Exploring dual diagnosis in opioid agonist treatment patients: a registry-linkage study in Czechia and Norway.

BACKGROUND: Knowledge of co-occurring mental disorders (termed 'dual diagnosis') among patients receiving opioid agonist treatment (OAT) is scarce. This study aimed (1) to estimate the prevalence and structure of dual diagnoses in two national cohorts of OAT patients and (2) to compare mental disorders between OAT patients and the general populations stratified on sex and standardized by age. METHODS: A registry-linkage study of OAT patients from Czechia (N = 4,280) and Norway (N = 11,389) during 2010-2019 was conducted. Data on mental disorders (F00-F99; ICD-10) recorded in nationwide health registers were linked to the individuals registered in OAT. Dual diagnoses were defined as any mental disorder excluding substance use disorders (SUDs, F10-F19; ICD-10). Sex-specific age-standardized morbidity ratios (SMR) were calculated for 2019 to compare OAT patients and the general populations. RESULTS: The prevalence of dual diagnosis was 57.3% for Czechia and 78.3% for Norway. In Czechia, anxiety (31.1%) and personality disorders (25.7%) were the most prevalent, whereas anxiety (33.8%) and depression (20.8%) were the most prevalent in Norway. Large country-specific variations were observed, e.g., in ADHD (0.5% in Czechia, 15.8% in Norway), implying differences in screening and diagnostic practices. The SMR estimates for any mental disorders were 3.1 (females) and 5.1 (males) in Czechia and 5.6 (females) and 8.2 (males) in Norway. OAT females had a significantly higher prevalence of co-occurring mental disorders, whereas SMRs were higher in OAT males. In addition to opioid use disorder (OUD), other substance use disorders (SUDs) were frequently recorded in both countries. CONCLUSIONS: Results indicate an excess of mental health problems in OAT patients compared to the general population of the same sex and age in both countries, requiring appropriate clinical attention. Country-specific differences may stem from variations in diagnostics and care, reporting to registers, OAT provision, or substance use patterns.

Electrophysiological biomarkers in dual pathology.

INTRODUCTION: The co-occurrence of substance use disorder with at least one other mental disorder is called dual pathology, which in turn is characterised by heterogeneous symptoms that are difficult to diagnose and have a poor response to treatment. For this reason, the identification and validation of biomarkers is necessary. Within this group, possible electroencephalographic biomarkers have been reported to be useful in diagnosis, treatment and follow-up, both in neuropsychiatric conditions and in substance use disorders. This article aims to review the existing literature on electroencephalographic biomarkers in dual pathology. METHODS: A narrative review of the literature. A bibliographic search was performed on the PubMed, Science Direct, OVID, BIREME and Scielo databases, with the keywords: electrophysiological biomarker and substance use disorder, electrophysiological biomarker and mental disorders, biomarker and dual pathology, biomarker and substance use disorder, electroencephalography, and substance use disorder or comorbid mental disorder. RESULTS: Given the greater amount of literature found in relation to electroencephalography as a biomarker of mental illness and substance use disorders, and the few articles found on dual pathology, the evidence is organised as a biomarker in psychiatry for the diagnosis and prediction of risk and as a biomarker for dual pathology. CONCLUSIONS: Although the evidence is not conclusive, it suggests the existence of a subset of sites and mechanisms where the effects of psychoactive substances and the neurobiology of some mental disorders could overlap or interact.

Managing the Dual Diagnosis Dilemma of Bipolar Disorder and Substance Abuse in Clinical Settings.

OBJECTIVE: Drug addiction is a chronic mental disorder that significantly impacts all aspects of an individual's life, and substance use disorder in patients with bipolar disorder. The objective of this study is to assess the frequency of substance abuse among patients with bipolar spectrum disorder. METHOD: This cross-sectional study evaluated the frequency of bipolar spectrum disorder in patients taking methadone through various screening measures, including Mini Mental State Examination (MMSE), DSM IV criteria, Mood Disorders Questionnaire (MDQ), Goodwin and Ghaemi's criteria, and Akiskal classification for bipolar disorders. RESULTS: Out of the total 197 participants in the study, 77 were identified as individuals engaging in poly-substance abuse. The investigation assessed the frequency of bipolar spectrum disorder based on various diagnostic criteria: 24% according to DSM-IV criteria, 29.9% using MDQ, 29.9% based on Ghaemi and Goodwin's criteria, and the highest rate at 48.2% when applying Akiskal's classification. CONCLUSIONS: This study highlights the high frequency of bipolar disorder among individuals with substance use disorder, especially those with concomitant depression. Therefore, it is crucial to pay special attention to individuals with substance use disorder with co-existing bipolar disorder.

Perceived advantages and disadvantages of substance use in a dual diagnosis population with severe mental disorders and severe substance use disorder. Considering the self-medication hypothesis.

AIM: Based on a large cohort of dual diagnosis patients, the aim of this study was to quantify the patient-perceived problems and advantages of their substance use and relate the quantity of problems to the substance type and psychiatric diagnosis. MATERIAL: Data comes from a naturalistic cohort admitted to an in-patient facility in Denmark specialized in integrated dual diagnosis treatment. We included 1076 patients at their first admission to the facility from 2010 to 2017. Participants completed 607 DrugCheck and 130 DUDIT-E questionnaires. METHOD: we analyzed the questionnaires and included admission diagnosis by use of t-test and ANOVA to depict the patterns in substance use in relation to psychiatric diagnosis. RESULTS: The three most common substance related problems according to the DrugCheck questionnaire were: feeling depressed, financial problems, and losing interest in daily activities. From DUDIT-E, the highest-ranking negative substance related effects were financial ruin, deterioration of health, and problems at work. Effects on social life relationships were also evident with more than 40% of participants. The top three positive substance related effects reported were relaxation, improved sleep, and control over negative emotions. The number of problems listed varied significantly with the type of preferred substance. Patients using pain medication, sedatives, central stimulants, and alcohol reported most problems. Diagnosis did not differentiate the problems experienced. Results partially support the broad self-medication hypothesis for patients with severe mental illness, but also points out that patients are well aware of negative effects.

Early prenatal diagnosis of causative homozygous variants in ASCC1 in a fetus with cystic hygroma and additional homozygous variants of unknown significance associated with a neurological phenotype not visible in early gestation: Dual diagnosis or not?

A consanguineous couple was referred at 10 weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing identified causative homozygous truncating variants in ASCC1 previously implicated in spinal muscular atrophy with congenital bone fractures. Prenatal manifestations in ASCC1 can usually include hydramnios, fetal hypo-/akinesia, arthrogryposis, contractures and limb deformities, hydrops fetalis and cystic hygroma. An additional truncating variant was identified in CSPP1 associated with Joubert syndrome. Presentations in CSPP1 include cerebellar and brainstem malformations with vermis hypoplasia and molar tooth sign, difficult to visualize in early gestation. A second pregnancy was marked by the recurrence of isolated increased nuchal translucency at 10 + 2 WG. Sanger prenatal diagnosis targeted on ASCC1 and CSPP1 variants showed the presence of the homozygous familial ASCC1 variant. In this case, prenatal exome sequencing analysis is subject to a partial ASCC1 phenotype and an undetectable CSPP1 phenotype at 10 weeks of gestation. As CSPP1 contribution is unclear or speculative to a potentially later in pregnancy or postnatal phenotype, it is mentioned as a variant of uncertain significance. The detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype-genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes, will encourage the clinical community to define future practices in molecular prenatal reporting.

Dual diagnosis of epilepsy and dissociative seizures: Prescription patterns, feasibility and safety of rationalising antiseizure medication.

BACKGROUND: Patients with a dual-diagnosis of epilepsy and dissociative seizures (DS) have received far less attention than those with single pathology. Anti-seizure medication (ASM) prescription patterns and safety of rationalisation have not been reviewed. METHODS: We undertook a retrospective cohort study of all patients with a dual-diagnosis admitted to the Scottish Epilepsy Centre between 2012-2020. ASM frequencies were compared across admission, discharge and follow-up and emergency hospital attendances compared a year before and after admission. Demographic data, seizure characteristics and mortality data were also reviewed. RESULTS: Across the 139 patients included in our study, ASM frequency at follow-up was significantly lower than on admission (mean 2.51 vs 2.14, Z = -2.11 p = 0.035, r = -0.215). Total hospital attendances in the year following admission were significantly lower than in the year before (mean 1.27 vs 0.77, Z = 2.306, p = 0.021, r = -0.262). Those with inactive epilepsy had their medications reduced to a greater extent that those with active epilepsy. 44 patients had their ASM frequency reduced during admission with a similar trend of reduced hospital attendances (mean 1.29 vs 0.43 Z = -3.162 p = 0.002). There was one epilepsy related death. CONCLUSIONS: Clinicians should consider the development of co-morbid DS in patients with epilepsy not responding to an escalation of ASM, especially if presenting with a new seizure type. Patients with a dual-diagnosis of epilepsy and DS, particularly those with well controlled epilepsy, are likely overtreated with ASM. Medication review in a tertiary epilepsy centre allows for safe rationalisation of ASM and likely contributes to the need for fewer hospital attendances.

Evaluation of clinical outcomes and employment status in veterans with dual diagnosis of traumatic brain injury and spinal cord injury.

PURPOSE: To examine clinical outcomes and employment status in Veterans with and without a dual diagnosis of traumatic brain injury (TBI) and spinal cord injury (SCI). METHODS: This cross-sectional study examined a national sample of Veterans enrolled in the VA Million Veteran Program who completed the Comprehensive TBI Evaluation (CTBIE) as part of the Veterans Health Administration's TBI Screening and Evaluation Program. Veterans (N = 12,985) were classified into the following TBI/SCI groups using CTBIE data: those with a dual diagnosis of TBI and SCI (TBI+/SCI+); those with a history of TBI but no SCI (TBI+/SCI-); and those with no history of TBI or SCI (TBI-/SCI-; i.e., the control group). CTBIE-derived outcomes included neurobehavioral symptoms, comorbid psychiatric symptoms, pain and pain interference, and employment status. RESULTS: Chi-square analyses showed significant associations between TBI/SCI group and all clinical outcomes evaluated (all p's < .001; V = 0.07-0.11). In general, the TBI+/SCI+ and TBI +/SCI- groups endorsed comparable levels of neurobehavioral symptoms, psychiatric symptoms, and pain, but significantly greater rates of symptoms and pain relative to the TBI-/SCI- group. Effect sizes for all pairwise comparisons were small (φ = 0.01-0.11). Finally, there was no significant association between TBI/SCI group and employment status (p = .170; V = 0.02), with all three groups showing relatively comparable rates of unemployment. CONCLUSIONS: Regardless of SCI status, Veterans with TBI history endorsed poorer clinical outcomes than Veterans without TBI and SCI. However, rates of unemployment were similarly high across all three groups. Findings suggest that any Veteran completing the CTBIE may be at risk for poor clinical and employment outcomes.

Comparison of Emotional Processing Between Patients with Substance Use Disorder and Those with Dual Diagnosis: Relationship with Severity of Dependence and Use During Treatment.

This study analyzed, in a Spanish sample, the differences in emotional processing in patients diagnosed with substance use disorder (SUD) and patients with a dual diagnosis (DD), and tested whether alterations in emotional regulation were related to the severity of dependence and consumption during treatment. A descriptive follow-up study was conducted with 88 adult outpatients (83% men) who were receiving treatment for alcohol and cocaine SUD. Of the sample, 43.2% presented dual diagnosis according to DSM-IV-TR criteria. Emotional processing was assessed with the IAPS, and dependence severity with the SDSS. Consumption was determined with self-reports and toxicological tests. Regression analyses revealed that the DD group had more difficulties in identifying the valence and arousal of the images than patients with SUD. Patients with DD presented more difficulty in identifying images in which valence was manipulated, but not in those in which arousal was manipulated. Cocaine use during treatment was associated with difficulties in identifying unpleasant (U = 734.0; p < .05) and arousing (U = 723.5; p < .05) images. Although these results are preliminary, findings suggest that impaired emotional processing is aggravated in dual patients, although it may be a common transdiagnostic factor in SUD and other comorbid mental disorders. Findings highlight the importance of evaluating emotional regulation to better understand its possible role in the maintenance of substance use.

Polypharmacy in antipsychotic pharmacological treatment among patients with dual diagnosis in Denmark.

INTRODUCTION: Antipsychotic polypharmacy is prevalent, however literature on antipsychotic polypharmacy during treatment among patients with dual diagnosis is largely non-existent. This study aims to investigating the extent of antipsychotic polypharmacy dual diagnosis patients during hospitalisations. METHODS: Utilizing cohort data from an integrated dual diagnosis in-patient facility from patients hospitalized between 1 March 2012, to 31 December 2016, we compared the mean antipsychotic medication administered at admission and discharge and examined covariate associations with logistic regressions. RESULTS: The study identified 907 hospital admissions, of which 641 were the first for each patient during the period. At admission, 74.1% received antipsychotics; polypharmacy spanned psychiatric disorders. categories. Patients with affective or personality spectrum disorders were less likely to have antipsychotic polypharmacy upon admission compared to those with psychosis spectrum disorders. 2013-2016 admissions presented less polypharmacy than 2012. Mean antipsychotic numbers remained unchanged for >30-day hospitalizations. Patients admitted without antipsychotic polypharmacy with an affective spectrum disorder or aged 41-50 or over 51 years old were less likely to be discharged with antipsychotic polypharmacy when compared to patients with psychosis spectrum disorder or aged 18-30 years old. CONCLUSION: Approximately three-quarters of admitted patients were treated with antipsychotic medication. Antipsychotic polypharmacy was observed across all psychiatric disorder categories, indicating potential off-label use. Addressing antipsychotic polypharmacy during treatment is challenging, even for specialised facilities. Rational antipsychotic prescribing, deprescribing protocols, and further prescription pattern research are needed.

JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome.

A 66-year-old male presented with hypereosinophilia, thrombocytosis, extensive thrombosis refractory to direct oral anticoagulant therapy, and evidence of end-organ damage, including rash, splenic infarcts, and pulmonary infiltrates. Bone marrow biopsy revealed myeloid malignancy consistent with both chronic eosinophilic leukemia and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with SF3B1 mutation and thrombocytosis. Next-generation sequencing of the patient's eosinophils and neutrophil compartments revealed pathologic variants in EZH2 and SF3B1 in addition to a noncanonical JAK2 R683S mutation that has not been previously described in myeloproliferative disorders or other chronic myeloid neoplasms. These mutations were not present in the patient's lymphoid cell fraction, suggesting that the hematopoietic malignancy arose in a myeloid-committed progenitor cell. Based on this case and previous work from our group, we propose that noncanonical JAK2 mutations may permit signal transduction that biases toward eosinophilic differentiation in chronic myeloid neoplasms. Although the patient's blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.

Fragile X Syndrome and Fetal Alcohol Syndrome: Occurrence of Dual Diagnosis in a Set of Triplets.

BACKGROUND: Fragile X syndrome (FXS) and fetal alcohol syndrome disorders are both common causes of intellectual disability in children. When both conditions are present in the same individual, the resultant phenotype may make identification of clinical issues and management challenging. CASE PRESENTATION: In this case report, we present a case of triplets who had significant in utero alcohol exposure; 2 of whom also have FXS and the other not having the fragile X mutation. The siblings with FXS have subtle differences in the physical phenotype compared with the other one, who has prominent features of partial fetal alcohol syndrome instead. However, all 3 siblings have intellectual impairment (although this is more severe in the 2 with FXS), meet diagnostic criteria for autism spectrum disorder, and present with severe behavioral challenges. The clinical presentation of the 2 siblings with FXS is much more severe as compared to a child with FXS alone, and this is likely due to the additive effect of in utero alcohol exposure and environmental factors. We discuss the combination of these 2 pathologies and how this can affect the overall clinical presentation. CONCLUSION: In the management of children with FXS, evaluation for other risk factors that can have neurobehavioral sequelae is important, and these can affect clinical presentation and prognosis.

AUTISM SPECTRUM DISORDER AND SCHIZOPHRENIA - SIMILARITIES BETWEEN THE TWO DISORDERS WITH A CASE REPORT OF A PATIENT WITH DUAL DIAGNOSIS.

This paper presents the genetic, molecular and neuroanatomical similarities between autism spectrum disorder (ASD) and schizophrenia using the case report of a 34-year-old female patient with a previous diagnosis of schizophrenia as an example. As a result of repeat hospitalization, expanded history, psychological testing and verification of persistent symptoms of psychopathology, a cooccurring diagnosis of autism spectrum disorder was made.

Coexistence of Genetic Diseases Is a New Clinical Challenge: Three Unrelated Cases of Dual Diagnosis.

Technological advancements in molecular genetics and cytogenetics have led to the diagnostic definition of complex or atypical clinical pictures. In this paper, a genetic analysis identifies multimorbidities, one due to either a copy number variant or a chromosome aneuploidy, and a second due to biallelic sequence variants in a gene associated with an autosomal recessive disorder. We diagnosed the simultaneous presence of these conditions, which co-occurred by chance, in three unrelated patients: a 10q11.22q11.23 microduplication and a homozygous variant, c.3470A>G (p.Tyr1157Cys), in the WDR19 gene associated with autosomal recessive ciliopathy; down syndrome and two variants, c.850G>A; p.(Gly284Arg) and c.5374G>T; p.(Glu1792*), in the LAMA2 gene associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A); and a de novo 16p11.2 microdeletion syndrome and homozygous variant, c.2828G>A (p.Arg943Gln), in the ABCA4 gene associated with Stargardt disease 1 (STGD1). The possibility of being affected by two relatively common or rare inherited genetic conditions would be suspected when signs and symptoms are incoherent with the primary diagnosis. All this could have important implications for improving genetic counseling, determining the correct prognosis, and, consequently, organizing the best long-term follow-up.

Dual diagnosis of autosomal dominant polycystic kidney disease and sickle cell disease in a teenage male.

BACKGROUND: Sickle cell disease (SCD) and autosomal dominant polycystic kidney disease (ADPKD) are relatively common genetic conditions with considerable overlap in clinical presentation. In addition to similarities between the signs and symptoms in sickle cell nephropathy and ADPKD, more than half of SCD patients have kidney cysts. The co-occurrence of these two diseases has not been previously reported in the literature. CASE DIAGNOSIS/TREATMENT: A 16-year-old Black male with SCD had bilateral kidney enlargement and multiple simple cysts on ultrasound. Although kidney cysts are significantly more common in individuals affected with SCD, genetic testing with a broad kidney gene panel was performed to explore the possible presence of another underlying genetic cause of his cysts, in addition to SCD. A dual diagnosis of SCD and ADPKD was made following the identification of two copies of the common pathogenic sickle cell HBB variant (c.20A > T, p.Glu7Val) and a pathogenic missense variant in PKD1 (c.8311G > A, p.Glu2771Lys). CONCLUSIONS: SCD and ADPKD differ in pathophysiological mechanisms and treatment regimens. As such, it will be paramount for this teenager to be closely monitored for signs of diminished kidney function and to be co-managed as he transitions to adult care to ensure proper treatment and management. Early identification of individuals with both SCD and a co-occurring condition is crucial to ensuring proper clinical management. Furthermore, identifying and reporting additional patients with SCD and ADPKD dual diagnoses will help us to understand the co-occurring disease course and optimal treatments.

The influence of childhood aspirations on the risk of developing psychotic disorders, substance use disorders, and dual diagnosis in adulthood based on the Metropolit 1953 Danish Male Birth Cohort.

The study aims to investigate the association of aspiration for future occupation, socioeconomic position, and intellectual abilities with risk of dual diagnosis, psychosis, substance use disorder (SUD) in later life, and to explore if social and intellectual disadvantage modify any effect of childhood aspirations on outcomes. The study included 7177 Danish boys born in 1953. We investigated childhood aspirations (preference regarding future occupation), socioeconomic position (paternal social group), and intellectual abilities (Härnquist intelligence score) on outcomes with dual diagnosis, psychotic disorder, or SUD in Danish registers. Combinations of variables were used for a two-way and three-way analysis (high and low levels of exposure variables). Cox regression with age as the underlying time scale was used for analysis. The separate analysis showed no associations between childhood aspirations and outcomes. Boys with low intelligence scores had an increased risk of developing psychotic disorders (aHR 1.5, 95% CI 1.1-2.1) and SUD (aHR 1.8, 95% CI 1.5-2.1) compared to high intelligence scores. The interaction analyses showed that individuals with a combination of low intelligence score, high aspirations, and/or high paternal social group might have an increased risk of developing dual diagnosis, psychotic disorders, or SUD in later life. This result should be interpreted with caution as interaction variables were not overall significant with the outcome of dual diagnosis or psychotic disorder. The findings suggest that childhood abilities and social position could be associated with the development of psychotic disorders and SUD in later life, however, further studies are needed to address the temporality of the association to gain an understanding of the underlying mechanism of the association.