Of those with schizophrenia, one third develop treatment-resistant illness. Nearly 60% of these benefit from clozapine- the only antipsychotic medication licensed in this group.

As treatment-resistant illness developed in the follow-up of a first-episode psychosis (FEP) cohort, clozapine was prescribed. This study retrospectively compared the clozapine prescribing patterns, within this cohort, to National Institute for Health and Care Excellence (NICE) guidelines. In addition, impact on hospitalisation, physical health monitoring and augmentation strategies employed following clozapine initiation were examined. Factors delaying initiation of clozapine treatment or contributing to its discontinuation were also explored.

The study included 339 individuals resident within an Irish community mental health team catchment area, referred with FEP from 1 January 2005 to 31 August 2016. Data were extracted from electronic medical records.

Within the cohort, clozapine was prescribed to 32 individuals (9.4%). The mean number of adequate trials of antipsychotic prior to starting clozapine was 2.74 (SD 1.13; range 1–5). The mean time to clozapine trial was 2.1 years (SD 1.95; range 0.17–6.25). Following initiation of clozapine, mean hospital admissions per year fell from 2.3 to 0.3 (p=0.00). Mean inpatient days pre- and post-clozapine also decreased (147 vs. 53; p=0.00). In all, 18 patients ceased use of clozapine, 5 temporarily and 13 permanently.

Patients are being prescribed clozapine earlier than previously demonstrated. However, delayed treatment remains common, and many patients discontinue clozapine. Further research is necessary to describe and address factors which contribute to its discontinuation.

No significant relationships.

Child abuse is associated with a wide range of mental disease including psychotic disorders. Few studies have investigated the role of child abuse in contributing to increase the risk of psychosis in migrant population.

To explore the risk of first episode psychosis (FEP) in migrants and natives for each type of trauma i.e. physical abuse (P.A.), sexual abuse (S.A.), emotional abuse (E.A.), physical neglect (P.N.) and emotional neglect (E.N.).

Within a large case- control incidence sample of FEP from the EU-GEI study (The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions) we evalued the assocition of childhood trauma with FEP in migrants and natives. Associations were adjusted for age, gender, social status, level of education, family history of psychosis and cannabis use. Trauma was assessed through Childhood Trauma Questionnaire (CTQ).

CTQ mean score was higher in FEP migrants (45.4, sd 15.6) than in FEP natives (41.7, sd 13.9) (p = 0.002). In natives every type of child abuse was associated with FEP. In migrants P.A., S.A., P.N. were associated with FEP. We found a dose – dependent relationship between trauma and FEP.

Child abuse is common in individuals with psychosis. FEP migrants are more exposed to childhood trauma. Clinicians should routinely assess patients for childhood trauma. When treating a FEP migrant patient, clinicians must be aware of an underlying traumatic childhood adversity more than of a traumatic migration history.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD.

Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals.

Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001)

Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

Depressive symptoms are highly prevalent among partnered dementia caregivers, but the mechanisms are unclear. This study examined the mediating role of loneliness in the association between dementia and other types of care on subsequent depressive symptoms.

Prospective data from partnered caregivers were drawn from the English Longitudinal Study of Aging. The sample consisted of 4,672 partnered adults aged 50–70 living in England and Wales, followed up between 2006–2007 and 2014–2015. Caregiving was assessed across waves 3 (2006–2007), 4 (2008–2009), and 5 (2010–2011), loneliness at wave 6 (2012–2013), and subsequent depressive symptoms at wave 7 (2014–15). Multivariable logistic regression models were used to assess the association between caregiving for dementia and depressive symptoms compared to caregiving for other illnesses (e.g., diabetes, coronary heart disease (CHD), cancer, and stroke). Binary mediation analysis was used to estimate the indirect effects of caregiving on depressive symptoms via loneliness.

Care for a partner with dementia was associated with higher odds of depressive symptoms at follow-up compared to those not caring for a partner at all (odds ratio [OR] = 2.6, 95% confidence intervals [CI]: 1.4, 5.1). This association was partially mediated by loneliness (34%). Care for a partner with other conditions was also associated with higher odds of depressive symptoms compared to non-caregiving partners (OR = 1.7, 95% CI: 1.2, 2.5), but there was no evidence of an indirect pathway via loneliness.

Loneliness represents an important contributor to the relationship between dementia caregiving and subsequent depressive symptoms; therefore, interventions to reduce loneliness among partnered dementia caregivers should be considered.

Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.

We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.

Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).

Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.

The COVID-19 pandemic has seen an increase in depression and anxiety among those with and without a history of mental illness. Commonly used forms of psychological therapy improve mental health by teaching psychotherapeutic strategies that assist people to better manage their symptoms and cope with life stressors. Minimal research to date has explored their application or value in managing mental health during significant broad-scale public health crises.

To determine which psychotherapeutic strategies people who have previously received therapy use to manage their distress during the COVID-19 pandemic, and whether the use and perceived helpfulness of these strategies has an effect on symptoms of depression and anxiety.

Data (N = 857) was drawn from multiple waves of a representative longitudinal study of the effects of COVID-19 on the mental health of Australian adults, which includes measures of anxiety, depression and experiences with psychotherapy and psychotherapeutic strategies.

Previous engagement in therapy with psychotherapeutic strategies had a protective effect on depressive but not anxiety symptoms. Common and helpful strategies used by respondents were exercise, mindfulness and breathing exercises. Using mindfulness and perceiving it to be helpful was associated with lower levels of depression and anxiety symptoms. No other strategies were associated with improved mental health.

Prior knowledge of psychotherapeutic strategies may play a role in managing mental health during unprecedented public health events such as a global pandemic. There may be value in promoting these techniques more widely in the community to manage general distress during such times.

Altered neurocognitive function in schizophrenia could reflect both genetic and illness-specific effects.

To use functional magnetic resonance imaging to discriminate between the influences of the genetic risk for schizophrenia and environmental factors on the neural substrate of verbal fluency, a candidate schizophrenia endophenotype using a case control twin design.

We studied 23 monozygotic twin pairs: 13 pairs discordant for schizophrenia and 10 pairs of healthy volunteer twins. Groups were matched for age, gender, handedness, level of education, parental socio-economic status, and ethnicity. Behavioural performance and regional brain activation during a phonological verbal fluency task were assessed.

Relative to healthy control twins, both patients and their non-psychotic co-twins produced fewer correct responses and showed less activation in the medial temporal region and inferior frontal gyrus. Twins with schizophrenia showed greater activation than both their non-psychotic co-twins and controls in right lateral temporal cortex, reflecting reduced deactivation during word generation while their non-psychotic co-twins showed greater activation in the left temporal cortex.

Both genetic vulnerability to schizophrenia and schizophrenia were associated with impaired verbal fluency performance, reduced engagement of the medial temporal region and dorsal inferior frontal gyrus. Schizophrenia was specifically associated with an additional reduction in deactivation in the right temporal cortex.

Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.

The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.

We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.

We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.

In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.

Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.

Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007).

We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls.

We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. All were recruited as part of the Genetic and Psychosis (GAP) study which studied all patients who presented to the South London and Maudsley Trust.

There was no significant difference in the life-time prevalence of cannabis use or age at first use between cases and controls. However, cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls. The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007).

Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.