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Summary: Background: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. Funding: European Union Horizon 2020.

Abstract Background Recently, cognitive deficits occurring in rheumatic diseases have attracted scientific attention. Cognitive symptoms in patients with Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc) have not been thoroughly studied. This study aimed to assess cognitive function and its relationship with depressive symptoms in RA and SSc and compare it to mild neurocognitive disorder due to Alzheimer’s disease (MiND) and to individuals without cognitive impairment. Methods Cognitive function and depressive symptoms were tapped with the Cognitive Telephone Screening Instrument plus (COGTEL+), the Serial Seven Test (SST), the Mini-Mental State Examination (MMSE) and the Geriatric Depression scale-15 (GDS), respectively. Statistical analyses included between groups-, correlation- and regression analyses. Demographic characteristics were considered in the regression models. Results The study included 30 individuals with RA, 24 with SSc, 26 adults without cognitive impairment and 33 individuals with MiND. Lower performance in verbal short-term memory, concentration/attention, verbal fluency and MMSE in patients with RA compared to individuals without cognitive impairment was detected. Of note, performance on verbal fluency, concentration/attention, inductive reasoning and MMSE was lower in RA compared to MiND. Individuals with SSc performed worse in verbal fluency and in MMSE in comparison to adults without cognitive deficits. Verbal fluency deficits in SSc exceeded that in MiND. Performance on MMSE, COGTEL+, prospective memory, working memory, verbal fluency and concentration/attention was related to GDS scores, which did not vary across the groups. Conclusions Patients with RA and SSc encountered cognitive dysfunction, which partially pertains to depressive symptoms. Of note, the severity of cognitive dysfunction in many cases exceeded that of MiND.

Background: Mitochondria are involved in energy production, oxidative balance, cell survival/apoptosis, immune response, and inflammation. A possible role in affective disorders has fueled research on mitochondrial targets for novel treatments. Methods: A systematic review of the literature was conducted, in Science Direct, Scopus and PubMed databases, from inception to 12th September 2022. Key words used were mitochondria AND/OR inflammation AND affective OR bipolar OR depression AND therapy OR treatment OR intervention. Results: Twenty-one studies were included in the analysis. Animal studies (n=16) have shown positive results for Nucleus Accumbens Deep Brain Stimulation (NAc DBS), Near-Infrared Photobiomodulation (NIR-PBM), exercise, 48-hour fasting, and fluoxetine, Li, valproate, BI-11A7 Bid inhibitor, methylene blue (MB), AC-5216, atractylenolide-III (ALT-III), ONO-2952, oxytocin (OT), tocopherol-a, Coenzyme Q10 (CoQ10). Human studies (n=5) have tested adjunctive therapies, with NAC plus antioxidant combination therapy, triacetyl-uridine (TAU), cytidine add-on, and andacetyl-l-carnitine and a-lipoic acid combination, with positive (TAU), negative, or difficult-to-interpret results. Limitations: The search was conducted on three databases only, and only articles written in English were included. Unpublished articles or research with negative results may have been missed. Conclusion: Mitochondria-targeting interventions are promising novel treatments for depression and bipolar disorder.

Background and Objectives: The study aims to provide a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It focuses on the critical aspects of cognitive impairments, diagnostic tools, intervention efficacy, and the roles of genetic and environmental factors in these disorders. The paper emphasizes the diagnostic significance of neuropsychological tests in identifying cognitive deficiencies and their predictive value in the early management of psychosis. Materials and Methods: The study involved a systematic literature review following the PRISMA guidelines. The search was conducted in significant databases like Scopus, PsycINFO, PubMed, and Web of Science using keywords relevant to clinical neuropsychology and psychotic spectrum disorders. The inclusion criteria required articles to be in English, published between 2018 and 2023, and pertinent to clinical neuropsychology’s application in these disorders. A total of 153 articles were identified, with 44 ultimately included for detailed analysis based on relevance and publication status after screening. Results: The review highlights several key findings, including the diagnostic and prognostic significance of mismatch negativity, neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups. The studies evaluated underline the role of neuropsychological tests in diagnosing psychiatric disorders and emphasize early detection and the effectiveness of intervention strategies based on cognitive and neurobiological markers. Conclusions: The systematic review underscores the importance of investigating the neuropsychological components of psychotic spectrum disorders. It identifies significant cognitive impairments in attention, memory, and executive function, correlating with structural and functional brain abnormalities. The paper stresses the need for precise diagnoses and personalized treatment modalities, highlighting the complex interplay between genetic, environmental, and psychosocial factors. It calls for a deeper understanding of these neuropsychological processes to enhance diagnostic accuracy and therapeutic outcomes.

Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.

Background: Alexithymia and atypical gut-brain signaling have been linked to the pathophysiology of inflammatory bowel disease (IBD). We herein assessed IBD patients' alexithymia levels and interoceptive abilities, and detected potential correlations with psychological distress, symptom severity and disease activity, and inflammation indices., Methods: Adult IBD outpatients and healthy controls were recruited. Alexithymia was assessed using the Toronto Alexithymia Scale, interoceptive accuracy using the Heartbeat Counting Test (cardiac interoception) and the Water Load Test-II (gastric interoception), and interoceptive sensibility using the Multidimensional Assessment of Interoceptive Awareness (MAIA)., Results: Forty-one patients with Crohn's disease (CD), 16 with ulcerative colitis (UC), and 50 healthy controls were included. In CD patients, the level of externally oriented thinking and total alexithymia score were correlated with disease activity (P=0.027 and P=0.047, respectively), while in UC patients difficulties in identifying emotions were linked to disease activity (P=0.007). In CD patients, the Noticing, Not-Worrying and Emotional Awareness MAIA subscale score were correlated with C-reactive protein levels (P=0.005, P=0.048 and P=0.005), the Noticing subscale score with interleukin (IL)-1β levels (r=-0.350, P=0.039), the Not-Distracting subscale score with IL-6 levels (r=-0.402, P=0.017), and the Emotional Awareness subscale score with IL-1β (r=-0.367, P=0.030) and IL-6 (r=-0.379, P=0.025) levels. Finally, in UC patients, the Not-Worrying subscale score was significantly associated with IL-6 levels (r=-0.532, P=0.049), while difficulties in identifying emotions were linked to IL-8 levels (r=0.604, P=0.022)., Conclusion: Emotional and interoceptive processing is associated with IBD disease activity, suggesting a potential implication for IBD pathophysiology., Competing Interests: Conflictof Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)