A considerable proportion of people with schizophrenia spectrum disorders do not take antipsychotic medication but seem to be functioning well. However, little is known about this group. To test the assumption that absence of medication is compensated for by more effective coping and increased social support, this study compared symptoms, functioning, coping strategies and social support in non-medicated and medicated individuals with schizophrenia spectrum disorders.

In all, 48 participants with a DSM-IV schizophrenia spectrum disorder who were taking (n = 25) or not taking antipsychotic medication (n = 23) were included. Assessment consisted of self-ratings of symptoms, symptom-related distress and social support combined with a semi-structured interview that assessed general and social functioning, subjective evaluation of symptoms and coping strategies.

Symptom severity and distress did not differ between the groups. However, the non-medicated participants had significantly higher levels of general functioning than medicated participants and a longer duration of being non-medicated was significantly associated with a higher level of general functioning. In contrast to the hypotheses, not taking medication was not associated with more effective coping strategies or with higher levels of social support. Medicated participants more frequently reported the use of professional help as a coping strategy.

Our results corroborate previous studies finding improved functioning in individuals with schizophrenia spectrum disorders who do not take medication compared with those who take medication, but do not support the notion that this difference is explicable by better coping or higher levels of social support. Alternative explanations and avenues for research are discussed.

The use of cannabis with higher Δ9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users.

The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment.

Across the whole sample, users of high-potency cannabis had higher total CC MD and higher total CC AD than both low-potency users and those who never used (p = 0.005 and p = 0.004, respectively). Daily users also had higher total CC MD and higher total CC AD than both occasional users and those who never used (p = 0.001 and p < 0.001, respectively). However, there was no effect of group (patient/individuals without psychosis) or group x potency interaction for either potency or frequency of use. The within-group analysis showed in fact that the effects of potency and frequency were similar in FEP users and in users without psychosis.

Frequent use of high-potency cannabis is associated with disturbed callosal microstructural organization in individuals with and without psychosis. Since high-potency preparations are now replacing traditional herbal drugs in many European countries, raising awareness about the risks of high-potency cannabis is crucial.

Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged.

Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel ‘escape’ rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of ‘secondary gain’.

CD patients had significantly more severe life events and ‘escape’ events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients – significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56–13.70] and healthy controls (OR 5.81, 95% CI 1.86–18.2). In the same time period 53% of CD patients had at least one ‘high escape’ event – again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05–23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events.

Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

Strategies are needed to identify youth developing schizophrenia. The present study aimed to determine whether adolescents treated for substance misuse were at elevated risk to develop schizophrenia, whether this risk has changed since the late 1960s, and whether substance misuse in adolescence predicted poorer outcomes through adulthood.

In a Swedish city, since the mid-1960s there has been only one clinic for adolescent substance misuse. Three samples from this clinic were studied: 1992 individuals treated from 1968 to 1971 followed to age 50 years; 1576 treated from 1980 to 1984 followed to age 35 years; and 180 treated in 2004 followed to age 22 years. Each clinical sample was matched on age, sex and place of birth to an equal, or larger, number of randomly selected individuals from the general population. Schizophrenia, substance use disorders, physical disorders related to substance misuse, criminal convictions, poverty and death were identified using national registers.

Individuals treated for substance misuse in adolescence were at increased risk to subsequently develop schizophrenia: in males the increase was approximately four-fold and in females between five- and seven-fold. There was no difference in risk for those treated in 1968–1971 and from 1980 to 1984 when cannabis use increased from 37.6% to 49.8% of the clinical samples. Among males who developed schizophrenia, treatment for substance misuse was associated with increased risk of substance use disorders and criminal convictions through adulthood.

Treatment programmes for adolescents misusing substances include a disproportionate number developing schizophrenia. Early detection and treatment have the potential to improve long-term outcomes.

Effect of cannabis use on memory function is a contentious issue, with effects being different in healthy individuals and patients with psychosis.

Employing a meta-analytic approach we investigated the effects of cannabis use on memory function in patients with psychosis and healthy individuals, and the effect of diagnosis, memory dimension and moderating factors. A total of 88 studies were identified through a systematic literature search, investigating healthy (n = 7697) and psychotic (n = 3261) individuals. Standardized mean differences between the cannabis user and non-user groups on memory tasks were estimated using random-effects models and the effect-size statistic Cohen's d. Effects of potential moderating factors were tested using mixed-effects models and subgroup analyses.

We found that cannabis use was associated with significantly (p ⩽ 0.05) impaired global (d = 0.27) and prospective memory (d = 0.61), verbal immediate (d = 0.40) and delayed (d = 0.36) recall as well as visual recognition (d = 0.41) in healthy individuals, but a better global memory (d = −0.11), visual immediate recall (d = −0.73) and recognition (d = −0.42) in patients. Lower depression scores and younger age appeared to attenuate the effects of cannabis on memory. Cannabis-using patients had lower levels of depression and were younger compared with non-using patients, whilst healthy cannabis-users had higher depression scores than age-matched non-users. Longer duration of abstinence from cannabis reduced the effects on memory in healthy and patient users.

These results suggest that cannabis use is associated with a significant domain-specific impairment in memory in healthy individuals but not in cannabis-using patients, suggesting that they may represent a less developmentally impaired subgroup of psychotic patients.

It has been observed that mental disorders, such as psychosis, are more common for people in some ethnic groups in areas where their ethnic group is less common. We set out to test whether this ethnic density effect reflects minority status in general, by looking at three situations where individual characteristics differ from what is usual in a locality.

Using data from the South East London Community Health study (n = 1698) we investigated associations between minority status (defined by: ethnicity, household status and occupational social class) and risk of psychotic experiences, common mental disorders and parasuicide. We used a multilevel logistic model to examine cross-level interactions between minority status at individual and neighbourhood levels.

Being Black in an area where this was less common (10%) was associated with higher odds of psychotic experiences [odds ratio (OR) 1.34 95% confidence interval (CI) 1.07–1.67], and attempted suicide (OR 1.84 95% CI 1.19–2.85). Living alone where this was less usual (10% less) was associated with increased odds of psychotic experiences (OR 2.18 95% CI 0.91–5.26), while being in a disadvantaged social class where this was less usual (10% less) was associated with increased odds of attempted suicide (OR 1.33 95% CI 1.03–1.71). We found no evidence for an association with common mental disorders.

The relationship between minority status and mental distress was most apparent when defined in terms of broad ethnic group but was also observed for individual household status and occupational social class.

A Callous-Unemotional trait specifier (termed ‘Limited Prosocial Emotions’) was added to the diagnosis of conduct disorder in DSM-5. The Inventory of Callous-Unemotional Traits (ICU) is a comprehensive measure of these traits assessing three distinct, yet correlated dimensions – Callousness, Uncaring, and Unemotional – all thought to reflect the general Callous-Unemotional construct. The present study was the first to examine the degree to which the aetiology of these dimensions is shared v. independent.

Parent-reported ICU data from 5092 16-year-old twin pairs from the Twins Early Development Study were subjected to confirmatory factor analysis. Multivariate genetic modelling was applied to the best-fitting structure.

A general-specific structure, retaining a general factor and two uncorrelated specific factors (Callousness-Uncaring, Unemotional), provided the best fit to the data. The general factor was substantially heritable (h2 = 0.58, 95% CI 0.51–0.65). Unusually, shared environmental influences were also important in accounting for this general factor (c2 = 0.26, 95% CI 0.22–0.31), in addition to non-shared environmental influences. The Unemotional dimension appeared phenotypically and genetically distinct as shown by the substantial loadings of unemotional items on a separate dimension and a low genetic correlation between Unemotional and Callousness-Uncaring.

A general factor, indicative of a shared phenotypic structure across the dimensions of the ICU was under substantial common genetic and more modest shared environment influences. Our findings also suggest that the relevance of the Unemotional dimension as part of a comprehensive assessment of CU traits should be investigated further.

No evidence exists on the association between genocide and the incidence of schizophrenia. This study aims to identify critical periods of exposure to genocide on the risk of schizophrenia.

This population-based study comprised of all subjects born in European nations where the Holocaust occurred from 1928 to 1945, who immigrated to Israel by 1965 and were indexed in the Population Register (N = 113 932). Subjects were followed for schizophrenia disorder in the National Psychiatric Case Registry from 1950 to 2014. The population was disaggregated to compare groups that immigrated before (indirect exposure: n = 8886, 7.8%) or after (direct exposure: n = 105 046, 92.2%) the Nazi or fascist era of persecutions began. The latter group was further disaggregated to examine likely initial prenatal or postnatal genocide exposures. Cox regression modelling was computed to compare the risk of schizophrenia between the groups, adjusting for confounders.

The likely direct group was at a statistically (p < 0.05) greater risk of schizophrenia (hazard ratio = 1.27, 95% confidence interval 1.06–1.51) than the indirect group. Also, the likely combined in utero and postnatal, and late postnatal (over age 2 years) exposure subgroups were statistically at greater risk of schizophrenia than the indirect group (p < 0.05). The likely in utero only and early postnatal (up to age 2 years) exposure subgroups compared with the indirect exposure group did not significantly differ. These results were replicated across three sensitivity analyses.

This study showed that genocide exposure elevated the risk of schizophrenia, and identified in utero and postnatal (combined) and late postnatal (age over 2 years) exposures as critical periods of risk.

Suicide message boards have been at the core of debates about negative influences of the Internet on suicidality. Nothing is currently known about communication styles that may help users to psychologically improve in these settings.

In all, 1182 archival threads with 20 499 individual postings from seven non-professional suicide message boards supporting an ‘against-suicide’, ‘neutral’ or ‘pro-suicide’ attitude were randomly selected and subject to content analysis. Initial needs of primary posters (i.e. individual who open a thread), their psychological improvement by the end of the thread, their responses received and indicators of suicidality were coded. Differences between ‘pro-suicide’, ‘neutral’ and ‘against suicide’ boards, and correlations between primary posters and respondents in terms of suicidality were assessed. Logistic regression was used to test associations with psychological improvement.

‘Pro-suicide’ boards (n = 4) differed from ‘neutral’ (n = 1) and ‘against-suicide’ (n = 2) boards in terms of communicated contents. Indicators of suicidality correlated moderately to strongly between primary posters and respondents on ‘pro-suicide’ message boards, but less on other boards. Several communicative strategies were associated with psychological improvement in primary posters, including the provision of constructive advice [adjusted odds ratio (aOR) 4.10, 95% confidence interval (CI) 2.40–7.03], active listening (aOR 1.60, 95% CI 1.12–2.27), sympathy towards the poster (aOR 2.22, 95% CI 1.68–2.95) and provision of alternatives to suicide (aOR 2.30, 95% CI 1.67–3.18).

Respondents resemble primary posters with regard to suicidality in ‘pro-suicide’ boards, which may hinder psychological improvement. Still, opportunities to intervene in these settings using simple communication techniques exist and need to be taken and evaluated.

Psychotic experiences (PE) are commonly reported in the general population, where they are associated with elevated clinical need and functional impairment. Research studies typically exclude PE that occur in the context of sleep or substance use (PE-SS), based on the assumption that they are normative within these contexts. This is the first study to formally test clinical and functional outcomes associated with PE that occur in the context of sleep or substance use.

Data from the Collaborative Psychiatric Epidemiology Surveys (n = 11 776) were used to assess the associations between both PE and PE-SS and a broad range of outcomes, including psychiatric co-morbidity, suicidal behavior, mental health treatment utilization and World Health Organization (WHO) domains of function, using logistic regression analyses. Lifetime PE and PE-SS were mutually exclusive categories, assessed using the WHO Composite International Diagnostic Interview psychosis screen.

PE were associated with all 10 clinical and functional outcomes. Similarly, respondents reporting PE-SS had greater clinical need and impaired function relative to controls, which was significant for seven of the 10 outcome variables. When directly compared, the PE and PE-SS groups differed only in their associations with role function (greater impairment for PE) and self-care (greater impairment for PE-SS).

PE-SS were associated with a broad range of clinical and functional outcomes in this large general population sample. These associations were similar to those found for PE. Future studies should investigate relative differences between sleep- and substance-induced PE.

Attention-deficit/hyperactivity disorder (ADHD) predisposes to drug abuse (DA) and twin studies suggest shared genetic effects. We here seek to determine, using adoption and adoption-like samples, the magnitude of the cross-generational transmission from DA in parents to ADHD in their children and clarify the degree to which this arises from genetic v. rearing effects.

We ascertained ADHD and DA from multiple Swedish registries. Statistical analysis was performed by Cox and path models.

Risk for ADHD was significantly and similarly increased in the offspring of biological mothers and fathers with DA who did v. did not rear their offspring. Risk for ADHD was not elevated in the offspring of adoptive or step-parents with DA.

Cross-generational transmission was observed from DA in parents to ADHD in their children. An analysis of adoptive and adoptive-like parent–offspring relationships suggested that this transmission results from genetic and not from rearing effects.

Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat.

We conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments.

PTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight-session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01–9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches.

Four sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215.

Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas.

We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10–50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks.

Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group × diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation.

These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.

In patients with psychotic disorders, the effects of psychological post-traumatic stress disorder (PTSD) treatment on symptoms of psychosis, depression and social functioning are largely unknown

In a single-blind randomized controlled trial (RCT) 155 outpatients in treatment for psychosis (61.3% schizophrenic disorder, 29% schizoaffective disorder) were randomized to eight sessions prolonged exposure (PE; n = 53) or eye movement desensitization and reprocessing (EMDR) (n = 55), or a waiting-list condition (WL, n = 47) for treatment of their co-morbid PTSD. Measures were performed on (1) psychosis: severity of delusions (PSYRATS-DRS), paranoid thoughts (GPTS), auditory verbal hallucinations (PSYRATS-AHRS), and remission from psychotic disorder (SCI-SR-PANSS); (2) depression (BDI-II); (3) social functioning (PSP). Outcomes were compared at baseline, post-treatment, 6-month follow-up and over all data points.

Both PE and EMDR were significantly associated with less severe paranoid thoughts post-treatment and at 6-month follow-up, and with more patients remitting from schizophrenia, at post-treatment (PE and EMDR) and over time (PE). Moreover, PE was significantly associated with a greater reduction of depression at post-treatment and at 6-month follow-up. Auditory verbal hallucinations and social functioning remained unchanged.

In patients with chronic psychotic disorders PE and EMDR not only reduced PTSD symptoms, but also paranoid thoughts. Importantly, in PE and EMDR more patients accomplished the status of their psychotic disorder in remission. Clinically, these effects are highly relevant and provide empirical support to the notion that delivering PTSD treatment to patients with psychotic disorders and PTSD deserves increasing recognition and acceptance among clinicians.

Understanding individual-level changes in mental health status after prison release is crucial to providing targeted and effective mental health care to ex-prisoners. We aimed to describe trajectories of psychological distress following prison discharge and compare these trajectories with mental health service use in the community.

The Kessler Psychological Distress Scale (K10) was administered to 1216 sentenced adult prisoners in Queensland, Australia, before prison release and approximately 1, 3 and 6 months after release. We used group-based trajectory modeling to identify K10 trajectories after release. Contact with community mental health services in the year following release was assessed via data linkage.

We identified five trajectory groups, representing consistently low (51.1% of the cohort), consistently moderate (29.8%), high increasing (11.6%), high declining (5.5%) and consistently very high (1.9%) psychological distress. Mood disorder, anxiety disorder, history of self-harm and risky drug use were risk factors for the high increasing, very high and high declining trajectory groups. Women were over-represented in the high increasing and high declining groups, but men were at higher risk of very high psychological distress. Within the high increasing and very high groups, 25% of participants accessed community mental health services in the first year post-release, for a median of 4.4 contact hours.

For the majority of prisoners with high to very high psychological distress, distress persists after release. However, contact with mental health services in the community appears low. Further research is required to understand barriers to mental health service access among ex-prisoners.

Learning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus.

Eighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2, s.d. = 9.1 years) and 27 never-depressed control participants (mean age = 63.9, s.d. = 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods.

Depressed subjects had smaller right anterior caudate (RAC) (t = 2.3, p = 0.026) and poorer memory compared to controls (t = 2.5, p < 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r = 0.3, p = 0.003) and older age (r = −0.46, p < 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (β = 0.25, t = 2.16, p = 0.033; β = 0.19, t = 1.71, p = 0.091).

In older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

Schizophrenia and bipolar disorder share genetic risk factors and one possible illness mechanism is abnormal myelination. T1-weighted magnetic resonance imaging (MRI) tissue intensities are sensitive to myelin content. Therefore, the contrast between grey- and white-matter intensities may reflect myelination along the cortical surface.

MRI images were obtained from patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast was computed at each vertex as the difference between average grey-matter intensity (sampled 0–60% into the cortical ribbon) and average white-matter intensity (sampled 0–1.5 mm into subcortical white matter), normalized by their average. Group differences were tested using linear models covarying for age and sex.

Patients with schizophrenia had increased contrast compared to controls bilaterally in the post- and precentral gyri, the transverse temporal gyri and posterior insulae, and in parieto-occipital regions. In bipolar disorder, increased contrast was primarily localized in the left precentral gyrus. There were no significant differences between schizophrenia and bipolar disorder. Findings of increased contrast remained after adjusting for cortical area, thickness, and gyrification. We found no association with antipsychotic medication dose.

Increased contrast was found in highly myelinated low-level sensory and motor regions in schizophrenia, and to a lesser extent in bipolar disorder. We propose that these findings indicate reduced intracortical myelin. In accordance with the corollary discharge hypothesis, this could cause disinhibition of sensory input, resulting in distorted perceptual processing leading to the characteristic positive symptoms of schizophrenia.

The attenuated positive symptoms syndrome (APSS) is considered an at-risk indicator for psychosis. However, the characteristics and developmental aspects of the combined or enriched risk criteria of APSS and basic symptom (BS) criteria, including self-experienced cognitive disturbances (COGDIS) remain under-researched.

Based on the Structured Interview of Prodromal Syndromes (SIPS), the prevalence of APSS in 13- to 35-year-old individuals seeking help in an early recognition program for schizophrenia and bipolar-spectrum disorders was examined. BS criteria and COGDIS were rated using the Schizophrenia Proneness Instrument for Adults/Children and Youth. Participants meeting APSS criteria were compared with participants meeting only BS criteria across multiple characteristics. Co-occurrence (APSS+/BS+, APSS+/COGDIS+) was compared across 13–17, 18–22 and 23–35 years age groups.

Of 175 individuals (age = 20.6 ± 5.8, female = 38.3%), 94 (53.7%) met APSS criteria. Compared to BS, APSS status was associated with suicidality, higher illness severity, lower functioning, higher SIPS positive, negative, disorganized and general symptoms scores, depression scores and younger age (18.3 ± 5.0 v. 23.2 ± 5.6 years, p < 0.0001) with age-related differences in the prevalence of APSS (ranging from 80.3% in 13- to 17-year-olds to 33.3% in 23- to 35-year-olds (odds ratio 0.21, 95% confidence interval 0.11–0.37). Within APSS+ individuals, fewer adolescents fulfilled combined risk criteria of APSS+/BS+ or APSS+/COGDIS+ compared to the older age groups.

APSS status was associated with greater suicidality and illness/psychophathology severity in this help-seeking cohort, emphasizing the need for clinical care. The age-related differences in the prevalence of APSS and the increasing proportion of APSS+/COGDIS+ may point to a higher proportion of non-specific/transient, rather than risk-specific attenuated positive symptoms in adolescents.

Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.

This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.

Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).

For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

Subthreshold depression (SUBD) in later life is common and important as prodromal state and prominent risk factor in the development of major depressive disorder (MDD). Indicated prevention can reduce the incidence of MDD among people with SUBD substantially, but needs to be targeted to those that are truly at risk of developing MDD.

N = 341 eligible participants with SUBD were included from the first (1992/1993), second (1995/1996) and third (1998/1999) cycle from the Longitudinal Aging Study Amsterdam (LASA) by using a two-stage screening design. LASA is an ongoing prospective cohort study in The Netherlands among the older population (55–85 years). At baseline (1992/1993) N = 3107 participants were interviewed and follow-up cycles were conducted every 3 years until 2008/2009, resulting in maximal 17 years of observational period. The proportion of people that developed MDD, remained SUBD, or recovered from SUBD was measured and Cox proportional regression analyses were performed to investigate 29 putative predictors of MDD and recovery from SUBD.

N = 153 (44.9%) recovered from SUBD, N = 138 (40.5%) remained chronically SUBD, and N = 50 (14.7%) developed MDD (incidence rate 15.1/1000 person-years). Women, high neuroticism, more chronic diseases, high body mass index, smoking and less social support predicted conversion to MDD. Men, low neuroticism and absence of pain predicted recovery from SUBD.

Although older people with SUBD are clearly at risk of developing MDD, the majority did not, even after a long and thorough follow-up. Given the risk factors that were uncovered, targeting and prevention of MDD in those at very high risk is feasible.