Patients with severe mental disorders have a significantly reduced life expectancy than the general population, often resulting from the increased prevalence of cardiovascular and metabolic diseases. Reasons include unhealthy lifestyle behaviours, reduced access to screening programs and adverse effects of many psychotropic drugs.

Our goal is to assess the efficacy of a psychosocial group intervention promoting healthy lifestyle behaviors compared to a brief psychoeducational group intervention in terms of improvement of severity of psychiatric symptoms and perceived quality of life, and a series of anthropometric and hematological parameters.

This is a multicenter randomized controlled trial. Patients between 18 and 35 years of age with a diagnosis of schizophrenia and other primary psychotic disorders, unipolar depression and bipolar disorder were recruited. Exclusion criteria were inability to perform moderate physical activity, pregnancy and breastfeeding and impaired cognitive functions.

401 patients were recruited and randomly assigned to receive the experimental intervention (LIFESTYLE) or a behavioural control intervention. About 57% of the sample were female, with a mean age of 45.8±11.8, and BMI of 32.5±5.5. All of them were receiving almost one psychotropic drug. At one year, we observed a reduction in HOMA-IR index (from 4.3 ± 5.5 to 3.1 ± 2.9, p<0.01) and triglycerides (from 162.5 ± 78.1 mg/dL to 131.4 ± 76.0 mg/dL, p<0.001), as well as an increase in HDL (from 46.2± 14.6 mg/dL to 50.9±26.7 mg/dL, p<0.05). Moreover, a reduction in the values of BPRS “Affectivity” (from 8.7±3.0 to 7.2±2.5, p<0.001), “Activity” (from 4.7±1.9 to 4.2±1.3, p<0.01) and “Negative Symptoms” subscale (from 7.7±3.1 to 7.0±2.7, p<0.001) was also observed, along with an improvement in perceived quality of life (MANSA total score from 4.0 ± 1.0 to 5.3 ± 0.8, p<0.01).

The results support the evidence that the LIFESTYLE intervention has long-lasting positive effects on physical and mental health of people with mental disorders. More efforts need to be done in order to increase the availability of these treatments in routine clinical settings.

None Declared

Mentalization-based therapy (MBT) and dialectical behavior therapy (DBT) are two treatments known to be effective for borderline personality disorder (BPD). However, head-to-head comparisons between those two treatments are scarce and their effectiveness in naturalistic clinical services, where BPD is often comorbid with other cluster B personality disorders (PD), needs to be further explored.

The study’s goal was to answer the following question: Is there a difference in emergency department visits, hospitalizations and dropout rates after one year of treatment in MBT compared to DBT for a clinical adult population with cluster B PD?

We compared the effectiveness of MBT and DBT in 288 patients between 2015 and 2019 with at least one cluster B PD by measuring their emergency services use and hospitalizations one year before and one year after beginning therapy. Drop-out rates for those two treatment modalities are also compared. Image 1 illustrates the patient distribution for the study.

In terms of reducing emergency room use, patients in each treatment group experienced a significant decrease with medium effect sizes (p < .001 for both, d=.768 for MBT and d=.640 for DBT).

In terms of reducing hospitalizations, the MBT group had a significant decrease (p < .05) with a medium effect size (d=.568) whereas the DBT group had a non-significant decrease (p = .595) with a negligible effect size (d=.140).

When we compare both therapies, no significant differences were found between them in terms of reductions in emergency room use (p = .358) and hospitalizations (p =.195), as well as dropout rates (p = .743). Image 2 further illustrates the dropout trends in the first year of treatment for both groups in intervals of 3 months.

Hospitalizations were rare in our population, which may hinder the validity of results containing this variable. In absolute numbers, total emergency room visits decreased from 119 to 37, whereas hospitalizations were reduced from 24 to 12. Drop-out rates before entering treatment were high (20.6%), as it was during treatment for both therapies (around 30% in the first year of treatment).

Image:

Image 2:

This study emphasizes that both DBT and MBT are linked to a reduction in service use over time. Dropout rates in both treatments are also similar to other studies. Therefore, future research should investigate the factors that can help clinicians guide individuals with PDs towards the type of therapy that is most suitable for them.

None Declared

Irvin D. Yalom defines existential psychotherapy as a dynamic therapeutic approach that focuses on concerns rooted in existence with the four ultimate concerns being death, isolation, meaning in life, and freedom. Patients in advanced stages of cancer often experience elevated levels of psychological distress, encompassing conditions such as depression, anxiety, and a sense of spiritual hopelessness. Recently, interest in spiritual well-being has prompted a new wave of interventions that directly target this population, namely logotherapy and other existential interventions based on existential principles.

In this review, the primary focus was to comprehend the current evidence on the application of existential psychotherapy for individuals coping with advanced cancer and give an overview of the therapy approaches used.

Narrative review of scientific literature using Pubmed search engine.

Terao and Satoh identified nine types of existential psychotherapies which were investigated using randomized controlled trials for patients with advanced cancer or in terminal care: Meaning-Centered Group Psychotherapy (MCGP), Individual Meaning-Centered Psychotherapy (IMCP), Meaning-Making intervention (MMi), Meaning of Life Intervention, Managing Cancer and Living Meaningfully (CALM), Hope Intervention, Cognitive and Existential Intervention, Dignity Therapy, and Life-Review Interviews. All deal with the issues pointed by Yalom. Existential or spiritual well-being improvements were validated in MCGP, IMCP, Meaning of Life intervention, and Life-Review intervention.

Current evidence is still based on a very limited number of studies. Additional research is needed to delve into the impact of existential psychotherapy on individuals facing advanced cancer.

None Declared

A complex, Nature-, and Adventure Therapy - integrated Schema Therapeutic program (N-ABST) and a related efficacy study was launched in 2022 April at the Psychotherapy Department, at Semmelweis University. The participants had the opportunity of having outdoor, experience based group processes – seven full days in a month - in addition to the classic Schema Therapy (ST) sessions. According to the study design, 4-week long traditional thematic ST programs and 4-week long N-ABST programs were taken place alternately.

Our aim was to compare the efficacy in a randomized, controlled design, short and medium terms. The participants of the programs and thus the target group of the research were adults, diagnosed mainly with Borderline Personality Disorder, inpatients in psychiatry.

This methodological innovation also meant the integration of two therapeutic teams in practice. When establishing the collaboration, we put emphasis on finding common points and understanding how N-AT contributes to schema therapy goals. During our joint work, it became clear that the elemental need for contact with nature enriched the schema therapy approach with a new basic need that was not included in it before. Measurements were taken before the start of the entire program and at the end of the 4-week cycle. Preliminary results are presented based on the Personality Inventory for DSM-5 - Hungarian Short Form (PID-5-HSF), and the Derogatis Symptom Checklist (SCL90).

In the N-ABST group (n=23) the PID5 “Dysinhibition” scale (p < .01, Cohen’s d = .636), and the “Negative Affectivity” scale (p < .05, Cohen’s d = .388) showed significantly lower scores after therapy. In the case of the “Detachment” we have found a tendency to decrease after the therapy. Regarding the comparison of the effectiveness of N-ABST and classical Schema Therapy - with the current state of analysis - there was a significant difference in the PID5 values for “Suspiciousness” and “Manipulativeness”. The former characteristic was reduced to a greater extent by the schema therapy, and the latter by the N-ABST therapy. Based on the SCL90, the N-ABST program resulted in a significant symptom reduction measured by the following subscales: somatization, obsessive compulsive, interpersonal sensitivity, depression, phobia. Global symptom severity also decreased significantly (p < .05, Cohen’s d = .588).

According to our results, Nature- Adventure Therapy enhanced Schema Therapy seems to be an innovative and efficient method in the psychotherapy of personality disorders. Besides the effectiveness, there is a great challenge to design programs that are sustainable and therefore serves therapy long term as well.

This study was supported by the National Research, Development and Innovation Office grant K 129195.

None Declared

Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatment choices for GAD, but which should be considered as first-line treatment still needs to be clarified.

To examine the most effective and accepted psychotherapy for GAD both in the short and long-term, via a network meta-analysis.

We searched MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials – CENTRAL, from database inception to January 1st, 2023, to find randomized controlled trials (RCTs) of psychotherapies for GAD. Eight psychotherapies (behaviour therapy, cognitive-behaviour therapy, cognitive restructuring, psychoeducation, psychodynamic therapy, relaxation therapy, supportive psychotherapy, and third-wave CBTs) were compared with each other and two control conditions (treatment as usual, waiting list). We followed Cochrane standards when extracting data and assessing data quality and used PRISMA guidelines for the reporting. We conducted random-effects model pairwise and network meta-analyses. We assessed risk of bias of individual studies through the second version of the Cochrane’s Risk of Bias tool and used the Confidence in Network Meta-Analysis (CINeMA) to rate certainty of evidence for meta-analytical results. Severity of GAD symptoms and acceptability of the psychotherapies were our outcomes of interest.

We analysed data from 66 RCTs. Effect size estimates on data from 5,597 participants suggest third wave cognitive-behavioural therapies (standardized mean differences [SMDs] =-0.78; 95%CI=-1.19 to -0.37; certainty=moderate), cognitive-behavioural therapy (CBT) (SMD=-0.68; 95%CI=-1.05 to -0.32 certainty=moderate), and relaxation therapy (SMD=-0.54; 95%CI=-1.04 to -0.05; certainty=low) reduced generalized anxiety symptoms more than treatment as usual (TAU). Relative risks for all-cause discontinuation signalled no differences compared with TAU for all psychotherapies. When excluding studies at high risk of bias, relaxation therapy lost its superiority over TAU. When considering anxiety severity at three to twelve months after completion of the intervention only CBT remained significantly more efficacious than TAU (SMD=-0.58; 95%CI=-0.93 to -0.23).

Image:

Given the evidence for both acute and long-term efficacy, CBT may represent the reasonable first-line psychological treatment for GAD. Third-wave CBT and relaxation therapy have short-term efficacy and may also be offered. Results from this investigation should inform patients, clinicians, and guidelines. This project is funded by the European Union’s HORIZON EUROPE research programme under grant agreement No 101061648.

None Declared

Headache is a very common health problem worldwide and in our country due to the increasing environmental damage and daily stress. The proportion of patients with headache in general practice is 4-5%, in neurology up to 30%. Chronic headache as a persistent stressor exhausts the body through central sensitisation, which can lead to the consolidation of maladaptive coping strategies such as avoidance, feelings of loss of control, catastrophising pain. This can lead to a deterioration in quality of life and depression also. The effectiveness of pharmacotherapy in coping with chronic pain is limited, so attention should be paid to modifying maladaptive pain behaviour, as recommended by the NICE guidelines. The international literature shows that mindfulness-based cognitive therapy (MBCT) has been shown to be effective in the management of chronic headache, primarily in improving quality of life, increasing self-efficacy and reducing pain catastrophisation and depression (Hunt et al., 2022).

Our first objective was to introduce mindfulness-based cognitive therapy in Hungary to patients suffering from chronic headache. Secondly, we wanted to measure the impact of the method on quality of life, coping with pain and depression.

N=28 patients, suffering from chronic headaches (tension headache and migraine) participated in the study at the Department of Clinical Psychology, Semmelweis University (BNO: G430, G431, G442). Selection criteria were: referral from a neurologist, age 18-65. The intervention was an 8-session mindfulness-based cognitive therapy for pain (Day, 2017) led by an MBCT teacher and a clinical psychology resident. Before the intervention, all patients had an individual first interview and filled in the questonnaires. Measures: Beck Depression Questionnaire, Pain Catastrophizing Scale, Comprehensive Headache-related Quality of life Questionnaire, Five Facet Mindfulness Questionnaire, Cognitive Emotion Regulation Questionnaire.

After the intervention, there was a significant reduction in the negative impact of pain on quality of life (p<0.05, Cohen’s d=0.6), pain catastrophization (p<0.01, Cohen’s d=0.74), and depression (p<0.001, Cohen’s d=0.84). In addition, several sub-factors of mindfulness increased, including non-reactivity and being non-judgemental (p<0.05, Cohen’s d=0.57), as well as adaptive cognitive emotion regulation strategies (p<0.05, Cohen’s d=0.49).

We can conclude, that in line with international findings, MBCT has been shown to be effective in reducing the negative impact of depressive symptoms, pain catastrophisation and headache on quality of life, and in helping people to cope with pain more adaptively, primarily through the acquisition of mindfulness skills.

None Declared

In the last decades, growing evidence suggests, that young adults and even adolescents consume more and more pornographic content, which might lead to behavioural addictions. Excessive pornography use was found to be associated with higher rates of sexual dysfunctions, such as genital dysfunction or disorders related to desire, arousal, orgasm and pain. The role of attachment style on sexual function has still rarely been investigated.

To examine associations between sexual dysfunction, problematic pornography use and attachment styles in a Spanish-Hungarian sample.

A cross-sectional comparative study was carried out in 2023 which included a Hungarian (N=447; 63% female; age: 30,5±9,8) and a Spanish sample (N=201; 72% female; age: 40,7±14) from the general population. In the online survey, we used the Arizona Sexual Experiences Scale (ASEX) to measure sexual dysfunction, the Problematic Pornography Use Scale (PPCS) to assess pornographic content consumption within the theoretical framework of addiction and the Relationships Questionnaire to explore the attachment styles of the subjects.

13% of the Hungarian sample and 19% of the Spanish sample reported severe sexual dysfunction (ASEXTotal >19). The Hungarian sample reported more problems related to orgasm (climax and satisfaction). Overall, 7% of the Hungarian sample and 1% of the Spanish sample reported very severe problems (PPCSTotal >76) with pornography use. We found significant differences in every subscale and the Hungarian sample reportedly showed more difficulties in every aspect, especially in salience and mood change. Regarding attachment styles, the samples also showed significant differences (Hungarian: 31% secure, 26% anxious-ambivalent, 20% avoidant, 23% disorganized; Spanish: 53% secure, 11% anxious-ambivalent, 23% avoidant, 13% disorganized). In the combined sample, secure attachment style was associated with the least difficulties in sexual functioning, whereas subjects with anxious-ambivalent style reported more problems in sexual drive, arousal and erection. Disorganized attachment style was associated with the most severe dysfunction in orgasm (climax and satisfaction). The association between problematic pornography use and attachment styles was more consistent. Secure attachment style showed the least of problems, whereas subjects with anxious-ambivalent and disorganized attachment styles reported the most, especially in salience and mood change.

Our findings showed significant intercultural differences between the two samples and highlighted the potential role of attachment styles in sexual functioning and problematic pornography use. A more profound understanding of the relationship between attachment and sexual functioning could facilitate potential treatment of sexual dysfunctions by addressing attachment issues in psychotherapy.

None Declared

Sexuality, although an essential component of human health, remains a controversial topic shrouded in stigma, particularly in the context of neurodiversity, which includes autism spectrum disorder (ASD), where the expression of sexuality presents unique challenges. Autism and sexuality is a complex and multifaceted topic that involves understanding the unique ways in which individuals on the autism spectrum experience and express their sexuality.

The purpose of this work is to address the complexity of the biopsychosocial sexuality components of people with autism, promoting a shift in the medical perspective, societal attitudes, and supporting greater inclusion of these individuals in current discussions regarding this area of human behavior and experience.

Evidence-based review, through research conducted on PubMed and selection of the most relevant studies on this topic, published in the last decade.

Sexuality in autism is now recognized as a normative and integral aspect of development and functioning. Existing research suggests that most individuals with ASD display a clear interest in sexuality and relationships, with a study reviling that 96% of the ASD sample expressed an interest in sexuality. Individuals with high autistic traits tended to identify themselves more times as bisexual or presented a sexuality not definable within the categories of heterosexual. The relationship between autism and gender dysphoria is an area of ongoing research and discussion. Studies have suggested a higher prevalence of gender diverse identities and experiences within the autism community compared to the general population. Various hypotheses have been proposed to explain the increased gender and sexual diversity among individuals with autism. People with ASD may face unique challenges when it comes to their sexuality. The impairments in social skills and communication central to ASD potentially impact an autistic individual’s expression and experience of sexuality by affecting their abilities to understand and interpret social cues, emotions, and nonverbal behaviors of others. Importantly, such individuals may be more vulnerable, as they may have different or even limited understanding of boundaries and consent. To address these challenges, it is important to acknowledge and respect the diversity of sexual experiences and desires among individuals with neuro(bio)logical differences. This can be done by providing accurate and inclusive sex education, creating safe spaces for such individuals to explore and express their sexuality, and working to address discrimination and abuse in intimate contexts.

Recognizing and respecting this diversity and fostering inclusive and accepting environments, we can help individuals with neurological differences to fully express and explore their sexuality and have satisfying sexual lives.

None Declared

Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and restricted interests. It has been reported that oxytocin may improve processing of social cues and emotions in adults with ASD.

The aim of this study was to evaluate the therapeutic effects and safety of intranasal oxytocin in this population.

Thirty-nine patients with ASD were randomly assigned to two groups: one group received intranasal oxytocin and the other group received a placebo, with 24 units administered every 12 hours for 8 weeks. The patients were evaluated using the Autism Quotient (AQ), Ritvo Autism Asperger Diagnostic Scale – Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI), and World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaires at weeks 0, 4, and 8.

The intervention group showed clinical improvements in RAADS-R (P=0.010), social communication subscale of SRS (P=0.002), CGI (P=0.000), physical (P=0.004), psychological (P=0.006), and social relationships (P=0.046) domains of WHOQL-BREF. Improvements reached their maximum at week 4 and were maintained until week 8 (Table 1).Table 1.

Effect of group, time time-group interaction and the effect size

The findings of this study suggest that nasal oxytocin therapy can significantly improve social skills and quality of life in individuals with ASD. Further research is needed to determine the timing and scope of oxytocin’s effects across the lifespan.

None Declared

Exploring the positive psychological and behavioural dimensions of people living with mental disorders can establish a firm ground in a therapeutic alliance for setting up positive life goals.

The present study aimed to explored whether the strength of the mental health capacities and the severity of mental disorder symptoms and the interaction of the two differ in the strength of their associations with several dimensions of well-being on Hungarian adult psychiatric and non-clinical community samples.

The psychiatric sample (129 patients (44 male, 85 female)) was collected in four Hungarian healthcare facilities using a cross-sectional design. The non-clinical community sample (253 adults (43 male, 210 female)) was collected online using a cross-sectional design. All the respondents completed the Mental Health Test, six well-being and mental health measures, and the Symptom Checklist-90-Revised.

Including both the mental health competencies and mental disorder symptoms variables in one regression model in both samples can predict patients’ well-being even more accurately. Mental health competencies related positively; mental disorder symptoms connected negatively to subjective well-being. In all models and both samples, mental health competencies were found to be a stronger determinant of well-being than the mental disorder symptoms. The interaction of mental health functioning and mental disorders is no more predictive of well-being in either psychiatric or non-clinical samples than when the effects of each are considered separately.

The assessment of mental health competencies has an important predictive value for well-being in the presence of psychopathological symptoms and/or mental disorders.

None Declared

Complementary and alternative therapy, especially yoga, is emerging as an important treatment modality for various complex disorders. Yoga therapy has reportedly been demonstrated to exhibit clinical benefits in schizophrenia. However, the modulatory effects of yoga therapy on the pathobiological pathways of schizophrenia are inadequately explored. Immune dysregulation is a widely recognized etiopathological construct of schizophrenia. It is not precisely known whether yoga therapy can modulate the expression of immune molecules by regulating gene expression and epigenetic processes in schizophrenia.

To understand the impact of 12-weeks add-on yoga therapy on the immune-inflammatory pathway in schizophrenia by examining plasma levels and gene expression levels of cytokines and complement proteins as well as by profiling promoter DNA methylation pattern of genes coding for cytokines and complement proteins.

Fifty-seven schizophrenia patients fulfilling DSM-V criteria were recruited into the study and randomized into Yoga therapy (n=28) and waitlist control (n=29) groups. Plasma levels of IL-1β, IL-6, IL-10, IL-17, C1q, C2, C3, C4, C5, C5a, Factor B and Factor H by Multiplex Suspension Assay, quantification of gene expression of Il1b, Il6, Il10, IL17, C3, C4 and C5 genes by quantitative PCR and promoter DNA methylation of Il1b, Il6, Il10, Il17, C3, C4 and C5 genes by pyrosequencing were carried out in all the study participants.

Plasma levels of IL-1β (Z score= 2.42, p=0.02) dropped significantly and C2 (Z score= 2.24, p=0.03) levels increased after 12-weeks of yoga therapy. The expression of Il1b (Z score=2.45, p=0.01) and Il6 (Z score=2.07, p=0.04) genes were significantly downregulated, while the levels of C4 (Z score=2.23, p=0.03) gene was upregulated in schizophrenia patients of yoga therapy group. Two CpG sites in the promoter region of Il1b (all p≤0.05) and Il6 (all p≤0.05) genes and three CpG sites in the promoter region of C4 (all p<0.05) gene were hypermethylated, while two CpG sites in the gene body of Il6 (all p≤0.05) gene and two CpG sites in the promoter region of Il10 (all p ≤0.05) gene were hypomethylated after 12-weeks of yoga therapy in schizophrenia patients.

Our findings provide important insights into the mode of action of yoga therapy in schizophrenia. This study for the first time reports the epigenetic effects of yoga therapy on immune-inflammatory pathway in schizophrenia.

None Declared

Previous research has implicated herpes simplex virus 1 (HSV1) and cytomegalovirus (CMV) in severe mental illness (SMI) with conflicting results. Both pathogens have high universal seroprevalence, are neurotropic and after the primary infection typically establish a persistent latent infection with periodic reactivations. Increased immunoglobin G (IgG) concentrations are considered to be attributable to an increased infection severity with more frequent reactivations or host immune system alterations.

We assessed the HSV1 and CMV IgG concentrations in previously infected (seropositive) patients with SMI and healthy controls (HC). We hypothesized that seropositive patients would show higher IgG concentrations than seropositive HC.

We included 765 patients, 515 with schizophrenia (SZ) and 250 with bipolar disorder (BP), and 541 HC. HSV1 and CMV IgG seropositivity and concentrations were measured with immunoassays. 355 patients, mean age 33 years, 45% females, and 238 HC, mean age 35 years, 44% females, were HSV1 seropositive (HSV1+) while 447 patients, mean age 33 years, 50% females, and 296 HC, mean age 34 years, 47% females, were CMV seropositive (CMV+). In our main analysis among seropositive participants, we investigated the main effect of patient/control status on HSV1 and CMV IgG concentrations.

There were no significant differences in CMV or HSV1 seropositivity frequencies between patients with SZ, patients with BP and HC. Among seropositive participants, patients had higher HSV1 (p<0.001) and CMV (p=0.018) IgG concentrations than HC; stratifying by diagnosis, both patients with SZ (p=0.001) and patients with BP (p=0.001) had higher HSV1 IgG concentrations than HC, while patients with SZ, but not BP, had higher CMV (p=0.045) IgG concentrations than HC (Image). For HSV1, higher IgG concentrations were associated with higher general (p=0.017), negative (p=0.041) and positive (p=0.028) psychotic symptom scores.

Image:

Seropositive patients with SMI showed higher HSV1 and CMV IgG concentrations than seropositive HC suggesting that patients suffer a more severe infection or exhibit an altered immune response when contracting the pathogens. For HSV1, higher IgG concentrations were linked to more psychotic symptoms.

D. Andreou: None Declared, N. E. Steen: None Declared, K. N. Jørgensen: None Declared, T. Ueland: None Declared, L. Wortinger: None Declared, L. Mørch-Johnsen: None Declared, R. Yolken: None Declared, O. Andreassen Consultant of: Consultant to HealthLytix, Speakers bureau of: Received speaker’s honorarium from Lundbeck and Sunovion, I. Agartz Speakers bureau of: Received speaker’s honorarium from Lundbeck

An early and comprehensive neurobiological characterization of severe mental disorders could elucidate mechanistic pathways, aid the development of novel therapeutics, and therefore enable timely and targeted intervention in at-risk youth and young adults. Therefore, we present an unsupervised transdiagnostic machine learning approach to investigate shared and distinct patterns of early-stage depressive and psychotic disorders on multiple clinical and neurobiological levels.

To derive multi-level neurobiological and clinical signatures of early-stage affective and psychotic disorders in adolescents and young adults.

From the multicenter prospective European PRONIA cohort, we acquired data from 678 individuals (51% female) comprising young, minimally medicated in- and outpatients with clinical high-risk (CHR) states for psychosis, with recent-onset depression (ROD) or psychosis (ROP), and healthy control (HC) individuals. Within repeated nested cross-validation frameworks, we employed Sparse Partial Least Squares Analysis to detect associations between blood markers and grey matter volume (GMV), followed by support vector machine prediction of these signatures using biographical, clinical, neurocognitive, proteomic, and functional data.

Our results demonstrated a psychosis staging signature separating ROP from CHR individuals via GMV patterns in the cortico-thalamo-cerebellar circuitry with a blood marker set of elevated of IL-6, TNF-α and CRP (ρ = 0.272; P = 0.002). A depression signature separated ROD from HC individuals via altered GMV in the limbic system with a blood marker set of elevated IL-1ß, IL-2, IL-4, S100B and BDNF (ρ = 0.186; P = 0.021). Only the psychosis staging signature showed a distinct proteomic enrichment regarding innate immune response, abnormal neutrophil function, cellular senescence, and anti-inflammatory drugs (Balanced Accuracy (BAC) = 87.73%; Area Under the Curve (AUC) = 0.94). Childhood trauma differentially predicted psychosis and depression signatures, while past level of functioning, personality and quality of life was predictive of both signatures (BAC = 67.19-78.00%; AUC = 0.71-0.83).

Image:

Image 2:

Image 3:

Psychosis and depression exhibit distinct multi-level signatures evident in early disease stages. Enhanced insight into these signatures could help delineate individual trajectories and potentially new mechanisms for pharmacological treatment.

None Declared

The synaptic pruning process is based on the joint action of the complement system and microglia. In schizophrenia, accumulating evidence support that abnormal synaptic pruning during adolescence may be due to an altered Complement system activity. While this hypothesis is supported by C4 overexpression in various brain regions of individuals with schizophrenia, such alterations should be replicated and extended to other brain regions. Moreover, transcriptional studies of genes encoding regulators of the complement system activity (complement control proteins, CCP) and microglia-specific genes are lacking. Furthermore, it remains unknown whether brain and peripheral expression of such genes are related.

To explore expression of C4 as well as 4 CCP encoding genes and 10 microglia-specific genes at the brain and peripheral levels in individuals with schizophrenia as compared to healthy controls.

We analyzed candidate gene expression from 9 Gene Expression Omnibus datasets obtained from 333 individuals with schizophrenia and 306 healthy controls (HC). We first compared expression of the candidate genes between individuals with schizophrenia and HC in postmortem brain samples from 7 different brain regions. Then, the same comparison was made in 4 different peripheral tissues.

Regarding the complement system, we observed C4 overexpression in the DLPFC, parietal, temporal cortex and associative striatum of individuals with schizophrenia. We report distinct altered expression patterns of CCP genes in the DLPFC, hippocampus and cerebellum of individuals with schizophrenia. Only CD46 expression was altered in the blood of individuals with schizophrenia. Regarding microglia, we report an underexpression of several microglia-specific genes in the cerebellum, associative striatum, hippocampus and parietal cortex of individuals with schizophrenia vs. HC. At the peripheral level, we observed a mixed altered expression pattern in the whole blood of individuals with schizophrenia.

Firstly, our results suggest that the CCP-mediated regulatory mechanisms of the Complement system are impaired in the brain of individuals with schizophrenia, potentially contributing to an excessive Complement system activity (CSA). Secondly, our results support the hypothesis of a widespread underexpression of microglia-specific genes in brain tissues of individuals with schizophrenia. Functionally, the observed transcriptional alterations may be related to the synaptic pruning impairment. Alternatively, they may translate a compensatory mechanism for neuroinflammation. In the whole blood, the altered transcriptional pattern may represent a potential peripheral signature of SZ.

None Declared

Given the negative impact of anxiety and depression on society and the shortage of new antidepressants, it is of paramount importance to make the best use of available treatment options. Therapeutic drug monitoring (TDM) in escitalopram treatment can potentially be clinically useful, as underexposed patients show reduced efficacy of escitalopram treatment and as adverse drug reactions (ADRs) of escitalopram are dose-dependent.

This prospective cohort study aimed to investigate whether escitalopram treatment efficacy or safety are associated with escitalopram dose adjustment based on TDM readouts.

89 included patients aged between 15 and 65 years who suffered from depression were enrolled in the study before starting treatment with escitalopram. Patients were assessed one day before starting treatment with the recommended dose of 10 mg/day escitalopram (baseline, visit 0) and at follow-up after four and eight weeks. Dose adjustment at four-week follow-up was based on the measured escitalopram plasma level two weeks after treatment initiation; patients who required dose increase to 15 or 20 mg/day comprised comparator group, patients who did not required dose increase comprised control group, while patients who did not reach optimal exposure at eight-week follow-up were characterized as non-compliers. Treatment efficacy was approximated by the relative change on the Hamilton Depression Rating Scale (HAMD), while safety was approximated based on the changes on the Scandinavian UKU side effect rating scale and ECG readouts. Changes in HAMD, UKU score and QTc interval were compared between groups by one-way ANOVA or chi-square tests.

Compared to baseline, significant reductions in HAMD scores of 36% (95%CI, 30%-43%) and 53% (95%CI, 47%-60%) were observed at four- and eight-week follow-up, respectively; however, there were no significant differences between groups (p > 0.1). In the groups adjusted to 15 and 20 mg, 15/26 and 19/33 patients, respectively, reported adverse effects, compared with 6/17 patients in the control group and 6/13 in the non-complier group (p>0.1). A significant mean QTc prolongation of 6.40 ms (95%CI, 3.27-9.53) was observed between the baseline and eight-week follow-up (p=0.0013), without significant differences in QTc interval prolongation between groups (p > 0.1).

Escitalopram dose adjustment resulted in optimal drug exposure and solid treatment response in the majority of patients; however, no differences in efficacy were found between the patients who required dose adjustments, the ones who did not, and the ones who ultimately did not achieve optimal exposure. In addition, the selective increase of the dose to the patients who did not reach optimal drug exposure on the recommended dose of 10 mg/day did not lead to significant increase in adverse drug reactions and QTc prolongation.

None Declared

Mental disorders often manifest broad cognitive deficits that detrimentally affect daily functioning. Stress indicated by heart rate variability (HRV) has been linked to these cognitive functions.

We aimed to develop a new method to assess cognitive performance and simultaneous measurement of psychophysiological signals related to stress and relaxation levels.

20 adult patients with mental disorders in a rehabilitation program were recruited along with 21 healthy volunteers. A test protocol was carried out with a purpose-developed computerized psychophysiological device. The protocol consisted of a relaxation period; digitized questionnaires on pathological distress (GHQ) and sense of coherence (SOC); gamified cognitive tasks to assess working memory, attention, and decision-making; and a final relaxation period. Acute stress was assessed by heart rate variability measured by a wireless ECG sensor. The inter-beat interval’s root mean square of successive differences (RMSSD) was calculated as an inverse stress measure. Relaxation levels were assessed by the relative power of the alpha frequency band measured by a commercial 4-channel EEG headband. Stress and relaxation levels were compared to the first relaxation period as a baseline.

Patients scored worse than the reference group both regarding distress (d=7, p=0.004) and sense of coherence (d=-8, p=0.047). The cognitive performance of patients was significantly lower (p<0.001) than the reference group for all tasks.

RMSSD at baseline tended to be lower for patients (d=-12.69, p=0.098), reflecting a higher level of physiological stress; 61% of patients started at an elevated stress level compared to 25% of the reference group. In addition, relative alpha levels at baseline were also lower (d=-5.8%, p=0.007) for patients.

Compared to baseline, RMSSD decreased on average to 94% during cognitive assessments in patients and decreased to 91% by the end of the final relaxation. RMSSD decreased to 76% in the reference group and reached a final value of 78% of the baseline. Alpha levels slightly increased among patients during the tasks (103.4%) and then returned close to baseline (99.1%). For the reference group, alpha decreased during the tasks (95.5%) and then slightly increased (97.3%).

Patients displayed heightened distress, reduced sense of coherence, and inferior cognitive scores compared to controls. While starting with higher stress, patients exhibited less elevation in stress during tasks, coupled with alterations in alpha levels, suggesting diminished engagement or focus. Our innovative method could aid in the diagnostics of cognitive performance in mental patients after further measurements for validation.

None Declared

Posttraumatic stress disorder (PTSD) and personality disorders (PD) often co-occur and treatment dropout remains a challenging problem for both disorders. The literature on predictors of treatment dropout is highly mixed and few reliable predictors have been identified for both PTSD and PD treatments separately, let alone for concurrent PTSD and PD treatment.

The aim of the present study was to identify predictors of treatment attendance among a wide range of variables in patients with PTSD and comorbid PD who received trauma-focused treatment with and without concurrent PD treatment.

Data were used from the prediction and outcome study in comorbid PTSD and personality disorders (PROSPER), a study consisting of two randomized clinical trials (RCT) testing the effectiveness of trauma-focused treatment (eye movement desensitization and reprocessing or imagery rescripting) with versus without concurrent PD treatment (dialectical behavior therapy or group schema therapy). 256 patients with PTSD and comorbid personality disorder participated in the study. The potential predictors included demographic (e.g. work status), patient severity (e.g. PTSD severity), patient-therapist (e.g. working alliance) and therapist (e.g. therapist experience) variables. The ordinal outcome variable was treatment attendance (0, 1-7, 8-11, 12+ trauma-focused treatment sessions). Relevant predictors were identified by a series of ordinal regression analyses (threshold for inclusion p < .10). Relevant predictors were then entered together in a final ordinal regression model. Multiple imputation was used to handle missing data.

The final model included ten predictor variables and provided a good fit for the data (pooled R2Nagelkerke = .29). Higher education level (OR = 1.22, p = .009), self-rated PTSD severity (OR = 1.04, p = .036) and working alliance (OR = 1.72, p = .047) were associated with a larger number of attended sessions. Higher levels of inadequate social support from a friend (OR = 0.90, p = .042) and being randomized in the concurrent treatment condition (OR = 0.52, p = .022) were associated with a smaller number of attended sessions.

In terms of treatment attendance rates, the results suggest that trauma-focused treatment is preferred over concurrent trauma-focused and personality disorder treatment for patients presenting with PTSD and PD. Clinicians should further be aware of the risk of lower treatment attendance for patients with a lower educational background and those reporting inadequate social support. Enhancing working alliance may protect against early treatment termination. Finally, patients with higher levels of PTSD severity at baseline may need a larger number of treatment sessions.

None Declared

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. It is considered that dysregulation of cytokine levels is related to the pathophysiological mechanism of OCD. However, the results of previous studies on cytokine levels in OCD are inconsistent.

To perform a meta-analysis assessing cytokine levels in peripheral blood of OCD patients.

We searched in PubMed, Web of Science, and Embase from inception to March 31, 2023 for eligible studies. We conducted multivariate meta-analysis in combined proinflammatory cytokines (interleukin-6 [IL-6], IL-1β, IL-2, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]) and combined anti-inflammatory cytokines (IL-10 and IL-4) respectively, and calculated the same meta-analysis in each cytokine. We also performed sensitivity analysis and publication bias tests, as well as subgroup analysis (i.e. different age groups, varied cytokine measurement methods, medication treated or naïve, and presence of psychiatric comorbidities) and meta-regression analysis (variables including patients’ sex ratio, age, age at symptom onset, illness duration, scores of Y-BOCS, family history of psychiatric disorders, and BMI).

17 original studies (13, 13, 10, 5, 4, 3, 2 studies for IL-6, TNF-α, IL-1β, IL-10, IL-2, IL-4, and IFN-γ, respectively), 573 patients (mean age, 25.2; 50.3% female) and 498 healthy controls (HC; mean age, 25.3; 51.4% female) were included. The results showed that the levels of combined pro- or anti-inflammatory cytokines and each signle cytokine were not significantly different between OCD patients and HC (all P>0.05), with significant heterogeneities in all analyses (I2 from 79.1% to 91.7%). We did not find between-group differences in cytokine levels in all subgroup analyses. Meta-regression analysis suggested that age at onset (P=0.0003) and family history (P=0.0062) might be the source of heterogeneity in TNF-α level. Sensitivity analysis confirmed that all results were stable, except for IL-4 where different cytokine measurement methods may be the contributing factor. Egger test did not find publication bias.

Our study showed no difference in cytokine levels between OCD patients and HC, but age at onset and family history may affect TNF-α level. Confounding factors such as age at onset, family history, and cytokine measurement methods should be controlled in future studies to further explore the immune mechanism of OCD.

None Declared

Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition characterized by a wide variety of phenotypic expressions. Several studies have reinforced the hypothesis of OCD heterogeneity by proposing subtypes based on predominant symptomatology (Mataix-Cols et al., 2005), course (Tukel et al., 2007), and comorbidities (Mahasuar et al., 2011). Early-onset OCD could be considered a neurodevelopmental subtype of OCD, with evidence of distinct neurocircuits supporting disease progression (Park et al., 2022).

The aim of the present study is to evaluate the sociodemographic and clinical differences between the early-onset and late-onset subtypes in a large patient cohort.

Two hundred and eighty patients diagnosed with OCD were consecutively recruited from the OCD Tertiary Clinic at Luigi Sacco University Hospital in Milan. Sociodemographic and clinical variables were analyzed for the entire sample and compared between the two subgroups (EO: early-onset, age <18 years [40%]; LO: late-onset, age ≥ 18 years [60%]).

The EO group showed a higher frequency of male gender (65.5% vs 34.5%, p< .001, see Figure 1a), a higher presence of lifetime psychiatric comorbidities (75.7% vs 24.3%, p =.025), and higher rates of Tic and Tourette disorders (7.2% vs 0%, p=.006) compared to the LO group. Additionally, in the EO subgroup, a longer duration of untreated illness was observed (9.05 ± 10.0 vs 5 ± 7.17; p<.001, see Figure 1b), along with a lower presence of insight (33.3% vs. 66.7%, p =.024). No significant differences emerged in the Yale-Brown Obsessive-Compulsive Scale scores between the groups.

Image:

Image 2:

The early-onset OCD subtype highlights a more severe psychopathological profile compared to the late-onset group. Exploring distinct manifestations and developmental trajectories of OCD can contribute to a better definition of homogeneous subtypes, useful for studying risk factors and defining targeted therapeutic strategies for treatment.

B. Benatti Speakers bureau of: Angelini, Lundbeck, Janssen, Rovi, N. Girone: None Declared, M. Vismara: None Declared, C. Bucca: None Declared, B. Dell’Osso Grant / Research support from: Angelini, Lundbeck, Janssen, Pfizer, Otzuka, Neuraxpharm, and Livanova, Speakers bureau of: Angelini, Lundbeck, Janssen, Pfizer, Otzuka, Neuraxpharm, and Livanova.

Panic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent.

This meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls.

We conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias and 10,000 Monte Carlo simulations to correct for multiple comparisons.

With data from 34 primary studies and a substantial sample size (N=2138), PD/AG participants, relative to age-matched healthy controls, exhibited a reliable pattern of statistically significant, (p<.05-0.0001; FWE-corrected) abnormal neural activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.

In this meta-analysis we found robust patterns of differential neural activation in participants diagnosed with PD/AG relative to age-matched healthy controls. These findings advance our understanding of the neural underpinnings of PD and AG and inform the development of brain-based clinical interventions such as non-invasive brain stimulation (NIBS) and treatment prediction and matching algorithms. Future studies should also investigate the neural similarities and differences between PD and AG to increase our understanding of possible differences in their etiology, diagnosis, and treatment.

None Declared