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It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76–0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.

BackgroundFirst episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.MethodsWe analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.ResultsCaseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).ConclusionsFEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.

There is mounting evidence to implicate the intrauterine environment as the initial pathogenic stage for neuropsychiatric disease. Recent developments in magnetic resonance imaging technology are making a multimodal analysis of the fetal central nervous system a reality, allowing analysis of structural and functional parameters. Exposures to a range of pertinent risk factors whether preconception or in utero can now be indexed using imaging techniques within the fetus’ physiological environment. This approach may determine the first “hit” required for diseases that do not become clinically manifest until adulthood, and which only have subtle clinical markers during childhood and adolescence. A robust characterization of a “multi-hit” hypothesis may necessitate a longitudinal birth cohort; within this investigative paradigm, the full range of genetic and environmental risk factors can be assessed for their impact on the early developing brain. This will lay the foundation for the identification of novel biomarkers and the ability to devise methods for early risk stratification and disease prevention. However, these early markers must be followed over time: first, to account for neural plasticity, and second, to assess the effects of postnatal exposures that continue to drive the individual toward disease. We explore these issues using the schizophrenia spectrum disorders as an illustrative paradigm. However, given the potential richness of fetal magnetic resonance imaging, and the likely overlap of biomarkers, these concepts may extend to a range of neuropsychiatric conditions.

Background Both chronic cannabis use and psychotic disorders are associated with abnormalities in visual attentional processing. Using functional magnetic resonance imaging (fMRI), we sought to determine whether there would be a difference in functional connectivity in patients and controls with and without a history of cannabis use in the visual and dorsal attention networks. Methods Resting-state fMRI data were acquired in patients with early psychosis with (EPC = 29) and without (EPNC = 25); and controls with (HCC = 16) and without (HCNC = 22) cannabis use. Results There was a patient effect in both Visual-Dorsal Attention Internetwork (F(1,87) = 5.326, P = .023) and the Visual Network (F(1,87) = 4.044, P = .047) and a cannabis effect in the Dorsal Attention Network (F(1,87) = 4.773, P = .032). These effects were specific to the networks examined with no evidence for significant patient or cannabis effects in other canonical networks. Patients with a history of cannabis use showed increased connectivity in the Dorsal Attention Network (134%, P = .019) and Visual Dorsal Attention Internetwork (285%, P = .036) compared to non-using controls. In the EPC group connectivity of the Visual Network (ρ = 0.379, P = .042) and Visual-Dorsal Attention Internetwork (ρ = 0.421, P = .023) correlated with visual hallucinations which were significantly different from EPNC (P = .011). Dorsal attention network strength correlated with severity of dependence for cannabis (ρ = 0.215, P = .04). Conclusion We demonstrate specific cannabis and patient effects in networks associated with visual attentional processing. There is a differential association with hallucinatory symptoms in patients with and without a history of cannabis use. This may indicate that dysconnectivity in these networks serves different roles in the context of cannabis use.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress – with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.

AimsAnxiety and depressive symptoms are frequent in people with alcohol use disorders (AUDs) (approximately 55%) and are associated with worse outcomes. Current interventions to treat mood symptoms in alcohol-dependent adults, including psychosocial therapies, anxiolytics and antidepressants have shown limited benefits to date. The efficacy of anticonvulsants and antipsychotics have been studied but never previously systematically reviewed. We aimed to assess the efficacy of anticonvulsants and antipsychotics in treating anxiety and depressive symptoms in alcohol-dependent adults.MethodA literature search of MEDLINE, EMBASE and PsycINFO was performed through October 2020 to identify all English-language articles of double-blinded randomised controlled trials that included adults with AUDs who were treated with an anticonvulsant or antipsychotic for at least four weeks. A combination of search terms was used to describe the AUDs, study medications and the primary outcome. Participants with other psychiatric disorders were excluded. Mean changes in anxiety and depressive scores were evaluated in addition to the adverse events and withdrawal rates. The risk of bias of each study was also assessed.ResultOf 393 citations identified, 23 studies (2823 participants) met the inclusion criteria. Eighteen studies examined ten different anticonvulsants, while five studies examined two antipsychotics. The heterogeneity between the trials' methodology led to conflicting results; however, as the low-quality trials were excluded, the majority agreed that anticonvulsants and antipsychotics were not superior in moderating anxiety and depressive symptoms of alcohol-dependent adults. All antipsychotics were safe and well-tolerated, but adverse events were associated with several anticonvulsants (high dose baclofen, gabapentin, topiramate and valproate).ConclusionCurrent information on anticonvulsants and antipsychotics is insufficient to extrapolate the benefits of treating anxiety and depressive symptoms in alcohol-dependent adults. Further research must be conducted into improving the quality of reporting and understanding the comorbidity's underlying mechanism, and alternative treatment approaches.

AimsMany patients with psychosis symptoms and schizophrenia use cannabis as a recreational drug. Patients who use cannabis respond differently to antipsychotic treatment compared to those who do not. Despite this, there is a lack of evidence, and therefore clinical guidance, pertaining to the best pharmacological treatment to improve psychosis or cannabis use in this population. This systematic review was carried out to assess the current evidence base regarding the most effective pharmacological treatment for patients with psychosis who also have a background of using cannabis. Our specific question was: ‘in patients with a dual diagnosis of psychosis and cannabis use, which pharmacological interventions have the most efficacy in improving psychosis or reducing cannabis use?’.MethodA search of EMBASE, PsychINFO, and MEDLINE(R) databases was carried out on September 30, 2020. Bibliographies of other studies were also searched for relevant articles. After exclusion of any articles which did not meet inclusion criteria for this review, eleven full texts remained; a qualitative analysis was carried out on these, but there was no meta-analysis. Only randomised control trials (RCTs) whose interventions and controls were pharmacological therapies, and which included patients with a background of cannabis use and psychosis, and which measured clinical outcomes, were included.ResultWe found 11 articles which analysed 10 RCT studies (n = 363) investigating risperidone, olanzapine, clozapine, haloperidol, ziprasidone and imipramine. 6/11 were double blind. The studies were small in size, varied in their methodology, exact inclusion criteria, exact outcomes, and all had a high risk of bias. Few significant findings were found. There is limited evidence for clozapine having anti-craving effect however whether this is associated with reduction in use remains to be demonstrated. We found no studies of adjunctive anticonvulsant agents, which are often used in psychotic disorders.ConclusionThis review underlines the paucity of studies on which to make evidence-based decisions. No new studies have been undertaken since the last systematic review in this area in the last 7 years. Due to the lack of high-quality evidence found by this review, there remains a considerable need for interventional, high-quality RCTs in this comorbid patient group.

BackgroundEvidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined.MethodsWe undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use.ResultsCessation of cannabis use was associated with greater psychotic-like experiences [p < 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179–1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p < 0.001, Exp(B) 0.717, 95% CI 0.662–0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p < 0.003, Exp(B) 1.131, 95% CI 1.044–1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p < 0.015, Exp(B) 0.892, 95% CI 0.814–0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences.ConclusionsElucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.

BACKGROUND: Oculomotor abnormalities are among the most widely replicated findings in psychotic disorders with impairments in Smooth Pursuit Eye Movements (SPEM) and Antisaccades (AS) tasks. Cannabis-use may be a clinically relevant demarcating factor in early psychosis seen in around half of FEP patients at presentation and indicative of worse prognosis. No study to date has aimed at differentiating cannabis-using from non-using patients using AS and SPEM. Differences in eye movement measures between groups would indicate altered neurobiology between cannabis-using and non-using patients. We thus aimed to determine whether abnormalities in SPEM and AS are indicative of neurobiological differences between Early Psychosis patients who use cannabis (EPC) and those who do not use cannabis (EPNC). METHODS: We undertook the EfCiP study (the Effect of Cannabis in Psychosis) consisting of four groups: Early Psychosis patients who used cannabis (EPC) (n=28), Early Psychosis patients who did not use cannabis (EPNC) (n=25), healthy controls who used cannabis (HCC) (n=16) and healthy controls who did not use cannabis (HCNC) (n=22). The smooth pursuit stimulus used a sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz) across a horizontal range. Participants performed 40 antisaccade trials using a horizontal step task with an equal number of left and right stimuli in randomised order. As primary outcomes we tested measures robustly associated with abnormalities in psychosis: maintenance gain to index smooth pursuit and antisaccade percentage errors. We used one-way ANCOVA on four levels (EPC, EPNC, HCC and HCNC) with post-hoc Bonferroni correction. Covariates entered into the model were age, sex, AUDIT and Fagerstrom’s scores. RESULTS: EPC and EPNC were clinically indistinguishable with no difference across clinical measures: including GAF, PANSS, duration since diagnosis, days spent in hospital, chlorpromazine equivalents, proportion with affective component to psychosis or schizophreniform spectrum disorder. Participants with EPC had higher indices of cannabis use and also scored higher on Fagerstrom’s and AUDIT scores to index smoking and alcohol use respectively. Repeated measures ANCOVA revealed a significant effect of task, indicating that mean gain decreased as SPEM frequency increased. There was a significant Group effect (F3,83=3.514, p=0.019, ηp(2)=0.113). Post-hoc tests revealed significantly reduced mean gain for EPNC vs EPC (p=0.021). There was no significant difference between HCC and HCNC (p=1). There was no significant effect on SPEM gain for any covariate. When controls were combined there was a significant reduction in SPEM gain for EPNC vs EPC (Hedge’s g=0.830, p=0.014) and trend level reduced gain for EPNC vs all controls (Hedge’s g=0.594, p=0.058) but no difference between EPC and all controls (p=0.998) There was a numerical decrease in antisaccades percentage error rate such that EPC≈EPNC>HCC>HCNC but there was no significant group effect (p>0.35). DISCUSSION: This study demonstrates neurobiological distinction between cannabis using and non-using patients. There is evidence of impairment of SPEM in the EPNC group but not in the EPC group, whereas there is no discernable effect of cannabis use on SPEM gain in the healthy situation. This is consistent with lower psychosis liability in EPC than EPNC and suggests an additive component for cannabis use in the EPC group. Differential performance in SPEM and AS may indicate impairments in specific circuitry between groups. Further work should look to delineate the neurobiological substrates for this distinction.

Background FEP patients who use cannabis experience more frequent intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in FEP patients and controls and whether this differs between groups. Methods We analysed data on lifetime cannabis using patients (n=655) and controls (n=654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and Factorial ANOVA to determine if there was an interaction between caseness and extent of use. Results Both psychotic-like and euphoric experiences were more frequent in cases vs controls (p

Background Understanding how the onset of psychosis affects patterns of substance use would inform the development of effective interventions. To date no study has compared substance misuse patterns over a life-course to a comparable control group to determine how patients who develop psychosis modify substance misuse patterns. Methods In a well-characterised clinical cohort of patients with psychotic disorders (n=257) we compared frequency of use of most common substances before and after development of psychotic disorder using a within subjects design. Using a between-subjects design we compared patients who had ever used cannabis (n=194) to a control non-clinical cohort of cannabis users (n=1055) over comparable periods in life, accounting for the effects of age, gender, other substance use and location. Results Patients reduced frequency of consumption of cannabis, alcohol, cocaine and ecstasy (p

Summary Background Although the link between cannabis use and development of psychosis is well established, less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis. We aimed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse. Methods In this systematic review and meta-analysis, we searched MEDLINE for articles published in any language from the database inception date up until April 21, 2015 that included a sample of patients with a pre-existing psychotic disorder with a follow-up duration of at least 6 months. We used a combination of search terms for describing cannabis, the outcome of interest (relapse of psychosis), and the study population. We excluded studies if continued cannabis use or discontinued cannabis use could not be established. We compared relapse outcomes between those who continued (CC) or discontinued (DC) cannabis use or were non-users (NC). We used summary data (individual patient data were not sought out) to estimate Cohen's d, which was entered into random effects models (REM) to compare CC with NC, CC with DC, and DC with NC. Meta-regression and sensitivity analyses were used to address the issue of heterogeneity. Findings Of 1903 citations identified, 24 studies (16 565 participants) met the inclusion criteria. Independent of the stage of illness, continued cannabis users had a greater increase in relapse of psychosis than did both non-users (d CC–NC =0·36, 95% CI 0·22–0·50, p CC–DC =0·28, 0·12–0·44, p=0·0005), as well as longer hospital admissions than non-users (d CC–NC =0·36, 0·13 to 0·58, p=0·02). By contrast, cannabis discontinuation was not associated with relapse (d DC–NC =0·02, −0·12 to 0·15; p=0·82). Meta-regression suggested greater effects of continued cannabis use than discontinued use on relapse (d CC–NC =0·36 vs d DC–NC =0·02, p=0·04), positive symptoms (d CC–NC =0·15 vs d DC–NC =–0·30, p=0·05) and level of functioning (d CC–NC =0·04 vs d DC–NC =–0·49, p=0·008) but not on negative symptoms (d CC–NC =-0·09 vs d DC–NC =–0·31, p=0·41). Interpretation Continued cannabis use after onset of psychosis predicts adverse outcome, including higher relapse rates, longer hospital admissions, and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users. These findings point to reductions in cannabis use as a crucial interventional target to improve outcome in patients with psychosis. Funding UK National Institute of Health Research.

Background:The anxiety disorders are a prevalent mental health problem in older age with a considerable impact on quality of life. Until recently there have been few longitudinal studies on anxiety in this age group, consequently most of the evidence to date has been cross-sectional in nature.Methods:We undertook a literature search of Medline, PsycINFO, the Cochrane trials database and the TRIP medical database to identify longitudinal studies which would help elucidate natural history and prognosis of anxiety disorders in the elderly.Results:We identified 12 papers of 10 longitudinal studies in our Review. This represented 34,691 older age participants with 5,199 with anxiety disorders including anxious depression and 3,532 individuals with depression without anxiety. Relapse rates of anxiety disorders are high over 6 year follow-up with considerable migration to mixed anxiety-depression and pure depressive mood episodes. Mixed anxiety-depression appears to be a poorer prognostic state than pure anxiety or pure depression with higher relapse rates across studies. In community settings treatment rates are low with 7–44% of the anxious elderly treated on antidepressant medications.Conclusions:To our knowledge this is the first Systematic Review of longitudinal trials of anxiety disorders in older people. Major longitudinal studies of the anxious elderly are establishing the high risk of relapse and persistence alongside the progression to depression and anxiety depression states. There remains considerable under-treatment in community studies. Specialist assessment and treatment and major public health awareness of the challenges of anxiety disorders in the elderly are required.

Aims First episode manic illness presenting over the age of 50, is an uncommon presentation, traditionally believed to have an organic basis. However to date there has been little systematic compilation of case reports. Methods We undertook a literature search on MEDLINE, PsychInfo and EMBASE to identify case reports of first of mania or hypomania presenting over the age of 50. Results 35 cases were identified. 29/35 (82%) had a suspected underlying organic cause. Organic causes included: vascular disease (including CADASIL), iatrogenic drug use, dementia, thyroid disease and meningitis. Vascular risk factors were present in 17/35 cases (48%). Focal imaging abnormalities were identified in 17/30 (57%) cases including basal ganglia, frontal lobe and thalamic lesions. In 10/35 (28%) of cases organic treatment contributed to successful remission of the manic episode. Conclusions This review of case reports appears to add evidence of late onset mania having an organic basis. Whether this is a separate organic syndrome remains to be established. Our provisional findings suggest that such patient have a thorough medical screening in identifying an underlying cause.