Does tobacco use cause psychosis? Systematic review and meta-analysis

Treatment of people at ultra-high risk for psychosis.

Investigating the relationship between premorbid and prodromal status and the clinical manifestations of the first psychotic episode is relevant for understanding the pathophysiology of psychosis and for improving management of the disease. This study examined patterns of premorbid functioning of persons interviewed during their first episode of psychotic illness and examined the relationship of premorbid characteristics with symptom severity and cognitive functioning during the first illness episode. The data were derived from the baseline assessments of a multicenter international drug trial that enrolled 535 patients in their first episode of psychosis. Subjects' scores on the Premorbid Adjustment Scale were used to assign them to groups according to whether their premorbid functioning was stable-good, stable-poor, or deteriorating. The three groups' scores on the Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, and a cognitive battery were compared. Almost half of the patients (47.5%) had stable-good premorbid functioning, 37.3% had stable-poor premorbid functioning, and 15.1% had initially good, but later deteriorating, premorbid functioning. Compared to the stable-poor and deteriorating groups, the stable-good group had lower (better) negative syndrome and general psychopathology scores on the Positive and Negative Syndrome Scale and a lower CGI severity scale score. Differences between the stable-poor and stable-good groups were also found on some cognitive measures and on the positive syndrome subscale of the Positive and Negative Syndrome Scale. More than half of the subjects, who were interviewed during their first episode of psychotic disorder, had evident premorbid behavioral disturbances. Poor premorbid functioning before onset of psychosis was associated with more severe symptoms and more severe cognitive manifestations of illness during the first illness episode.

BodyPrevention of the First Episode of Psychosis: What Have we Reached by 2021? The first episode of psychosis is usually preceded by a prodromal period or stage of psychosis, where early signs of symptoms indicating onset of first episode psychosis (FEP) occur. In the last twenty years, enormous progress was made in the tretment of FEP and subsequently schizophrenia, as the focus of treatment of FEP shifted to this prodromal period with the aim of preventing the first episode of psychosis in people at risk.Treatment for the prodromal stage of psychosis is provided within specialized early intervention services, which are somtimes part of the services for the treatment of FEP. Early intervention services, which have been gradually developed in many countries worldwide, usually incorporate multimodal treatment approaches (pharmacotherapy, psychotherapy and psychosocial interventions). However, there are still many differences in the treatment of prodromes across early intervention services, even within one country, leaving open the questions on what kind or combinations of treatments really work in the prevention of FEP. The methods of studies in the scientific psychiatric literature do not allow easy translation of scientific data to clinical practice. In the presentation, an up-to-date overview of the available treatments offered witin early intervention services for prevention of FEP is given.DisclosureNo significant relationships.

Aberrant social cognition is a core feature of schizophrenia, persisting from clinical high-risk and genetic high-risk states to the first episode of psychosis. This study aimed to identify shared and distinct social cognition-related functional alterations across clinical high-risk, genetic high-risk, and first episode of psychosis groups, shedding light on varying risk levels for first episode of psychosis development. Meta-analyses were performed on 38 whole-brain task-based functional magnetic resonance imaging studies (12 clinical high risk, 15 genetic high risk, 11 first episode of psychosis) using Seed-based d Mapping. Function abnormalities were assessed within each patient group, with quantitative comparisons made against controls. Clinical high-risk and genetic high-risk individuals showed neither shared nor distinct abnormal brain activation during social cognition tasks. A shared cluster of increased activation in the right anterior cingulate cortex was observed between genetic high-risk and first episode of psychosis groups. However, no conjunction or disjunction results were found between clinical high-risk and first episode of psychosis groups. Meta-regression analyses revealed accelerated age-related greater activation decline in the left insula in individuals with clinical high risk. In conclusion, the absence of shared social cognition-related brain activation between clinical high risk and genetic high risk may signify differences in neural correlates underlying social cognition deficits between these groups and they follow distinct neural pathways toward first episode of psychosis. The shared abnormal anterior cingulate cortex activation in genetic high risk and first episode of psychosis may represent an endophenotype of schizophrenia.

To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.

T248. Insulin Action and Cognition in Patients With First-Episode Psychosis

At present, no reliable predictors exist to distinguish future responders from nonresponders to treatment during the first episode of psychosis. Among potential neuroimaging predictors of treatment response, gyrification represents an important marker of the integrity of normal cortical development that may characterize, already at illness onset, a subgroup of patients with particularly poor outcome. To determine whether patients with first-episode psychosis who do not respond to 12 weeks of antipsychotic treatment already have significant gyrification defects at illness onset. Case-control study with 12 weeks' longitudinal follow-up to determine treatment response. Secondary psychiatric services in an inner-city area (South London, England). A total of 126 subjects, including 80 patients presenting with first-episode psychosis and 46 healthy controls. Patients were scanned at the outset and received various antipsychotic medications in a naturalistic clinical setting. They were followed up for 12 weeks and classified as responders or nonresponders if they reached criteria for symptom remission, evaluated with the Psychiatric and Personal History Schedule. Patients were exposed to naturalistic antipsychotic treatment for 12 weeks following a magnetic resonance imaging scan. Cortical gyrification was assessed using local gyrification index in a vertexwise fashion across the entire cortical surface with correction for multiple testing using permutation analysis. Differences in local gyrification index were assessed between responders, nonresponders, and healthy controls. The effect of diagnosis (affective vs nonaffective psychosis) on the local gyrification index was also investigated in responders and nonresponders. Patients with first-episode psychosis showed a significant reduction in gyrification (hypogyria) across multiple brain regions compared with healthy controls. Interestingly, nonresponders showed prominent hypogyria at bilateral insular, left frontal, and right temporal regions when compared with responders (all clusters significant at P < .05). These effects were present for both affective and nonaffective psychoses. Gyrification appears to be a useful predictor of antipsychotic treatment response. Early neurodevelopmental aberrations may predict unfavorable prognosis in psychosis, irrespective of the existing diagnostic boundaries.

Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis

Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder. In 785 patients with a non-affective psychotic disorder, regression analysis was used to investigate the independent effects of gender, cannabis use and other drug use on age at onset of first psychosis. Age at onset was 1.8 years earlier in cannabis users compared to non-users, controlling for gender and other possible confounders. Use of other drugs did not have an additional effect on age at onset when cannabis use was taken into account. In 63.5% of cannabis-using patients, age at most intense cannabis use preceded the age at onset of first psychosis. In males, the mean age at onset was 1.3 years lower than in females, controlling for cannabis use and other confounders. Cannabis use and gender are independently associated with an earlier onset of psychotic illness. Our findings also suggest that cannabis use may precipitate psychosis. More research is needed to clarify the neurobiological factors that make people vulnerable to this precipitating effect of cannabis.

Several lines of evidence implicate immunological/inflammatory factors in development of schizophrenia. Complement is a key driver of inflammation, and complement dysregulation causes pathology in many diseases. Here we explored whether complement dysregulation occurred in first episode psychosis (FEP) and whether this provides a source of biomarkers. Eleven complement analytes (C1q, C3, C4, C5, factor B [FB], terminal complement complex [TCC], factor H [FH], FH-related proteins [FHR125], Properdin, C1 inhibitor [C1inh], soluble complement receptor 1 [CR1]) plus C-reactive protein (CRP) were measured in serum from 136 first episode psychosis (FEP) cases and 42 mentally healthy controls using established in-house or commercial ELISA. The relationship between caseness and variables (analytes measured, sex, age, ethnicity, tobacco/cannabis smoking) was tested by multivariate logistic regression.When measured individually, only TCC was significantly different between FEP and controls (p=0.01). Stepwise selection demonstrated interdependence between some variables and revealed other variables that significantly and independently contributed to distinguishing cases and controls. The final model included demographics (sex, ethnicity, age, tobacco smoking) and a subset of analytes (C3, C4, C5, TCC, C1inh, FHR125, CR1). A receiver operating curve analysis combining these variables yielded an area under the curve of 0.79 for differentiating FEP from controls. This model was confirmed by multiple replications using randomly selected sample subsets.The data suggest that complement dysregulation occurs in FEP, supporting an underlying immune/inflammatory component to the disorder. Classification of FEP cases according to biological variables rather than symptoms would help stratify cases to identify those that might most benefit from therapeutic modification of the inflammatory response.

IntroductionOnly two out of three patients diagnosed with First Episode Psychosis (FEP) achieve symptom remission after the administration of two different antipsychotics, illustrating the high prevalence of treatment-resistance in FEP. Of those, 84% are treatment-resistant since illness onset. Response to initial treatment is one of the main long-term illness course predictors. The only medication approved for treatment-resistant psychosis is clozapine and studies have demonstrated its superior antipsychotic effect among this drug class.ObjectivesThe aims of this communication are to describe a clinical case of FEP with symptom remission achieved only with clozapine and to review the literature regarding the pattern of clozapine use in FEP, the main difficulties of implementing it and its impact on the prognosis of this patients.MethodsRelevant data from the patient’s medical record were collected. Pubmed database was searched using the terms “clozapine” and “first episode psychosis”.ResultsA 50 year old woman without previous contact with psychiatric services was taken to the emergency room following behavioural disorganisation and heteroagressive conduct. Poisoning and referential delusions, as well as alienation of personal action and elementary auditory hallucinations were found and the patient was admitted in the psychiatric unit. She began treatment with Aripiprazole without therapeutic benefit and a switch to Paliperidone was made, with the same result. Clozapine was then titrated to a dose of 100mg/day, with resolution of all the positive symptoms mentioned above and she acquired total insight to the disease and need for treatment, being discharged with a diagnosis of schizophrenia. 9 articles, all from 2017 onwards, were collected from the Pubmed database.ConclusionsThere’s reluctance in prescribing clozapine in treatment-resistance FEP. This is evidenced by the mean number of antipsychotic prescribed before clozapine - 2.74 to 4.85 - as well as the delay on its prescription - 294 to 2447 days - and its prescription to only 16% in a cohort of patients with FEP. The main reasons for this hesitation are the serious, albeit rare, side-effects, such as agranulocytosis and myocarditis, as well as the difficulty in implementing it in community services, with mandatory weekly blood tests and very slow titration of the drug and treatment compliance issues, making it a very resource-consuming drug. However, in that same cohort, there was a significant reduction of the number of admissions, re-admissions and duration of hospitalisation, highlighting the need for earlier consideration in treatment-resistant FEP. The identification of treatment-resistance should then be proactive by the mental-health services, ensuring an earlier clozapine initiation with the goal of greatly improving the prognosis of these patientsDisclosure of InterestNone Declared

Innovations: Psychoeducation: Multifamily Group Treatment in a Program for Patients With First-Episode Psychosis: Experiences From the TIPS Project

Therapy initiation during a first acute episode psychosis in the psychiatric department of Mahdia

Predicting relapse after a first episode of non-affective psychosis: A three-year follow-up study

Abrupt cessation of heavy cannabis use can cause a withdrawal syndrome characterised by irritability, anxiety, insomnia, reduced appetite and restlessness. Recent reports have also described people in whom cannabis withdrawal immediately preceded the acute onset of psychosis. To identify cases of psychosis associated with cannabis withdrawal. We completed a systematic review of the literature, which comprised case reports, case series and other studies. We also searched a large electronic database of psychiatric healthcare records. The systematic review identified 44 individuals from 21 studies in whom cannabis withdrawal preceded the development of acute psychosis. In the health record study, we identified another 68 people, of whom 47 involved a first episode of psychosis and 21 represented further episodes of an existing psychotic disorder. Almost all people were daily cannabis users who had stopped using cannabis abruptly. Individuals who continued to use cannabis after the acute psychotic episode had a much higher risk of subsequent relapse than those who abstained (odds ratio 13.9 [95% CI: 4.1 to 56.9]; χ2 = 20.1, P < 0.00001). Abrupt cannabis withdrawal may act as a trigger for the first episode of psychosis and a relapse of an existing psychosis. Acute psychotic symptoms can emerge after the cessation, as well as following the use, of cannabis.