Umeå University's logo

Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence). Evidence supports the notion that ketamine, an anesthetic and rapid-acting antidepressant drug, holds promise as a candidate for OUD treatment, including the management of acute withdrawal somatic symptoms, negative affect during protracted opioid abstinence, and prevention of retaking nonmedical opioids. In this review, we comprehensively discuss preclinical and clinical research that has evaluated ketamine and its metabolites as potential novel therapeutic strategies for treating OUD. Furthermore, we examine evidence that supports the relevance of the molecular targets of ketamine and its metabolites in relation to their potential effects and therapeutic outcomes in OUD. Overall, existing evidence demonstrates that ketamine and its metabolites can effectively modulate pathophysiological processes affected in OUD, suggesting a promising therapeutic role in the treatment of OUD and the prevention of return to opioid use during abstinence.

Background: Genetic testing in psychiatry has gained attention, raising questions about its application and impact. Understanding stakeholders’ perspectives, including healthcare providers and patients, is vital for informed policy development. The aim of this systematic review was to focus on the perceptions and concerns of patients and healthcare workers in psychiatry regarding the use of genetic testing.

Methods: We conducted a systematic review following PRISMA guidelines, for the period 1/2/2014, to 1/1/2024, via PubMed and Embase databases identifying 50 articles in total. After excluding duplicates (n = 12), 38 articles went through screening. After careful full-text article assessment for eligibility and applying the inclusion and exclusion criteria, only fifteen (n = 15) of the articles were included.

Results: Among 15 selected studies involving 3,156 participants (2,347 healthcare professionals; 809 patients), thematic analysis identified four primary themes: Organizational-implementation concerns, Ethical Considerations, Concerns on changes in clinical praxis, and Legal implications. Despite these concerns, seven out of eleven studies indicated that healthcare workers viewed genetic testing in psychiatry positively. Patients’ perspectives varied, with two of the four studies reflecting positive attitudes. No pervasive negative sentiment was observed.

Conclusion: Our review highlights the multidimensional perspectives of healthcare professionals and patients surrounding the application of genetic testing in psychiatry. These considerations need to be addressed to facilitate the implementation of genetic testing in clinical praxis in psychiatry. Further research is needed for validation of the results and to guide policies and clinicians in the integration of genetic testing into mental healthcare practice.

Background: Chronic and acute inflammation of the mucosa-associated lymphoid tissue have been positively linked to the development of psychiatric disorders in observational studies. However, it remains unclear whether this association is causal. In the present study, we investigated this association, using as proxies genetically predicted tonsillectomy, appendectomy and appendicitis on psychiatric disorders including major depressive disorder (MDD), schizophrenia (SCZ), bipolar depression (BD) and anxiety (ANX) via a two-sample Mendelian randomization (MR) analysis.

Methods: Genetic association summary statistics for tonsillectomy, appendectomy and appendicitis were sourced from FinnGen Consortium, comprising data from 342,000 participants. Genetic correlations between all exposures and outcome were calculated with Linkage Disequilibrium Score (LDSC) Regression analysis. MR estimates were then calculated to assess their impact on the risk of developing psychiatric disorders. Sensitivity analysis was employed to test for any directional pleiotropy.

Results: Our results suggest that there is no direct causal association between tonsillectomy, appendectomy or appendicitis with a heightened risk for development of psychiatric disorders. The robustness of the results of the main MR analysis was further confirmed with additional sensitivity analyses. However, a moderate inverse genetic correlation was observed between tonsillectomy and MDD traits (r_g=-0.39, p-value (P)=7.5x10^-5).

Conclusion: Our findings provide, for the first time, evidence that there is no causal association between tonsillectomy or appendectomy on subsequent vulnerability of developing psychiatric disorders. Future studies using larger sample size GWAS should focus on unraveling the confounding factors and mediators to investigate this relationship further.

Background: The Republic of Cyprus has recorded the greatest increase in suicide mortality among Eastern Mediterranean countries, with an average annual increase of 5.1% in 2000-2019.

Aims: To investigate trends in suicide mortality rates between 2004 and 2020 in the Republic of Cyprus, with a focus on age, gender and suicide methods.

Method: Suicide deaths (ICD-10 taxonomy, including 'undetermined' code) and population denominators were obtained from the National Mortality Registry and Statistical Office, respectively. Directly standardised (European Standard) mortality rates were calculated for four gender and age groups. Annual change was estimated using Poisson regression models with interaction terms to assess differential trends over different time periods.

Results: There were 560 suicide deaths; these were four times more frequent in men, and approximately 80% were classified as 'violent' for both genders. The male suicide rate doubled from 4-5 to 9-10 per 100 000, mostly before 2012, representing a 9% annual change (rate ratio = 1.09, 95% CI 1.03, 1.15; P = 0.002). From 2013, the trend reversed (effect modification P < 0.001) with a 4% annual decrease (95% CI -9%, 1%). Declines were not uniform across all age groups; rates in males aged 45-64 years continued to rise, surpassing the previously high rate in males aged 25-44 years. Rates in females declined from 4-5 per 100 000 to 2-3 over the study period. Overall, the male-to-female suicide rate ratio was 5.33 (95% CI 3.46, 8.19) in 2017-2020, compared with 2.73 (1.88, 3.95) in 2004-2008.

Conclusion: Although suicide rates remain relatively low, the gender differential has widened in the Republic of Cyprus. Further analysis of trends in relation to unemployment and other socioeconomic indicators is warranted.

Background: There is limited evidence on the association between cognitive function, psychotic symptoms and doses of antipsychotics in adults under compulsory psychiatric care.

Aims: We assessed (a) the degree of cognitive impairment in adults involuntarily hospitalised for compulsory psychiatric care and (b) correlation of Montreal Cognitive Assessment (MoCA) score with psychotic symptoms, polypharmacy and prescription of high-dose antipsychotics.

Method: This was a nationwide, cross-sectional study, conducted at the only referral state hospital for compulsory psychiatric care in Cyprus (December 2016-February 2018). Τhe MoCA was applied for the assessment of cognitive functioning. The Positive and Negative Syndrome Scale (PANSS) was applied for the assessment of psychotic symptoms.

Results: The sample comprised 187 men and 116 women. The mean MoCA score was 22.09 (reported scale range (RSR): 3-30); the mean PANSS general symptoms subscale score was 49.60 (RSR = 41-162). The participants who reported positive psychiatric history (mean 21.71, s.d. 5.37), non-adherence to pharmacotherapy (mean 21.32, s.d. 5.56) and prescription of high-dose antipsychotics (with medication prescribed as needed: mean 21.31, s.d. 5.70; without medication prescribed as needed: mean 20.71, s.d. 5.78) had lower mean MoCA scores compared with those who reported negative psychiatric history (mean 23.42, s.d. 4.51; P = 0.017), adherence to pharmacotherapy (mean 23.10, s.d. 6.61; P = 0.003) and no prescription of high-dose antipsychotics (with medication prescribed as needed: mean 22.56, s.d. 4.90; without medication prescribed as needed: mean 22.60 s.d. 4.94; P = 0.045-0.005), respectively. Mean MoCA score was mildly and inversely associated with total PANSS score (r = -0.15, P = 0.03), PANSS general (r = -0.18, P = 0.002) and PANSS negative (r = -0.16, P = 0.005) symptoms subscales, respectively.

Conclusions: Our findings support the evaluation of cognitive functioning in adults under compulsory psychiatric care via the MoCA tool, with focus on those prescribed high-dose antipsychotics, with positive mental health history and non-adherence to pharmacotherapy.

Background: Several studies have shown that autoimmune diseases are associated with psychiatric diseases like depression and psychosis. Genetic evidence supports this association. The aim of this study was to investigate if genetic variants predisposing to autoimmune diseases and psychiatric disorders are genetically linked, constructing the common haplotypes.

Methods: All registered single nucleotide polymorphisms (SNPs) in the Genome-wide association studies (“GWAS catalog”) having been associated with autoimmune rheumatic and endocrine diseases were investigated for being in linkage disequilibrium with any psychiatric disorders’ associated SNPs. Analysis was performed by the LDtrait and LDhap bioinformatics tools.

Results: Multiple chromosomal regions have been detected containing rheumatic/endocrine diseases’ predisposing SNPs and psychiatric disorders’ predisposing SNPs. The genetic haplotypes have been constructed for some of these genetic regions. Six of the autoimmune rheumatic and endocrine diseases examined here share a common haplotype with psychiatric diseases at the HLA locus 6p21-22.

Conclusion: Our study shows that autoimmune diseases and psychiatric diseases are genetically linked. Genetic haplotypes have been constructed, showing in detail this genetic linkage.

Objectives: To systematically assess the magnitude of suicidal behavior among PsA patients and identify associated risk factors. Also identify common genes or coinherited single nucleotide polymorphisms (SNPs) implicated in suicidal behavior and PsA.

Methods: Based on the PRISMA guidelines, we conducted a systematic literature review of the online databases PubMed/Medline, Web of Science, and EMBASE from inception to May 2022. Full-text original articles that describe suicidal behavior in PsA patients were eligible. All registered genome-wide association study (GWAS) data in the GWAS catalog database for PsA and psychiatric traits, such as suicidal behavior, and depression, were downloaded for further analysis.

Results: A total of 48 articles were identified, and 6 were relevant to the study question. Among the 122,160 PsA patients, 700 had suicidal behavior (0,57%). The range of age in one study was between 30 and 49 years, and 64% of PsA patients with suicidal behavior were female. Among 13,899 PsA patients 74 had suicidal ideation (0.53%) and 125 suicide attempts occurred (0.9%). In two studies, among 17,383 patients, 13 complete suicides occurred (0.07%). A genetic haplotype on chromosomal region 6p21.1, spanning from 29,597,596 to 32,251,264 Mb, contains predisposing SNPs for PsA and depression. 6p21.1–6p21.3 is the chromosomal region containing the HLA genes of classes I, II and III.

Conclusion: Suicide behavior in PsA patients was associated with depression and other psychiatric comorbidities. Further evidence supports a genetic origin, at least partly. Awareness of these findings can help clinicians to recognize suicide behavior and prevent suicide attempts.

Background: Precision medicine is growing due to technological advancements including next generation sequencing techniques and artificial intelligence. However, with the application of precision medicine many ethical and potential risks may emerge. Although, its benefits and potential harms are relevantly known to professional societies and practitioners, patients' attitudes toward these potential ethical risks are not well-known. The aim of this systematic review was to focus on patients' perspective on ethics and risks that may rise with the application of precision medicine.

Methods: A systematic search was conducted on 4/1/2023 in the database of PubMed, for the period 1/1/2012 to 4/1/2023 identifying 914 articles. After initial screening, only 50 articles were found to be relevant. From these 50 articles, 24 articles were included in this systematic review, 2 articles were excluded as not in English language, 1 was a review, and 23 articles did not include enough relevant qualitative data regarding our research question to be included. All full texts were evaluated following PRISMA guidelines for reporting systematic reviews following the Joanna Briggs Institute criteria.

Results: There were eight main themes emerging from the point of view of the patients regarding ethical concerns and risks of precision medicine: privacy and security of patient data, economic impact on the patients, possible harms of precision medicine including psychosocial harms, risk for discrimination of certain groups, risks in the process of acquiring informed consent, mistrust in the provider and in medical research, issues with the diagnostic accuracy of precision medicine and changes in the doctor-patient relationship.

Conclusion: Ethical issues and potential risks are important for patients in relation to the applications of precision medicine and need to be addressed with patient education, dedicated research and official policies. Further research is needed for validation of the results and awareness of these findings can guide clinicians to understand and address patients concerns in clinical praxis.

Suicide attempts (SA) are associated with excess non-suicidal mortality, putatively mediated in part by premature cellular senescence. Epigenetic age (EA) estimators of biological age have been previously demonstrated to strongly predict physiological dysregulation and mortality risk. Herein, we investigate if violent SA with high intent-to-die is predictive of epigenetics-derived estimates of biological aging. The genome-wide methylation pattern was measured using the Illumina Infinium Methylation EPIC BeadChip in whole blood of 88 suicide attempters. Subjects were stratified into two groups based on the putative risk of later committed suicide (low- [n = 58] and high-risk [n = 30]) in dependency of SA method (violent or non-violent) and/or intent-to-die (high/low). Estimators of intrinsic and extrinsic EA acceleration, one marker optimized to predict physiological dysregulation (DNAmPhenoAge/AgeAccelPheno) and one optimized to predict lifespan (DNAmGrimAge/AgeAccelGrim) were investigated for associations to severity of SA, by univariate and multivariate analyses. The study was adequately powered to detect differences of 2.2 years in AgeAccelGrim in relation to SA severity. Baseline DNAmGrimAge exceeded chronological age by 7.3 years on average across all samples, conferring a mean 24.6% increase in relation to actual age. No individual EA acceleration marker was differentiated by suicidal risk group (p > 0.1). Thus, SA per se but not severity of SA is related to EA, implicating that excess non-suicidal mortality in SA is unrelated to risk of committed suicide. Preventative healthcare efforts aimed at curtailing excess mortality after SA may benefit from acting equally powerful to recognize somatic comorbidities irrespective of the severity inherent in the act itself.