Sexual dysfunction is common in psychotic disorder but it is not clear whether it is intrinsic to the development of the illness or secondary to other factors.

To compare sexual function in people at ultra-high risk (UHR) of a psychotic disorder, patients with first-episode psychosis predominantly taking antipsychotic drugs and healthy volunteers.

Sexual function was assessed in a UHR group (n = 31), a group with first-episode psychosis (n = 37) and a matched control group of healthy volunteers (n = 56) using the Sexual Function Questionnaire.

There was a significant effect of group on sexual function (P<0.001). Sexual dysfunction was evident in 50% of the UHR group, 65% of first-episode patients and 21% of controls. Within the UHR group, sexual dysfunction was more marked in those who subsequently developed psychosis than in those who did not. Across all groups the severity of sexual dysfunction was correlated with the severity of psychotic symptoms (P<0.001). Within the first-episode group there was no significant difference in sexual dysfunction between patients taking prolactin-raising v. prolactin-sparing antipsychotics.

Sexual dysfunction is present prior to onset of psychosis, suggesting it is intrinsic to the development of illness unlikely to be related to the prolactin-raising properties of antipsychotic medication.

Systematic studies on the outcome of treatment-resistant depression are scarce.

To describe the longer-term outcome and predictors of outcome in treatment-resistant depression.

Out of 150 patients approached, 118 participants with confirmed treatment-resistant depression (unipolar, n= 7; bipolar, n=27; secondary, n=14) treated in a specialist in-patient centre were followed-up for between 8 and 84 months (mean=39, s.d.=22).

The majority of participants attained full remission (60.2%), most of whom (48.3% of total sample) showed sustained recovery (full remission for at least 6 months). A substantial minority had persistent subsyndromal depression (19.5%) or persistent depressive episode (20.3%). Diagnosis of bipolar treatment-resistant depression and poorer social support were associated with early relapse, whereas strong social support, higher educational status and milder level of treatment resistance measured with the Maudsley Staging Method were associated with achieving quicker remission. Exploratory analysis of treatment found positive associations between treatment with a monoamine oxidase inhibitor (MAOl) in unipolar treatment-resistant depression and attaining remission at discharge and at final follow-up, and duloxetine use predicted attainment of remission at final follow-up.

Although many patients with treatment-resistant depression experience persistent symptomatology even after intensive, specialist treatment, most can achieve remission. The choice of treatment and presence of good social support may affect remission rates, whereas those with low social support and a bipolar diathesis should be considered at higher risk of early relapse. We suggest that future work to improve the long-term outcome in this disabling form of depression might focus on social interventions to improve support, and the role of neglected pharmacological interventions such as MAOIs.

Thoughts about death and self-harm in old age have been commonly associated with the presence of depression, but other risk factors may also be important.

To determine the independent association between suicidal ideation in later life and demographic, lifestyle, socioeconomic, psychiatric and medical factors.

A cross-sectional study was conducted of a community-derived sample of 21290 adults aged 60-101 years enrolled from Australian primary care practices. We considered that participants endorsing any of the four items of the Depressive Symptom Inventory - Suicidality Subscale were experiencing suicidal thoughts. We used standard procedures to collect demographic, lifestyle, psychosocial and clinical data. Anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale.

The 2-week prevalence of suicidal ideation was 4.8%. Male gender, higher education, current smoking, living alone, poor social support, no religious practice, financial strain, childhood physical abuse, history of suicide in the family, past depression, current anxiety, depression or comorbid anxiety and depression, past suicide attempt, pain, poor self-perceived health and current use of antidepressants were independently associated with suicidal ideation. Poor social support was associated with a population attributable fraction of 38.0%, followed by history of depression (23.6%), concurrent anxiety and depression (19.7%), prevalent anxiety (15.1%), pain (13.7%) and no religious practice (11.4%).

Prevalent and past mood disorders seem to be valid targets for indicated interventions designed to reduce suicidal thoughts and behaviour. However, our data indicate that social disconnectedness and stress account for a larger proportion of cases than mood disorders. Should these associations prove to be causal, then interventions that succeeded in addressing these issues would contribute the most to reducing suicidal ideation and, possibly, suicidal behaviour in later life.

Little is known about the prevalence of attention-deficit hyperactivity disorder (ADHD) among older adults.

To estimate the prevalence of the syndromatic and symptomatic DSM-IV ADHD diagnosis in older adults in The Netherlands.

Data were used from the Longitudinal Aging Study Amsterdam (LASA). At baseline, 1494 participants were screened with an ADHD questionnaire and in 231 respondents a structured diagnostic interview was administered. The weighted prevalence of ADHD was calculated.

The estimated prevalence rate of syndromatic ADHD in older adults was 2.8%; for symptomatic ADHD the rate was 4.2%. Younger elderly adults (60–70 years) reported significantly more ADHD symptoms than older elderly adults (71–94 years).

This is the first epidemiological study on ADHD in older persons. With a prevalence of 2.8% the study demonstrates that ADHD does not fade or disappear in adulthood and that it is a topic very much worthy of further study.

We previously documented that cigarette smoking is a risk factor for subsequent alcohol and drug misuse and dependence in adolescent girls with attention-deficit hyperactivity disorder (ADHD).

To revisit this hypothesis with a large longitudinal sample of both genders followed up for 10 years into young adulthood.

We used data from two identically designed, longitudinal, case–control family studies of boys and girls with and without ADHD ascertained from psychiatric and paediatric sources. We studied 165 individuals with ADHD and 374 controls followed up longitudinally and masked for 10 years. We assessed ADHD, smoking and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models.

Youth with ADHD who smoked cigarettes (n = 27) were significantly more likely to subsequently develop drug misuse and dependence compared with youth with ADHD who did not smoke (n = 138, P<0.05).

These results confirm that cigarette smoking increases the risk for subsequent drug and alcohol use disorders among individuals with ADHD. These findings have important public health implications, and underscore the already pressing need to prevent smoking in children with ADHD.

Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear.

To investigate the relationship between baseline and incident depression and progression of white matter changes.

In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale.

Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline.

Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.

Atypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored.

To evaluate olanzapine monotherapy in patients with bipolar depression.

Patients with bipolar depression received olanzapine (5–20mg/day, n = 343) or placebo (n = l71) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included: Clinical Global impression - Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (≥50% reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus treatment completion) and remission (MADRS ≤8). The trial was registered with ClinicalTrials.gov (NCT00510146).

Olanzapine demonstrated: significantly greater (P<0.04) improvements on MADRS (least-squares mean change -13.82 v. -11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P≤0.05) more response and remission, but not recovery; significantly (P<0.01) greater mean increases in weight, fasting cholesterol and triglycerides; and significantly more (P<0.001) patients gained ≥7% body weight.

Olanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.

Autobiographical memory retrieval is impaired in schizophrenia.

To determine the neural basis of this impairment.

Thirteen patients with schizophrenia and 14 healthy controls performed an autobiographical memory retrieval task based on cue words during functional magnetic resonance imaging. Patients were selected on the basis of their ability to perform the task and all participants received training.

Although patients and controls activated a similar brain network during autobiographical memory retrieval, patients displayed decreased activation in several of these regions, including the anterior cingulate cortex, left lateral prefrontal cortex, right cerebellum and ventral tegmental area (k ≥ 10, P < 0.001, uncorrected). In addition, activation of the caudate nuclei was negatively correlated with retrieval performance in controls but positively correlated with performance in patients.

The autobiographical memory retrieval brain network is impaired in schizophrenia. Patients with schizophrenia display decreased activation of the cognitive control network during retrieval, possibly due to aberrant functioning of the dorsal striatum.

In 2005 Andreasen proposed criteria for remission in schizophrenia. It is unclear whether these criteria reflect symptom reduction and improved social functioning in daily life.

To investigate whether criteria for symptomatic remission reflect symptom reduction and improved functioning in real life, comparing patients meeting remission criteria, patients not meeting these criteria and healthy controls.

The Experience Sampling Method (ESM), a structured diary technique, was used to explore real-life symptoms and functioning in 177 patients with (remitted and non-remitted) schizophrenia spectrum disorders and 148 controls.

Of 177 patients, 70 met criteria for symptomatic remission. These patients reported significantly fewer positive and negative symptoms and better mood states compared with patients not in remission. Furthermore, patients in remission spent more time in goal-directed activities and had less preference for being alone when they were with others. However, the patient groups did not differ on time spent in social company and doing nothing, and both the remission and non-remission groups had lower scores on functional outcome measures compared with the control group.

The study provides an ecological validation for the symptomatic remission criteria, showing that patients who met the criteria reported fewer positive symptoms, better mood states and partial recovery of reward experience compared with those not in remission. However, remission status was not related to functional recovery, suggesting that the current focus on symptomatic remission may reflect an overly restricted goal.

Within the ICD and DSM review processes there is growing debate on the future classification and status of adjustment disorders, even though evidence on this clinical entity is scant, particularly outside specialised care.

To estimate the prevalence of adjustment disorders in primary care; to explore whether there are differences between primary care patients with adjustment disorders and those with other mental disorders; and to describe the recognition and treatment of adjustment disorders by general practitioners (GPs).

Participants were drawn from a cross-sectional survey of a representative sample of 3815 patients from 77 primary healthcare centres in Catalonia. The prevalence of current adjustment disorders and subtypes were assessed face to face using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Multilevel logistic regressions were conducted to assess differences between adjustment disorders and other mental disorders. Recognition and treatment of adjustment disorders by GPs were assessed through a review of patients' computerised clinical histories.

The prevalence of adjustment disorders was 2.94%. Patients with adjustment disorders had higher mental quality-of-life scores than patients with major depressive disorder but lower than patients without mental disorder. Self-perceived stress was also higher in adjustment disorders compared with those with anxiety disorders and those without mental disorder. Recognition of adjustment disorders by GPs was low: only 2 of the 110 cases identified using the SCID-I were detected by the GP. Among those with adjustment disorders, 37% had at least one psychotropic prescription.

Adjustment disorder shows a distinct profile as an intermediate category between no mental disorder and affective disorders (depression and anxiety disorders).

Reasons for the increased prevalence of cigarette smoking in schizophrenia are unclear. Studies assessing clinical symptoms have sampled heterogeneous populations, with discrepant findings.

To examine the relationship between clinical features, social adjustment and nicotine dependence in a geographically defined population of people with schizophrenia.

Cross-sectional clinical study of 131 people with schizophrenia in Nithsdale, Scotland.

Smokers were younger, mostly males and three times more likely to be unemployed. Those with severe nicotine dependence had greater scores on the positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were prescribed higher doses of antipsychotic. Those with mild–moderate dependence had greater scores on the PANSS negative subscale. Greater symptom severity was associated with poorer social adjustment. Psychopathology and social adjustment were similar in quitters and never-smokers.

Our findings indicate an association between nicotine dependence, clinical symptoms and social adjustment in schizophrenia. Although causal links cannot be inferred, identifying the relationship between nicotine dependence and psychopathology may have some value in the management of smoking in schizophrenia. Further longitudinal studies are required to explore this relationship.

Clozapine is the only antipsychotic drug licensed for treatment-resistant schizophrenia but its use is often delayed. Since previous studies, national guidelines on the use of clozapine and other antipsychotics have been disseminated to clinicians.

To determine the theoretical delay to clozapine initiation and to quantify the prior use of antipsychotic polypharmacy and high-dose antipsychotic treatment.

Clinico-demographic data were extracted from the treatment records of all patients commencing clozapine in our centre between 2006 and 2010.

Complete records were available for 149 patients. The mean theoretical delay in initiating clozapine was 47.7 months (s.d. = 49.7). Before commencing clozapine, antipsychotic polypharmacy and high-dose treatment was evident in 36.2 and 34.2% of patients respectively. Theoretical delay was related to illness duration (β = 0.7, P<0.001) but did not differ by gender or ethnicity.

Substantial delays to clozapine initiation remain and antipsychotic polypharmacy and high doses are commonly used prior to clozapine, despite treatment guidelines.

Late-life depression is a common and heterogeneous illness, associated with structural abnormalities in both grey and white matter.

To examine the relationship between age at onset and magnetic resonance imaging (MRI) measures of grey and white matter to establish whether they support particular hypotheses regarding the anatomy and aetiology of network disruption in late-life depression.

We studied 36 participants with late-life depression. Grey matter was examined using T1-weighted MRI and analysed using voxel-based morphometry. The hippocampus was automatically segmented and volume and shape analysis performed. White matter was examined using diffusion tensor imaging and analysed using tract-based spatial statistics.

Later age at onset was significantly associated with reduced fractional anisotropy of widespread tracts, in particular the anterior thalamic radiation and superior longitudinal fasciculus. Earlier age at onset was associated with reduced hippocampal volume normalised to whole brain size bilaterally. However, no significant correlations were detected using hippocampal shape analysis or voxel-based morphometry.

Overall, the results were compatible with the vascular hypothesis, and provided some support for the glucocorticoid cascade hypothesis.

Despite gradual understanding of the multidimensional health consequences of betel-quid chewing, information on the effects of dependent use is scant.

To investigate the 12-month prevalence patterns of betel-quid dependence in six Asian populations and the impact of this dependence on oral potentially malignant disorders (OPMD).

A multistage random sample of 8922 participants was recruited from Taiwan, mainland China, Indonesia, Malaysia, Sri Lanka and Nepal. Participants were evaluated for betel-quid dependency using DSM-IV and ICD-10 criteria and assessed clinically for oral mucosal lesions.

The 12-month prevalence of dependence was 2.8-39.2% across the six Asian samples, and 20.9-99.6% of those who chewed betel-quid were betel-quid dependent. Men dominated the prevalence among the east Asian samples and women dominated the prevalence in south-east Asian samples. ‘Time spent chewing’ and ‘craving’ were the central dependence domains endorsed by the Chinese and southern/south-east Asian samples respectively, whereas the Nepalese samples endorsed ‘tolerance’ and ‘withdrawal’. Dependency was linked to age, gender, schooling years, drinking, smoking, tobacco-added betel-quid use and environmental accessibility of betel-quid. Compared with non-users, those with betel-quid dependency had higher pre-neoplastic risks (adjusted odds ratios 8.0-51.3) than people with non-dependent betel-quid use (adjusted odds ratio 4.5-5.9) in the six Asian populations.

By elucidating differences in domain-level symptoms of betel-quid dependency and individual and environmental factors, this study draws attention to the population-level psychiatric problems of betel-quid chewing that undermine health consequences for OPMD in six Asian communities.

Reports of neuroleptic malignant syndrome (NMS) induced by second-generation antipsychotic drugs highlight a propensity for atypical clinical presentations.

To systematically compare the clinical profile of NMS induced by first- (1G-NMS) and second-generation antipsychotic drugs (2G-NMS).

The Australian Adverse Drug Reaction Advisory Committee (ADRAC) database was searched to identify individuals with NMS reported between April 1994 and September 2010. The clinical characteristics of 208 people with NMS induced by monotherapy with first- or second-generation antipsychotic drugs, as well as presenting features of NMS, were compared.

The individuals with 2G-NMS were younger and more likely to have a psychotic disorder diagnosis. The features of NMS in the two groups were very similar, except that people with 2G-NMS were less likely to present with rigidity or extrapyramidal signs compared with those with 1G-NMS. This difference was due to the lower rates of rigidity in those with clozapine-induced NMS. Mortality was considerably lower for those with 2G-NMS (3.0%) compared with 1G-NMS (16.3%), and the former were more likely to have received supportive treatment.

The clinical profile of 2G-NMS is largely similar to 1G-NMS, with clozapine-induced NMS being differentiated by the relative lack of rigidity as a feature. Mortality is lower for 2G-NMS.

Very limited evidence is available on how to treat adults with anorexia nervosa and treatment outcomes are poor. Novel treatment approaches are urgently needed.

To evaluate the efficacy and acceptability of a novel psychological therapy for anorexia nervosa (Maudsley Model of Anorexia Nervosa Treatment for Adults, MANTRA) compared with specialist supportive clinical management (SSCM) in a randomised controlled trial.

Seventy-two adult out-patients with anorexia nervosa or eating disorder not otherwise specified were recruited from a specialist eating disorder service in the UK. Participants were randomly allocated to 20 once weekly sessions of MANTRA or SSCM and optional additional sessions depending on severity and clinical need (trial registration: ISRCTN62920529). The primary outcomes were body mass index, weight and global score on the Eating Disorders Examination at end of treatment (6 months) and follow-up (12 months). Secondary outcomes included: depression, anxiety and clinical impairment; neuropsychological outcomes; recovery rates; and additional service utilisation.

At baseline, patients randomised to MANTRA were significantly less likely to be in a partner relationship than those receiving SSCM (3/34 v. 10/36; P < 0.05). Patients in both treatments improved significantly in terms of eating disorder and other outcomes, with no differences between groups. Strictly defined recovery rates were low. However, MANTRA patients were significantly more likely to require additional in-patient or day-care treatment than those receiving SSCM (7/34 v. 0/37; P=0.004).

Adults with anorexia nervosa are a difficult to treat group. The imbalance between groups in partner relationships may explain differences in service utilisation favouring SSCM. This study confirms SSCM as a useful treatment for out-patients with anorexia nervosa. The novel treatment, MANTRA, designed for this patient group may need adaptations to fully exploit its potential.

Although techniques such as latent class analysis have been used to derive empirically based subtypes of depression in adult samples, there is limited information on subtypes of depression in youth.

To identify empirically based subtypes of depression in a nationally representative sample of US adolescents, and to test the comparability of subtypes of depression in adolescents with those derived from a nationally representative sample of adults.

Respondents included 912 adolescents and 805 adults with a 12-month major depressive disorder, selected from the National Comorbidity Survey Adolescent Supplement and the National Comorbidity Survey Replication samples respectively. Latent class analysis was used to identify subtypes of depression across samples. Sociodemographic and clinical correlates of derived subtypes were also examined to establish their validity.

Three subtypes of depression were identified among adolescents, whereas four subtypes were identified among adults. Two of these subtypes displayed similar diagnostic profiles across adolescent and adult samples (P=0.43); these subtypes were labelled ‘severe typical’ (adults 45%, adolescents 35%) and ‘atypical’ (adults 16%, adolescents 26%). The latter subtype was characterised by increased appetite and weight gain.

The structure of depression observed in adolescents is highly similar to the structure observed in adults. Longitudinal research is necessary to evaluate the stability of these subtypes of depression across development.