This issue features groups of papers dealing with nosology of depression and psychoses, biology of depression, structural brain MRI in schizophrenia and autism, together with papers on other topics.

Background. The DSM concept of ‘major depression’ has accrued increased status but demonstrated limited utility since inception.

Method. An historical overview of models of depression and the initially perceived advantages presented by the concept of ‘major depression’ are presented before detailing its limitations in application.

Results. Challenges to the utility of ‘major depression’ are provided by examining its conceptual model, its validity, its utility and the limited information generated in aetiological and treatment efficacy studies.

Conclusion. It is argued that the concept of ‘major depression’ has led to sterility in depression research and clinical practice, and that there is a need for a paradigm shift in modelling and classifying the depressive disorders.

Background. Expert committees of clinicians have chosen diagnostic criteria for psychiatric disorders with little guidance from measurement theory or modern psychometric methods. The DSM-III-R criteria for major depression (MD) are examined to determine the degree to which latent trait item response models can extract additional useful information.

Method. The dimensionality and measurement properties of the 9 DSM-III-R criteria plus duration are evaluated using dichotomous factor analysis and the Rasch and 2 parameter logistic item response models. Quantitative liability scales are compared with a binary DSM-III-R diagnostic algorithm variable to determine the ramifications of using each approach.

Results. Factor and item response model results indicated the 10 MD criteria defined a reasonably coherent unidimensional scale of liability. However, person risk measurement was not optimal. Criteria thresholds were unevenly spaced leaving scale regions poorly measured. Criteria varied in discriminating levels of risk. Compared to a binary MD diagnosis, item response model (IRM) liability scales performed far better in (i) elucidating the relationship between MD symptoms and liability, (ii) predicting the personality trait of neuroticism and future depressive episodes and (iii) more precisely estimating heritability parameters.

Conclusions. Criteria for MD largely defined a single dimension of disease liability although the quality of person risk measurement was less clear. The quantitative item response scales were statistically superior in predicting relevant outcomes and estimating twin model parameters. Item response models that treat symptoms as ordered indicators of risk rather than as counts towards a diagnostic threshold more fully exploit the information available in symptom endorsement data patterns.

Background. The latent structure of depression was examined using taxometric analysis, a family of statistical procedures designed specifically to test whether a given construct is best conceptualized as a distinct category or a continuous dimension.

Method. Data were derived from the Australian National Survey of Mental Health and Well-Being, a large epidemiological survey that measured the prevalence of the major DSM-IV and ICD-10 mental disorders. Two taxometric procedures, maximum covariance (MAXCOV) and mean above minus below a cut (MAMBAC), were carried out on a sample of 1933 community volunteers. Simulated categorical and dimensional datasets aided in the interpretation of the research data.

Results. The results of the taxometric analyses in the subsample who endorsed at least one symptom of depression were consistent with a dimensional latent structure of depression.

Conclusions. The findings of the current study suggest that depression, as measured in this subsample, is best conceptualized, measured and classified as a continuously distributed syndrome rather than as a discrete diagnostic entity. Incorporation of dimensional measurement into psychiatric classification systems remains a challenge for the future.

Background. Classification of psychosis lacks a biological basis and current diagnostic categories may obscure underlying continuities. Data reduction methods of symptom profiles within a population-based cohort of people with a wide range of affective and non-affective psychoses may permit an empirical classification of psychosis.

Method. OPCRIT (operational criteria) analysis was performed on 387 adults aged 18–65 years in an attempted ascertainment of all patients with psychosis from a geographical area with a stable population. The data were analysed firstly using principal components analysis with varimax rotation to identify factors, and secondly to establish latent classes. Information relating to key variables known to be of relevance in schizophrenia was coded blind to the establishment of the classes and dimensions.

Results. Striking correspondence was obtained between the two methods. The four dimensions emerging were labelled ‘depression’, ‘reality distortion’, ‘mania’ and ‘disorganization’. Latent classes identified were ‘depression’, ‘bipolar’, ‘reality distortion/depression’ and ‘disorganization’. The latent classes corresponded well with DSM-III-R diagnoses, but also revealed groupings usually obscured by diagnostic boundaries. The latent classes differed on gender ratio, fertility, age of onset and self-harming behaviour, but not on substance misuse or season of birth.

Conclusions. Both dimensional and categorical approaches are useful in tapping the latent constructs underlying psychosis. Broad agreement with other similar studies suggests such findings could represent discrete pathological conditions. The four classes described appear meaningful, and suggest that the term non-affective psychosis should be reserved for the disorganization class, which represents only a subgroup of those with schizophrenia.

Background. Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported.

Method. A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline.

Results. Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic antidepressant, were less likely to have bipolar II disorder, had a higher tryptophan:large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter.

Conclusions. These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing.

Background. We reported previously that the socio-economic status (SES) of individuals predicts variation in brain serotonergic responsivity, as assessed by neuropharmacological challenge in an adult community sample, and that this association is qualified by allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR). Here we examine whether serotonergic responsivity covaries similarly with the SES of communities, as indexed by US Census data in the same study sample.

Method. Community SES was defined by levels of income, economic disadvantage, housing costs, and educational attainment of census tracts in which 249 locally recruited study participants (54% male) resided. Serotonergic responsivity was assessed as the baseline-adjusted, peak plasma prolactin (Prl) concentration following acute administration of the serotonin-releasing agent, fenfluramine; tissue for DNA extraction and 5-HTTLPR genotyping was available on 131 participants.

Results. Subjects residing in census tracts of lower SES showed a blunted Prl response to fenfluramine (diminished serotonergic responsivity) relative to individuals living in more affluent neighborhoods. When adjusted for personal income and education, SES at the community level continued to predict fenfluramine-stimulated Prl responses and did so independently of 5-HTTLPR genotype.

Conclusions. Area-level indices of relative social and economic disadvantage covary with individual differences in brain serotonergic responsivity, and this association is, in part, independent of individually defined SES. These findings may be relevant to reported effects of low community SES on the prevalence of psychiatric disorders or behaviors associated with dysregulation of central serotonergic function, such as depression, impulsive aggression, and suicide.

Background. Case control studies have supported a relationship between low folic acid and vitamin B12 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations.

Method. A random subsample of 412 persons aged 60–64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging.

Results. Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables.

Conclusions. Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

Background. The quality of subjective experience of dysphoria may predict persistence of depression, independently of severity. This is tested in a clinic sample of adolescents with first episode of major depression using the Depressed States Checklist adapted for adolescents.

Method. Ninety-four adolescents with DSM-IV major depressive disorder (MDD) were followed up at 12 months. Self-devaluative components of dysphoric experience, ruminative style, overgeneral autobiographical memory, and self-reported and observer-rated measures of depression severity were assessed at presentation and evaluated as predictors of persistent MDD.

Results. Persistent MDD was predicted by the independent additive effects of the higher self-devaluative component of dysphoria, lower general intelligence and greater observer-rated severity of depression at presentation. Neither self-reported depression score, overgeneral memory retrieval nor ruminative style contributed.

Conclusions. High levels of self-devaluative dysphoric experience increase the liability for persistence of first-episode MDD. Other affective-cognitive components also contribute. The adolescent version of the Depressed States Checklist is a useful brief measure of cognitive vulnerability for persistence in currently depressed young people.

Background. Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia.

Method. Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus.

Results. Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus.

Conclusions. Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.

Background. To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions.

Method. Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status.

Results. Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients.

Conclusions. High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

Background. Cognitive performance was compared in the genetically and neurobiologically related disorders of Tourette's syndrome (TS) and obsessive–compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control.

Method. Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making.

Results. Compared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group.

Conclusions. TS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology.

Background. The aim of this study was to design a self-report measure of behavioural responses during the acute phase of an illness, in order to assess the importance of these behaviours in the development of ongoing medically unexplained syndromes.

Method. An initial pool of items derived from theoretical models and clinical observation, was piloted on a group of 312 university students to assess the factor structure of the scale and the best fit items. The scale was further validated in a second study of 758 patients who were experiencing Campylobacter gastroenteritis. At 3 months post-infection, patients were sent a second questionnaire assessing symptoms of irritable bowel syndrome (IBS).

Results. Principal components analysis of the items in the student sample yielded a four-factor solution, labelled all-or-nothing behaviour, limiting behaviour, emotional support seeking and practical support seeking. The factor structure was confirmed in the Campylobacter sample, and internal reliability was good. All-or-nothing behaviour was associated with IBS at 3 months post-infection. In contrast, limiting behaviour and practical support seeking at the time of infection appeared to be protective.

Conclusion. The results suggest that this is a valid and reliable measure that can predict the development of a medically unexplained syndrome after acute infection. Overdoing things at the time of infection and then needing to rest for prolonged periods (all-or-nothing behaviour), appears to be a particular risk factor for the development of IBS. Targeted interventions at the time of infection may improve coping and prevent symptoms from becoming chronic.