Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72–1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach. Full article

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. Full article

Health-related quality of life (HRQoL) assessment has interest as an indicator of degree of affectation and prognosis in mental disorders. HRQoL is impaired in both Substance Use Disorder (SUD) and Major Depressive Disorder (MDD), two conditions highly prevalent, although less studied when both are coexisting (SUD + MDD). Hence, we decided to explore HRQoL with the SF-36 survey in a sample of 123 SUD and 114 SUD + MDD patients (51 symptomatic and 63 asymptomatic of depressive symptoms) under treatment. We performed analyses to examine HRQoL among groups, and its predictive value at 3-, 6- and 12-month follow-ups through regression models. Patients with SUD + MDD had worse HRQoL than SUD patients and population norms. For Mental Health, Vitality, and General Health dimensions, lower scores were observed for SUD + MDD regardless the presence/absence of depressive symptoms. For Physical Functioning and Health Change, depressive symptomatology and not the comorbidity of SUD + MDD diagnoses explained HRQoL limitations. At 3-, 6- and 12-month follow-ups we observed two predictors of relapses, General Health for asymptomatic SUD + MDD, and Physical Functioning for SUD. Improving HRQoL in SUD + MDD may be targeted during patient’s treatment; future studies should explore the influence of HRQoL on patient’s prognosis taking into account the presence/absence of depressive symptomatology. Full article

Background: 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). Methods: Analysis of data in the first interview at the Addictions Unit of the Department of Psychiatry at the University of Salamanca Health Care Complex between October 2017 and January 2020. The sample consists of 398 patients. We studied the association between different variables: origin of patients (Inpatient Dual Diagnosis Detoxification Unit (IDDDU) vs. Outpatient Drug Clinic (ODC), presence of affective disorder, psychotic disorder, type of drug used, and treatment. Results: Of patients with DD, 62% had more delayed sleep induction, sleep fragmentation, early awakening, and nightmares. Outpatients had more difficulty falling asleep because, in many cases, they had not previously sought any medical assistance. On the other hand, 67% of the patients with insomnia presented depression. Conclusions: There is evidence of a harmful association between DD and SD. Full article

Background: In clinical practice, there is the need to have clinical and biological markers to identify induced depression. The objective was to investigate clinical, biological and genetic differences between Primary Major Depression (Primary MD) and Alcohol Induced MD (AI-MD). Methods: Patients, of both genders, were recruited from psychiatric hospitalisation units. The PRISM instrument was used to establish the diagnoses. Data on socio-demographic/family history, clinical scales for depression, anxiety, personality and stressful life events were recorded. A blood test was performed analysing biochemical parameters and a Genome Wide Association Study (GWAS) to identify genetic markers associated with AI-MD. Results: A total of 80 patients were included (47 Primary MD and 33 AI-MD). The AI-MD group presented more medical comorbidities and less family history of depression. There were differences in traumatic life events, with higher scores in the AI-MD (14.21 ± 11.35 vs. 9.30 ± 7.38; p = 0.021). DSM-5 criteria were different between groups with higher prevalence of weight changes and less anhedonia, difficulties in concentration and suicidal thoughts in the AI-MD. None of the genetic variants reached significance beyond multiple testing thresholds; however, some suggestive variants were observed. Conclusions: This study has found clinical and biological features that may help physicians to identify AI-MD and improve its therapeutic approach. Full article

Psychological trauma has been identified in substance use disorders (SUD) as a major etiological risk factor. However, detailed and systematic data about the prevalence and types of psychological trauma in dual disorders have been scarce to date. In this study, 150 inpatients were recruited and cross-sectionally screened on their substance use severity, psychological trauma symptoms, comorbidities, and clinical severity. One hundred patients fulfilled criteria for a dual disorder, while 50 patients were diagnosed with only SUD. Ninety-four percent of the whole sample suffered from at least one lifetime traumatic event. The prevalence rates of Posttraumatic Stress Disorder diagnosis for dual disorder and only SUD was around 20% in both groups; however, patients with dual disorder presented more adverse events, more childhood trauma, more dissociative symptoms, and a more severe clinical profile than patients with only SUD. Childhood maltreatment can also serve as a predictor for developing a dual disorder diagnosis and as a risk factor for developing a more complex and severe clinical profile. These data challenge our current clinical practice in the treatment of patients suffering from dual disorder or only SUD diagnosis and favor the incorporation of an additional trauma-focused therapy in this population. This may improve the prognosis and the course of the illness in these patients. Full article

Post-traumatic stress disorder (PTSD) is highly prevalent among patients hospitalized for an alcohol use disorder (AUD). Hospitalization can improve PTSD and AUD outcomes in some but not all patients, but we lack data on the baseline predictors of PTSD non-remission. This study aimed to determine the baseline risk factors for non-remitted PTSD in patients hospitalized for an AUD. Of 298 AUD inpatients recruited in a rehabilitation center (Le Courbat, France), we included 91 AUD inpatients with a co-occurring PTSD and a longitudinal assessment at baseline (T1) and before discharge (T2: 8 weeks later). Patients were assessed for PTSD diagnosis/severity (PCL-5=PTSD Checklist for DSM-5), different types of trauma including childhood trauma (LEC-5=Life Events Checklist for DSM-5/CTQ-SF=Childhood Trauma Questionnaire, Short-Form), and AUD diagnosis/severity (clinical interview/AUDIT=Alcohol Use Disorders Identification Test). Rate of PTSD remission between T1 and T2 was 74.1%. Non-remitted PTSD at T2 was associated with a history of childhood trauma (physical, emotional or sexual abuse, physical negligence), but not with other types of trauma experienced, nor baseline PTSD or AUD severity. Among patients hospitalized for an AUD with co-occurring PTSD, PTSD remission was more strongly related to the existence of childhood trauma than to AUD or PTSD severity at admission. These patients should be systematically screened for childhood trauma in order to tailor evidence-based interventions. Full article

Background: Sleep problems are particularly frequent in psychiatric disorders, but their bidirectional intersection is poorly clarified. An especial link between substance use and sleep seems to exist. While dual disorder patients are certainly at higher risk of experiencing sleep problems, very limited research is available today. Methods: Forty-seven dual disorder hospitalized patients were included in this first study. A complete psychiatric evaluation was performed, and sleep habits, patterns and potential disorders were evaluated with specific sleep scales, as well as anxiety. Results: The global prevalence of insomnia symptoms was considerably higher compared with the general population. Different abuse patterns as a function of concurrent psychiatric diagnosis were found, with no significant gender differences. The association between the investigated sleep parameters and any specific substance of abuse was minor. The addict behavior started in more than half of the patients prior to the main psychiatric diagnosis and close to the beginning of sleep problems. Men had a higher prevalence of insomnia symptoms, together with a higher incidence of anxiety. Overall, subjective daytime functioning was not altered as a consequence of poor sleep. Conclusion: Dual disorder patients face significant sleep disturbances, with low sleep quality. The role of sleep in addiction and dual disorders deserves greater research. Full article

Personality traits are relevant in understanding substance use disorders (SUD) and schizophrenia (SZ), but few works have also included patients with dual schizophrenia (SZ+) and personality traits. We explored personality profile in a sample of 165 male patients under treatment, using the Temperament and Character Inventory-Revised. The participants were assigned to three groups of 55 patients each, according to previous diagnosis: SUD, SZ- and SZ+ (without/with SUD). We analyzed their clinical characteristics, relating them to personality dimensions. The SUD and SZ+ groups scored higher than SZ- in Novelty/Sensation Seeking. SZ- and SZ+ presented higher Harm Avoidance and lower Persistence than the SUD group. SZ+ patients showed the lowest levels of Self-directedness, while SZ- and SZ+ had higher scores in Self-transcendence than the SUD group. Several clinical characteristics were associated with personality dimensions depending on diagnosis, and remarkably so for psychiatric symptoms in the SZ- and SZ+ groups. The three groups had a maladaptive personality profile compared to general population. Our results point to different profiles for SUD versus SZ, while both profiles appear combined in the SZ+ group, with extreme scores in some traits. Thus, considering personality endophenotypes in SZ+ could help in designing individualized interventions for this group. Full article

Background: The landscape of attitudes, legal status and patterns of use of cannabis is rapidly changing in the United States and elsewhere. Therefore, the primary aim of this narrative review is to provide a concise overview of the literature on the comorbidity of cannabis use and cannabis use disorder (CUD) with other substance use and psychiatric disorders, and to use this information to accurately guide future directions for the field. Methods: A literature review of PubMed was conducted for studies relating to cannabis use, CUD, and a co-occurring psychiatric disorder. To provide an overview of representative data, the literature review focused on national-level, population-based work from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and National Survey on Drug Use and Health (NSDUH) surveys. Considering rapidly changing cannabis laws, recent (past five-year) studies were addressed. Results: A strong body of literature shows associations between cannabis use and CUD with other drug use, psychosis, mood disorders, anxiety disorders, and personality disorders. The strongest evidence of a potential causal relationship exists between cannabis use and psychotic disorders. While some evidence shows potential directionality between cannabis use and mood and anxiety disorders, results are inconsistent. Studies have established higher rates of CUD among those with personality disorders, but little about the specifics of this relationship is understood. Conclusions: Although the general population in the United States increasingly perceives cannabis to be a harmless substance, empirical evidence shows that cannabis use is associated both with CUD and comorbid psychiatric illness. However, there is mixed evidence regarding the role of cannabis in the etiology, course, and prognosis of a co-occurring disorder across all categories of psychiatric disorders. Future research should expand on the existing body of literature with representative, longitudinal data, in order to better understand the acute and long-term effects of cannabis on comorbid psychiatric illness. Full article

Concurrent disorder refers to a diverse set of combinations of substance use disorders and mental disorders simultaneously in need of treatment. Concurrent disorders are underdiagnosed, undertreated, and more complex to manage, practicing the best recommendations can support better outcomes. The purpose of this work is to systematically assess the quality of the current concurrent disorders’ clinical recommendation management guidelines. Literature searches were performed by two independent authors in electronic databases, web, and gray literature. The inclusion criteria were English language clinical management guidelines for adult concurrent disorders between 2000 and 2020. The initial search resulted in 8841 hits. A total of 24 guidelines were identified and assessed with the standardized guidelines assessment tool: AGREE II (Appraisal of Guidelines for Research and Evaluation). Most guidelines had acceptable standards, however, only the NICE guidelines had all detailed information on all AGREE II Domains. Guidelines generally supported combinations of treatments for individual disorders with a very small evidence base for concurrent disorders, and they provided little recommendation for further structuring of the field, such as level of complexity or staging, or evaluating different models of treatment integration. Full article

When psychiatric illness and substance use disorder coexist, the clinical approach to the patient is, unsurprisingly, awkward. This fact is due to a cultural context and, more directly, to the patient’s psychiatric condition and addiction behaviors—a situation that does not favor a scientific approach. In dual disorder facilities, several types of professionals work together: counselors, social workers, psychologists, and psychiatrists. Treatment approaches vary from one service to another and even within the same service. It is crucial to provide dual disorder patients with multiple treatments, comprising hospitalization, rehabilitative and residential programs, case management, and counselling. Still, when treating dual disorder (DD) heroin use disorder (HUD) patients, it is advisable to follow a hierarchical algorithm. First, we must deal with addiction: by detoxification, whenever possible. This means starting most patients on anti-craving pharmacological maintenance, though aversion therapy may be appropriate for a few of them. Opiate antagonists may be used with heroin-addicted patients as long as those patients are only mildly ill. In contrast, agonist opioid medications, i.e., buprenorphine and methadone suit moderately and severely ill patients, respectively. Achieving control of mood instability or psychotic episodes is the next step, to be followed by a prevention strategy to counteract residual cravings and dominate mood disorders or psychotic episodes through long-term pharmacological maintenance that is focused on a double target. Full article