Recent work suggests that heavy use of cannabis is associated with an increased risk of schizophrenia-like psychosis. However, there is a dearth of experimental studies of the effects of the constituents of cannabis, such as Δ9-tetrahydrocannabinol (THC). In a study of intravenous (i.v.) synthetic THC in healthy humans, we aimed to study the relationship of the psychotic symptoms induced by THC to the consequent anxiety and neuropsychological impairment.

Twenty-two healthy adult males aged 28±6 years (mean±s.d.) participated in experimental sessions in which i.v. THC (2.5 mg) was administered under double-blind, placebo-controlled conditions. Self-rated and investigator-rated measurements of mood and psychosis [the University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experiences (CAPE)] were made at baseline and at 30, 80 and 120 min post-injection. Participants also completed a series of neuropsychological tests [the Rey Auditory Verbal Learning Task (RAVLT), Digit Span, Verbal Fluency and the Baddeley Reasoning Task] within 45 min of injection.

THC-induced positive psychotic symptoms, and participant- and investigator-rated measurements of these were highly correlated. Participants showed an increase in anxiety ratings but there was no relationship between either self- or investigator-rated positive psychotic symptoms and anxiety. THC also impaired neuropsychological performance but once again there was no relationship between THC-induced positive psychotic symptoms and deficits in working memory/executive function.

These findings confirm that THC can induce a transient, acute psychotic reaction in psychiatrically well individuals. The extent of the psychotic reaction was not related to the degree of anxiety or cognitive impairment.

Despite the increasing development of early intervention services for psychosis, little is known about their cost-effectiveness. We assessed the cost-effectiveness of Outreach and Support in South London (OASIS), a service for people with an at-risk mental state (ARMS) for psychosis.

The costs of OASIS compared to care as usual (CAU) were entered in a decision model and examined for 12- and 24-month periods, using the duration of untreated psychosis (DUP) and rate of transition to psychosis as key parameters. The costs were calculated on the basis of services used following referral and the impact on employment. Sensitivity analysis was used to test the robustness of all the assumptions made in the model.

Over the initial 12 months from presentation, the costs of the OASIS intervention were £1872 higher than CAU. However, after 24 months they were £961 less than CAU.

This model suggests that services that permit early detection of people at high risk of psychosis may be cost saving.

This study reports on a preliminary evaluation of a cognitive behavioural intervention to improve social recovery among young people in the early stages of psychosis showing persistent signs of poor social functioning and unemployment. The study was a single-blind randomized controlled trial (RCT) with two arms, 35 participants receiving cognitive behaviour therapy (CBT) plus treatment as usual (TAU), and 42 participants receiving TAU alone. Participants were assessed at baseline and post-treatment.

Seventy-seven participants were recruited from secondary mental health teams after presenting with a history of unemployment and poor social outcome. The cognitive behavioural intervention was delivered over a 9-month period with a mean of 12 sessions. The primary outcomes were weekly hours spent in constructive economic and structured activity. A range of secondary and tertiary outcomes were also assessed.

Intention-to-treat analysis on the combined affective and non-affective psychosis sample showed no significant impact of treatment on primary or secondary outcomes. However, analysis of interactions by diagnostic subgroup was significant for secondary symptomatic outcomes on the Positive and Negative Syndrome Scale (PANSS) [F(1, 69)=3.99, p=0.05]. Subsequent exploratory analyses within diagnostic subgroups revealed clinically important and significant improvements in weekly hours in constructive and structured activity and PANSS scores among people with non-affective psychosis.

The primary study comparison provided no clear evidence for the benefit of CBT in a combined sample of patients. However, planned analyses with diagnostic subgroups showed important benefits for CBT among people with non-affective psychosis who have social recovery problems. These promising results need to be independently replicated in a larger, multi-centre RCT.

This study examined the magnitude of neurocognitive change during 1 year of community-based psychosocial intervention, whether neurocognitive change and functional change were linked, and how neurocognitive change combined with service intensity to facilitate functional change.

A total of 130 individuals diagnosed with schizophrenia were recruited upon admission to four community-based psychosocial rehabilitation programs. Subjects were assessed at baseline, 6 and 12 months on role functioning and symptom measures. Neurocognition was measured at baseline and 12 months. Service intensity was the number of days of treatment attendance during the study period. Latent mean difference tests and Latent Growth Curve Models (LCGMs) were used to examine the study hypotheses.

There was statistically and clinically significant functional improvement over 12 months. Neurocognition improved significantly over time. Seventy-six (58%) of the sample showed neurocognitive improvement and 54 (42%) did not. There was a significant rate of functional enhancement in the neurocognitive improver group. There was a non-significant rate of functional change in the neurocognitive non-improver group. Neurocognitive improvers showed functional improvement that was 350% greater than neurocognitive non-improvers. Service intensity did not vary between neurocognitive improvers and non-improvers but there was a strong interaction between neurocognitive improvement, service intensity and rate of functional improvement such that service intensity was strongly related to functional improvement for neurocognitive improvers but not for neurocognitive non-improvers. Medication usage and symptomatology did not confound these findings.

These findings suggest that neurocognitive improvement may be a foundation for functional change and treatment responsiveness during community-based psychosocial rehabilitation for individuals with schizophrenia.

Neuropsychological deficits in schizophrenia patients and their relatives have been thought to represent possible genetic vulnerability markers or endophenotypes of the disorder. The present study describes results from the Edinburgh High Risk Study of computerized testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) on a group at genetic high risk (HR) of schizophrenia and a control group.

A total of 97 HR and 25 control participants were assessed on three tests from the CANTAB – spatial span, spatial working memory, and Stockings of Cambridge. Analyses of covariance were used to compare the HR and control groups on the main outcome measures whilst controlling for intelligence quotient (IQ). Subsequent analysis examined the effects of the presence of symptoms on group differences.

HR participants had significantly reduced spatial memory capacity [F(1, 118)=4.06, p=0.046] and significantly reduced planning processing speed [F(1, 116)=4.16, p=0.044] compared with controls even after controlling for general intelligence (IQ). Although HR individuals made more errors and showed poorer problem-solving and strategy performance compared with controls, these differences were not significant after controlling for IQ. Subsequent analysis indicated that the presence or absence of psychotic symptoms in the HR group did not influence these specific cognitive deficits.

Spatial memory capacity and planning processing speed may represent cognitive endophenotypes characterising the genetic predisposition to schizophrenia in this HR group.

Schizophrenia is a complex disorder with a high heritability. Family members have an increased risk not only for schizophrenia per se but also for schizophrenia spectrum disorders. Impairment of neuropsychological functions found in schizophrenia patients are also frequently observed in their relatives. The dystrobrevin-binding protein 1 (DTNBP1) gene located at chromosome 6p22.3 is one of the most often replicated vulnerability genes for schizophrenia. In addition, this gene has been shown to modulate general cognitive abilities both in healthy subjects and in patients with schizophrenia.

In a sample of 521 healthy subjects we investigated an association between the DTNBP1 genotype [single nucleotide polymorphism (SNP) rs1018381], personality traits [using the NEO Five-Factor Inventory (NEO-FFI) and the Schizotypal Personality Questionnaire – Brief Version (SPQ-B)] and cognitive function (estimated IQ, verbal fluency, attention, working memory and executive function).

Significantly lower scores on the SPQ-B (p=0.0005) and the Interpersonal Deficit subscale (p=0.0005) in carriers of the A-risk allele were detected. There were no differences in any of the cognitive variables between groups.

The results indicate that genetic variation of the DTNBP1 genotype might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.

Schizophrenic patients have fewer offspring than the general population but it is unclear whether (i) this persists for more than one generation, (ii) the reduced fertility is compensated by increased fertility in unaffected relatives, (iii) sociodemographic factors confound or interact with the association, and (iv) patients with affective psychosis have a similar fertility disadvantage. This study measured biological fitness over two generations in patients with schizophrenia or affective psychosis, and their unaffected siblings.

We conducted a historical cohort study using a Swedish birth cohort of 12 168 individuals born 1915–1929 and followed up until 2002. We compared biological fitness over two generations in patients with schizophrenia (n=58) or affective psychosis (n=153), and their unaffected siblings, with the population, adjusting for a range of sociodemographic variables from throughout the lifespan.

Patients with schizophrenia had fewer children [fertility ratio (FR) 0.42, 95% confidence interval (CI) 0.29–0.61] and grandchildren (FR 0.51, 95% CI 0.33–0.80) than the population. Some of this reduction was related to lower marriage rates in schizophrenic patients. The unaffected siblings of schizophrenic patients showed no evidence of any compensatory increase in fitness, but there was a trend towards enhanced fertility among the offspring of schizophrenia patients. Patients with affective psychosis and their relatives did not differ from the general population on any fertility measure.

Schizophrenia, but not affective psychosis, is associated with reduced biological fertility; this disadvantage is partly explained by marital status and persists into the second generation.

Depressive symptoms above screening thresholds have been shown to predict functional decline in older adults. Less is known about the impact of subthreshold depression, and whether more symptoms confer significantly greater risk compared to fewer symptoms.

Using data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) collected over 10 years, we used repeated-measures mixed models to predict functional change by depression status at the prior (index) in-person interview. Depressive symptoms were measured using a modified version of the Center for Epidemiologic Studies Depression Scale (CES-D). Subthreshold depression was operationalized as 6–8 symptoms and CES-D-defined depression as 9–20 symptoms in the previous week. Three domains of functional status were assessed at the subsequent in-person interview: limitations in basic activities of daily living (ADL), instrumental ADL (IADL) and mobility.

Controlling for race, sex, age, education, marital status, cognitive status, health status, self-perceived health, perceived social support and functional status at the index interview, having ⩾6 depressive symptoms predicted an increase of 0.12 IADL limitations 3–4 years later (p=0.03). The incremental effect of CES-D-defined depression (⩾9 symptoms compared to 6–8 symptoms) was not significant, suggesting that the effect of more symptomatic depression did not add to that of subthreshold depression. CES-D score modeled as a continuous variable predicted functional change for all domains, but the relationship was not linear, supporting a possible threshold effect.

The relationship between depressive symptoms and functional change is complex, not necessarily linear, and may vary by tasks assessed.

The authors used results from a 20-year, high-intensity follow-up to measure the influence of ageing, and of age at onset, on the long-term persistence of symptoms in major depressive disorder (MDD).

Subjects who completed a 20-year series of semi-annual and then annual assessments with a stable diagnosis of MDD or schizo-affective disorder other than mainly schizophrenic (n=220) were divided according to their ages at intake into youngest (18–29 years), middle (30–44 years) and oldest (>45 years) groups. Depressive morbidity was quantified as the proportion of weeks spent in major depressive or schizo-affective episodes. General linear models then tested for effects of time and time×group interactions on these measures. Regression analyses compared the influence of age of onset and of current age.

Analyses revealed no significant time or group×time effects on the proportions of weeks in major depressive episodes in any of the three age groups. Earlier ages of onset were associated with greater symptom persistence, particularly in the youngest group. The proportions of weeks ill showed intra-individual stability over time that was most evident in the oldest group.

These results indicate that the persistence of depressive symptoms in MDD does not change as individuals move from their third to their fifth decade, from their fourth to their sixth decade, or from their sixth to their eighth decade. An early age of onset, rather than youth per se, is associated with greater morbidity over two decades.

Depressive disorders are known to often be chronic and recurrent both in the general population and in psychiatric settings. However, despite its importance for public health and services, the outcome of depression in primary care is not well known.

In The Vantaa Primary Care Depression Study (PC-VDS), 1111 consecutive primary-care patients were screened for depression with the Prime-MD screen, and 137 diagnosed with DSM-IV depressive disorders by interviewing with the Structured Clinical Interview for DSM-IV (SCID)-I/P and SCID-II. This cohort was prospectively followed-up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the 18-month follow-up, including 79 with major depressive disorder (MDD) and 44 with subsyndromal disorders. Duration of the index episode and the timing of relapses/recurrences were examined using a life-chart.

Of the patients with MDD, only a quarter [25% (20/79)] achieved and remained in full remission, while another quarter [25% (20/79)] persisted in major depressive episode for 18 months. The remaining 49% (39/79) suffered from residual symptoms or recurrences. In Cox regression models, time to remission and recurrences were robustly predicted by severity of depression, and less consistently by co-morbid substance-use disorder, chronic medical illness or cluster C personality disorder. Of the subsyndromal patients, 25% (11/44) proceeded to MDD.

This prospective medium-term study verified the high rate of recurrences and chronicity of depression also in primary care. Severity of depressive symptoms and co-morbidity are important predictors of outcome. Development of chronic disease management for depression is warranted in primary care.

Millions of people seek emergency department (ED) care for injuries each year, the majority for minor injuries. Little is known about the effect of psychiatric co-morbid disorders that emerge after minor injury on functional recovery. This study examined the effect of post-injury depression on return to pre-injury levels of function.

This was a longitudinal cohort study with follow-up at 3, 6 and 12 months post-injury: 275 adults were randomly selected from those presenting to the ED with minor injury; 248 were retained over the post-injury year. Function was measured with the Functional Status Questionnaire (FSQ). Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR disorders (SCID).

During the post-injury year, 18.1% [95% confidence interval (CI) 13.3–22.9] were diagnosed with depression. Adjusting for clinical and demographic covariates, the depressed group was less likely to return to pre-injury levels of activities of daily living [odds ratio (OR) 8.37, 95% CI 3.78–18.53] and instrumental activities of daily living (OR 3.25, 95% CI 1.44–7.31), less likely to return to pre-injury work status (OR 2.37, 95% CI 1.04–5.38), and more likely to spend days in bed because of health (OR 2.41, 95% CI 1.15–5.07).

Depression was the most frequent psychiatric diagnosis in the year after minor injury requiring emergency care. Individuals with depression did not return to pre-injury levels of function during the post-injury year.

It is unclear whether Axis II psychopathology or co-morbid clinical syndromes result in the treatment-seeking behaviour and social impairment of patients with borderline personality disorder (BPD). This study examined the independent associations between social functioning and service use and Axis I and Axis II disorders in persons with BPD in the national household population of Britain.

The study was a cross-sectional survey of adults aged 16–74 years in households (n=8397). Data included self-reported consultations with health-care professionals and behavioural problems. Diagnosis was determined by computer-assisted interviews. Analyses included logistic regression adjusting for demography, co-morbid Axis I clinical syndromes and other Axis II disorders.

Consultation in the past year was reported by 57.5% of persons with BPD but only 13.4% reported lifetime psychiatric admission. BPD was not independently associated with impaired functioning but was associated with co-morbid psychotic, depressive and anxiety disorders. Only general practitioners (GPs) were consulted for problems independently due to BPD.

Functional effects of BPD are mediated through co-morbid clinical syndromes, not Axis II psychopathology. A subgroup do not have co-morbid disorders or seek treatment, and are high functioning.

The aim of this study was to investigate the functioning of patients with borderline personality disorder (BPD) compared to healthy controls on five neuropsychological domains, with regard to the possible effect of differences in IQ.

Out-patients and in-patients with BPD (n=35) and healthy comparison subjects (n=35) were tested with an extensive neuropsychological battery, where most cognitive domains were covered by several tests.

When controlling for the effect of IQ, patients were found to have reduced executive functioning as compared to healthy controls. With regard to the other neuropsychological domains (working memory, attention, long-term verbal memory, and long-term non-verbal memory), no differences were found between the two groups. Within-subject analyses also identified executive functioning as a selective deficit among patients whereas long-term verbal memory was identified as a relative strength. An association was identified between the covariate general intellectual functioning and every neuropsychological domain. No statistically significant differences were found between the subgroups of patients with and without co-morbid post-traumatic stress disorder (PTSD) or between those with and without co-morbid major depression, or between the medicated and unmedicated subgroups on any of the neuropsychological domains.

Patients with BPD demonstrate a selective deficit in executive functioning. This corroborates studies that have identified frontal regions as potential neurobiological substrates of the BPD syndrome. The relative strength of the verbal long-term memory function raises pertinent questions regarding the presumed importance of hippocampal structures.

Detecting genetic factors involved in attention deficit hyperactivity disorder (ADHD) is complicated because of their small effect sizes and complex interactions. The endophenotype approach eases this by coming closer to the relevant genes. Different aspects of temporal information processing are known to be affected in ADHD. Thus, some of these aspects could represent candidate endophenotypes for ADHD.

Fifty-four sib-pairs with at least one child with ADHD and 40 control children aged 6–18 years were recruited and asked to perform two duration discrimination tasks, one with a base duration of 50 ms on automatic timing and one with a base duration of 1000 ms on cognitively controlled timing.

Whereas children with ADHD, but not their unaffected siblings, were impaired in discrimination of longer intervals, both groups were impaired in discriminating brief intervals. Furthermore, a significant within-family correlation was found for discrimination of brief intervals. Task performances of subjects of the control group correlated with individual levels of hyperactivity/impulsivity for discrimination of brief intervals, but not of longer intervals.

Cognitively controlled and also automatic processes of temporal information processing are impaired in children with ADHD. Discrimination of longer intervals appears as a typical ‘disease marker’ whereas discrimination of brief intervals shows up as a ‘vulnerability marker’. Discrimination of brief intervals was found to be familial and linked to levels of hyperactivity/impulsivity. Taken together, discrimination of brief intervals represents a candidate endophenotype of ADHD.