Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2).

BACKGROUND: Available evidence suggests that adjunctive treatment with immunomodulatory medications may be effective in the treatment of major depressive disorder (MDD). A pilot trial of the tetracycline minocycline as adjunctive treatment in treatment-resistant depression (TRD), produced promising results, however, a larger scale trial is needed to confirm the antidepressant actions of this drug. METHODS: This is a 12-week double blind, placebo-controlled, randomized trial of minocycline as an add-on to standard antidepressants for adults (age > 18) with DSM-5 major depressive episode, who have failed to respond to at least two adequate trials of antidepressant treatment. It is a parallel-arm study with 50 participants in each group. The primary outcome measure is change in 17-item Hamilton Depression Rating Scale (HRSD-17) total scores from baseline to week 12. Secondary measures include the Clinical Global Impression (CGI) scale, World Health Organization Quality of Life Short Version (WHOQOL-BREF) and the Generalized Anxiety Disorder scale (GAD-7). Peripheral inflammatory biomarkers will be collected at baseline, week 6 and 12. DISCUSSION: If minocycline is well tolerated and effective in reducing depressive symptoms in patients with TRD, it would warrant genuine consideration as a treatment option for TRD. Additionally, if results demonstrate that minocycline has antidepressant properties, and that changes in inflammatory status are associated with its antidepressant action, it will inform the development of individualized treatment for a subset of patients with MDD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03947827. Registered 13th May, 2019.

Relationship between tobacco and cannabis use status in outpatients with schizophrenia.

BACKGROUND AND OBJECTIVE: While high prevalence of tobacco and cannabis use are well established in schizophrenia, reports on their co-morbid use is limited. We explored the links between tobacco and cannabis use in an outpatient population meeting DSM-IV criteria for schizophrenia. METHODS: Cigarette smoking behaviors were assessed in an outpaitent population with schizophrenia (N=54) with current (n=18), former (n=24), and no lifetime cannabis dependence (n=12). RESULTS: We found significant differences in cigarettes per day (CPD) across groups: current dependent patients smoked less CPD than patients with former dependence and those with no history of dependence; former dependent patients smoked significantly less than patients with no history of cannabis dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Preliminary results support an effect of cannabis use status on tobacco consumption. In the absence of cannabis, patients may increase cigarette smoking, suggesting state-dependent effects of cannabis on tobacco. Prospective designs should further examine this relationship between cannabis and tobacco in schizophrenia versus non-psychiatric controls.

Environmental factors selectively impact co-occurrence of problem/pathological gambling with specific drug-use disorders in male twins.

AIMS: Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence. DESIGN: Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence. SETTING: Computer-assisted telephone interviews in the community. PARTICIPANTS: Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry. MEASUREMENTS: Life-time DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule. FINDINGS: All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA = 0.22; 95% confidence interval (CI) = 0.10-0.34] and non-shared environmental components (environmental correlation rE = 0.24; 95% CI = 0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA = 0.32; 95% CI = 0.05-1.0; rE = 0.36; 95% CI = 0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA = 0.58; 95% CI = 0.45-0.73). CONCLUSIONS: Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help to diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders.

Pathological gambling severity and co-occurring psychiatric disorders in individuals with and without anxiety disorders in a nationally representative sample.

While anxiety disorders (ADs) and pathological gambling (PG) frequently co-occur with each other and other Axis I and Axis II disorders, previous studies have not examined the relative influence of ADs on the co-occurrences between PG severity and non-anxiety psychopathologies. The current study used data from the National Epidemiologic Survey on Alcohol and Related Conditions (N=43,093) to examine the influence of past-year ADs on the associations between past-year PG severity measures based on DSM-IV criteria for PG and non-anxiety psychiatric disorders. The findings revealed that increased PG severity was associated with Axes I and II psychopathology in both the groups with and without ADs. Significant anxiety-by-gambling-group interactions were also observed, particularly with respect to mood and personality disorders. The interactions indicate a stronger relationship between PG severity and psychopathology in participants without ADs than in those with ADs. Future research should investigate specific factors contributing to the co-occurrence of anxiety, gambling, and other psychiatric disorders and how the co-occurrences might influence clinically relevant phenomena such as treatment selection or course.

Shared genetic contributions to anxiety disorders and pathological gambling in a male population.

BACKGROUND: Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. METHOD: Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). RESULTS: While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. LIMITATIONS: Results may be limited to middle aged males. CONCLUSIONS: The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences.