In mental health, the term dual-diagnosis is used for the co-occurrence of Substance Use Disorder (SUD) with another mental disorder. These co-occurring disorders can have a shared cause, and can cause/intensify each other's expression. Forming a threat to health and society, dual-diagnosis is associated with relapses in addiction-related behavior and a destructive lifestyle. This is due to a persistent failure to control impulses and the maintaining of inadequate self-regulatory behavior in daily life. Thus, several aspects of executive functioning like inhibitory, shifting and updating processes seem impaired in dual-diagnosis. Executive (dys-)function is currently even seen as a shared underlying key component of most mental disorders. However, the number of studies on diverse aspects of executive functioning in dual-diagnosis is limited. In the present review, a systematic overview of various aspects of executive functioning in dual-diagnosis is presented, striving for a prototypical profile of patients with dual-diagnosis. Looking at empirical results, inhibitory and shifting processes appear to be impaired for SUD combined with schizophrenia, bipolar disorder or cluster B personality disorders. Studies involving updating process tasks for dual-diagnosis were limited. More research that zooms in to the full diversity of these executive functions is needed in order to strengthen these findings. Detailed insight in the profile of strengths and weaknesses that underlies one's behavior and is related to diagnostic classifications, can lead to tailor-made assessment and indications for treatment, pointing out which aspects need attention and/or training in one's self-regulative abilities.

Background: Approximately 25-50% of people diagnosed with substance use disorder experience psychiatric disorders, and this percentage is even higher if subclinical psychopathological symptomatology is taken into consideration. "Dual diagnosis" implies the comorbidity of two disorders (mental disorder and addiction), but in a clinical setting, numerous dual diagnoses involve multiple addictions (polysubstance use means the concurrent use of more than one psychoactive substance). Clinical observations and epidemiological studies showed that the use of stimulants in combination with other substances results in additional risks. Apart from the clinical significance of the specificity of stimulants used in combination with other substances, only non-exhaustive research on the specificity of this comorbidity has been performed to date. The aim of the study was to analyze polymorphisms of the genes (DRD4 VNTR in exon III Ex3, DRD2 rs1076560, rs1800498, rs1079597, rs6276, as well as in the PROM promoter region (rs1799732, ANKK1 Tag1A rs1800497, DAT) in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, and the co-occurrence of specific mental disorders in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, compared to the group of patients diagnosed with polysubstance use disorder. Methods: The study group consisted of 601 male volunteers with psychoactive substance dependence (n = 300) and non-dependent controls (n = 301). The genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. All computations were performed using STATISTICA 13. Results: Psychotic disorders were significantly more common in the group of males with polysubstance addiction, including addiction to stimulants, compared to the group of males with polysubstance addiction without addiction to stimulants. In our own research, different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group. Psychotic disorders were more common in people addicted to stimulants compared to people addicted to other substances. Conclusions: In our study, psychotic disorders occurred more frequently in the study group of patients with polysubstance addiction, including addiction to stimulants, compared to the control group of patients with polysubstance addiction, but with no addiction to stimulants. Different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group, while the l/l genotype was less frequent in the study group. In DRD2 PROM rs 1799732, the del allele occurred more often than the ins allele in the study group. In the DRD4 Ex3 gene polymorphism, the s allele was more common in the study group, and the l allele was less frequent. In the DRD4 Ex3 gene polymorphism for the s/s genotype, psychotic disorders and generalized anxiety were more common, while for the s/l and l/l genotype, they were less frequent. The DRD4 Ex3 polymorphism s alleles were more common for depressive episode, dysthymia, and psychotic disorders as well as generalized anxiety disorder. We see a clear genetic aspect here. However, we want to be careful and draw no definite conclusions.

Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects.

Do patients with dual diagnosis (DD) with an early initiation of substance use and subsequent early onset substance use disorder (EOS) differ from those with late onset substance use disorder (LOS) regarding characteristics, sex-related risk behaviors, course, and outcome?

It is estimated that up to 75% of patients with severe mental illness (SMI) also have substance use disorder (SUD). The aim of this systematic review was to explore the scope, quality and inclusivity of international clinical guidelines on mental health and/or substance abuse in relation to diagnosis and treatment of co-existing disorders and considerations for wider social and contextual factors in treatment recommendations.

Psychiatric patients are more likely to be victims of crime than others in the community. Dual diagnosis patients with comorbid psychiatric and substance use disorders are especially prone to victimization. Victimization is associated with substance abuse, more severe symptomatology and homelessness. There is a strong need for interventions to reduce victimization in this population. We developed the Self-wise, Other-wise, Streetwise (SOS) training to reduce victimization in patients with dual diagnosis.

In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process.

Differentiation of mild cognitive impairment from depression in elderly adults is a clinically relevant issue which is not sufficiently solved. Gait and dual task (DT) parameters may have the potential to complement current diagnostic work-up, as both dementia and depression are associated with changes of gait and DT parameters.

Sleep disorders are often associated with drug use. Nearly 70% of patients admitted for detoxification report sleep problems. Dual disorder (DD) is the comorbidity between mental disorders in general and disorders related to psychoactive substance use. The association between substance use and sleep disorders (SD) appears to be bidirectional. Our objective is to analyze the association between sleep disturbance history and drug use pattern (alcohol, cannabis, opioids, and cocaine).

Background: Previous studies in Mexico undertaken at residential facilities for treating substance use disorders (SUDs) reported that the prevalence of Dual Disorders (DDs) is over 65%. DDs pose a major challenge for the Mexican health system, particularly for community-based residential care facilities for SUDs, due to the shortage of certified professionals to diagnose and treat these patients. Moreover, the lack of standardized algorithms for screening for and evaluating DDs to refer patients to specialized services (whether private or public) hinders timely care, delaying the start of integrated treatment. The use of new technologies provides a strategic opportunity for the timely detection of DDs through the development of standardized digital applications for the timely detection of DDs. Objective: To develop an app to screen for DDs, which will contribute to referral to specialized services in keeping with the level of severity of psychiatric and addictive symptomatology, and be suitable for use by community-based residential care facilities for SUDs. Method: The research project was implemented in two stages. Stage 1 involved obtaining the psychometric properties of the Dual Diagnosis Screening Interview (DDSI). Stage 2 consisted of two steps to test the Beta version of the app and the quality of version 1.0. Results: The DDS obtained sensitivity and specificity scores above 85%. The app and its algorithm to screen for and refer DDs proved to be efficient and easy to apply with satisfactory community acceptance. Conclusion: The app promises to be a useful screening tool at residential addiction treatment centers.

Human genome sequencing has transformed our understanding of genomic variation and its relevance to health and disease, and is now starting to enter clinical practice for the diagnosis of rare diseases. The question of whether and how some categories of genomic findings should be shared with individual research participants is currently a topic of international debate, and development of robust analytical workflows to identify and communicate clinically relevant variants is paramount.

RORα, the RAR-related orphan nuclear receptor alpha, is essential for cerebellar development. The spontaneous mutant mouse staggerer, with an ataxic gait caused by neurodegeneration of cerebellar Purkinje cells, was discovered two decades ago to result from homozygous intragenic Rora deletions. However, RORA mutations were hitherto undocumented in humans. Through a multi-centric collaboration, we identified three copy-number variant deletions (two de novo and one dominantly inherited in three generations), one de novo disrupting duplication, and nine de novo point mutations (three truncating, one canonical splice site, and five missense mutations) involving RORA in 16 individuals from 13 families with variable neurodevelopmental delay and intellectual disability (ID)-associated autistic features, cerebellar ataxia, and epilepsy. Consistent with the human and mouse data, disruption of the D. rerio ortholog, roraa, causes significant reduction in the size of the developing cerebellum. Systematic in vivo complementation studies showed that, whereas wild-type human RORA mRNA could complement the cerebellar pathology, missense variants had two distinct pathogenic mechanisms of either haploinsufficiency or a dominant toxic effect according to their localization in the ligand-binding or DNA-binding domains, respectively. This dichotomous direction of effect is likely relevant to the phenotype in humans: individuals with loss-of-function variants leading to haploinsufficiency show ID with autistic features, while individuals with de novo dominant toxic variants present with ID, ataxia, and cerebellar atrophy. Our combined genetic and functional data highlight the complex mutational landscape at the human RORA locus and suggest that dual mutational effects likely determine phenotypic outcome.

BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to warfarin for treatment of atrial fibrillation (AF). Evidence demonstrating the efficacy and safety of DOACs has primarily been from clinical trial settings. The real-world effectiveness of DOACs in specific nontrial populations that differ in age, comorbidity burden, and socioeconomic status is unclear. OBJECTIVE: To compare total downstream medical expenditure between AF patients treated with warfarin and DOACs dually enrolled in the Veterans Affairs (VA) Healthcare System and fee-for-service Medicare. METHODS: This was an exploratory treatment effectiveness study that analyzed VA administrative data and Medicare claims. We examined patients with an incident diagnosis for AF and initiated warfarin or DOAC treatment between 2012 and 2015. The primary outcome was total medical expenditure over 3 years following treatment initiation. To address potential informative censoring, we applied a multipart estimator that extends traditional 2-part models to separate differences between groups due to survival and cost accumulation effects. Inverse probability weighting was applied to address potential treatment selection bias. RESULTS: We identified 31,276 and 17,021 patients receiving warfarin and DOACs, respectively. Mean unadjusted (SD) expenditure was higher for warfarin ($56,265 [$96,666]) compared with DOAC patients ($32,736 [$52,470]). Compared with patients receiving DOACs, adjusted 3-year expenditure was $25,688 (P < 0.001) higher for patients receiving warfarin. CONCLUSIONS: VA patients with AF initiating warfarin incurred markedly higher downstream expenditure compared with similar patients receiving DOACs. The benefits of DOACs found in previous clinical trials were present in this population, suggesting that these DOACs may be the preferred option for treatment of AF in older VA patients. DISCLOSURES: This study was funded by a VA Health Services Research and Development Investigator Initiated Research Award (IIR 15-139). Support for VA/CMS data was provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center (Project Numbers SDR 02-237 and 98-004). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the University of Washington, Northeastern University, and Boston University. The authors declare no conflicts of interest. This research includes data obtained from the VHA Office of Performance Measurement (17API2), which resides within the Office of Analytics and Performance Integration (API), under the Office of Quality and Patient Safety (QPS; formerly known as RAPID). An oral presentation documenting a subset of the findings from this study was presented at the 2020 AcademyHealth Annual Research Meeting, delivered virtually on July 29, 2020.

There are contemporary indicators that parent proxy-ratings and child self-ratings of a child's quality of life (QoL) are not interchangeable. This review examines dual informant studies to assess parent-child agreement on the QoL of children with attention-deficit/hyperactivity disorder. A systematic search of four major databases (PsycINFO, MEDLINE, EMBASE and Cochrane databases) was completed, and related peer-reviewed journals were hand-searched. Studies which reported quantitative QoL ratings for matched parent and child dyads were screened in accordance with relevant inclusion and exclusion criteria. Key findings were extracted from thirteen relevant studies, which were rated for conformity to the recommendations of an adapted version of the STROBE statement guidelines for observational studies. In the majority of studies reviewed, children rated their QoL more highly than their parents. There was some evidence for greater agreement on the physical health domain than psychosocial domains.

Cortical-striatal circuit dysfunction in mental illness may enhance addiction vulnerability. Neonatal ventral hippocampal lesions (NVHL) model this dual diagnosis causality by producing a schizophrenia syndrome with enhanced responsiveness to addictive drugs. Rat genome-wide microarrays containing >24 000 probesets were used to examine separate and co-occurring effects of NVHLs and cocaine sensitization (15 mg/kg/day × 5 days) on gene expression within medial prefrontal cortex (MPFC), nucleus accumbens (NAC), and caudate-putamen (CAPU). Two weeks after NVHLs robustly amplified cocaine behavioral sensitization, brains were harvested for genes of interest defined as those altered at P < 0.001 by NVHL or cocaine effects or interactions. Among 135 genes so impacted, NVHLs altered twofold more than cocaine, with half of all changes in the NAC. Although no genes were changed in the same direction by both NVHL and cocaine history, the anatomy and directionality of significant changes suggested synergy on the neural circuit level generative of compounded behavioral phenotypes: NVHL predominantly downregulated expression in MPFC and NAC while NVHL and cocaine history mostly upregulated CAPU expression. From 75 named genes altered by NVHL or cocaine, 27 had expression levels that correlated significantly with degree of behavioral sensitization, including 11 downregulated by NVHL in MPFC/NAC, and 10 upregulated by NVHL or cocaine in CAPU. These findings suggest that structural and functional impoverishment of prefrontal-cortical-accumbens circuits in mental illness is associated with abnormal striatal plasticity compounding with that in addictive disease. Polygenetic interactions impacting neuronal signaling and morphology within these networks likely contribute to addiction vulnerability in mental illness.

Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction. Neonatal ventral hippocampal lesions (NVHL) have previously been demonstrated to produce post-adolescent-onset, pharmacological, neurobiological and cognitive-deficit features of schizophrenia. Here, we show that NVHLs increase adult nicotine self-administration, potentiating acquisition-intake, total nicotine consumed and drug seeking. Behavioral sensitization to nicotine in adolescence prior to self-administration is not accentuated by NVHLs in contrast to increased nicotine self-administration and behavioral sensitization documented in adult NVHL rats, suggesting periadolescent neurodevelopmental onset of nicotine addiction vulnerability in the NVHL model. Delivering a nicotine regimen approximating the exposure used in the sensitization and self-administration experiments (i.e. as a treatment) to adult rats did not specifically reverse NVHL-induced cortical-hippocampal-dependent cognitive deficits and actually worsened cognitive efficiency after nicotine treatment stopped, generating deficits that resemble those due to NVHLs. These findings represent the first prospective evidence demonstrating a causal link between disease processes in schizophrenia and nicotine addiction. Developmental cortical-temporal limbic dysfunction in mental illness may thus amplify nicotine's reinforcing effects and addiction risk and severity, even while producing cognitive deficits that are not specifically or substantially reversible with nicotine.

Assertive Community Treatment (ACT) is more successful in reducing hospitalization when baseline use is high. However, with a growing recovery-focus, ACT may be useful for people with severe mental illness who are difficult to engage but not high users of inpatient services. This study investigated hospitalization 2 years before and 2 years after ACT enrollment amongst patients both with and without high inpatient services use before enrollment into ACT.

Methamphetamine (MA) remains one of the most commonly used amphetamine-type stimulants, accounting for the second most widely-used substance after marijuana. Due to increased use of MA, a wide variety of research has focused on the patterns of MA use initiation among adolescents. Nevertheless, there are few data available for people who use MA. The present study set out to assess the sequential patterns of substance use initiation in patients with MA use disorders in Iran.

Genetic factors involved in the susceptibility to drug addiction still remain largely unknown. MiRNAs seem to play key roles in the drug-induced plasticity of the brain that likely drives the emergence of addiction. In this work we explored the role of miRNAs in drug addiction. With this aim, we selected 62 SNPs located in the 3'UTR of target genes that are predicted to alter the binding of miRNA molecules and performed a case-control association study in a Spanish sample of 735 cases (mainly cocaine-dependent subjects with multiple drug dependencies) and 739 controls. We found an association between rs1047383 in the PLCB1 gene and drug dependence that was replicated in an independent sample (663 cases and 667 controls). Then we selected 9 miRNAs predicted to bind the rs1047383 region, but none of them showed any effect on PLCB1 expression. We also assessed two miRNAs binding a region that contains a SNP in linkage disequilibrium with rs1047383, but although one of them, hsa-miR-582, was found to downregulate PLCB1, no differences were observed between alleles. Finally, we explored the possibility that PLCB1 expression is altered by cocaine and we observed a significant upregulation of the gene in the nucleus accumbens of cocaine abusers and in human dopaminergic-like neurons after cocaine treatment. Our results, together with previous studies, suggest that PLCB1 participates in the susceptibility to drug dependence.

Background: Structural imaging studies of cannabis users have found evidence of both cortical and subcortical volume reductions, especially in cannabinoid receptor-rich regions such as the hippocampus and amygdala. However, the findings have not been consistent. In the present study, we examined a sample of adult heavy cannabis users without other substance abuse to determine whether long-term use is associated with brain structural changes, especially in the subcortical regions. Method: We compared the gray matter volume of 14 long-term, heavy cannabis users with non-using controls. To provide robust findings, we conducted two separate studies using two different MRI techniques. Each study used the same sample of cannabis users and a different control group, respectively. Both control groups were independent of each other. First, whole-brain voxel-based morphometry (VBM) was used to compare the cannabis users against 28 matched controls (HC1 group). Second, a volumetric analysis of subcortical regions was performed to assess differences between the cannabis users and a sample of 100 matched controls (HC2 group) obtained from a local database of healthy volunteers. Results: The VBM study revealed that, compared to the control group HC1, the cannabis users did not show cortical differences nor smaller volume in any subcortical structure but showed a cluster (p < 0.001) of larger GM volume in the basal ganglia, involving the caudate, putamen, pallidum, and nucleus accumbens, bilaterally. The subcortical volumetric analysis revealed that, compared to the control group HC2, the cannabis users showed significantly larger volumes in the putamen (p = 0.001) and pallidum (p = 0.0015). Subtle trends, only significant at the uncorrected level, were also found in the caudate (p = 0.05) and nucleus accumbens (p = 0.047). Conclusions: This study does not support previous findings of hippocampal and/or amygdala structural changes in long-term, heavy cannabis users. It does, however, provide evidence of basal ganglia volume increases.