ACTA NEUROPSYCHIATRICA

Leptin and leptin receptor gene polymorphisms and depression treatment response
Tavast IM, Solismaa A, Lyytikäinen LP, Mononen N, Moilanen E, Hämäläinen M, Lehtimäki T and Kampman O
Associations between leptin () and leptin receptor () gene polymorphisms and mood disorders have been found but not yet confirmed in multiple studies. The aim of our study was to study the associations between and single nucleotide polymorphisms (SNPs) and treatment response of depression. Associations between leptin levels and depression severity were also investigated.
Investigation of the Relationship of Sleep Disorder Occurring in Fibromyalgia with Central Nervous System and Pineal Gland Volume
Uçar İ, Çiçek F, Seber T, Ülkü Demir FG and Çiftçi AT
Mechanisms of sleep disorders in fibromyalgia (FM) patients, such as insomnia, early morning awakenings and poor quality sleep, have not yet been proven and no consistent and effective treatment is yet available. The aim of this study was to investigate the pineal gland volume and the relationship between total fiber count, total fiber volume and total fiber length of the spinoreticular tract involved in regulation of sleep and wakefulness in terms of the mechanism of sleep disturbance.
A randomised study and an extension study of brexpiprazole in patients with borderline personality disorder
Rothman B, Brewer C, Chang D, Hobart M, Hefting N, McQuade RD and Grant JE
No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.
Placebo and nocebo effects in gambling disorder pharmacological trials: a meta-analysis
Ioannidis K, Huneke NTM, Solly JE, Fusetto Veronesi G, Tzagarakis C, Parlatini V, Westwood SJ, Del Giovane C, Baldwin DS, Grant JE, Cortese S and Chamberlain SR
Placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder.
Phelan-McDermid Syndrome-associated Psychosis: A Systematic Review
Colijn MA
Phelan-McDermid syndrome is a rare genetic disorder characterized by various neurodevelopmental, medical, and psychiatric issues. Although bipolar disorder-like presentations and catatonia are particularly common, psychosis has also been reported but is less well described. As such, this systematic review sought to characterize the phenomenology of psychosis in Phelan-McDermid syndrome, clarify the association of psychotic symptoms with other neuropsychiatric features of the disorder, and describe antipsychotic treatment response.
Use of generative artificial intelligence (AI) in psychiatry and mental health care: a systematic review
Kolding S, Lundin RM, Hansen L and Østergaard SD
Tools based on generative artificial intelligence (AI) such as ChatGPT have the potential to transform modern society, including the field of medicine. Due to the prominent role of language in psychiatry, e.g., for diagnostic assessment and psychotherapy, these tools may be particularly useful within this medical field. Therefore, the aim of this study was to systematically review the literature on generative AI applications in psychiatry and mental health.
The shape of the corpus callosum is different in bipolar disorder
Namli MN, Baykara S, Gul O and Baykara M
Bipolar disorder (BD) is a recurrent chronic disorder characterised by fluctuations in mood and energy disposition. Diseases could lead to degenerative alterations in brain structures such as corpus callosum (CC). Studies demonstrated that abnormalities in CC are associated with BD symptoms. The present study aims to analyse the CC of the patients with statistical shape analysis (SSA) and compare the findings with healthy controls.
Significant haematological alterations in clozapine-treated patients: prevalence and clinical correlation
Tabara MF, Akar CB, Atdagi MK, Gurok MG and Atmaca M
Clozapine is an atypical antipsychotic crucial for treatment-resistant schizophrenia, characterised by its multi-receptor targeting, including serotonin (5-HT2A, 5-HT2C) and dopamine (D1, D2, D3, D4) receptors, among others. This broad mechanism is effective against positive symptoms of schizophrenia with a lower incidence of extrapyramidal side effects. However, clozapine poses significant haematological risks, notably agranulocytosis, necessitating stringent blood monitoring protocols.
Network meta-analysis of the effectiveness of psychotherapies with or without medication for treating adult depression
Fukumori M, Kikuchi T, Zhou Y, Hattori S and Kudo T
To ascertain whether psychotherapies combined with medication are more efficacious than those without medication and determine which combinations yield the best results.
A double-blind, placebo-controlled, randomised withdrawal study of adjunctive brexpiprazole maintenance treatment for major depressive disorder
McIntyre RS, Sundararajan K, Behl S, Hefting N, Jin N, Brewer C, Hobart M and Thase ME
To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).
Exploring the potential link between ΔFosB and -acetylcysteine in craving/relapse dynamics: can -acetylcysteine stand out as a possible treatment candidate?
Arjmand S, Ilaghi M, Shafie'ei M, Gobira PH, Grassi-Oliveira R and Wegener G
From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that -acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.
Precision psychiatry needs causal inference
Bernstorff M and Jefsen OH
Psychiatric research applies statistical methods that can be divided in two frameworks: causal inference and prediction. Recent proposals suggest a down-prioritisation of causal inference and argue that prediction paves the road to 'precision psychiatry' (i.e., individualised treatment). In this perspective, we critically appraise these proposals.
Gene expression of kynurenine pathway enzymes in depression and following electroconvulsive therapy
Ryan KM, Corrigan M, Murphy TM, McLoughlin DM and Harkin A
This study aimed to investigate changes in mRNA expression of the kynurenine pathway (KP) enzymes (), and 2 (, ), and 2 (), () and () in medicated patients with depression ( = 74) compared to age- and sex-matched healthy controls ( = 55) and in patients with depression after electroconvulsive therapy (ECT). Associations with mood score (24-item Hamilton Depression Rating Scale, HAM-D24), plasma KP metabolites and selected glucocorticoid and inflammatory immune markers known to regulate KP enzyme expression were also explored.
The therapeutic potential of cannabidiol in neuropsychiatric and neurodegenerative disorders
Joca S and Guimarães FS
Advancing the understanding of cannabinoids in psychiatry
Wegener G
Obsessive-compulsive symptoms relating to psychosocial functioning for people with schizophrenia, schizoaffective disorder, or bipolar disorder
Grootendorst-van Mil N, Chang CK, Chandran D, Schirmbeck F, van Beveren N, Shetty H, Stewart R, Ahn-Robbins D, de Haan L and Hayes RD
To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.
International trends in male youth suicide and suicidal behaviour
Rice T, Livshin A, Rihmer Z, Walther A, Bhuiyan M, Boude AB, Chen YY, Gonda X, Grossberg A, Hassan Y, Lafont E, Serafini G, Vickneswaramoorthy A, Shah S and Sher L
Suicide and suicidal behaviour strongly contribute to overall male youth mortality. An understanding of worldwide data contextualises suicide and suicidal behaviour in young men within any given country.
Advancing psychiatric nosology through philosophical inquiry
Arjmand S, Saboori Amleshi R, Guimarães FS and Wegener G
Here, we have utilised the concept of fuzzy logic and Karl Popper's notion of verisimilitude to advocate navigating the complexity of psychiatric nosology, emphasising that psychiatric disorders defy Boolean logic. We underscore the importance of embracing imprecision and collecting extensive data for a more nuanced understanding of psychiatric disorders, asserting that falsifiability is crucial for scientific progress. We encourage the advancement of personalised psychiatric taxonomy, urging the continual accumulation of data to inform emerging advancements like artificial intelligence in reshaping current psychiatric nosology.
Anxiolytic-like effects of acute serotonin-releasing agents in zebrafish models of anxiety: experimental study and systematic review
Näslund J, Landin J, Hieronymus F, Banote RK and Kettunen P
Though commonly used to model affective disorders, zebrafish display notable differences in terms of the structure and function of the brain serotonin system, including responses to pharmacological interventions, as compared to mammals. For example, elevation of brain serotonin following acute administration of serotonin reuptake inhibitors (SRIs) generally has anxiogenic effects, both in the clinical situation and in rodent models of anxiety, but previous research has indicated the opposite in zebrafish. However, several issues remain unresolved. We conducted a systematic review of SRI effects in zebrafish models of anxiety and, on the basis of these results, performed a series of experiments further investigating the influence of serotonin-releasing agents on anxiety-like behaviour in zebrafish, with sex-segregated wild-type animals being administered either escitalopram, or the serotonin releaser fenfluramine, in the light-dark test. In the systematic review, we find that the available literature indicates an anxiolytic-like effect of SRIs in the novel-tank diving test. Regarding the light-dark test, most studies reported no behavioural effects of SRIs, although the few that did generally saw anxiolytic-like responses. In the experimental studies, consistent anxiolytic-like effects were observed with neither sex nor habituation influencing treatment response. We find that the general effect of acute SRI administration in zebrafish indeed appears to be anxiolytic-like, indicating, at least partly, differences in the functioning of the serotonin system as compared to mammals and that caution is advised when using zebrafish to model affective disorders.
RNA mA methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat
Kanarik M, Liiver K, Norden M, Teino I, Org T, Laugus K, Shimmo R, Karelson M, Saarma M and Harro J
Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N (mA) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that mA mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA mA methylation has potential for neuropsychiatric drug development.
Relationship between early traumatic experiences and emotional regulation skills in major depressive and bipolar disorders
Park Y, Lee CW, Jang Y, Kwon SS, Yu H, Yoon J, Park YS, Ryoo HA, Jang J, Lee HJ, Lee YC, Won HH, Ha TH and Myung W
Childhood trauma can cause deficits in emotional regulation. However, few studies have investigated childhood trauma and emotional regulation skills in patients with mood disorders. We aimed to investigate how childhood trauma and Emotion Regulation Skills Questionnaire (ERSQ) scores are associated with mood disorders.This study included 779 patients with mood disorders (major depressive disorder [MDD, = 240], bipolar I disorder [BDI, = 121], and bipolar II disorder [BDII, = 418]). We used their Childhood Trauma Questionnaire-Short Form (CTQ) and ERSQ scores for the evaluation.The between-group differences in CTQ and ERSQ scores were examined. The CTQ and ERSQ total scores were negatively correlated. Among the CTQ subscales, emotional neglect showed a significant correlation with the ERSQ total score, whereas acceptance and tolerance showed higher negative correlations with the CTQ than with the other ERSQ subscales. The negative relationship between emotional regulation and childhood trauma varied significantly depending on the group, with the BDI group showing a more prominent association than the other groups.Based on various mood disorders, we observed associations between childhood trauma and emotional regulation skills. Consequently, our study offers notable insights for future research on the impact of childhood trauma on ERSQ.