Despite being a clinical identifiable entity, major depressive disorder (MDD) is an heterogenous clinical syndrome, with a variety of clinical presentations which likely reflects different biological underpinnings. The identification of biologically-based depression symptoms profiles would be of great importance to unravel different pathophysiological pathways in MDD and therefore to achieve more precise and personalized therapeutical approaches as well as preventive strategies.

Converging evidence from epidemiological and clinical studies, points to the importance of inflammation in MDD, shown by increased levels of pro-inflammatory proteins and increased inflammation-related comorbidities, including metabolic diseases. In fact, there exists a bidirectional relationship between inflammation and metabolic dysfunction that could be linked to multiple factors, including life style, stress and genetic predisposition. MDD patients exhibit several metabolic disturbances such as overweight, insuline resistance and dyslipidemia, among others, which are not always fully explained by life style factors. These findings have led to the formulation of an immunometabolic hypothesis, which could be present in a subgroup of MDD patients, associated to specific symptoms and clinical features.

In this presentation, data reflecting the complex relationships and interactions between immune and metabolic disturbances in MDD will be shown. In particular, it will be shown how machine learning approaches can be useful to disentangle the clinical and biological heterogeneity of MDD, using immunometabolic biomarkers.

P. Lopez-Garcia Grant / Research support from: Grant from Carlos III Health Institute ref PI15/00204 and FEDER funding from the EU

Recently, the diffusion of sophisticated neuroimaging techniques has tremendously advanced our understanding of brain structure and function. Nevertheless, the current knowledge of the neurobiology of complex mental illnesses - like major psychoses and depression - is limited, hindering the development and validation of biomarkers for diagnosis, prognosis, and prediction of treatment response.

Increasing evidence is suggesting a crucial role of environmental, personal, and behavioral processes, interacting among themselves and with genetics, in shaping mental functioning and psychopathological risk. In this context, the study of brain maturation trajectories and of their association with genetic and environmental factors can provide key insights on the risk for the emergence of mental illnesses over lifetime.

The present lecture will provide an overview of our recent research on the brain underpinnings of psychotic and affective disorders onsetting during either adolescence/young adulthood or late adulthood. Evidence obtained from young samples of twins will be presented to provide useful information on the genetic and environmental determinants of physiological and pathological neurodevelopmental trajectories. The complex relationships among life events, brain morphology and connectivity, and psychopathology will be discussed by showing our recent findings on multicentric transdiagnostic samples of young adults and elders. Special focus will be given to the brain mechanisms affected by social stressors, including discrimination and bullyism, as well as chronic stress, and their possible role in facilitating the onset or in enhancing the severity of psychotic and affective disorders.

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The comorbidity of mental and physical disorders is gradually becoming recognized as a major problem for health care. Its public health importance is vast and growing for a variety of reasons including the extension of life expectancy, the imperfection of currently available treatments of mental and many physical disorders and the tendency of fragmentation of medicine into ever more limited specialties. The problems related to comorbidity are also rapidly increasing in low- and middle-income countries where in addition to the issues mentioned above there is also a scarcity of means to deal with them.

The presentation will remind the audience of the complexity of the problems and draw attention to action that could be taken by public health authorities and the medical profession in the areas of teaching, organization of service and research.

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Anorexia nervosa is a persistent and often difficult to treat eating disorder with significant physical and mental health consequences. While it is known that the disorder is associated with alterations in brain functional connectivity during the phase of acute underweight, the effect of weight normalization on brain connectivity remains unclear.

This talk focuses on the recovery of intrinsic brain connectivity during weight normalization in severe anorexia nervosa, presenting data from a longitudinal study. Using resting-state functional magnetic resonance imaging, we assessed brain connectivity at three different stages of inpatient treatment. Our findings indicate that patients with severe anorexia nervosa have weaker intrinsic connectivity and altered network topology, which do not improve during treatment. These persistent disruptions in brain networks suggest that severe anorexia nervosa may have long-term effects on the way the brain processes information, even after weight is restored.

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People with eating disorders (EDs) exhibit a prevalence of childhood maltreatment higher than general population and, as for other psychiatric conditions, a history of childhood maltreatment in the context of EDs has been found associated with an earlier age at onset, a greater clinical severity, a more frequent comorbidity with other psychiatric conditions and a poorer treatment response . Neuroendocrine modifications as well as a heightened biological and emotional vulnerability to acute social stressor exposure and cortical measures alterations have been reported in people with EDs and history of childhood maltreatment. This evidence suggests the possibility to identify a “maltreated ecophenotype” also in people affected by EDs which recommends grouping individuals affected by the same psychiatric condition into subgroups characterized by different clinical and biological correlates in order to tailor treatements.

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The burden on society by depression is undisputable, partly due to a chronic course pattern and depression’s large heterogeneity that contributes to non-response to standard treatments. Using data from the Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl), Penninx will illustrate both points. When examining the course of depression, especially when also considering the transitions into other affective disorders over time, chronicity is clearly more the rule than the exception (Verduijn et al. BMC Med 2017). Considering depression’s heterogeneity could lead to precision psychiatry approaches that help reduce depression’s chronicity. Immuno-metabolic dysregulations seem to vary as a function of depression heterogeneity: dysregulations map more consistently to “atypical” neurovegetative symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis). Findings are confirmed when utilizing genome-wide gene expression as well as DNA information (Milaneschi et al. Biol Psychiatry 2020). Preliminary treatment studies suggest that the presence of immuno-metabolic dysregulations in depression moderates antidepressant effects of standard or novel (immunomodulatory) interventions. An immuno-metabolic depression dimension could dissect depression’s heterogeneity and potentially match depressed subgroups to treatments with higher likelihood of clinical success.

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Attention deficit/hyperactivity disorder (ADHD) often co-occurs with substance use disorders (SUD). Together, these disorders are associated with significantly more burden for patients and society, than each alone. Patients with SUD and underlying ADHD have more complex SUD and have more poly-substance use compared with SUD patients without ADHD. A correct identification of ADHD in adult and adolescent individuals with SUD remains important regarding treatment, treatment effectiveness, and treatment retention.

Several screening tools are available and have been validated in individuals with ADHD and comorbid SUD. It is highly recommended that these are used routinely, followed by an ADHD diagnostic process initiated as soon as possible. While several treatment options are accessible, randomized controlled trials show only limited effect sizes of standard pharmacotherapy in adult and adolescent ADHD patients with comorbid SUD. Simultaneous and integrated treatment, with a combination of pharmacotherapy and psychotherapy and for both ADHD and SUD, should preferably be initiated.

We present an overview of the current international guidelines on screening, diagnosis and treatment of ADHD adults and adolescents with comorbid substance use disorders.

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Apathy and goal-oriented behaviors are key dimensions of late-life depression (LLD) and are iteratively associated with cognitive decline in most neuropsychiatric disorders. However, scales and criteria remains insufficient to provide robust individual biomarkers that could foster personalized therapeutic approaches. Therefore, dimensional and digital phenotyping offer new possibilities of stratifying LLD population. This presentation will show our recent results of functional connectivity cerebral networks associated with multidimensional paper-and-pen measures of apathy, including the default mode and the cingulo-opercular networks. We will also show how dimensional reduction (functional principal component analysis) of 3 days actimetry measures are associated with both FC and inflammatory measures (diffusion and multicompartment indices such as free water and neurite orientation dispersion), providing arguments for different pathophysiological mechanisms underlying goal-oriented behaviors and reinforcing actimetry as a good candidate for individual biomarker of cognitive decline in LLD. Finally, machine learning approaches using combination of different, yet correlated, indices of actimetry will be presented and discussed with their corresponding classifying accuracies (outside of cerebral imaging). Altogether, this presentation aims at bridging the gap between cerebral imaging and digital phenotyping to enhance personalized medicine in the field of old-age psychiatry and cognitive decline prevention.

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The ghrelin system is a key regulator of appetite and food intake across species. LEAP-2, a recently discovered ghrelin antagonist, appears to be up-regulated in obesity and opposes to the orexigenic drive of ghrelin. The evolution of LEAP-2 levels could be an interesting insight to reflect the regulation of appetite in eating disorders such as anorexia nervosa (AN). We provide the first study exploring the ghrelin and LEAP-2 regulation in long-term food restriction followed by refeeding in both mice and patients suffering from AN.

Using a translational strategy, we compared the regulation of ghrelin and LEAP-2 concentrations in blood during food restriction and after refeeding in female mice exposed to a 14 days protocol combining quantitative food restriction and running wheel activity followed by progressive refeeding. We compared these results to clinical data fom in an ongoing longitudinal study of patients with AN evaluated before and after refeeding as well as 6 months after hospital discharge.

Long-term food restriction in mice was associated with increased ghrelin and decreased LEAP-2 concentrations compared to ad libitum fed controls. Refeeding led to an increase in LEAP-2 concentrations. Patients with AN displayed increased ghrelin levels but also higher LEAP-2 concentrations on admission than after refeeding. LEAP-2 decreased with refeeding. On 17 patients re-evaluated 6 months after discharge, patients with unstable weight gain exhibited a greater decrease of LEAP-2 concentrations during refeeding compared to patient with stable weight gain. Decreasing LEAP-2 concentrations was able to predict a negative outcome (i.e. unstable weight gain) in 80% of the cases.

We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN as it is in the case of a physiological adaptation to food restriction. Our clinical data suggest that the evolution of LEAP-2 concentrations during refeeding is opposed to data from preclinical model and could give new insights on the outcome of weight gain in AN.

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The hormonal mediators of the stress response, such as glucocorticoids and catecholamines, have both protective and damaging effects on the body. In the short term, they are essential for adaptation, maintenance of homeostasis, and survival; but chronic exposure to stress or abnormalities in the modulation of the stress response can become maladaptive, leading to a broad range of physical and mental problems.

Allostatic load refers to the activation of physiological regulatory systems in response to stress and “the cost” of the effects of these systems on the body. Results from isolated biomarkers and allostatic load measures based on the stress response system (hypothalamic-pituitary-adrenal axis, autonomic nervous system and immuno-metabolic biomarkers) and its relationships with clinical outcomes, such as cognition, in a clinical sample of major depression patients will be presented. The usefulness and relevance in the clinical practice of those biomarkers and the allostatic load concept will be discussed. The integration of several biomarkers translating the biological and psychological impact of stress on depression development and its clinical trajectories could contribute toward understanding how to prevent and improve outcomes in major depression.

V. Soria Grant / Research support from: Instituto de Salud Carlos III and the Bellvitge Biomedical Research Institute

Late-life depression (LLD) is currently a hot topic for neuroimaging studies, while an increasing number of imaging modalities are now available for the characterization of brain structure and function. Changes in brain volumes, including hippocampal volume, have been observed in LLD, although results are inconsistent. Vascular lesions are more consistently associated with LLD and may constitute factors of poor prognosis. More recent MRI modalities, including fMRI and DTI, also show interesting results, notably to assess treatment response in LLD. Molecular Imaging also has the potential to improve our understanding of the pathophysiology of LLD, using imaging such as PET-FDG and Amyloid PET. Finally, there are emerging studies with novel neuroimaging modalities such as Ultrasound to measure subtle mechanical properties in the brain of patients with LLD. Finally, we contend that neuroimaging has the potential to provide markers for the identification of subcategories of LLD (vascular depression, amyloid depression, etc.) as well as prognostic values and markers for treatment response.

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A paradox of the modern world is represented by the increasing rate of comorbidities, although the life expectancy is increasing worldwide, the number of disease-free years is not improving consequently. Physical comorbidities are often overlooked in people with severe mental disorders, although this problem needs to be adequately managed since it is associated with a worse quality of life and a poorer personal and social functioning. In particular, in people with severe mental disorders is very common the contemporary presence of infectious diseases (mainly TBC and HIV) and other physical conditions, which worsen the long-term prognosis.

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The current scientific literature has increased our understanding of how medication could be beneficial for patients with eating disorders (EDs) on a molecular, functional, and behavioural level. Based on theoretical considerations about neurotransmitters, hormones and neural circuits, possible drug targets for the treatment of EDs may include signal molecules and receptors of the self-regulatory system such as serotonin, norepinephrine and glutamate; the hedonic system including opioids, cannabinoids and dopamine; and the hypothalamic homeostatic system including histamine, ghrelin, leptin, and insulin.

The currently approved pharmacological treatments for EDs are limited to fluoxetine for bulimia nervosa (BN) and - in some countries – lisdexamfetamine (LDX) for binge eating disorder (BED). Topiramate might be an additional option for people with BN and BED.

There are no approved pharmacological options for anorexia nervosa (AN), even though study results for olanzapine and dronabinol are promising. Psilocybin, ketamine, and metreleptin have recently been considered and tried in AN.

Case reports and studies regarding the drug treatment of the new DSM-5 EDs include the use of mirtazapine for avoidant restrictive food intake disorder (ARFID); fluoxetine for pica; and levosulpiride and baclofen for rumination disorder.

This talk is based on a comprehensive review of the scientific literature regarding the pharmacological treatment for EDs and will include a preview of the 2023 update of the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders.

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Andrea Gmeiner1, Melanie Trimmel1, Amy Gaglia1,2, Beate Schrank3, Stefanie Süßenbacher-Kessler1, Michaela Amering1

1Division of Social Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria 2Division of Psychology, Bangor University Wales,UK 3Department of Psychiatry, Karl Landsteiner University for Health Sciences, Austria

Gender parity, authorship, geographic and subject matter diversity are declared goals in the academic publishing world. Recent data on the progress towards these goals suggest that changes and a shift towards diversity have been happening over the last decades. Examples include significantly increasing numbers of female first and senior authors between 2008 and 2018 (Hart et al, 2019) over a wide range of journals. Our own data on trends in three high-impact psychiatric journals over a 25-year time period from 1994 until 2019 suggest that female first, female senior, and female overall authorship have increased significantly over the quarter of a century covered. Results do indicate that gender parity in first authorship was reached in the category of original research articles for the first time in 2019 (Gmeiner et al, 2022). However, data also showed the remaining underrepresentation of women in senior authorship positions in line with the leaky pipeline phenomenon. Gender differences in publication trends with regards to subject matters and topics in the 2004/14/19 part of this sample showed the percentage of female first authors exceeding 50% in the two most frequent subject matters ‘basic biological research’ and ‘psychosocial epidemiology’ in 2019 (Trimmel et al, submitted for publication). Although the percentage of female first authors in the three most common target populations under study (mood disorders, schizophrenia, general mental health) increased from 2004 to 2019, gender equality has not yet been achieved in these fields. Consistent monitoring of publication trends and gender distribution by researchers and academic journals needs to identify and counteract the areas of underrepresentation of women.

Hart, K. L., Frangou, S., & Perlis, R. H. (2019). Gender Trends in Authorship in Psychiatry Journals From 2008 to 2018. Biological psychiatry, 86(8), 639–646.; Gmeiner A, Trimmel M, Gaglia-Essletzbichler A, Schrank B, Süßenbacher-Kessler S, Amering M, (2022). Diversity in high-impact psychiatric publishing: gender parity within reach? Archives of women’s mental health, 25(2), 327–333.

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The leaky pipeline is a visual metaphor for the under-representation of women in leadership positions in Academic Psychiatry despite their over-representation in medical schools, residency programs, and junior academic positions. The presentation focuses on the key obstacles that pertain to personal and societal attitudes and institutional barriers and proposes empirically tested and pragmatic solutions.

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This presentation is titled " Case scenarios 1: Trauma based approach: from instability to stability". You will be given a case based oriented insight into the relationship between substance use disorder and forced displacement and treatment options that are based upon the trauma some has been experienced. A focus will be on factors that contribute on psychological stability in extreme situations. Thus you will be presented preliminary results of our ongoing study funded by the Heidelberg Academy of Sciences and Humanities that dedicated to the question of how mental stability and health-related quality of life of individuals change over time.

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Although in many countries in the meantime more women than men choose medicine and later psychiatry for their training, key positions in hospitals and research are still mainly held by men. The professional career of women is impeded not only by institutional, but also by psychological barriers such as gender role behavior and gender role stereotypes. Mentoring can help young women to overcome these barriers.

But usually mentoring starts too late. As studies have shown, important decisions about future career steps are taken already towards the end of medical studies. Therefore, gender sensitive teaching and mentoring should start already at university and should not only address young women, but also young men as potential partners and future colleagues - especially regarding their gender role behavior and stereotypes. Mentoring programs considering gender-specific needs should be implemented in the regular teaching during medical studies and in psychiatric training.

Furthermore, women should be coached during their further career steps since there is not only a “glass ceiling” that excludes young women from achieving leadership roles. When they finally have achieved such a role, women often face further difficulties stemming from gender stereotypes and traditional gender roles.

University teachers and employers should be addressed, as well as politicians. Otherwise, psychiatry not only loses a great potential of talents, but might also miss the chance of reforms towards a more gender-sensitive psychiatry and psychotherapy.

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Syndemics are synergistically interacting epidemics (for example, the epidemics of substance use disorders and forced displacement) in a particular context with shared drivers such as pre-existing political, structural, social and health conditions. Policymakers may ask what the risks of and needs are for forcibly displaced people with regards to substance use disorder (SUD). Working from a syndemics framework, we would argue that multiple risk and resiliency factors relating to both forced displacement and SUD work synergistically, and impact more significantly upon some populations than others. These risk factors include structural inequality and racism, social deprivation, violence, homelessness, trauma, childhood adversity, and co-morbid physical and mental health disorders. Individuals may become vulnerable while experiencing displacement, during transition, settlement or resettlement, and also through their life across and across generations. In this perspective, our answers to policymakers becomes more nuanced. We may argue for integrated, multi-modal interventions, cross-disciplinary collaborations, cross-pollination of ideas and knowledge and embedding lived experience to bridge gaps and make use of limited resources in sustainable ways. This presentation will detail aspects of the application of a syndemic lens to the evidence base on SUD among forcibly displaced people and generate discussion on what scientists, clinicians and policymakers can and may do with these insights.

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Journal editors can promote gender equality in various ways. The main ones are consideration of gender when inviting editorial board members, peer reviewers, and authors of solicited opinion pieces or reviews. As in many areas, the problem can be that the pool of suitable women is perceived to be small and the same women are asked to perform multiple tasks in addition to their academic and clinical duties. Journal editors need to seek women who are less well known but competent for the task required. To increase the pool of qualified candidates, editors should promote training using existing resources, such as online peer reviewer courses, or develop in-house initiatives, such as The Lancet Psychiatry’s Editorial Board Development Programme. It is important to make public commitments to gender balance, for example as part of a diversity pledge, with specific targets, and to collect and report data with regular updates. Gender balance should be an integral part of information templates in manuscript handling systems, such as asking authors and peer reviewers to consider women when recommending alternative peer reviewers. Where relevant, journal editors can also consider gender balance in their use of images, cover art, podcast or interview subjects, profiles, news and features, and social media content.

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This presentation will share data from a new meta-analysis of RCT studies using cognitive remediation to treat children and adolescents with ADHD. For this matter, 25 studies were accessed, and results will focus on outcomes immediately after the end of the program and in follow-up. Outcomes include subjective measures of functioning (through validated scales), neuropsychological measurements and academic performance. Comparisons regarding length of training, intensity, concomitant use of pharmacological treatments will also be provided. These findings will build on previous meta-analysis on the issue that were performed in the past.

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