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Abstract Psychosis progresses along a continuum. While heterogeneity is evident across the continuum, it remains unknown whether this is also reflected in white matter (WM) heterogeneity and whether parsing WM heterogeneity may reveal subgroups with more pronounced clinical features. This analysis included 212 participants consisting of healthy controls (HC, n = 59), individuals with high schizotypy (SPT, n = 27), at-risk mental state (ARMS, n = 35), and patients with first episode psychosis (FEP, n = 50) and schizophrenia (SZ, n = 41). Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI), and fibre density (FD), a non-tensor-derived diffusion marker, was computed. The Person-Based-Similarity Index (PBSI) and Coefficient of Variation Ratio (CVR) were computed to assess global and local heterogeneity. ANOVAs were performed to determine whether people with deviating PBSIs exhibit more pronounced clinical features. Global heterogeneity for all diffusion parameters significantly differed across groups, with greatest difference in heterogeneity between SZ and HC. Results further indicate that FA deviators exhibit lower global functioning and higher negative symptoms. Local FA heterogeneity was greater in FEP relative to ARMS and HC in almost all WM tracts, while SZ patients specifically showed greater heterogeneity in the right thalamic radiation and the left uncinate compared to HCs. Group differences in WM heterogeneity might be indicative of symptom specificity and duration. While these findings offer valuable insights into the neurobiological variability of psychosis, they are primarily hypothesis-generating. Future large-scale studies are warranted to test the robustness of diffusion markers and their clinical relevance.

Academic psychiatry is essential for advancing mental health understanding and treatments. However, women encounter more obstacles hindering their progress in academia than men. This Editorial aims to highlight these obstacles and propose strategies to address them, advocating for a more supportive environment for women psychiatrists’ ongoing growth and development. The importance of supportive environments, fair access to opportunities and structural changes, including initiatives for mentorship, funding and flexible work arrangements, are crucial. Collaboration among governments, institutions and organisations is needed to enhance research infrastructure and promote gender equality. Encouraging and recognising women's contributions in research fosters inclusivity and innovation. Prioritising these efforts is vital for the existence, well-being and success of women in academic psychiatry.

IntroductionThe Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome.MethodA sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses.ResultWe extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups.ConclusionPsychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability.

Abstract Background Despite efforts toward greater gender equality in clinical and academic psychiatry in recent years, more information is needed about the challenges in professional development within psychiatry, and how these may vary with gender. Methods A cross-sectional 27-item online survey was conducted with psychiatrists and psychiatric trainee members of the European Psychiatric Association. Results A total of 561 psychiatrists and psychiatric trainees from 35 European countries participated representing a response rate of 52.8% for women and 17.7% for men from a total sample of 1,580. The specific challenges that women face in their professional development fall into two categories. One comprised women’s negative attitudes concerning their abilities in self-promotion and networking. The other identified environmental barriers related to lack of opportunity and support and gender discrimination. Compared to men, women reported higher rates of gender discrimination in terms of professional advancement. Women were less likely to agree that their institutions had regular activities promoting inclusion, diversity, and training to address implicit gender bias. Working in high-income countries compared to middle-income countries relates to reporting institutional support for career progression. Conclusions These findings are an open call to hospital leaders, deans of medical schools, and department chairs to increase efforts to eradicate bias against women and create safer, inclusive, and respectful environments for all psychiatrists, a special call to women psychiatrists to be aware of inner tendencies to avoid self-promotion and networking and to think positively and confidently about themselves and their abilities.

Abstract Background Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR). Methods In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview. Results At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment. Conclusions ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.

Background Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. Method Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance. Results The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. Conclusions We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.

ObjectivePeople at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown.MethodsWe investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS.ResultsWe identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = −10.40, SE = 3.41, p = 0.003; ES = −22.36, SE = 10.07, p = 0.027), Increasing (ES = −11.35, SE = 4.55, p = 0.014; ES = −25.58, SE = 13.17, p = 0.050) and Low (ES = −11.38, SE = 3.29, p = 0.001; ES = −27.55, SE = 9.78, p = 0.005) classes, respectively.ConclusionsThese findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on the potential of modifying smoking behavior and its relation to clinical outcomes.

In community studies, both attenuated psychotic symptoms (APS) and basic symptoms (BS) were more frequent but less clinically relevant in children and adolescents compared to adults. In doing so, they displayed differential age thresholds that were around age 16 for APS, around age 18 for perceptive BS, and within the early twenties for cognitive BS. Only the age effect has previously been studied and replicated in clinical samples for APS. Thus, we examined the reported age effect on and age thresholds of 14 criteria-relevant BS in a patient sample at clinical-high risk of psychosis (N = 261, age 15–40 yrs.), recruited within the European multicenter PRONIA-study. BS and the BS criteria, “Cognitive Disturbances” (COGDIS) and “Cognitive-perceptive BS” (COPER), were assessed with the “Schizophrenia Proneness Instrument, Adult version” (SPI-A). Using logistic regressions, prevalence rates of perceptive and cognitive BS, and of COGDIS and COPER, as well as the impact of social and role functioning on the association between age and BS were studied in three age groups (15–18 years, 19–23 years, 24–40 years). Most patients (91.2%) reported any BS, 55.9% any perceptive and 87.4% any cognitive BS. Furthermore, 56.3% met COGDIS and 80.5% COPER. Not exhibiting the reported differential age thresholds, both perceptive and cognitive BS, and, at trend level only, COPER were less prevalent in the oldest age group (24–40 years); COGDIS was most frequent in the youngest group (15–18 years). Functional deficits did not better explain the association with age, particularly in perceptive BS and cognitive BS meeting the frequency requirement of BS criteria. Our findings broadly confirmed an age threshold in BS and, thus, the earlier assumed link between presence of BS and brain maturation processes. Yet, age thresholds of perceptive and cognitive BS did not differ. This lack of differential age thresholds might be due to more pronounced the brain abnormalities in this clinical sample compared to earlier community samples. These might have also shown in more frequently occurring and persistent BS that, however, also resulted from a sampling toward these, i.e., toward COGDIS. Future studies should address the neurobiological basis of CHR criteria in relation to age.

There has been considerable interest in the role of synchronous brain activity abnormalities in the pathophysiology of psychotic disorders and their relevance for treatment; one index of such activity are EEG resting-state microstates. These reflect electric field configurations of the brain that persist over 60–120 ms time periods. A set of quasi-stable microstates classes A, B, C, and D have been repeatedly identified across healthy participants. Changes in microstate parameters coverage, duration and occurrence have been found in medication-naïve as well as medicated patients with psychotic disorders compared to healthy controls. However, to date, only two studies have directly compared antipsychotic medication effects on EEG microstates either pre- vs. post-treatment or between medicated and unmedicated chronic schizophrenia patients. The aim of this study was therefore to directly compare EEG resting-state microstates between medicated and medication-naïve (untreated) first-episode (FEP) psychosis patients (mFEP vs. uFEP). We used 19-channel clinical EEG recordings to compare temporal parameters of four prototypical microstate classes (A–D) within an overall sample of 47 patients (mFEP n = 17; uFEP n = 30). The results demonstrated significant decreases of microstate class A and significant increases of microstate class B in mFEP compared to uFEP. No significant differences between groups were found for microstate classes C and D. Further studies are needed to replicate these results in longitudinal designs that assess antipsychotic medication effects on neural networks at the onset of the disorder and over time during illness progression. As treatment response and compliance in FEP patients are relatively low, such studies could contribute to better understand treatment outcomes and ultimately improve treatment strategies.

AbstractBackground.Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.Methods.The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).Results.Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.Conclusions.Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

BackgroundDeficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis.MethodsA total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. ResultsThe n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms.ConclusionsPartially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group.Clinical Trial RegistrationANZCTR, identifier: 12608000475347

Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage.Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms (“ultra high risk” OR “clinical high risk” OR “at risk mental state”) AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation.Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell’s C-statistic 0.655, 95% confidence interval (CIs), 0.627–0.682].Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.

Symptoms of attention-deficit/hyperactivity disorder (ADHD) and psychosis risk share features which might represent an early vulnerability marker for schizophrenia. Early detection of individuals with this symptomatic overlap is relevant and may assist clinicians in their decision making for diagnosis and treatment. This study sought to analyze the capability of different instruments in the screening of patients for ADHD symptoms or at psychosis risk, assess their classification accuracy, and describe the extent of symptoms overlap between them. 243 adult patients completed one instrument screening for ADHD and two instruments screening for psychosis risk symptoms [Adult ADHD Self-Report Scale Symptom Checklist (ASRS-v1.1); Prodromal Questionnaire Brief Version (PQ-16); Self-Screen Prodrome (SPro)]. The ability of these instruments to distinguish between the symptomaticity of these patients appears modest. The most satisfactory scale to identify subjects at psychosis risk was SPro with its subscale psychosis risk. ASRS-v1.1 showed good reliability in assessing individuals as not having ADHD symptoms and had higher probability to achieve its own and the cut-off of another questionnaire. Subjects having symptoms of psychosis risk and ADHD showed elevated symptomatology. Reliable instruments capable of separating ADHD symptoms from those of psychosis risk are needed to better identify the symptomatic overlap of this two conditions.

Background/aimsAttention-deficit/hyperactivity disorder (ADHD) is often overlooked in adults; moreover, the problem seems to be even more critical in women. In the present, observational screening study, a clinical, particularly adult outpatient population was examined regarding frequency and severity of a likely ADHD, whereby sex differences were of particular interest.Methods224 participants, 146 men and 78 women, were included. Based on data recorded with the self-rating WHO screening instrument Adult ADHD Self-Report Scale (ASRS-v1.1), it was examined how many participants were conspicuous for adult ADHD by exceeding a predefined cutoff value (COV) (COV ≥ 4 for ASRS-6, and ≥12 for ASRS-18). To examine frequency distributions, χ2 tests were conducted. For the inferential statistical comparison of means, t-tests for independent samples or Mann–Whitney U tests were calculated.Results34.4% of the sample was screened positive in the ASRS-v1.1 screener short version, ASRS-6, while 17.4% were conspicuous in the symptom checklist, ASRS-18. There were indeed more men screened positive, but the difference in the frequency between the sexes was not statistically significant, indicating a balanced sex ratio. Further, severity of ADHD core symptoms inattention and hyperactivity/impulsivity was examined by comparing ASRS-18 symptom subscale scores. In concordance with the hypothesis, men and women did not differ in severity of symptoms.ConclusionResults indicate that women might be affected by ADHD in a comparable manner as men; this emphasizes the importance for the awareness of ADHD in both sexes in clinical practice.

There is strong evidence for abnormal salience processing in patients with psychotic experiences. In particular, there are indications that the degree of aberrant salience processing increases with the severity of positive symptoms. The aim of the present study was to elucidate this relationship by means of brain imaging.Functional magnetic resonance imaging was acquired to assess haemodynamic responses during the Salience Attribution Test, a paradigm for reaction time that measures aberrant salience to irrelevant stimulus features. We included 42 patients who were diagnosed as having a psychotic disorder and divided them into two groups according to the severity of their positive symptoms. Whole brain analysis was performed using Statistical Parametric Mapping.We found no significant behavioural differences with respect to task performance. Patients with more positive symptoms showed increased haemodynamic responses in the left insula corresponding to aberrant salience than in patients with less positive symptoms. In addition, left insula activation correlated negatively with cumulative antipsychotic medication. Aberrant salience processing in the insula may be increased in psychosis, depending on the severity of positive symptoms. This study indicates that clinically similar psychosis manifestations share the same functional characteristics. In addition, our results suggest that antipsychotic medication can modulate insular function.