four of five previously chronically depressed patients), 55% remained unchanged and 18% worsened; and the number of episodes per year declined. Patients initially diagnosed with neurotic or endogenous depression had similar long-term outcomes. The criteria for a current DSM-III-R disorder were met by 37% of DEPs, including 11% with depression or dysthymia. On the global assessment of functioning scale 78% of the DEPs had some impairment compared to 62% of psychiatric controls and 40% of surgical controls.

Conclusion. Even after 25 years, severe depressive disorders appear to have poor long-term outcomes. Patients with chronic outcomes over 15 years can improve when followed over longer periods.

Background. The temporal relationship between depression and adverse functional outcomes in older adults is ambiguous. In the present eight-wave prospective community-based study, the longitudinal effect of depression on functional limitations and disability (in terms of disability days and bed days) was studied, thereby taking into account the role of chronic physical diseases.

Methods. The study is based on a sample which at the outset consisted of 325 non-depressed and 327 depressed persons (55–85 years) drawn from a larger random community based sample in the Netherlands. Generalized estimating equations time-lag models were used to examine the longitudinal relation between depression and both functional limitations and disability.

Results. Functional limitations were very persistent over time, whereas disability days and bed days were more fluctuating functional outcomes. Only in the presence of chronic physical diseases, there was a significant longitudinal association between depression at the previous measurement and functional limitations, disability days and bed days at the next measurement. The effect on functional limitations was small, which was probably partly due to their persistent nature.

Conclusions. The finding of a longitudinal relationship between depression and functional outcomes in older adults with a compromised health status provides a rationale for treatment of chronic physical diseases as well as depression in depressed chronically ill elderly, in order to prevent a spiralling decline in psychological and physical health.

Background. Relatively little is known regarding stability or change over time in milder psychiatric disorder identified in epidemiological studies.

Methods. Data were analysed on 2890 subjects from the 1946 British birth cohort study. Psychiatric disorder was identified at age 36 years using the Present State Examination Index of Definition and 7 years later at age 43 using a symptom scale, employing a threshold to give identical 6% prevalence of disorder. Predictors were derived from recent social data and information collected earlier in childhood and younger adulthood.

Results. Over 7 years, there was considerable movement between case and non-case status. Only 1·7% of the sample satisfied case criteria at both points. Approximately two-thirds of cases at age 36 had fallen below case levels at age 43 and two-thirds of cases at age 43 were new cases. Most onsets and remissions were between definite case and non-case levels, rather than around the threshold. The strongest predictors of onset and remission were recent demographic, social and life stress variables, and earlier reported nervous disorder, with contributions from parental social background, and life history variables in adolescence.

Conclusions. There is considerable change over 7 years in milder psychiatric disorder, with around two-thirds of it episodic or fluctuating and one-third chronic. Recent social variables are strong predictors of change or chronicity, with some lasting contributions from childhood social setting and earlier life history.

Background. Previous field studies have indicated that children's cognitive performance is impaired by chronic aircraft noise exposure. However, these studies have not been of sufficient size to account adequately for the role of confounding factors. The objective of this study was to test whether cognitive impairments and stress responses (catecholamines, cortisol and perceived stress) are attributable to aircraft noise exposure after adjustment for school and individual level confounding factors and to examine whether children exposed to high levels of social disadvantage are at greater risk of noise effects.

Methods. The cognitive performance and health of 451 children aged 8–11 years, attending 10 schools in high aircraft noise areas (16 h outdoor Leq > 63 dBA) was compared with children attending 10 matched control schools exposed to lower levels of aircraft noise (16 h outdoor Leq < 57 dBA).

Results. Noise exposure was associated with impaired reading on difficult items and raised annoyance, after adjustment for age, main language spoken and household deprivation. There was no variation in the size of the noise effects in vulnerable subgroups of children. High levels of noise exposure were not associated with impairments in mean reading score, memory and attention or stress responses. Aircraft noise was weakly associated with hyperactivity and psychological morbidity.

Conclusions. Chronic noise exposure is associated with raised noise annoyance in children. The cognitive results indicate that chronic aircraft noise exposure does not always lead to generalized cognitive effects but, rather, more selective cognitive impairments on difficult cognitive tests in children.

Background. Psychosocial interventions for bipolar patients often include teaching patients to recognize prodromal symptoms and tackle them early. This prospective study set out to investigate which bipolar prodromal symptoms were reported frequently and reliably over a period of 18 months. Furthermore, we have also investigated which types of coping strategies were related to good outcome.

Method. Forty bipolar patients were interviewed for their bipolar prodromal symptoms and their coping strategies at recruitment and 18 months later. Patients were also assessed as to whether they had experienced relapses.

Results. Bipolar patients were able to report bipolar prodromal symptoms reliably. Mania prodromal symptoms tended to be behavioural symptoms. A quarter of patients reported difficulties in detecting depression prodromes, which tended to be more diverse and consisted of a mix of behavioural, cognitive and somatic symptoms. Significantly fewer patients who reported the use of behavioural coping strategies to curb excessive behaviour during the mania prodromal stage experienced a manic episode. Similarly, significantly fewer patients who reported the use of behavioural coping strategies experienced depression relapses. How well patients coped with mania prodromes predicted bipolar episodes significantly when the mood levels at baseline were controlled. Ratings of how well subjects coped with mania prodromal symptoms also predicted manic symptoms significantly at T2 when manic symptom at T1 was controlled.

Conclusion. Our study suggests that bipolar patients are able to report prodromal symptoms reliably. It is advisable to teach patients to monitor their moods systematically and to promote good coping strategies.

Background. Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders.

Methods. Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 54·9 years, S.D. = 14·1) and 22 healthy control subjects (mean age = 55·5 years, S.D. = 9·6).

Results. Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0·01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0·05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0·05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3·8, 95% CI = 1·1–12·9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression.

Conclusions. Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Background. It is not known if a subject's characteristic level of self-rated depression symptoms index their genetic or environmental liability to major depressive disorder when measurement error and other occasion-specific influences are taken into account.

Method. Monozygotic (N = 408) and dizygotic (N = 295) adult female twin pairs from a population-based registry were surveyed twice with an average follow-up interval of 61 months. At each occasion subjects completed a structured clinical interview (SCID) to assess lifetime history of major depression and the subject-rated Symptom Check List (SCL) to assess current level of depressive symptomatology. A bivariate measurement model was used to estimate the genetic and environmental correlations between liability to reliably diagnosed lifetime history of major depression and the characteristic or temporally stable SCL depression score.

Results. The genetic and non-familial environmental correlation between liability to reliably diagnosed major depression and the characteristic level of SCL depression symptoms (and the proportion of variance shared between measures) is +0·70 and +0·24 respectively.

Conclusions. When allowance is made for diagnostic unreliability and temporal fluctuations in the level of subject-rated symptoms, 70% of the variance in genetic risk factors and 24% of the variance in environmental risk factors is shared by a diagnosis of lifetime major depression and total SCL depression symptom score. SCL depression scores may therefore be a useful screening measure for many of the genetic risk factors which influence liability to major depression.

Background. Previous neuroimaging studies of children with attention deficit hyperactivity disorder (ADHD) have demonstrated anatomic and functional abnormalities predominantly in frontal and striatal grey matter. Here we report the use of novel image analysis methods, which do not require prior selection of regions of interest, to characterize distributed morphological deficits of both grey and white matter associated with ADHD.

Methods. Eighteen children with a refined phenotype of ADHD, who also met ICD-10 criteria for hyperkinetic disorder (mean age 10·4 years), and 16 normal children (mean age 10·3 years) were compared using magnetic resonance imaging. The groups were matched for handedness, sex, height, weight and head circumference. Morphological differences between groups were estimated by fitting a linear model at each voxel in standard space, applying a threshold to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels, and testing cluster ‘mass’, or the sum of suprathreshold voxel statistics in each 2D cluster, by repeated random resampling of the data.

Results. The hyperkinetic children had significant grey matter deficits in right superior frontal gyrus (Brodmann area (BA) 8/9), right posterior cingulate gyrus (BA 30) and the basal ganglia bilaterally (especially right globus pallidus and putamen). They also demonstrated significant central white matter deficits in the left hemisphere anterior to the pyramidal tracts and superior to the basal ganglia.

Conclusions. This pattern of spatially distributed grey matter deficit in the right hemisphere is compatible with the hypothesis that ADHD is associated with disruption of a large scale neurocognitive network for attention. The left hemispheric white matter deficits may be due to dysmyelination.

Background. Neuroimaging studies of tuberous sclerosis complex (TSC) have previously focused mainly on tubers or subependymal nodules. Subtle pathological changes in the structure of the brain have not been studied in detail. Computationally intensive techniques for reliable morphometry of brain structure are useful in disorders like TSC, where there is little prior data to guide selection of regions of interest.

Methods. Dual-echo, fast spin-echo MRI data were acquired from 10 TSC patients of normal intelligence and eight age-matched controls. Between-group differences in grey matter, white matter and cerebrospinal fluid were estimated at each intracerebral voxel after registration of these images in standard space; a permutation test based on spatial statistics was used for inference. CSF-attenuated FLAIR images were acquired for neuroradiological rating of tuber number.

Results. Significant deficits were found in patients, relative to comparison subjects, of grey matter volume bilaterally in the medial temporal lobes, posterior cingulate gyrus, thalamus and basal ganglia, and unilaterally in right fronto-parietal cortex (patients −20%). We also found significant and approximately symmetrical deficits of central white matter involving the longitudinal fasciculi and other major intrahemispheric tracts (patients −21%); and a bilateral cerebellar region of relative white matter excess (patients +28%). Within the patient group, grey matter volume in limbic and subcortical regions of deficit was negatively correlated with tuber count.

Conclusions. Neuropathological changes associated with TSC may be more extensive than hitherto suspected, involving radiologically normal parenchymal structures as well as tubers, although these two aspects of the disorder may be correlated.

Background. The usefulness of the concept of personality disorder has not been properly tested outside psychiatric services. We set out to examine this in primary care, by examining the ability of the diagnosis to predict health status and patterns of service use.

Method. A cohort of consecutive attenders, who had previously been rated for the presence of personality disorder using a standardized assessment, was followed-up at 1 year. The participating general practitioners also rated the personalities of, and their attitudes towards, a proportion of this sample of attenders.

Results. After adjusting for the effects of all covariates, a rating of personality disorder (generated by the standardized assessment) was associated with frequent attendance to general practice and fewer referrals to secondary care. A GP rating of personality disorder was associated with the prescription of psychotropic medication. The level of agreement between a GP rating of personality disorder and the standardized assessment was poor. GPs rated personality disorder more frequently in participants who were perceived to be less compliant, less likeable and more stressful to deal with. Participants with a psychiatric rating of personality disorder did not attract these negative perceptions.

Conclusions. Personality disorder, as rated by a research interview, is a predictor of health service usage. There is a significant disparity between a research rating of personality disorder and the diagnostic ratings made by GPs. The GP ratings of personality disorder were strongly associated with adverse perceptions of the patient's consulting behaviour.

Background. Although psychiatric patients with eating disorders are known to be at risk for a variety of health problems, relatively little is known about eating disorders and associated health problems in other populations. An epidemiological study was conducted to investigate health problems and impairment associated with bulimia nervosa (BN) and binge eating disorder (BED) among female primary care and obstetric gynaecology patients.

Methods. Psychiatric disorders, physical illnesses, disabilities, functional status and stress were assessed among 4651 female patients (age range:18 to 99 years) at 8 primary care and 7 obstetric gynaecology clinics throughout the United States.

Results. Two hundred eighty-nine women (6·2%) were diagnosed with BN or BED. The prevalence of BN was approximately 1% among young and middle-aged women. The prevalence of BED increased steadily from early (3·3%) through middle (8·5%) adulthood. Anxiety disorders, mood disorders and diabetes were much more common among women with BN or BED than among women without these eating disorders. Women with BN or BED reported markedly poorer functioning and much higher levels of disability, health problems, insomnia, psychosocial stress and suicidal thoughts than did women without BN or BED, after co-occurring psychiatric disorders were controlled statistically. Yet, fewer than one of ten cases of BN or BED was recognized by the patients’ physicians.

Conclusions. Patients with BN or BED often experience considerable disability, impairment, distress and co-occurring illnesses. Increased recognition of eating disorders may be a crucial step towards encouraging more patients to seek treatment for these disabling conditions.

Background. During recent years hypotheses about the pathophysiology of seasonal affective disorder/winter type (SAD) have focused monoaminergic mechanisms. There is substantial evidence that serotonergic systems play an important role. The potential role of catecholaminergic pathways has not been fully explored.

Methods. Eleven drug-free, symptomatic depressed patients with SAD and 11 healthy age- and gender-matched healthy controls were invited to participate in a 123Iβ-CIT single photon emission computed tomography (SPECT) study to assess striatal density of dopamine transporters (DATs). The cerebellum was used as reference region. Ratios were calculated between mean counts in left and right striatum and cerebellum. These ratios minus 1 represent specific/non-displaceable binding and are assumed to be directly related to DAT availability at the time of binding equilibrium.

Results. Displaceable 123Iβ-CIT binding in the area corresponding to the left striatum was significantly reduced in SAD patients compared to healthy controls (10·49±0·91 v. 11·95±1·54, respectively; 2-tailed P = 0·017, Mann–Whitney U test).

Conclusions. These data suggest reductions in the availability of striatal DAT binding sites in untreated symptomatic depressed SAD patients. It remains unclear whether these reductions represent a primary defect or an attempt to overcome a state of possible lowered dopamine availability in the synaptic cleft during a depressive episode of SAD. However, these findings provide evidence that brain dopaminergic systems may be involved in the pathophysiology of SAD.

Background. Carers of patients with clinical dementia have increased rates of depressive illness but the biological mechanisms by which the stress of caring can lead to mood disorders is not well understood.

Methods. We recruited 30 full-time carers of patients with dementia and 28 age and gender-matched controls. None of the subjects were suffering from a significant depressive disorder. We measured salivary cortisol at four time points throughout a single day and also took a single fasting morning blood sample for plasma tryptophan.

Results. Salivary cortisol levels were significantly higher in carers than controls at 12.00 h and 22.00 h. Plasma total tryptophan but not free tryptophan levels were significantly lower in carers.

Conclusions. The changes found in these non-depressed carers were essentially similar to those in patients with major depression. We suggest that increased cortisol secretion and lowered tryptophan availability increase the risk of mood disorders in carers.