[Genome-wide studies of comorbidity of somatic and mental diseases]. / Polnogenomnye issledovaniya komorbidnosti somaticheskikh i psikhicheskikh zabolevanii.

Studies of the genomic architecture of complex phenotypes, which include common somatic and mental diseases, have shown that they are characterized by a high degree of polygenicity, i.e. participation of a large number of genes associated with the risk of developing these diseases. In this regard, it is of interest to establish the genetic overlapping between these two groups of diseases. The aim of the review is to analyze genetic studies of the comorbidity of somatic and mental diseases in terms of the universality and specificity of mental disorders in somatic diseases, the reciprocal relationships of these types of pathologies, and the modulating influence of environmental factors on comorbidity. The results of the analysis indicate the existence of a common genetic predisposition to mental and somatic diseases. At the same time, the presence of common genes does not exclude the specificity of the development of mental disorders depending on a specific somatic pathology. It can be assumed that there are genes that are both unique to a particular somatic and comorbid mental illness, and genes that are common to these diseases. Common genes may have varying degrees of specificity, that is, they may be of a universal nature, which, for example, manifests itself in the development of MDD in various somatic diseases, or be specific only for a couple of individual diseases (schizophrenia - breast cancer). At the same time, common genes can have a multidirectional effect, which also contributes to the specificity of comorbidity. In addition, when searching for common genes for somatic and mental diseases, it is necessary to take into account the modulating influence of such confounders as treatment, unhealthy life style, behavioral characteristics, which can also differ in specificity depending on the diseases under consideration.

Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS.

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision's connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers. Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups. Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. Superficial amygdala hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms. Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was found to be an early finding in patients with 22q11.2DS, which contributes to impaired tolerance to stress.

Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis.

BACKGROUND: To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. METHODS: FEP (N = 191) were recruited from in- and outpatient services 1997-2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15-65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. RESULTS: CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. CONCLUSION: Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

Chaos analysis of the cortical boundary for the recognition of psychosis.

BACKGROUND: Structural MRI studies in people with first-episode psychosis (FEP) and those in the clinical high-risk (CHR) state have consistently shown volumetric abnormalities that depict changes in the structural complexity of the cortical boundary. The aim of the present study was to employ chaos analysis in the identification of people with psychosis based on the structural complexity of the cortical boundary and subcortical areas. METHODS: We performed chaos analysis of the grey matter distribution on structural MRIs. First, the outer boundary points for each slice in the axial, coronal and sagittal view were calculated for grey matter maps. Next, the distance of each boundary point from the centre of mass in the grey matter was calculated and stored as spatial series, which was further analyzed by extracting the Largest Lyapunov Exponent (lambda [λ]), a feature depicting the structural complexity of the cortical boundary. RESULTS: Structural MRIs were acquired from 77 FEP, 73 CHR and 44 healthy controls. We compared λ brain maps between groups, which resulted in statistically significant differences in all comparisons. By matching the λ values extracted in axial view with the Morlet wavelet, differences on the surface relief are observed between groups. LIMITATIONS: Parameters were selected after experimentation on the examined sample. Investigation of the effectiveness of the method in a larger data set is needed. CONCLUSION: The proposed framework using spatial series verifies diagnosis-relevant features and may contribute to the identification of structural biomarkers for psychosis.

Can Epigenetics Predict Drug Efficiency in Mental Disorders?

Psychiatric disorders affect millions of individuals and their families worldwide, and the costs to society are substantial and are expected to rise due to a lack of effective treatments. Personalized medicine-customized treatment tailored to the individual-offers a solution. Although most mental diseases are influenced by genetic and environmental factors, finding genetic biomarkers that predict treatment efficacy has been challenging. This review highlights the potential of epigenetics as a tool for predicting treatment efficacy and personalizing medicine for psychiatric disorders. We examine previous studies that have attempted to predict treatment efficacy through epigenetics, provide an experimental model, and note the potential challenges at each stage. While the field is still in its infancy, epigenetics holds promise as a predictive tool by examining individual patients' epigenetic profiles in conjunction with other indicators. However, further research is needed, including additional studies, replication, validation, and application beyond clinical settings.

Stressful life events and relapse of psychosis: analysis of causal association in a 2-year prospective observational cohort of individuals with first-episode psychosis in the UK.

BACKGROUND: Despite accumulating evidence of an association between stressful life events and psychosis relapse, the extent to which this is a causal relationship remains unclear. We aimed to examine the association between exposure to, and number of, stressful life events after initial psychosis onset and psychosis relapse. METHODS: In this 2-year prospective observational study, we recruited individuals with first-episode psychosis, aged 18-65 years, who presented to psychiatric services in south London, UK. Participants were assessed via interview, with additional data obtained from electronic clinical records. Stressful life events were recorded at psychosis onset and during the 2-year follow-up using a brief questionnaire that assesses 12 major life events. Psychosis relapse was defined as inpatient admission because of symptom exacerbation within 2 years from psychosis onset. We examined the time to first psychosis relapse and the number and length of relapses using survival and binomial regression analyses. We used fixed-effects regression and cross-lagged path analysis to examine the directionality of effects and control for unmeasured confounders. FINDINGS: Between April 12, 2002, and July 26, 2013, 256 individuals with first-episode psychosis (100 [39%] female and 156 [61%] male; 16 [6%] Asian, 140 [55%] Black African or Caribbean, 86 [34%] White, and 14 [6%] mixed ethnicity) were recruited, with a mean age of onset of psychosis of 28·06 years (SD 8·03; range 17·21-56·03). 93 (36%) participants experienced at least one relapse during the 2-year follow-up. 253 individuals had all relevant data and were included in analyses. For people exposed to stressful life events after the onset of psychosis, the adjusted hazard (hazard ratio [HR] 2·60, 95% CI 1·63-4·16, p<0·0001), incidence (incidence rate ratio [IRR] 1·87, 1·24-2·80, p=0·0026), and length (IRR 2·53, 1·40-4·67, p=0·0011) of relapse were greater than for those who were unexposed. These relationships were dose dependent (HR 1·36; 1·09-1·69, p=0·0054; incidence IRR 1·26, 1·02-1·53, p=0·023; length IRR 1·52, 1·12-2·12, p=0·0028). Adjusted fixed-effects models showed a higher (odds ratio [OR] 3·82, 1·82-8·00, p=0·0004) and dose-dependent (OR 1·62, 1·18-2·21, p=0·0028) risk of relapse when stressful life events preceded relapse compared with the period when they did not. Cross-lagged path analysis confirmed an effect of stressful life events on the number of subsequent relapses (ß=0·66, p=0·0055) that was dose dependent (ß=0·29, p=0·029), but it did not show an effect of relapses on subsequent risk or number of stressful life events. INTERPRETATION: These results provide converging evidence of a causal effect of stressful life events on the risk of relapse in psychosis. They suggest that there is a need to develop interventions at the individual and health-service level that could mitigate the harmful effects of stressful life events. FUNDING: National Institute for Health Research, UK.

Psychiatric aspects of ophthalmic disorders: A narrative review.

Ophthalmic disorders have psychiatric aspects associated with them at various levels. Psychological factors have a well-documented role in the causation, aggravation, and maintenance of various ophthalmic conditions, including glaucoma, central serous retinopathy, dry eye disease, and retinitis pigmentosa. Many ophthalmic conditions, including blindness, have psychological manifestations as well, which need to be addressed, in addition to the ophthalmic pathology. There is also significant overlap in the treatment of the two disciplines in many ways. For instance, many ophthalmic drugs have psychiatric side effects. Even ophthalmological surgeries have psychiatric aspects associated with them, which primarily include black patch psychosis and anxiety in the operation theater. This review will be useful for psychiatrists and ophthalmologists, for their clinical practice and research. Future research should focus on this interface to give it its well-deserved attention.

Complementary/Integrative Medicine Treatment and Prevention of Youth Psychosis.

The rationale for CIM treatments in youth psychoses is to optimize treatment by targeting symptoms not resolved by antipsychotics, such as negative symptoms (major drivers of disability). Adjunctive omega-3 fatty acids (ω-3 FA) or N-acetyl cystine (NAC usage for > 24-week) can potentially reduce negative symptoms and improve function. ω-3 FA or exercise may prevent progression to psychosis in youth (in prodromal stage). Weekly 90-minute moderate to vigorous physical activity or aerobic exercise can reduce positive and negative symptoms. Awaiting better research, CIM agents are also recommended because they are devoid of any serious side-effects.

Predictors of cognitive changes in patients with schizophrenia undergoing electroconvulsive therapy.

INTRODUCTION: Previous studies on the effects of electroconvulsive therapy (ECT) on cognition in schizophrenia have been inconclusive. This study aimed to identify factors that may predict cognitive improvement or deterioration in patients with schizophrenia after-ECT. MATERIALS & METHODS: Patients with schizophrenia or schizoaffective disorder with predominantly positive psychotic symptoms, who were treated with ECT at the Institute of Mental Health (IMH), Singapore, between January 2016 and January 2018, were assessed. Montreal Cognitive Assessment (MoCA), Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Function (GAF) were performed before and after ECT. Patients with clinically significant improvement, deterioration or no change in MoCA scores were compared on demographics, concurrent clinical treatment and ECT parameters. RESULTS: Of the 125 patients analysed, 57 (45.6%), 36 (28.8%) and 32 (25.6%) showed improvements, deterioration and no change in cognition respectively. Age and voluntary admission predicted MoCA deterioration. Lower pre-ECT MoCA and female sex predicted MoCA improvement. Patients showed improvements in GAF, BPRS and BPRS subscale scores on average, except for the MoCA deterioration group, who did not show statistically significant improvement in negative symptom scores. Sensitivity analysis showed that nearly half the patients (48.3%) who were initially unable to complete MoCA pre-ECT were able to complete MoCA post-ECT. CONCLUSIONS: The majority of patients with schizophrenia demonstrate improved cognition with ECT. Patients with poor cognition pre-ECT are more likely to see improvement post-ECT. Advanced age may be a risk factor for cognitive deterioration. Finally, improvements in cognition may be associated with improvements in negative symptoms.

[Electroconvulsive Therapy in the New National Guideline Depression: Effectiveness, Evidence, and Grade of Recommendation]. / Elektrokonvulsionstherapie in der neuen NVL Depression: vom Unterschied zwischen Effektivität, Evidenz und Empfehlungsgraden.

In comparison to the previous version, the new national guideline 'Unipolar Depression' comprises more differentiated statements and recommendations regarding the use of electroconvulsive therapy (ECT). In principle, this is most welcome, as it clarifies the particular significance of ECT in different clinical situations. In parallel, this differentiation of recommendations depending on the presence of specific features of depressive disorders (e. g., psychotic symptoms, suicidality) led to different grades of recommendations for ECT. This may be correct and rational under the strict methodology of a guideline process, but nevertheless may appear confusing and contradictory in clinical practice. This article describes the relationships and putative discrepancies between the effectiveness of ECT, scientific evidence, and grading of guideline recommendations with comments on these for clinical practice from experts' point of view.

Experiences of Self-Stigma in People with Chronic Psychosis: A Qualitative Study.

We present the results of a phenomenological study understanding the personal meaning of self-stigma in people with chronic psychosis. Self-stigma is a frequent phenomenon in the lives of people with psychosis and their families and it functions as a barrier to recovery. Semi-structured in-depth interviews were conducted with fourteen outpatients that suffer from chronic psychosis during January 2020. Data analysis was carried out using an inductive approach as described by Graneheim and Lundman through the MAXQDA 2022 program. The themes observed were: "Contextual Stigma", "Components of Self-Stigma", "Skills Loss" and "Coping with Self-Stigma". The main categories and subcategories were avoidance and escape behaviours from their social environment, labelling, loss of social relationships, negative impact and self-concealment of the diagnosis. Our results revealed influence on each other, forming a looping effect that explains and amplifies the lived experience of self-stigma. These findings highlight the need to implement strategies in nursing practice aimed at training the acceptance and distancing necessary to minimize the impact of self-stigma on people with chronic psychosis. This study adheres to the EQUATOR guidelines for the Consolidated Criteria for Reporting Qualitative Research (COREQ).

Experiences of a Digital Mental Health Intervention from the Perspectives of Young People Recovering from First-Episode Psychosis: A Focus Group Study.

Horyzons is a digital health intervention designed to support recovery in young people receiving specialized early intervention services for first-episode psychosis (FEP). Horyzons was developed in Australia and adapted for implementation in Canada based on input from clinicians and patients (Horyzons-Canada Phase 1) and subsequently pilot-tested with 20 young people with FEP (Horyzons-Canada Phase 2). OBJECTIVE: To understand the experiences of young adults with FEP who participated in the pilot study based on focus group data. METHODS: Among the twenty individuals that accessed the intervention, nine participated across four focus groups. Three team members were involved in data management and analysis, informed by a thematic analysis approach. A coding framework was created by adapting the Phase 1 framework to current study objectives, then revised iteratively by applying it to the current data. Once the coding framework was finalized, it was systematically applied to the entire dataset. RESULTS: Four themes were identified: (1) Perceiving Horyzons-Canada as helpful for recovery; (2) Appreciating core intervention components (i.e., peer networking; therapeutic content; moderation) and ease of use; (3) Being unaware of its features; and (4) Expressing concerns, suggestions, and future directions. CONCLUSIONS: Horyzons-Canada was well received, with participants wanting it to grow in scale, accessibility, and functionality.

Redefining Autoimmune Disorders' Pathoetiology: Implications for Mood and Psychotic Disorders' Association with Neurodegenerative and Classical Autoimmune Disorders.

Although previously restricted to a limited number of medical conditions, there is a growing appreciation that 'autoimmune' (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell 'autoimmune'-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many 'autoimmune'/'immune-mediated' disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.

Considerations toward an epigenetic and common pathways theory of mental disorder.

Psychopathology emerges from the dynamic interplay of physiological and mental processes and ecological context. It can be seen as a failure of recursive, homeostatic processes to achieve adaptive re-equilibrium. This general statement can be actualized with consideration of polygenic liability, early exposures, and multiunit (multi-"level") analysis of the psychological action and the associated physiological and neural operations, all in the context of the developmental exposome. This article begins by identifying key principles and clarifying key terms necessary to mental disorder theory. It then ventures a sketch of a model that highlights epigenetic dynamics and proposes a common pathways hypothesis toward psychopathology. An epigenetic perspective elevates the importance of developmental context and adaptive systems, particularly in early life, while opening the door to new mechanistic discovery. The key proposal is that a finite number of homeostatic biological and psychological mechanisms are shared across most risky environments (and possibly many genetic liabilities) for psychopathology. Perturbation of these mediating mechanisms leads to development of psychopathology. A focus on dynamic changes in these homeostatic mechanisms across multiple units of analysis and time points can render the problem of explaining psychopathology tractable. Key questions include the mapping of recursive processes over time, at adequate density, as mental disorders unfold across development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Statistical analysis plans for two randomised controlled trials of the Narrative Experiences Online (NEON) Intervention: impact of receiving recorded mental health recovery narratives on quality of life in people experiencing psychosis (NEON) and people experiencing non-psychosis mental health problems (NEON-O).

BACKGROUND: Mental health recovery narratives are a first-hand account of an individual's recovery from mental health distress, access to narratives can aid recovery. The NEON Intervention is a web-application providing access to a managed collection of narratives. We present the statistical analysis plan for assessing the effectiveness of the NEON Intervention in improving quality of life at 1-year post-randomisation. We pay particular focus on the statistical challenges encountered due to the online nature of this trial. METHODS AND DESIGN: The NEON Intervention is assessed in two trial populations, one for people with experience of psychosis in the last 5 years, and mental health distress in the last six months (NEON Trial) and one for people with experience of non-psychosis mental health problems (NEON-O Trial). Both NEON trials are two-arm randomised controlled superiority trials comparing the effectiveness of the NEON Intervention with usual care. The target sample size is 684 randomised participants for NEON and 994 for NEON-O. Participants were randomised centrally in a 1:1 ratio. RESULTS: The primary outcome is the mean score of subjective items on the Manchester Short Assessment of Quality-of-Life questionnaire (MANSA) at 52 weeks. Secondary outcomes are scores from the Herth Hope Index, Mental Health Confidence Scale, Meaning of Life questionnaire, CORE-10 questionnaire and Euroqol 5-Dimension 5-Level (EQ-5D-5L). CONCLUSION: This manuscript is the statistical analysis plan (SAP) for the NEON trials. Any post hoc analysis, such as those requested by journal reviewers will be clearly labelled as such in the final trial reporting. Trial registration Both trials were prospectively registered. NEON Trial: ISRCTN11152837, registered on 13 August 2018. NEON-O Trial: ISRCTN63197153, registered on 9 January 2020.

Effectiveness of Providing Information on Antipsychotic Medication to Patients with Psychotic Disorders: An Integrative Review.

The aim of this integrative literature review is to describe the information provided to patients with psychotic disorders regarding their medication and to consider the effectiveness of providing such information. Searches of four databases identified 16 articles that met inclusion criteria. Results indicated that patients had relatively poor knowledge about their medications overall. Knowledge about side effects was found to improve significantly following education, with better knowledge leading to positive patient outcomes including increased adherence. Findings offer a comprehensive description of antipsychotic medication information provided to patients and an indication of the positive impact of information provision.