Findings demonstrate the high comorbidity of posttraumatic stress disorder (PTSD) and chronic pain following exposure to trauma. In exposure to child abuse (CA) in particular, findings imply that CA survivors are at a higher risk of suffering from chronic pain. However, the underlying mechanisms of these processes are yet to be uncovered.

This study examined a new mechanism pertaining to the potential role of intrusive pain flashbacks for explaining the link between CA, C/PTSD, and chronic pain following interpersonal trauma.

A community sample of 430 women (Sample A), and a sample of 164 women who were exposed to CA (Sample B) completed questionnaires assessing pain flashbacks, CA, C/PTSD symptoms, the experience of pain during the trauma, and chronic pain.

The findings showed that 8.9% of Sample A (N = 36), and 23.1% of Sample B (N = 37) reported experiencing pain flashbacks. In both samples, participants who experienced pain flashbacks reported more severe C/PTSD (p<0.001), compared to participants who experienced flashbacks without pain and those who did not experience pain flashbacks. Participants who experienced pain flashbacks reported more pain during CA (p = 0.001), which corresponded with the pain flashbacks areas (Figure 1). Finally, pain flashbacks were correlated with a higher risk of suffering from chronic pain in Sample B (p=0.002).

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The findings of this study reveal that pain flashbacks are associated with more rampant CA and are linked to greater psychopathology. The findings call for further investigation of the role of pain flashbacks in explaining the link between exposure to trauma, C/PTSD and later chronic pain.

None Declared

A variety of dimensions of psychopathology are observed in psychosis. However, the validation of clinical assessment scales, and their latent variable structure, is often derived from cross-sectional rather than longitudinal data, limiting our understanding of how variables interact and reinforce one another.

Using experience sampling methodology (ESM) and analytic approaches optimised for longitudinal data, we assess potential latent variables of commonly-reported symptoms in psychosis, and explore the temporal relationship between them.

N=36 participants with a diagnosis of schizophrenia or schizoaffective disorder provided data for up to one year, as part of the Sleepsight study. Using a smartphone app, participants self-reported clinical symptoms once daily for a mean duration of 323 days (SD: 88), with a response rate of 69%. Symptoms were rated using seven-point Likert scale items. Items included symptoms traditionally implicated in psychosis (feeling “cheerful”, “anxious”, “relaxed”, “irritable”, “sad”, “in control”, “stressed”, “suspicious”, “trouble concentrating”, “preoccupied by thoughts”, “others dislike me”, “confused”, “others influence my thoughts” and “unusual sights and sounds”). We used a sparse PCA (SPCA) model to identify latent variables in the longitudinal data. SPCA has previously been applied to longitudinal ESM data, and was developed to achieve a compromise between the explained variance and the interpretability of the principal components. We then used a multistage exploratory and confirmatory differential time-varying effect model (DTVEM) to explore the temporal relationship between the latent variables. DTVEM generates a standardised β coefficient reflecting the strength of relationship between variables across multiple time lags. Only significant lags (p<0.05) are reported here.

The SPCA analysis identified five latent variables, explaining 61.4% of the total variance. Tentative interpretation of the SPCA loadings suggested these latent variables corresponded to i) cognitive symptoms, ii) feeling in-control, iii) thought interference and perceptual disturbance, iv) irritability and stress and v) paranoia. Time lag analysis revealed an effect of feeling in-control on subsequent cognitive symptoms (β=-0.19), and of cognitive symptoms on subsequent thought interference and perceptual disturbance (β=0.14). Irritability and stress was also associated with subsequent cognitive symptoms (β=0.09).

Using longitudinal data, we employ novel methodology to identify potential latent symptoms among commonly reported symptoms in psychosis. We identify five latent symptoms, and elucidate important temporal relationships between them. These findings may inform our understanding of the psychopathology of psychosis, potentially offering data-driven simplification of clinical assessment and novel insights for future research.

None Declared

Excessive mind wandering is a common feature of ADHD in adulthood also referred to as mental restlessness and ceaseless mental overactivity. ADHD is a predisposing factor for many psychiatric symptoms, especially negative emotions such as depression and anxiety. Rumination is thought to be a mediator for depression in individuals with ADHD. The above-mentioned mental processes may reduce the ability of individuals with ADHD to be mindful.

This study investigates whether the mentation processes (excessive mind wandering, rumination, mindfulness) mediate the relationship between ADHD symptoms and anxiety, and depression in adults with ADHD.

Medication-free 175 individuals with ADHD who were referred to the Adult Neurodevelopmental Disorders Clinic, Department of Psychiatry, Selçuk University were invited to the study. After initial diagnostic examination including The Structured Clinical Interview for DSM-5 (SCID 5), all participants completed a test battery that included a sociodemographic form, the Adult ADHD Severity Rating Scale, the Hospital Anxiety Depression Scale, the Mind Excessively Wandering Scale, the Ruminative Response Scale, and the Freiburg Mindfulness Inventory. The data of 159 patients whose ADHD diagnosis was confirmed, who did not have any mood episodes and psychotic symptoms at the time of inclusion of the study, and who filled out the forms completely, were included in the analysis. The study was approved by the Selçuk University Local Ethics Committee.

Participants ages ranged from 18 to 39 (mean of 22.93 ± 4.36), and 57.2% (n = 91) were women. Also, their 48.6% (n = 77) reported that they alcohol use, and 21.1% (n = 34) had substance use history. According to SCID 5 interview, participants 64.2% had comorbid psychiatric conditions. Pearson correlation analysis revealed that ADHD symptoms, rumination, excessive mind wandering, anxiety, and depression scores were significantly positively correlated with each other, but all were negatively correlated with mindfulness. Linear regression analysis showed mindfulness association with rumination, excessive mind wandering, anxiety, and depression scores, but not with ADHD symptoms. Thereupon, a conducted mediation regression analysis showed that ADHD symptoms indirectly worsened depression and anxiety through increased rumination and excessive mind wandering, and decreased mindfulness ability (Figure 1).

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Adults with ADHD have distressing mentation patterns which worsened their anxiety and depression. Mindfulness-based cognitive behavioral therapy modalities may help improve excessive mind wandering and rumination in ADHD. Our findings should be warranted in future studies of functional brain connectivity patterns that may serve as a mentation endophenotypes in ADHD.

None Declared

Borderline personality disorder (BPD) is a severe mental disorder characterized by affective, behavioral and relational instability, along with interpersonal hypersensitivity and unstable affective relationships (APA 2013). Poor interpersonal functioning could be associated with critical deficits in the ability to mentalize in these patients, together with high levels of impulsivity. Although most studies have described hypermentalization deficits among BPD patients (Bora Psychol Med 2021;51 2541-2551), existing literature is still scarce on this aspect, as well as its relationship with the impulsive behavior.

1) to assess specific mentalizing deficits in BPD compared to healthy controls in a complex ecological mentalization task; 2) evaluate the relationship between mentalization and impulsivity in BPD.

63 patients diagnosed with borderline personality disorder and 31 control subjects were studied using the Movie for the Assessment of Social Cognition -MASC- (Dziobeck et al. J Autism Dev Disord 2006; 36 623-636) and the Barratt Impulsivity Scale -BIS-11- (Patton et al. J Clin Psychol 1995; 51 768-774), as well as other sociodemographic and clinical factors. The clinical research study was approved by the Clinical Research Ethics Committee of the Hospital Clínico San Carlos (Madrid, Spain).

The results showed significant differences in the scores related to correct mentalization, hypomentalization, and non-mentalizing responses between patients and controls, with BPD patients showing worse performance. A significant negative relationship was also observed between impulsivity scores and correct mentalizing responses in BPD patients.

The results showed a deficit in the ability to mentalize in BPD patients, compared to control subjects, characterized by a hypomentalization and an absence of mentalization. Likewise, this deficit in mentalization ability was related to greater impulsive behavior in patients. These results would be consistent with the hyperarousal hypothesis in BPD, which would reduce inhibitory control, causing mentalization deficits (Euler et al. J Pers Disord. 2021; 35 177-193). Future studies will try to associate specific impulsive behaviors associated with the characteristics of hypomentalization and absence of mentalization observed in our results.

None Declared

Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment and rTMS protocols have been included in international guidelines for patients with treatment-resistant depression (TRD). The daily administration of standard rTMS protocols, typically over several weeks, could be a limiting factor (e.g., time off from work, commuting issues). To intensify the antidepressant response and to reduce the number of stimulation days, it has been proposed that increasing the number of rTMS sessions performed per day could be more effective and help to reduce the burden for patients and clinicians. Although there is much interest in accelerated TMS protocols, little is known about their efficacy and tolerability, and the literature on the topic is still scarce.

To compare the efficacy and tolerability of two rTMS protocols (standard vs. accelerated) as augmentative strategies in patients with TRD.

In the present ongoing, open-label, trial 14 patients meeting DSM-5 criteria for major depressive episode (either unipolar or bipolar), classified as partial responders or non-responders to adequate pharmacological treatment, were randomized to receive either standard (one session per day, five days a week, for four weeks; n= 7) or accelerated (two sessions per day, five days a week, for two weeks; n=6) rTMS treatment protocols. In both cases, rTMS was performed on the left dorsolateral prefrontal cortex, high frequency (10 Hz) at 120% of the motor threshold, 3000 pulses per sessions. Primary outcome measures included HAM-D, MADRS, and CGI-S scores at baseline (T0), at the end of rTMS treatment (T1), and after 1 month (T2), as well as tolerability based on adverse effects. Paired Samples t-Test for continuous variables was used to compare psychometric scales at each timepoint, while t-Test was used to compare differences between the two groups.

With respect to total sample, in terms of primary outcome measures a significant reduction of HAM-D, MADRS and CGI-S total scores between T0 and T1 (t: 3.01, p<0.05; t: 1.692, p<0.5; t:3.207, p<0.05 respectively), T1 and T2 (t: 3.264, p<0.05: t:2.669, p<0.05; t:.085, p=0.437 respectively) and T0 and T2 (t:5.669, p<0.05; t=4.711, p<0.05; t:2.551, p<0.05 respectively) was found. No significant differences in terms of efficacy were found between the two groups. One patient dropped-out for reasons not related to rTMS treatment. Mild and transient headache during the stimulation was the only side effect reported (4 patients).

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Consistently with previous literature studies, our preliminary results supported the evidence of comparable efficacy and tolerability between accelerated and standard rTMS protocols. In the future, larger, blinded, and controlled trials might support these conclusions and further address treatment parameters of novel accelerated rTMS protocols.

None Declared

Eye movement desensitization and reprocessing (EMDR) is a psychotherapeutic approach that has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD). The technique is known to facilitate the reprocessing of maladaptive memories thought to be at the heart of this pathology.

Strong evidence shows that traumatic events can contribute to the onset of serious mental disorders and can worsen their prognosis.

Therefore, research on EMDR therapy has increased beyond PTSD and several studies have analyzed the effect of this therapy in other mental health conditions such as psychosis, bipolar disorder, depression, anxiety disorders, substance use disorders and chronic pain.

The objective of this systematic review is to summarize the most important results of available studies conducted in this area.

We performed a systematic literature search among PubMed, ScienceDirect and Scopus. Studies included work published up to 2021

The search was performed automatically by title in each database and included the keywords “EMDR”, “Eye Movement Desensitization and Reprocessing” excluding those focusing on trauma and PTSD

Studies are still sparse in these comorbid conditions, but available evidence suggests that EMDR therapy improves trauma-associated symptoms and has a minor effect on primary disorders by achieving partial symptomatic improvement. A positive effect has been reported in many pathological situations, including addictions, somatoform disorders, sexual dysfunctions, eating disorders, adult personality disorders, mood disorders, severe stress reaction, anxiety disorders, pain, neurodegenerative disorders, mental disorders of childhood and adolescence and sleep.

Despite a generally positive view of EMDR as an alternative treatment option, more methodologically rigorous studies are needed.

None Declared

Early life stress (ELS) associates with unfavourable outcome in Major depressive disorder (MDD) and treatment-resistant depression (TRD). Trauma-focused psychotherapy benefits TRD patients exposed to ELS. Epigenetic processes are altered in stress-related disorders, but few studies show epigenetic signatures associated with trauma.

We performed an epigenome-wide association study (EWAS) to explore the relation between methylation changes in TRD patients characterized for recent and ELS and trauma-focused psychotherapy outcomes.

Thirty TRD patients participated. They underwent psychotherapy, from which 12 cognitive behavioural therapy and 18 Eye Movement Desensitization and Reprocessing (EMDR). We used validated interviews and questionnaires for symptom evaluation and stress exposure. Patients were evaluated at T0 (baseline), T8 (end of psychotherapy), T12 (follow-up) and T26. Methylation was profiled with Illumina Infinium EPIC array for T0, T8 and T12. Methylation levels were quantified after quality control and normalization using ChAMP R package. We tested the association between B-values for each CpG site (each probe set) and each phenotype/condition using a linear model approach (with paired values) as implemented in the Limma R package. P-values were adjusted using Benjamini & Hochberg method. Probe sets were considered significant with an adjusted p-value q ≤ 0.05. CpG site annotation was performed using IlluminaHumanMethylationEPICanno.ilm10b2.hg19 R package (hg19 genome reference).

Association analyses between baseline methylation levels and emotional abuse resulted in two significant probe sets annotated in SLCO4A1 (p=1,72E-08; q=0,008), involved in sodium independent transmembrane substrate transport, and GPNMB (p=1,53E-07; q=0,022), involved in cell differentiation. Associations between baseline methylation levels and physical abuse resulted in one significant probe set annotated in DDIT4L (p=4,77E-08; q=0,035), involved in cell growth.

In longitudinal analyses, association between T0-T8 methylation levels and response at T8 resulted in two significant probe sets annotated in PLEKHB1 (p=3,54E-08; q=0,013), involved in cell differentiation, and NUDT4P2 (p=1,34E-07; q=0,032). Longitudinal T12-T0 EWAS analyses in patients undergoing EMDR resulted in 44 significant probe sets annotated in genes, highlighting MAD1L1 (p=6,28E-07; q=0,035), involved in cell division, and TNFAIP3 (p=3,00E-06; q=0,045), which regulates immunity.

We identified epigenetic signatures of ELS in TRD patients, suggesting that ELS may modulate the intensity of epigenetic alterations. Longitudinal methylation analyses along psychotherapy showed significant genes in relation to response, especially for patients undergoing EMDR. Some genes are associated with post-traumatic stress disorder (MAD1L1) and anxiety disorders and MDD (TNFAIP3).

None Declared

Cancer treatments can have a detrimental impact on cancer survivors’ cognitive function. Cognitive rehabilitation is considered the first-line intervention to address cognitive difficulties of cancer survivors. Nevertheless, its efficacy remains unclear.

This meta-analysis aimed to understand the effects of cognitive rehabilitation in non-central system (non-CNS) cancer survivors, through the assessment of the overall efficacy on subjective cognitive outcomes.

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. An electronic search on the databases PubMed, Scopus, and Web of Science was conducted in May 2021, considering the past 15 years, by two independent authors. Studies were eligible if they included cancer survivors (excluding CNS cancers) who were exposed to cognitive rehabilitation interventions, in which the subjective cognitive effects were measured through self-report questionnaires. The quality of studies was assessed using the Cochrane Risk of Bias Tool for Randomized Trials. The effect size was the standardized mean difference in the cognitive assessment, between baseline and post-intervention. Statistical heterogeneity was assessed using I2 Statistic. Publication bias was evaluated with Egger’s test. P<0.05 was considered statistically significant. The meta-analysis was performed using R software.

Among 14 studies, with 1115 cancer survivors, one study included a pediatric population, other young adult survivors, and the remaining adult population. The most used scale for measuring cognitive changes was the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and, as recommended, the Perceived Cognitive Impairments (PCI) subscale was used as the primary measure of subjective cognitive function. Results indicated beneficial effects following cognitive rehabilitation, with an overall standard mean difference between pre- and post-treatment of 3.4447, with CI95% [1.5543; 5.3350], p-value<0.0004. The subgroup analysis between the measures of cognitive outcomes showed that the heterogeneity is Group=Other 0.00% (I2) and for the Group=FACT-Cog PCI is 86% (I2). Analyzing the FACT-Cog PCI, the CI95% [-2.93; 6.43] includes 0, meaning that the overall effect in this subgroup is non-significant. The meta-analysis does not demonstrate publication bias (p-value of the Egger test=0.3220).

Improvement of cognitive function in non-CNS survivors throughout cognitive rehabilitation appears to be effective. The findings of this meta-analysis can help inform clinical practice and assist practitioners in recommending and developing interventions of cognitive rehabilitation and deciding how to evaluate them. Further research is required to strengthen this evidence.

None Declared

Many people with lived experience from psychosis recover and thrive, contrary to the common stigmatizing belief that they will be chronic “patients”. But there are several ways to understand recovery, one is as a subjective process best explored through qualitative interviews with people who have recovered from psychosis. However, there is a need for more qualitative interview studies exploring what has been important for long-term subjective recovery for people with lived experience from psychosis outside of treatment. Exploring themes that are novel than previous research will have important clinical implications.

This study aims to qualitatively explore what people with lived experience from psychosis believe has been the most important to attain and sustain their long-term personally defined recovery.

Qualitative interviews with 20 individuals participating in two follow-up-studies (TOP and TIPS-study) 10 and years 20 years after first treatment for a psychotic disorder (schizophrenia- or bipolar spectrum), respectively. All participants were in either clinical recovery (symptom remission and adequate functioning) or personal recovery (self-rated questionnaire) or both. Interviews were analyzed with thematic analysis in group meetings between the PhD-candidate, the main supervisor, a professor emerita in qualitative method and a co-researcher with lived experience from bipolar disorder.

Participants defined recovery differently, but: “understanding myself”, “stable symptoms” and “finding the life that is right for you” were of the most common definitions. Tentatively, five main themes appear to be the most salient contributions to recovery: 1. Balance stress management with taking risks and following personal goals. 2. Accepting experience/”owning your story” in order to strategically disclose and manage stigma. 3. Taking agency over own recovery and mastery of everyday life. 4. Social support is crucial, but should change over time depending on need. 5. Feeling a sense of belonging to society does not need to entail “normality”.

Recovery was defined differently by each participant, but common themes across participants highlight that appropriate risk-taking, accepting your experience/owning your story, sense of agency, social support and inclusion are important to long-term recovery in psychosis.

None Declared

Major Depressive Disorder is a frequent and disabling condition. More than 20% of patients do not respond to pharmacotherapy alone, so there is the need to find alternative strategies in order to potentiate the drugs. Therapeutic alternatives include repetitive Transcranial Magnetic Stimulation (rTMS), which has shown an antidepressant effect in the last decades.

Comparison of the efficacy of accelerated repetitive Transcranial Magnetic Stimulation (aTMS) treatment (4 sessions/day for 5 days) with the standard rTMS protocol treatment (1 session/day for 4 weeks), using the FDA-approved parameters.

33 patients affected by Major Depressive Episodes treated with either Fluvoxamine or Venlafaxine were enrolled. Patients were randomly assigned to the two protocol groups: standard rTMS protocol (15 patients) and aTMS protocol (18 patients). In the standard protocol, patients received 1 rTMS session/day for 4 weeks, while in the aTMS protocol they received 4 rTMS sessions/day for 5 days. Symptomatological improvement was evaluated through MADRS, BDI-II and SSI rating scales administered on day: 0, 1, 2, 3, 4, 5, 14, 21, 28, 56. The study is single-blind, since the clinical rater was unaware of the treatment protocol group. Response and remission rates were calculated, defined respectively as a reduction ≥50% in the MADRS score and a MADRS score <10.

The analysis was carried out on 32 patients (18 in the aTMS group and 14 in the rTMS group). ANOVA for repeated measures shows a statistically significant difference in the MADRS scores on day 5 (p=0.001) and on day 56 (p=0.037). Regarding the BDI-II evaluation, the differences were not fully statistically significant on day 5 and not significant on day 56. No statistically significant differences between the two protocols were observed in the SSI assessment. The aTMS and rTMS response rates were respectively 84.6% vs 45.5% on day 28 (p=0.043) and 92.3% vs 45.5% on day 56 (p=0.012). The aTMS and rTMS group remission rates were respectively 76.9% vs 18.2% on day 28 (p=0.004) and 69.2% vs 36.4% on day 56 (p=0.107). Concerning side effects, no statistically significant differences were observed between the two groups.

Treatment with aTMS seems faster and more effective than treatment with standard rTMS in improving the clinical condition in patients with Major Depressive Episodes, allowing to treat patients in just 5 days instead of 4-6 weeks, without impacting on side effects and tolerability.

None Declared

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19.

The main objective was two-fold: (i) to test the hypothesis that the prevalence of antidepressant use in patients hospitalized with COVID-19 would be lower than in patients with similar characteristics hospitalized without COVID-19, and (ii) to examine, among patients hospitalized with COVID-19, whether antidepressant use is associated with reduced 28-day mortality. Our secondary aim was to examine whether this potential association could only concern specific antidepressant classes or molecules, is dose-dependent, and/or only observed beyond a certain dose threshold.

We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP–HP (Assistance Publique–Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482) (Figure 1).

Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35–0.41, p < 0.001) (Figure 2). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41–0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents (Figure 3). Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations.

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Antidepressant use is associated with a reduced likelihood of hospitalization in patients infected with SARS-CoV-2 and with a reduced risk of death in patients hospitalized with COVID-19. These associations were stronger for molecules with high FIASMA activity. These findings posit that prospective interventional studies of antidepressants with the highest FIASMA activity may be appropriate to help identify variant-agnostic, affordable, and scalable interventions for outpatient and inpatient therapy of COVID-19.

None Declared

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19.

The aim of this sudy was to test the potential antiviral and anti-inflammatory activities of fluoxetine against SARS-CoV-2 in a K18-hACE2 mouse model of infection, and against several variants of concern in vitro, and test the hypothesis of the implication of ceramides and/or their derivatives hexosylceramides.

We evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5.

Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres (Figure 1) and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10) (Figure 2). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects (Figure 3).

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Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.

None Declared

Many different long-term neuropsychiatric sequelae of the novel Coronavirus have been described after the pandemic outbreak. One of the most common symptoms in the months following infection is related to “brain fog”. This condition includes several signs of cognitive impairment like mental slowness, deficits in attention, executive functions, processing, memory, learning, and/or psychomotor coordination, which can be perceived on a subjective level and further confirmed by objective data. Since this kind of mental status has been documented in previous viral infections, and the SARS-COV-2 has been characterized by a worldwide diffusion, investigation into this condition in post-covid individuals is warranted. Currently, several hypotheses on its pathophysiology have been put forward, mostly hypothesizing a direct effect of the virus on the central nervous system or indirect consequences of the inflammatory response.

The aim of our research is to analyze brain correlates of subjective cognitive complaints in Covid-19 survivors using multimodal brain imaging.

We performed a voxel-based morphometry (VBM) and a resting state functional connectivity analysis on 60 post-COVID-19 individuals recruited from the San Raffaele Hospital in Milan, that underwent a 3 tesla MRI scan. We assessed the perceived cognitive impairment both after the infection and at the time of the MRI scan through the PROMIS Cognitive Abilities scale. The difference of the two scores (delta PROMIS) was calculated as a measure of cognitive improvement over time.

We found the perceived amelioration of cognitive abilities (delta PROMIS) to be positively associated to grey matter volumes in the bilateral caudate, putamen and pallidum (pFWE: ˂0.001). Moreover, in the resting state fMRI analysis, subjective cognitive status at MRI was found to be associated with functional connectivity between the right putamen and pallidum, and two clusters belonging to the attentional (pFWE: ˂0.001) and salience (pFWE: 0.02) networks.

This is one of the first studies investigating brain correlates of subjective cognitive impairment after COVID-19 infection; our main finding is the convergence of structural and functional results on brain areas located within the basal ganglia, implying their possible role in the pathophysiology of the condition. Moreover, this research could be interpreted as the first step toward understanding a very complex condition, with potential implications for the development of treatment and neurorehabilitative strategies.

None Declared

Cross-sectional data has shown that compassion for self and from others may be a protective factor for greater psychosocial wellbeing in the COVID-19 pandemic whilst fears of compassion act as a risk factor for experiencing mental health difficulties.

The current study sought out to explore the natural fluctuation of compassion (for self, for others and from others) and of fears of compassion (for self, for others and from others) across time during the COVID-19 pandemic in a multinational community sample.

Data from 4057 participants from 21 countries was collected at 3 time points during the pandemic (baseline, 3 months and 6 months). Other than demographic variables, participants completed the Compassionate Engagement and Action Scales and the Fears of Compassion Scales. Multilevel latent growth modelling was used to investigate the main aims.

There was a significant increase in compassion for self and from others, whilst compassion for others remained unchanged throughout the 3 time points [Chi square 349.30(df=50) p< .001; RMSEA .035; CFI .93; TLI .91; SRMR (within) .043; SRMR (between) .70]. Fears of self-compassion and compassion for others significantly reduced throughout the pandemic whilst fears of compassion from others remained stable [Chi square 406.57(df=50) p< .001; RMSEA .038; CFI .96; TLI .94; SRMR (within) .042; SRMR (between) .35].

The findings from this study seem to suggest that in a period of shared suffering people from multiple countries and nationalities tend to become more compassionate and less afraid of and resistant to compassion for and from others.

None Declared

The COVID-19 pandemic caused significant disruption to the lives of children and their families. Pre-school children may have been particularly vulnerable to the effects of the pandemic, with the closure of childcare facilities, playgrounds, playcentres and parent and toddler groups limiting their opportunities for social interaction at a crucial stage of development. Additionally, for parents working from home, caring for pre-school aged children who require high levels of support and care, was likely challenging

We aimed to conduct an intensive longitudinal study to examine trajectories of pre-schoolers’ mental symptoms in the United Kingdom during the first year of the COVID-19 pandemic.

UK‐based parents and carers (n = 1520) of pre-school‐aged children (2 to 4 years) completed monthly online surveys about their pre-schoolers’ mental health between April 2020 and March 2021. The survey examined changes in children’s emotional symptoms, conduct problems and hyperactivity/inattention.

Pre-schoolers’ emotional problems and hyperactivity/inattention symptoms declined from April through summer 2020 and then increased again during the autumn and winter 2020/2021 as lockdowns were re-introduced. Pre-schoolers who attended childcare showed greater decline in symptom severity than those who did not. Older children, compared to younger, showed greater lability of emotion symptom severity. Attending childcare predicted lower symptom severity across all three domains of conduct problems, emotional symptoms, and hyperactivity/inattention, while the opposite pattern was observed for children whose parent had a mental health problem.

Our findings reinforce the importance of examining pre-schoolers’ mental health in the context of micro and macro-level factors. Interventions focusing on family factors such as parent mental health, as well as continued provision of childcare, may have most potential to mitigate the impact of COVID-19 on young children’s mental health.

None Declared

After coronavirus disease 2019 (COVID-19) infection, many individuals reported neurological and psychiatric sequelae, including cognitive impairment, even several months after the acute infection.

The present study aims to provide a critical overview of the literature on the relationships between post-acute COVID-19 infection and cognitive impairment, highlighting limitations and confounding factors.

A systematic search of articles published from January 1st, 2020, to July 1st, 2022 was performed in Pubmed/Medline. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Only studies using validated instruments for the assessment of cognitive impairment were included. Out of 5478 screened records, 72 studies met inclusion criteria. Time of patients’ assessment varied from 4 weeks to 12 months after the infection. The available evidence revealed the presence of impairment in executive functions, attention and memory in subjects recovered from COVID-19. However, several limitations of the literature reviewed should be highlighted: most studies were performed on small samples, not stratified by severity of disease and age, used a cross-sectional or a short-term longitudinal design, and provided a limited assessment of the different cognitive domains. Few studies investigated neurobiological correlates of cognitive deficits in individuals recovered from COVID-19.

Based on the literature reviewed, it is difficult, to date, to draw conclusions about the relationships between COVID-19 infection and cognitive impairment. Therefore, further studies with an adequate methodological design are needed in order to better understand these relationships, identify neurobiological correlates of COVID-related cognitive deficits and evaluate their course over time. Enhancing the knowledge on this topic could favor the development of effective therapeutic strategies for cognitive deficits in individuals recovered from COVID-19.

None Declared

Sexual and gender minority (SGM) college students endorsed higher psychological distress and worsened mental health outcomes than their cisgender heterosexual peers. Such disparity is exacerbated during the COVID-19 pandemic, during which SGM youth may be sent home to unaccepting environments or presented with fewer healthcare options. The “Black lives matter (BLM)” and “Anti-Asian Hate” also exposed college students disproportionally to more witnessed discrimination and poorer social cohesion, which in turn, might negatively affect the mental health outcomes.

The present study aims to explore the mental health outcome profile within SGM college students by (1) identify mental health disparities across different sexual and gender identities and (2) evaluating the impacts of discrimination, social cohesion and other factors on mental health outcomes of college students with different sexual and gender identities.

The study utilizes the 2020-2021 Healthy Minds Study data with 139,470 college students across 60 U.S. campuses. Multivariable regression models are built with minority status to predict mental health outcome (depression, anxiety, and suicidal ideation).

SGM students reported higher symptoms of depression, anxiety, and suicidal ideation. Besides, SGM individuals having experienced or witnessed discrimination or hostile behaviors due to their race/ethnicity also showed worse mental health outcomes. Noted, perceived stronger social cohesion is a protective factor for lower depression (OR: 0.59; 95%CI: 0.45, 0.78) and anxiety (OR: 0.69; 95%CI: 0.51, 0.93) symptoms in SGM, while perceived weaker social cohesion is a risk factor for depression (OR: 1.37; 95%CI: 1.14, 1.64) and anxiety symptoms (OR:1.32; 95%CI:1.09-1.59) in cisgender heterosexual individuals.

These findings acknowledge the negative impact of discrimination on mental health, highlight the importance of recognizing social cohesion affect differently in SGM and their peers, and enhance the understanding of differential impact of social cohesion to inform public policy and early intervention in vulnerable populations during COVID-19 pandemic.

None Declared

Covid -19 pandemic challenged health care personnel, especially frontline employees. The increased workload was unevenly distributed.

The aim of the present study is to assess potentially traumatic pandemic work-related events (PTEs), psychological distress and insomnia symptoms especially among employees who were in the frontline June 2020, after 24 -month follow-up.

Participants were recruited from the Helsinki University Central Hospital personnel on June 2020 and followed via electronic surveys for 24 months. Mental Health Index 5 (MHI-5) and Insomnia Severity Index (ISI) was used to assess psychological distress and insomnia symptoms. Potentially traumatic events related to pandemic work (PTEs) were asked. The study is described in detail elsewhere (R1, R2).

On May 2022, early frontline employees from June 2020 (N=1171) continued to report a greater frequency of PTEs compared to those not in early frontline (N=3623) (19.4% vs. 9.5%; OR = 2.29, 95% CI = 1.51–3.46). They did not report statistically significantly greater frequency of psychological distress (14.2% vs. 9.9%; OR = 1.5, CI = 0.96–2.35), nor sleep problems (8.9% vs. 5.8%; OR = 1.57, CI = 0.91–2.72). The difference was not quite significant for the continuously varying MHI-5 scores either (p = 0.058 in t-test and p = 0.064 for Kruskal-Wallis test), but the continuous ISI scores at the last follow up were still statistically significantly higher for the early frontline employees than for the non-frontline employees (6.82 vs. 5.51; p = 0.001 in t-test and p = 0.001 in Kruskal-Wallis test). Attrition from the study was higher among the early frontline personnel compared to others. The odds of no show at 24-month wave were 1.42-fold for those at the frontline (95% CI = 1.2–1.68). This effect was not fully explained by age, sex, profession or having experienced a potentially traumatic event at the baseline.

Early frontline employees who participated the 24 -month follow-up, did not report significantly more psychological distress than other employees. Subthreshold changes in insomnia scale are in line with a recent meta-analysis R3.

R1. Haravuori H, Junttila K, Haapa T et al. Personnel Well-Being in the Helsinki University Hospital during the COVID-19 Pandemic-A Prospective Cohort Study. Int J Environ Res Public Health. 2020 Oct 28;17(21):7905.

R2. Laukkala T, Suvisaari J, Rosenström T et al. COVID-19 Pandemic and Helsinki University Hospital Personnel Psychological Well-Being: Six-Month Follow-Up Results. Int J Environ Res Public Health. 2021 Mar 4;18(5):2524.

R3. AlRasheed MM, Fekih-Romdhane F, Jahrami H et al. The prevalence and severity of insomnia symptoms during COVID-19: A global systematic review and individual participant data meta-analysis. Sleep Med. 2022 Aug 8;100:7-23.

None Declared

Persisting and disabling depressive symptomatology represent a prominent feature of the post-acute COVID-19 syndrome. Sars-CoV-2-induced immune system dysregulation mainly result in a cytokine storm. Once in the brain, inflammatory mediators negatively affect neurotransmission, microglia activation, and oxidative stress, possibly disrupting critical brain neurocircuits which underpin depressive symptoms. So far, only inflammatory markers based on leukocyte counts have been linked to depressive outcome in COVID survivors. However, an accurate immune profile of post-COVID depression has yet to be elucidated.

Identify inflammatory mediators that predict post-COVID depression among a panel of cytokines, chemokines, and growth factors, with a machine learning routine.

88 COVID age- and sex-matched survivors’ (age 52.01 ± 9.32) were screened for depressive symptomatology one month after the virus clearance through the Beck Depression Inventory (BDI-13), with 12.5% of the individuals scoring in the clinical range (BDI-13 ≥ 9). Immune assay was performed through Luminex system on blood sampling obtained in the same context. We entered 42 analytes into an elastic net penalized regression model predicting presence of clinical depression, applied within a 5-fold nested cross-validation machine learning routine running in MATLAB. Significance of predictors was evaluated according to variable inclusion probability (VIP), as returned by 5000 bootstraps. Socio-demographics, previous psychiatric history, hospitalization, time after discharge were used as covariates.

The model reached a balance accuracy of 73% and AUC of 77%, correctly identifying 73% of people suffering from clinically relevant depressive symptoms (Figure1). Depressive symptomatology was predicted by high levels of CCL17, ICAM-1, MIF, whereas CXCL13, CXCL12, CXCL10, CXCL5, CXCL2, CCL23, CCL15, CCL8, GM-CSF showed a protective effect (Figure2).

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This is the first study highlighting a putative inflammatory signature of post-COVID depression. Consistently to the immune profile of Major Depressive disorder, upregulation of innate immunity mediators seems to foster depressive symptoms in the aftermath of COVID. Interestingly, recruiters of B and T cells promoting a physiological adaptive response to viral infection also mitigate its psychiatric sequelae. Understanding the biological basis of post-COVID depression could pave the way for personalized treatments capable of reducing its add-on burden.

None Declared

Schizophrenia patients are at an increased risk for severe SARS-CoV-2 illness. Recent studies indicate that vaccines reduce morbidity gaps between schizophrenia patients and the general population; nonetheless, the ongoing emergence of COVID-19 variants and the increased frequency of breakthrough infections might lead to changes in these risk profiles.

In this study we aimed to bridge this gap by assessing the risk of COVID-19 infection, hospitalization, and mortality among vaccinated individuals with schizophrenia, as compared to vaccinated individuals with no schizophrenia, matched for age, sex, and vaccination coverage (first, second, and booster) throughout the first year of the vaccination plan.

The study included 50,958 vaccinated individuals: 25,479 individuals with schizophrenia and 25,479 without schizophrenia. Data were derived from the databases of Clalit Health Services, the largest healthcare organization in Israel.

Findings indicated that differences among vaccinated schizophrenia patients and controls were non-significant after adjusting for infection (HR = 0.93, 95%CI 0.84-1.03, p = 0.14) and mortality rates (HR = 2.18, 95%CI 0.80-5.90, p = 0.12). Nonetheless, differences in rates of hospitalization remained significant even after controlling for demographic and clinical factors (HR = 2.68, 95%CI 1.75-4.08, p<0.001). A longitudinal assessment of relative risk indicated that the rate ratio of differences between the groups increased during the fourth infection wave of the B.1.617.2 (delta) variant across all parameters, with schizophrenia patients demonstrating higher relative risk of hospitalization (RR = 4.19, 95%CI 2.41-7.23) and mortality (RR = 7.61, 95%CI 0.93-61.89) during the relevant periods.

These findings suggest that vaccination coverage is effective in narrowing overall morbidity and mortality gaps; nonetheless, individuals with schizophrenia are still at risk for severe COVID-19 outcomes.

None Declared