Background. Etiologic research on complex disorders including alcohol dependence requires informative phenotypes. Information is lost when categorical variables represent inherently dimensional conditions. We investigated the validity of DSM-IV alcohol dependence as a dimensional phenotype by examining evidence for linearity and thresholds in associations with validating variables.

Method. Current drinkers in the National Longitudinal Alcohol Epidemiologic Survey (NLAES) (n=18352) and National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) (n=20836) were analyzed. Validating variables included family alcoholism, early-onset drinking, and alcohol treatment. Logistic or Poisson regression modeled the relationships between the validating variables and dependence in categorical, dimensional or hybrid forms, with severity defined as number of current DSM-IV alcohol-dependence criteria. Wald tests assessed differences between models.

Results. No evidence was found for boundaries between categories. Instead, the association of alcohol dependence with the validating variables generally increased in linear fashion as the number of alcohol-dependence criteria increased. For NLAES models of family alcoholism, early-onset drinking and treatment, the lines had zero intercepts, with slopes of 0·18, 0·27, 0·70, respectively. For NESARC models of family history and early-onset drinking, the zero intercept lines had slopes of 0·20, 0·33, and 0·77, respectively. Wald tests indicated that models representing alcohol dependence as a dimensional linear predictor best described the association between dependence criteria and the validating variables.

Conclusions. The sample sizes allowed strong tests. Diagnoses are necessary for clinical decision-making, but a dimensional alcohol-dependence indicator should provide more information for research purposes.

Background. Item response theory (IRT) was used to determine whether the DSM-IV diagnostic criteria for alcohol abuse and dependence are arrayed along a continuum of severity.

Method. Data came from a large nationally representative sample of the US population, 18 years and older. A two-parameter logistic IRT model was used to determine the severity and discrimination of each DSM-IV criterion. Differential criterion functioning (DCF) was also assessed across subgroups of the population defined by sex, age and race-ethnicity.

Results. All DSM-IV alcohol abuse and dependence criteria, except alcohol-related legal problems, formed a continuum of alcohol use disorder severity. Abuse and dependence criteria did not consistently tap the mildest or more severe end of the continuum respectively, and several criteria were identified as potentially redundant. The drinking in larger amounts or for longer than intended dependence criterion had the greatest discrimination and lowest severity than any other criterion. Although several criteria were found to function differentially between subgroups defined in terms of sex and age, there was evidence that the generalizability and validity of the criterion forming the continuum remained intact at the test score level.

Conclusions. DSM-IV diagnostic criteria for alcohol abuse and dependence form a continuum of severity, calling into question the abuse–dependence distinction in the DSM-IV and the interpretation of abuse as a milder disorder than dependence. The criteria tapped the more severe end of the alcohol use disorder continuum, highlighting the need to identify other criteria capturing the mild to intermediate range of the severity. The drinking larger amounts or longer than intended dependence criterion may be a bridging criterion between drinking patterns that incur risk of alcohol use disorder at the milder end of the continuum, with tolerance, withdrawal, impaired control and serious social and occupational dysfunction at the more severe end of the alcohol use disorder continuum. Future IRT and other dimensional analyses hold great promise in informing revisions to categorical classifications and constructing new dimensional classifications of alcohol use disorders based on the DSM and the ICD.

Background. Few studies have focused on factors that uniquely distinguish suicide attempters from suicide ideators. This study assesses prevalence of suicide attempts among suicide ideators within a community sample; explores demographics, employment status, mental and physical health conditions, personality, life stresses and social environment as factors that may distinguish these groups; examines effects of age and gender upon suicide attempts and associated factors; and investigates the increase in suicide attempts when multiple factors related to this behaviour are present.

Method. Data were drawn from the PATH Through Life Project, a community survey of 7485 people in Canberra, Australia. A subsample of 522 suicide ideators were used for this study.

Results. Logistic regression was used to identify factors associated with suicide attempts. Physical medical conditions (OR 1·95) and negative interactions with friends (OR 1·20) were associated with an increased likelihood of suicide attempts among suicide ideators. Age and gender interaction effects for suicide attempts were found involving physical medical condition and mastery among men (OR 3·78 and 0·83 respectively) and not being employed for those aged 40–44 years (OR 8·94). A cumulative effect was found when multiple factors associated with suicide attempts were present, and the probability of an attempt was significantly elevated.

Conclusions. Factors distinguishing those who attempt suicide from suicide ideators involve being unemployed, physical ill health and relationship difficulties. Contrary to expectation, this study found that ideators and attempters experience comparable levels of depression and anxiety.

Background. Previous work suggests that subthreshold depression and subthreshold (hypo)mania are common, although little is known about the prognosis in terms of transition to clinical disorder. This paper presents data on the temporal relationship between subthreshold and clinical expression of mood phenotypes.

Method. In a random general population sample of 7076 individuals, symptoms of depression and (hypo)mania were measured with the Composite International Diagnostic Interview (CIDI) at baseline, after 1 year, and 2 years later.

Results. At baseline, the lifetime prevalences of depressive and (hypo)manic symptoms were 17·2% and 1·2% respectively. Predictive values of mood symptoms for a DSM-III-R mood disorder ranged from 14·3% to 50%. (Hypo)manic mood symptoms had much higher predictive values than unipolar manifestations, not only for bipolar disorder but also for major depression.

Conclusions. The subthreshold expressions of depression and (hypo)mania are prevalent and continuous with more severe clinical states. The cross-prediction of mood symptoms may support a continuum from depressive to (hypo)manic symptoms. The high predictive value of (hypo)manic symptoms for mood disorders suggests that the experience of (hypo)manic symptoms is a stronger indicator of vulnerability for mood dysregulation than the experience of depressive symptoms.

Background. The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk.

Method. We identified all people (n=568) aged 16–64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated.

Results. We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9·1, manic psychosis 8·0) and Black Africans (schizophrenia 5·8, manic psychosis 6·2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study.

Conclusions. Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.

Background. Patients with schizophrenia have an impaired ability to generate activity that is appropriate to current circumstances and goals.

Method. We report a study using functional magnetic resonance imaging (fMRI) to examine cerebral activity during a three-tone auditory oddball target detection task in a sample of 28 patients with schizophrenia and 28 healthy controls.

Results. The patients exhibited significantly less activation in response to target stimuli relative to baseline in an extensive set of sites in association neocortex, paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a normal level of activation in the sensorimotor cortex. Comparison of activity elicited by rare target stimuli with that elicited by equally rare novel stimuli makes it possible to distinguish cerebral activity associated with attention to behaviourally salient stimuli from activity associated with attending to other attention-capturing stimuli. This comparison revealed that the patients with schizophrenia also exhibited a deficit in activation of basal forebrain areas that mediate motivation during the processing of behaviourally salient stimuli, including the amygdala, ventral striatum, orbital frontal cortex and rostral anterior cingulate cortex.

Conclusion. Patients with schizophrenia have a deficit in function of the brain system concerned with mediating motivation, in addition to a more general deficit in the cerebral response to attention-captivating stimuli.

Background. There is evidence to indicate that peripheral glucocorticoid receptor (GR) function is reduced in major depression, and a possible molecular explanation for this is the impact of raised pro-inflammatory cytokines. The topical steroid vasoconstriction assay provides a convenient probe of peripheral GR function. The present study sought to assess the sensitivity of peripheral GRs in antidepressant-resistant major depressives and investigate the association between GR sensitivity and circulating plasma cytokines.

Method. Nineteen antidepressant-resistant depressives together with age- and sex-matched healthy controls underwent the steroid vasoconstriction assay using three commercial preparations of corticosteroids containing clobetasol propionate 0·05%, betamethasone valerate 0·1%, and clobetasone butyrate 0·05%, corresponding to very potent, potent, and moderately potent steroid creams respectively. The pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assays. The severity of the depressive episode was assessed using the Hamilton Depression Scale (HAMD).

Results. Depressed subjects had a significantly reduced vasoconstriction response across all three strengths of steroid. They also had significantly higher concentrations of TNF-α and IL-6. There was a significant inverse correlation between TNF-α concentration and vasoconstriction response and also between the HAMD score and vasoconstriction response.

Conclusions. These findings suggest that cutaneous GR function is abnormal in antidepressant-resistant depression, that circulating TNF-α may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.

Background. Adults in their twenties appear to be at high risk for suicidal behaviors (SBs) and there is substantial evidence suggesting that certain personality traits may increase individual vulnerability to suicide.

Method. We investigated relationships of personality traits with two SBs in a cohort (n=1140) of 21- to 24-year-old adults, representative of the general population of Quebec. Subjects were assessed using a series of structured diagnostic and personality trait questionnaires. Multivariate logistic regression analyses were employed to identify personality trait correlates of suicide-attempt history and serious suicidal ideation in the context of other known risk factors, such as psychopathology and experiences of childhood sexual and physical abuse.

Results. Traits of conduct problems contributed to both suicide attempts [odds ratio (OR) 1·03, 95% confidence interval (CI) 1·01–1·06] and suicidal ideation (OR 1·04, 95% CI 1·02–1·07), while identity problems (OR 1·10, 95% CI 1·07–1·13) and gender-moderated impulsivity contributed exclusively to suicidal ideation.

Conclusions. Personality traits may make independent contributions to current suicidal ideation and previous suicide attempts in certain subgroups of suicidal individuals. In order to further explore their utility as markers of suicide risk and targets of intervention further investigation in clinical samples and other cultural and age groups is necessary.

Background. We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol.

Method. Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ).

Results. Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups.

Conclusions. Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Background. Prevalence of childhood anxiety disorders at specific ages and genetic etiological influences on anxiety disorders in young children have been little studied. The present study reports prevalence estimates in a community sample of 6-year-old twins, and patterns of genetic and environmental influences on these early-onset anxiety disorders.

Method. Using a two-phase design 4662 twin-pairs were sampled and 854 pairs were assessed in the second phase by maternal-informant diagnostic interview using DSM-IV criteria.

Results. The most common conditions were separation anxiety disorder (SAD) [2·8%, 95% confidence interval (CI) 2·1–3·8, for current disorder] and specific phobia (10·8%, 95% CI 8·4–13·6, for current disorder). Behavioral genetic modeling was feasible for these two conditions, applied to two phenotypes: symptom syndrome (regardless of impairment) and the narrower one of diagnostic status (symptom syndrome with associated impairment). The heritability estimate for SAD diagnostic status was high, 73%, with remaining variance attributed to non-shared environment. The heritability estimates for specific phobia were also high, 80% for the symptom syndrome and 60% for diagnostic status, with remaining variance attributed in both cases to non-shared environment.

Conclusions. Compared with previous epidemiological surveys of children and adolescents in wide age-bands, the current estimates suggest that rates of anxiety disorders assessed in young childhood are generally at least as high and perhaps higher compared with those found in older children. The heritability estimates suggest that the genetic effects on these early-onset anxiety disorders are substantial and more significant than environmental effects, whether shared or non-shared.

Background. Formal thought disorder (FTD) has long been regarded as a key sign of schizophrenia but little is known about its origins or aetiology. One suggestion is that it is directly related to disordered language functioning; a second is that it is a reflection of poor neurocognitive functioning. A current model posits that it is related to a combination of executive dysfunction and impaired semantic processing.

Method. To examine these alternative ideas, a heterogeneous group of 30 patients, all carrying a diagnosis of schizophrenia, and 18 non-patient controls completed a series of neurocognitive and psycholinguistic tests, and a clinical review that, inter alia, permitted assessment of thought disorder (TD) using the Thought, Language and Communication Scale (TLC).

Results. Patients generally performed at a lower level on most components of the test battery, but there was little evidence of a relationship between TD and syntactic psycholinguistic function. However, schizophrenic patients manifesting higher levels of TD performed at a lower level on tests sensitive to executive dysfunction and semantic impairments.

Conclusions. The origins of TD seem more closely linked to deficits in executive functioning and semantic processing than to impairments in other language functions or general cognition.

Background. Adverse life events and social support may influence the outcome of major depressive disorder (MDD). We hypothesized that outcome would depend on the level of depressive symptoms present at the outset, with those in partial remission being particularly vulnerable.

Method. In the Vantaa Depression Study (VDS), patients with DSM-IV MDD were interviewed at baseline, and at 6 and 18 months. Life events were investigated with the Interview for Recent Life Events (IRLE) and social support with the Interview Measure of Social Relationships (IMSR) and the Perceived Social Support Scale – Revised (PSSS-R). The patients were divided into three subgroups at 6 months, those in full remission (n=68), partial remission (n=75) or major depressive episode (MDE) (n=50). The influence of social support and negative life events during the next 12 months on the level of depressive symptoms, measured by the Hamilton Rating Scale for Depression (HAMD), was investigated at endpoint.

Results. The severity of life events and perceived social support influenced the outcome of depression overall, even after adjusting for baseline level of depression and neuroticism. In the full remission subgroup, both severity of life events and subjective social support significantly predicted outcome. However, in the partial remission group, only the severity of events, and in the MDE group, the level of social support were significant predictors.

Conclusions. Adverse life events and/or poor perceived social support influence the medium-term outcome of all psychiatric patients with MDD. These factors appear to have the strongest predictive value in the subgroup of patients currently in full remission.

Background. Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression.

Method. We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on ‘neutral’ (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task).

Results. Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for ‘sad’ targets was not evident on the affective go/no-go task.

Conclusions. We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.

Background. Both generalized anxiety disorder (GAD) and stressful life events (SLEs) are established risk factors for major depressive disorder, but no studies exist that examine the interrelationship of their impact on depressive onsets. In this study, we sought to analyze the joint effects of prior history of GAD and recent SLEs on risk for major depressive episodes, comparing these in men and women.

Method. In a population-based sample of 8068 adult twins, Cox proportional hazard models were used to predict onsets of major depression from reported prior GAD and last-year SLEs rated on long-term contextual threat.

Results. For all levels of threat, prior GAD increases risk for depression, with a monotonic relationship between threat level and risk. While females without prior GAD consistently show higher depressive risk than males, this is no longer the case in subjects with prior GAD who have experienced SLEs. Rather, males appear to be more vulnerable to the depressogenic effects of both prior GAD and SLEs.

Conclusion. The effects of prior GAD and SLEs jointly increase the risk of depression in both sexes, but disproportionately so in males.

Background. To examine sex differences in DSM-IV subclinical and pathological gambling in nationally representative data of the US population.

Method. Data come from a large (n=43093) representative sample of the adult US population.

Results. The lifetime prevalence rate of DSM-IV pathological gambling was 0·64% (95% CI 0·50–0·78) for men and 0·23% (95% CI 0·17–0·29) for women, whereas the lifetime prevalence of subclinical pathological gambling was 6·79% (95% CI 6·32–7·26) for men and 3·26% (95% CI 2·93–3·59) for women. For subclinical pathological gambling, men were significantly (p<0·01) more likely than women to have smoked more than two packs of cigarettes a day, to be classified as heavy drinkers and to have lifetime diagnoses of alcohol and drug use disorders. Women with subclinical and pathological gambling were significantly more likely than men to have lifetime mood and anxiety disorders. With respect to pathological gambling, women had later ages of onset of the disorder, and were significantly more likely than men to report gambling to relieve depressed mood and to prefer casino gambling. Rates of treatment-seeking for DSM-IV pathological gambling were low for both men and women.

Conclusions. There are important sex differences in the prevalence, symptom pattern, sociodemographic and clinical correlates and course of DSM-IV subclinical and pathological gambling. Results underscore the need to investigate sex differences in the social determinants, neurobiology and treatment response of DSM-IV subclinical and pathological gambling.

Background. Most national suicide prevention strategies set improved detection and management of depression in primary health care into a central position. However, suicidal behaviour among primary-care patients with depressive disorders has been seldom investigated.

Method. In the Vantaa Primary Care Depression Study, a total of 1119 primary-care patients in the City of Vantaa, Finland, aged 20 to 69 years, were screened for depression with the Primary Care Evaluation of Mental Disorders (PRIME-MD) questionnaire. Depressive disorders were diagnosed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and the 137 patients with depressive disorder were included in the study. Suicidal behaviour was investigated cross-sectionally and retrospectively in three time-frames: current, current depressive episode, and lifetime. Current suicidal ideation was measured with the Scale for Suicidal Ideation (SSI), and previous ideation and suicide attempts were evaluated based on interviews plus medical and psychiatric records.

Results. Within their lifetimes, 37% (51/137) of the patients had seriously considered suicide and 17% (23/137) attempted it. Lifetime suicidal behaviour was independently and strongly predicted by psychiatric treatment history and co-morbid personality disorder, and suicidal behaviour within the current episode was predicted most effectively by severity of depression.

Conclusions. Based on these findings and their convergence with studies of completed suicides, prevention of suicidal behaviour in primary care should probably focus more on high-risk subgroups of depressed patients, including those with moderate to severe major depressive disorder, personality disorder or a history of psychiatric care. Recognition of suicidal behaviour should be improved. The complex psychopathology of these patients in primary care needs to be considered in targeting preventive efforts.

Background. Recently accumulated evidence has demonstrated that bright-light therapy in combination with antidepressants is effective in patients with non-seasonal major depression. Whether bright light has a sustained effect after discontinuation is, however, poorly investigated.

Method. In this double-blind randomized study we report the results from a 4-week follow-up period in patients with major non-seasonal depression who had been treated for 5 weeks with sertraline combined with bright-light therapy or sertraline combined with dim-light therapy. At the beginning of the follow-up period the light therapy was stopped while sertraline treatment continued for 4 weeks.

Results. Depression scores decreased substantially in both groups, resulting in high response and remission rates in both groups after 9 weeks of treatment. The difference in depression scores at week 5, favouring the bright-light-treated group, disappeared gradually in the 4-week follow-up period, resulting in similar end-point scores.

Conclusions. Bright light did not have a sustained effect after discontinuation. The offset of effect was complete after 4 weeks.

Background. Most research has indicated that neuroticism (or trait anxiety) is associated with only negative outcomes. Such a common, heritable and variable trait is expected to have beneficial as well as detrimental effects. We tested the hypothesis that trait anxiety in childhood reduces the risk of dying from accidental causes in early adult life.

Method. A longitudinal, population-based, birth cohort study of 4070 men and women born in the UK in 1946. Trait anxiety as judged by teachers when the participants were 13 and 15 years old, and the neuroticism scale of a Maudsley Personality Inventory (MPI) when the participants were 16 years old. Outcomes were deaths, deaths from accidents, non-fatal accidents, and non-fatal accidents requiring medical intervention.

Results. Adolescents with low trait anxiety had higher rates of accident mortality to age 25 [low anxiety at 13, hazard ratio (HR) 5·9, low anxiety at 15, HR 1·8]. Low trait anxiety in adolescence was associated with decreased non-accidental mortality after age 25 (low anxiety at 13, HR 0; low anxiety at 15, HR 0·7; low neuroticism at 16, HR 0·7).

Conclusions. High trait anxiety measured in adolescence is associated with reduced accidents and accidental death in early adulthood but higher rates of non-accidental mortality in later life.

Background. There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis and provides the opportunity to investigate psychological mechanisms that may confer vulnerability to psychosis.

Method. Fifty-eight patients at ultra-high risk of developing a first episode of psychosis were compared with 56 non-patients matched for age and occupational status on measures of meta-cognition, schizotypal traits, dysfunctional attitudes and distress.

Results. Analyses of covariance revealed that people at high risk of developing psychosis scored higher on measures of cognitive vulnerability, including negative meta-cognitive beliefs, beliefs about rejection and criticism from others, and discrepancies in self-perception, schizotypal traits and general mental distress. Correlational analyses revealed that negative meta-cognitive beliefs, dysfunctional attitudes and beliefs about rejection and criticism from others were positively associated with several dimensions of symptomatology in at-risk mental states (ARMS) patients.

Conclusions. Cognitive and personality factors appear to characterize people at high-risk of developing psychosis and are associated with their distressing experiences. The clinical implications of these findings are discussed.

Objective. The substantial literature examining social reasoning in people with delusions has, to date, neglected the commonest form of decision making in daily life. We address this imbalance by reporting here the findings of the first study to explore heuristic reasoning in people with persecutory delusions.

Method. People with active or remitted paranoid delusions, depressed and healthy adults performed two novel heuristic reasoning tasks that varied in emotional valence.

Results. The findings indicated that people with persecutory delusions displayed biases during heuristic reasoning that were most obvious when reasoning about threatening and positive material. Clear similarities existed between the currently paranoid group and the depressed group in terms of their reasoning about the likelihood of events happening to them, with both groups tending to believe that pleasant things would not happen to them. However, only the currently paranoid group showed an increased tendency to view other people as threatening.

Conclusion. This study has initiated the exploration of heuristic reasoning in paranoia and depression. The findings have therapeutic utility and future work could focus on the differentiation of paranoia and depression at a cognitive level.