High BMI has been associated with psychiatric rehospitalisation.

We aimed to replicate this finding in a large Swiss psychiatric cohort and to examine whether other metabolic disturbances are independently associated with psychiatric readmission.

Data on 16’727 hospitalizations of 7’786 patients admitted between January 1st, 2007 and December 31st, 2019 at the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to International Diabetes Federation definition. Generalized Linear Mixed Models were used to investigate the associations between psychiatric readmission and metabolic syndrome and/or its five components.

The readmitted population (N=2’935; 37.7% patients) had higher BMI, and were more likely to have central obesity, hypertriglyceridemia, and hypertension. Multivariate analyses confirmed that having a BMI ≥ 25 kg.m-2 was associated with psychiatric readmission (25 kg.m-2≤ BMI< 30 kg.m-2: OR = 1.88; 95%CI [1.55-2.29]; BMI≥30 kg.m-2: OR = 3.5; 95%CI [2.85-4.30]) when compared to patients with 18.5≤BMI<25 kg.m-2. Interestingly, novel factors associated with readmission were identified including metabolic syndrome (OR = 1.57, 95%CI [1.05-2.33]), central obesity (OR = 1.81, 95%CI [1.33-2.46]), hypertriglyceridemia (OR = 1.59; 95%CI [1.38-1.83]), HDL hypocholesterolemia (OR = 1.22; 95%CI [1.06-1.40]) and hyperglycemia (OR = 1.58; 95%CI [1.35-1.85]).

Metabolic syndrome, central obesity, hypertriglyceridemia, HDL hypocholesterolemia, hyperglycemia and obesity were associated with psychiatric readmission. Possible causes will be presented and discussed (e.g. reduced adherence to treatment in patients with metabolic disorders, multiple psychotropic treatments in non-responders increasing the risk of metabolic worsening).

No significant relationships.

Many psychotropic drugs can induce weight gain with differences in their metabolic risk profiles (i.e. high, medium or low-risk).

To compare the weight evolution of patients switching versus patients keeping their psychotropic drugs with different risk-profiles.

Data for patients switching or keeping the same drug were obtained from the Psyclin (from 2007 to 2015) and Psymetab (2007- 2019) cohort studies, conducted at the Lausanne University Hospital, Switzerland. Patients either switched from a high to a low-risk, a high to a medium-risk, a medium to a low-risk drug, or for a drug with the same risk category. Patients not switching either kept a high, medium or low-risk drug. The evolution of weight is currently being analyzed using a linear mixed-effect model.

Preliminary results showed that switching from a high to low-risk molecule had the strongest impact on weight changes. The analysis being ongoing, the quantitative results will be presented at the congress.

Switching from a high-risk to a low-risk molecule is likely to have the strongest impact on weight changes.

No significant relationships.

Metabolic side effects of psychotropic medications are a major drawback to patients’ effective treatment. Among the mechanisms underlying their development, DNA methylation may be involved.

The aim of this study was to estimate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and baseline DNA methylation or 1-month DNA methylation changes, using an epigenome-wide approach.

Seventy-nine psychiatric patients recruited as part of PsyMetab study, who started a treatment with either an antipsychotic, a mood stabilizer or mirtazapine were selected. Epigenome-wide DNA methylation was measured using the Illumina Methylation EPIC BeadChip at baseline and after one month of treatment.

A global methylation increase was observed after 1 month of treatment, which was more pronounced in patients whose weight remained stable (i.e., <2.5% weight increase). Epigenome-wide significant methylation changes were observed at 52 loci in the whole cohort and at one site, namely cg12209987, located in an intergenic region within an enhancer, specifically in patients who underwent important early weight gain (i.e., ≥5% weight increase) during the same period of treatment (p<5*10-8). Multivariable analysis confirmed an association between an increase in methylation at this locus and weight gain in the whole cohort (p=0.004). Epigenome-wide association analyses failed to identify any significant link between other metabolic changes (e.g. glucose or lipid levels) and methylation data.

These findings give new insight into the mechanisms of psychotropic drug-induced weight gain. With improved understanding of the metabolic side effects, the use of precision medicine with epigenetics may become possible

No significant relationships.

To assess the prevalence and correlates of childhood and adolescence sexual and/or physical abuse (SPA) in bipolar I disorder (BD) patients treated for a first episode of psychotic mania.

The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 first episode psychosis (FEP) patients between 1998 and 2000. Data were collected from patients’ files using a standardized questionnaire. 704 files were available, 43 were excluded because of a non-psychotic diagnosis at endpoint and 3 due to missing data regarding past stressful events. Among 658 patients with available data, 118 received a final diagnosis of BD and were entered in this study.

80% of patients had been exposed to stressful life events during childhood and adolescence and 24.9% to SPA: in particular, 29.8% of female patients had been exposed to sexual abuse. Patients who were exposed to SPA had poorer pre-morbid functioning, higher rates of forensic history, were less likely to live with family during treatment period and were more likely to disengage from treatment

Sexual and/or physical abuse is highly prevalent in BD patients presenting with a first episode of psychotic mania; exposed patients have lower pre-morbid functional levels and poorer engagement with treatment. The context in which such traumas occur must be explored in order to define if early intervention strategies may contribute to diminish their prevalence. Specific psychological interventions must also be developed.

Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative “high-risk” studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a subgroup of at-risk subjects.

Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses.

Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania.

This is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies.

Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD may be a sign of impending first episode mania.

Age at onset of psychosis (AAO) may be younger in patients with cannabis use disorders (CUD) compared to those without CUD (NCUD). Most previous studies did not control for potential confounders, did not report effect sizes and included mostly adult patients from non-representative samples.

Controlling for relevant confounders, differences in AAO between patients with and without lifetime CUD were analysed in a large epidemiologically based cohort of 606 first-episode psychosis (FEP) patients (age 14 to 29 years) admitted within three years to the Melbourne Early Psychosis Prevention and Intervention Centre. Data were collected from medical files using a standardized scale.

Overall, AAO was not significantly different in CUD (n = 449; 74.1%) compared to NCUD, neither univariate nor when controlling for gender and premorbid functioning. However, AAO was younger in those with early CUD (starting before age 14) compared to NCUD (F(1) = 11.3; p = 0.001; partial η2 = 0.042). When considering the subgroups of early versus late onset psychosis, AAO was even later in early onset psychosis patients with CUD compared to those with NCUD (F(1) = 8.4; p = 0.004; partial η2 = 0.072). These findings were consistent for patients with non-affective psychoses, in those with CUD without other substance use disorders and in those with CUD explicitly starting in the pre-psychotic phase. Notably, 89.1% started cannabis before the onset of psychotic symptoms.

CUD starting before age 14 was associated with an earlier AAO at a small effect size, but only in adult onset FEP patients.

We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive and discriminant validity of these criteria were tested in help seeking adolescents and young adults.

This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24 years and living in metropolitan Melbourne, Australia. BAR criteria were applied to the intake assessments of all non-psychotic patients who were being treated in OYH on 31 January.08. All entries were then checked for conversion criteria. Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania.

The BAR criteria were applied to 173 intake assessments. Of these, 22 patients (12.7%) met BAR criteria. The follow-up period of the sample was 265.5 days on average (SD 214.7). There were significantly more cases in the BAR group (22.7%, n = 5) than in the non-BAR group (0.7%, n = 1) who met conversion criteria (p < .001).

These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase. The proposed criteria need further evaluation in prospective clinical trials.

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence.

The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment.

The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P<0.001), extrapyramidal (P<0.05) and psychic side effects (P<0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P<0.05), were more doubtful about their efficacy (P<0.01) and were less likely to encourage a relative to take such a medication in case of need (P<0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects.

All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Previous studies on the impact of cannabis use disorders (CU) on outcome in psychosis were mostly based on non-representative samples, have often not controlled for confounders and rarely focused on adolescents. Thus, the aims of the present study were to assess;

• (i) prevalence of CU;

• (ii) pre-treatment and baseline differences between CU and those without CU (NCU); and

• (iii) the impact of baseline and course of CU on 18-month outcomes in a representative cohort of adolescents with early onset first episode psychosis (EOP).

The sample comprised 99 adolescents (age 14 to 18) with EOP (onset age 14 to 17), admitted to the Early Psychosis Prevention and Intervention Centre in Australia. Data were collected from medical files using a standardized questionnaire.

Prevalence of lifetime CU was 65.7%, baseline CU 53.5%, and persistent CU 26.3%. Baseline CU compared to NCU was associated with higher illness-severity, lower functioning, less insight, lower premorbid functioning and longer duration of untreated psychosis. Compared to both NCU and those who decreased or stopped CU during treatment, only persistent CU was linked to worse outcomes and more service disengagement. Effect sizes were medium controlling for relevant confounders. Medication non-adherence did not explain the link between persistent CU and worse outcome.

The prevalence of CU in adolescents with EOP is high, while only persistent CU use was associated with worse outcome with medium effect sizes. Specific needs of adolescent patients with respect to cannabis interventions within integrated care settings should be addressed in future studies.

While early detection strategies have been developed for schizophrenia, affective psychoses have long been relatively neglected in this domain. However, considering the difficulties met when attempting to define the onset of bipolar disorder, we felt prodrome to first episode mania would be a clinically relevant initial target for study.

Based on an extensive literature review we identified symptoms, risk factors and associated clinical features that may be present in the phase preceding first episode mania onset. In a sample of 20 first episode mania patients, we explored which of these elements were present in at least 50% of cases.

The study confirmed that a prodrome phase can be identified before onset of first episode mania. The symptoms presented felt under 3 categories (sleep problems, irritability, mood symptoms) and were rather unspecific. Various risk factors and markers of vulnerability could be identifed. On this basis a multi-dimensional scale grouped in 3 sub-scales was constructed.

Our exploration suggests that identification of patients in the prodromal phase to first episode mania needs to be based on a combination of dimensions rather than on symptoms only. The scale still needs to be validated prospectively.

Previous studies on the impact of cannabis use disorders (CU) on outcome in psychosis were predominantly based on non representative samples, often have not controlled for confounders and rarely focused on adolescent patients. Thus, the aims of the present study were to assess: (i) prevalence of CU; (ii) baseline and pretreatment differences between CU and those without CU (NCU); (iii) the impact of baseline and course of CU on 18-month outcomes in a representative cohort of adolescents with early onset first episode psychosis (EOP).

The sample comprised 99 adolescents (age 14 to 18) with EOP (onset age 14 to 17), admitted to the Early Psychosis Prevention and Intervention Centre in Australia. Data were collected from medical files using a standardized questionnaire.

Prevalence of lifetime CU was 65.7%, of current CU at baseline 53.5%, and of persistent CU throughout treatment 26.3%. Baseline CU compared to NCU had significantly higher illness-severity, lower psychosocial functioning, less insight, lower premorbid functioning and longer duration of untreated psychosis. Compared to all other groups, only persistent CU was linked to worse outcomes and more service disengagement. Effect sizes were medium controlling for relevant confounders. Medication non-adherence did not explain the association between persistent CU and worse outcome.

Baseline CU was associated with worse baseline characteristics, but only persistent CU was linked with worse outcome. About half of those with baseline CU reduced cannabis during treatment. For these, effectively treating the psychotic disorder may already be beneficial. However, future research is necessary on the reasons for persistent CU in EOP and its treatment.

Atypical antipsychotics and some other psychotropic drugs such as valproate, lithium or mirtazapine are known to induce several metabolic complications. However there is an inter-individual variability in developing metabolic features which may be explained by clinical and genetic factors.

To determine whether weight gain and/or appetite change after one month are predictors for a weight gain after 3 and 12 months of treatment.

A longitudinal clinical and pharmacogenetic study is presently ongoing in the Department of Psychiatry-CHUV. Several clinical data have been recorded over one year following the introduction of psychotropic treatment. 406 patients with weight at baseline, after one month and with at least a third weight measure during the first year of treatment were included in the present study.

Using Receiver Operating Characteristic (ROC) analyses, an initial weight increase of 5% was found to be a good predictor for a consequent weight gain at 3 months (ROCAUC=77) and one year (ROCAUC=68). By using a generalized linear mixed model corrected by several confounders, this weight change of 5% was found to be significantly associated (p-value<0.0001) with an important weight change (10 to 20% increase from baseline value) over one year. Appetite was not found to be good a predictor of weight gain over one year.

An initial weight gain of 5% during the first month following an introduction of atypical antipsychotics, lithium, valproate and/or mirtazapine is a predictor for further weight gain and should be a warning sign to introduce weight lowering strategies.

Intervention in the prodromal phase of psychosis remains controversial due to poor specificity of current criterion and ethical issues arising when developing interventions. There is less controversy regarding the need for specialist first episode psychosis intervention programs.

In the context of the implementation of an early intervention strategy in Lausanne, we focused on a first episode psychosis program and checked if need for an early detection program for UHR subjects would emerge over time. We recently structured a specialist At Risk Mental State (ARMS) clinic.

Help seeking patients aged 14–35, referred for a 'prodromal psychotic state” are assessed with: Mini-SCID; SPI-A; SIPS-PANSS; MARDS; Yung Mania scale and classified as ARMS on the basis of SPI-Cy (COPER and COGDIS criteria) and SIPS criteria (APS; BLIPS or Genetic Criterion).

Since January 2014, twenty-four patients were addressed to our clinic, and diagnoses were: ARMS (33%); first episode psychosis (8%); schizotypal disorder (25%); other axis I or II diagnosis (13%); drop out before diagnosis (5%); still in investigation (16%).

Our data shows that there is a need for specialist ARMS clinic when developing early intervention programs. The proximity with a well implanted first episode program offers the possibility to treat patients who have already developed full blown psychosis or for those who make the transition. Ethically, it is our impression that having both structures is necessary in order to have adequate treatment to offer is patients develop full blown psychosis.

Weight gain and obesity are serious problems associated with psychiatric diseases, in which psychotropic treatments play an important role. The CREB-regulated transcription coactivator 3 (CRTC3) gene was linked to energy balance in animal models, and in humans CRTC3 rs8033595 polymorphism was associated with obesity markers only in Mexican-Americans, a population with a high prevalence of obesity.

To determine whether polymorphisms within the CRTC3 gene are associated with adiposity markers in Caucasian psychiatric patients, a population with also a high prevalence of obesity.

The association of the CRTC3 rs8033595 and 2 other selected CRTC3 polymorphisms (rs3743401 and rs3902286) was investigated in three independent groups of Caucasian psychiatric patients taking weight gain-inducing psychotropic drugs such as atypical antipsychotics, lithium and valproate (n1=168, n2=188, and n3=448). Body mass index (BMI) was chosen as a marker for obesity. Generalized Additive Mixed Model (GAMM) was used to test the association of CRTC3 polymorphisms with BMI.

Obesity prevalence was high in the three psychiatric populations (n1:40%, n2:28% and n3:19%). The three CRTC3 polymorphisms did not deviate from Hardy-Weinberg equilibrium and the minor allelic frequency (MAF) was 44%, 25% and 19% for CRTC3 rs8033595, rs3743401 and rs3902286, respectively. None of the CRTC3 polymorphisms were found to be associated with BMI in any of the three psychiatric samples and when analyzing the combined samples together.

CRTC3 polymorphisms seem not to have an influence on adiposity markers (BMI) in Caucasian psychiatric patients receiving drugs inducing weight gain.

While there is suggestion that early onset of psychosis is a determinant of outcome; knowledge regarding correlates of later onset age is more limited. This study explores the characteristics of patients developing psychosis after age 26, towards the end of the usual age range of early intervention programs, in order to identify potential specific needs of such patients.

Two hundred and fifty-six early psychosis patients aged 18–35 were followed-up prospectively over 36 months. Patients with onset after 26 (“later onset”, LO) were compared to the rest of the sample.

LO patients (32% of the sample) had shorter DUP, were less likely to be male, had better premorbid functioning and were more likely to have been exposed to trauma. They had greater insight at presentation and less negative symptoms overall. The trajectories for positive and depressive symptoms were similar in both groups. Evolution of functional level was similar in both groups, but while LO patients recovered faster, they were significantly less likely to return to premorbid functional level.

Later psychosis onset correlates with better premorbid functioning and higher rate of trauma exposure; the latter should therefore be a treatment focus in such patients. LO patients were less likely to return to premorbid functional level, which suggests that current treatment strategies may not be efficient to help patients maintain employment. The possibility of distinct illness mechanisms according to onset age and the more central role for trauma in patients with onset after age 26 needs to be further explored.

Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.

The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.

There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.

Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Studies conducted in child psychiatry suggest that patients with earlier onset of psychosis have poorer outcome. Similar findings have been published regarding onset of bipolar disorder. However, few studies have been conducted in youth mental health program where these patients may actually receive treatment. Identification of subgroups with distinct need and outcome among first episode mania patients would facilitate the development of specific treatment strategies better suited to the actual needs of patients.

Sixty-seven patients with a first episode of psychotic mania were followed up over 12 months after recovery from this initial episode. Syndromic and symptomatic outcome were determined with the brief psychiatric rating scale, functional outcome with the quality of life scale and premorbid adjustment scale sub items.

While 90% of patients achieved syndromic recovery (disappearance of manic syndrome) at 6 and 12 months, 40% had not recovered symptomatically, still presenting with depression and anxiety. Return to previous level of functioning was achieved only by 34% of patients at 6 months and 39% at 12 months. Age at the time of first manic episode with psychotic features was a significant predictor of recovery of functional level.

While manic symptoms reduce quickly in most patients after a first episode of psychotic mania, an important number of patients still display symptoms of depression and anxiety after 12 months and 2/3 do not reach functional recovery. Younger age at first episode predicts risk of poorer functional outcome.

The authors have not supplied their declaration of competing interest.