Cannabis use and its association with psychopathological symptoms in a Swiss adult population: a cross-sectional analysis.

Background: As the most commonly used illicit substance, cannabis is gaining global acceptance through increasing legalization efforts. This shift intensifies the need for research to guide policymakers and healthcare providers in harm reduction and treatment strategies. Nonetheless, the relationship between psychopathological symptoms and cannabis use remains inadequately understood. Methods: A sample of regular cannabis consumers completed self-reported assessments for depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), Attention-Deficit/Hyperactivity Disorder (ADHD; Adult ADHD Self-Report Scale V1.1), and psychosis (Early Recognition Inventory based on IRAOS) as well as previous black-market cannabis use patterns. Cannabis Use Disorder Identification Test Revised (CUDIT-R) was used to identify cannabis use disorder (CUD). To understand psychopathological symptom load related to cannabis consumption as well as cannabis use motives, multiple regression models were performed to identify psychopathological variables predicting cannabis use frequency and quantity. Linear regression and correlation analyses were conducted, adjusting for relevant covariates (age, gender, education, alcohol, other substance use). Results: Three-hundred-sixty regular cannabis users interested in a study on regulated cannabis access in Basel, Switzerland were examined. In bivariate analysis, cannabis use frequency correlated with depressive (r(358) = 0.16, p = 0.003) and anxiety symptom load (r(358) = 0.11, p = 0.034). Cannabis quantity correlated with depressive (r(358) = 0.15, p = 0.005), ADHD (r(358) = 0.14, p = 0.008), and psychosis symptom load (r(358) = 0.16, p = 0.002). However, in the adjusted regression models only depressive and ADHD symptom loads were significantly associated with cannabis use frequency (p = 0.006 and p = 0.034, respectively) and quantity (p = 0.037 and p = 0.019, respectively). No significant correlations between cannabis consumption and anxiety or psychosis remained after adjustment. Conclusion: ADHD and depressive symptoms correlate with increased cannabis use in a cohort of regular users, suggesting potential self-medication in nonclinical populations. With the rising availability of cannabis worldwide, these results highlight the necessity for longitudinal studies to disentangle the complex dynamics between cannabis consumption and mental health symptoms.

Brain alterations in individuals with exercise dependence: A multimodal neuroimaging investigation.

Background: Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. Methods: In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups. Results: No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups. Discussion: The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

Homo- and heterobimetallic transition metal cluster derived from [Cp*Fe(η5-E5)] (E = P, As) - unprecedented structural motifs of the resulting polypnictogen ligands.

A general synthetic procedure to neutral homo- and heterobimetallic cage compounds exhibiting various structural motifs of the polypnictogen ligands starting from [Cp*Fe(η5-E5)] (E = P (1), As (2); Cp* = C5Me5) is reported. The impact of the implemented transition metal precursors {Cp'''M} (M = Cr, Mn, Fe, Ni; Cp''' = 1,2,4-tBu3C5H2) emphasises the variability of the isolated complexes exhibiting a broad variety of structural motifs of the pnictogen ligands. Spectroscopic, crystallographic, and theoretical investigations provide insight into the structure of the partially unprecedented polypnictogen ligands.

Synthesis and Structure of [η5-1,2,4-(Me3Si)3C5H2]2Th(bipy) and Its Reactivity toward Small Molecules.

Halide exchange of (Cp3tms)2ThCl2 (1; Cp3tms = η5-1,2,4-(Me3Si)3C5H2) with Me3SiI furnishes (Cp3tms)2ThI2 (2), which is then reduced with potassium graphite (KC8) in the presence of 2,2'-bipyridine to give the thorium bipyridyl metallocene (Cp3tms)2Th(bipy) (3) in good yield. Complex 3 was fully characterized and readily reacted with various small molecules. For example, 3 may serve as a synthetic equivalent for the (Cp3tms)2Th(II) fragment when exposed to CuI, Ph2S2, organic azides, and CS2. Moreover, upon the addition of thiobenzophenone Ph2CS, p-methylbenzaldehyde (p-MeC6H4)CHO, benzophenone Ph2CO, amidate PhCONH(p-tolyl), seleno-ketone (p,p'-dimethoxy), selenobenzophenone (p-MeOPh)2CSe, di(p-tolyl)methanimine (p-tolyl)2C═NH, 1,2-di(benzylidene)hydrazine (PhCH═N)2, and nitriles PhCN, PhCH2CN, and Ph2CHCN C-C coupling results to give (Cp3tms)2Th[(bipy)(Ph2CS)] (8), (Cp3tms)2Th[(bipy)(p-MePhCHO)] (9), (Cp3tms)2Th[(bipy)(Ph2CO)] (10), (Cp3tms)2Th[(bipy){(p-tolylNH)(Ph)CO}] (11), (Cp3tms)2Th[(bipy){(p-MeOPh)2CSe}] (12), (Cp3tms)2Th[(bipy){(p-tolyl)2CNH}] (13), (Cp3tms)2Th[(bipy)(PhCHNN═CHPh)] (14), (Cp3tms)2Th[(bipy)(PhCN)] (16), (Cp3tms)2Th[(bipy)(PhCH2CN)] (17), and (Cp3tms)2Th[(bipy)(Ph2CHCN)] (18), respectively. However, when thiazole is added to 3, the dimeric sulfido complex [(Cp3tms)2Th]2[µ-(bipy)CH2NCHCHS]2 (15) can be isolated. Moreover, the addition of isonitriles such as Me3CNC and PhCH2NC to 3 results in C-N bond cleavage and C-C coupling processes to form the thorium isocyanido amido complexes (Cp3tms)2Th[4-(Me3C)bipy](NC) (19) and (Cp3tms)2Th[4-(PhCH2)bipy](NC) (20), respectively. Nevertheless, upon exposure of 3 to (trimethylsilyl)diazomethane Me3SiCHN2, the bis-amido complex (Cp3tms)2Th[5,6-(Me3SiCH)bipy] (21), concomitant with N2 release, is isolated.

Geometry and electronic structure of Yb(III)[CH(SiMe3)2]3 from EPR and solid-state NMR augmented by computations.

Characterization of paramagnetic compounds, in particular regarding the detailed conformation and electronic structure, remains a challenge, and - still today it often relies solely on the use of X-ray crystallography, thus limiting the access to electronic structure information. This is particularly true for lanthanide elements that are often associated with peculiar structural and electronic features in relation to their partially filled f-shell. Here, we develop a methodology based on the combined use of state-of-the-art magnetic resonance spectroscopies (EPR and solid-state NMR) and computational approaches as well as magnetic susceptibility measurements to determine the electronic structure and geometry of a paramagnetic Yb(III) alkyl complex, Yb(III)[CH(SiMe3)2]3, a prototypical example, which contains notable structural features according to X-ray crystallography. Each of these techniques revealed specific information about the geometry and electronic structure of the complex. Taken together, both EPR and NMR, augmented by quantum chemical calculations, provide a detailed and complementary understanding of such paramagnetic compounds. In particular, the EPR and NMR signatures point to the presence of three-centre-two-electron Yb-γ-Me-ß-Si secondary metal-ligand interactions in this otherwise tri-coordinate metal complex, similarly to its diamagnetic Lu analogues. The electronic structure of Yb(III) can be described as a single 4f13 configuration, while an unusually large crystal-field splitting results in a thermally isolated ground Kramers doublet. Furthermore, the computational data indicate that the Yb-carbon bond contains some π-character, reminiscent of the so-called α-H agostic interaction.

How mood is affected by environment and upsetting events: The moderating role of psychological flexibility.

OBJECTIVE: Patients suffering from psychological disorders report decreased quality of life and low mood. The relationship of these symptoms to daily upsetting events or environments, and in the context of active coping mechanisms is poorly understood. The present study thus investigates the association between mood, psychological flexibility, upsetting events, and environment in the daily life of outpatients. METHOD: We investigated 80 outpatients at the beginning of treatment, using event sampling methodology (ESM). Patients' mood, occurrence of upsetting events, current environment, and psychological flexibility were sampled six times per day during a one-week intensive longitudinal examination. Data were analyzed using linear mixed models (LMMs). RESULTS: Participants reported worse mood the more upsetting events they experienced. Further, participants reported better mood when in private environments (e.g., with friends), and worse mood when at the hospital, compared to being at home. Higher levels of psychological flexibility, however, were associated with better mood, irrespective of the occurrence of upsetting events or current environment. CONCLUSION: Results suggest that mood is positively associated with psychological flexibility, not despite, but especially during the dynamic and context-specific challenges of daily life. Psychological flexibility may thus potentially act as a buffer against distress-provoking situations as patients go about their daily lives. TRIAL REGISTRATION: ISRCTN.org identifier: ISRCTN11209732.

Uranium versus Thorium: A Case Study on a Base-Free Terminal Uranium Imido Metallocene.

The structure of and bonding in two base-free terminal actinide imido metallocenes, [η5-1,2,4-(Me3C)3C5H2]2An═N(p-tolyl) (An = U (1), Th (1')) are compared and connected to their individual reactivity. While structurally rather similar, the U(IV) derivative 1 is slightly more sterically crowded. Furthermore, density functional theory (DFT) studies imply that the 5f orbital contribution to the bonding within the individual actinide imido An═N(p-tolyl) moieties is significantly larger for 1 than for 1', which makes the bonds between the [η5-1,2,4-(Me3C)3C5H2]2U2+ and [(p-tolyl)N]2- fragments more covalent. Therefore, steric and electronic factors impact the reactivity of these imido complexes. For example, complex 1 is inert toward internal alkynes, but it readily forms Lewis base adducts [η5-1,2,4-(Me3C)3C5H2]2U═N(p-tolyl)(L) (L = OPMe3 (6), dmap (9), PhCN (14), and 2,6-Me2PhNC (17)) with Me3PO, 4-dimethylaminopyridine (dmap), nitrile, PhCN, or isonitrile 2,6-Me2PhNC. It may also react as a nucleophile or undergo a [2 + 2] cycloaddition with CS2, isothiocyanates, thio-ketones, ketones, lactides, and acyl nitriles, forming the four- or five-membered metallaheteroacycles, terminal sulfido, or oxido complexes, and cyanide amidate complexes, respectively. In contrast, after the addition of aldehyde p-tolylCHO, the tetranuclear complex [η5-1,2,4-(Me3C)3C5H2]4[OCH(p-tolyl)CH(p-tolyl)O]2U4O4 (10) is isolated. However, while 1 is unreactive toward dicyclohexylcarbodiimide (DCC), an equilibrium exists in benzene solution between N,N'-diisopropylcarbodiimide (DIC), 1, and the four-membered metallaheterocycle [η5-1,2,4-(Me3C)3C5H2]2U[N(p-tolyl)C(═NiPr)N(iPr)] (12). Furthermore, 1 may also engage in single- and two-electron transfer processes. It is singly oxidized by Ph3CN3, CuI, Ph2S2, and Ph2Se2, yielding the uranium(V) imido complexes [η5-1,2,4-(Me3C)3C5H2]2U═N(p-tolyl)(X) (X = N3 (20), I (22), PhS (23), and PhSe (24)), or is doubly oxidized by organic azides (RN3) and 9-diazofluorene, forming the uranium(VI) bis-imido metallocenes [η5-1,2,4-(Me3C)3C5H2]2U═N(p-tolyl)(=NR) (R = p-tolyl (18), mesityl (19)) and [η5-1,2,4-(Me3C)3C5H2]2U=N(p-tolyl)[=NN=(9-C13H8)] (21), respectively.

Evaluating the Psychometric Properties of the German Self and Interpersonal Functioning Scale (SIFS).

The Self and Interpersonal Functioning Scale (SIFS) is a 24-item self-report questionnaire assessing personality functioning according to the alternative DSM-5 model for personality disorders. We evaluated the German SIFS version in a total sample of 886 participants from Germany and Switzerland. Its factor structure was investigated with confirmatory factor analysis comparing bifactor models with two specific factors (self- and interpersonal functioning) and four specific factors (identity, self-direction, empathy, and intimacy). The SIFS sum and domain scores were tested for reliability and convergent validity with self-report questionnaires and interviews for personality functioning, -organization, -traits, -disorder categories, and well-being. None of the bifactor models yielded good model fit, even after excluding two items with low factor loadings and including a method factor for reverse-keyed items. Based on a shortened 22-item SIFS version, models suggested that the g-factor explained 52.9-59.6% of the common variance and that the SIFS sum score measured the g-factor with a reliability of .68-.81. Even though the SIFS sum score showed large test-retest reliability and correlated strongly with well-established self-report questionnaires and interviews, the lack of structural validity appears to be a serious disadvantage of the SIFS compared to existing self-reports questionnaires of personality functioning.

Experimental and Computational Studies on Uranium Diazomethanediide Complexes.

Uranium diazomethanediide complexes can be prepared and their synthesis, structure and reactivity were explored. Reaction of the uranium imido compound [η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 U=N(p-tolyl)(dmap) (1) or [η5 -1,3-(Me3 C)2 C5 H3 ]2 U=N(p-tolyl)(dmap) (4) with Me3 SiCHN2 cleanly yields the first isocyanoimido metal complexes [η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 U(=NNC)(µ-CNN=)U(dmap)[η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 (2) and {[η5 -1,3-(Me3 C)2 C5 H3 ]2 U[µ-(=NNC)]}6 (5), respectively. Both compounds exhibit remarkable thermal stability and were fully characterized. According to density functional theory (DFT) studies the bonding between the Cp2 U2+ and [NNC]2- moieties is strongly polarized with a significant 5 f orbital contribution, which is also reflected in the reactivity of these complexes. For example, complex 5 acts as a nucleophile toward alkylsilyl halides and engages in a [2+2] cycloaddition with CS2 , but no reaction occurs in the presence of internal alkynes.

Reactivity of a Lewis base-supported uranium terminal imido metallocene towards small molecules.

The Lewis base-supported uranium terminal imido metallocene [η5-1,2,4-(Me3Si)3C5H2]2UN(p-tolyl)(dmap) (1) readily reacts with various small molecules such as internal alkynes, isothiocyanates, thioketones, amidates, organic nitriles and imines, chlorosilanes, copper iodide, diphenyl disulfide, organic azides and diazoalkane derivatives. For example, treatment of 1 with PhCCCCPh and PhNCS forms metallaheterocycles originating from a [2 + 2] cycloaddition to yield [η5-1-(p-tolyl)NC(Ph)CHCC(Ph)CH2Si(Me)2-2,4-(Me3Si)2C5H2][η5-1,2,4-(Me3Si)3C5H2]U (2) and [η5-1,2,4-(Me3Si)3C5H2]2U[N(p-tolyl)C(NPh)S](dmap) (3), respectively. The reaction of 1 with the thioketone Ph2CS forms the known uranium sulfido complex [η5-1,2,4-(Me3Si)3C5H2]2US(dmap) (4), which reacts with a second molecule of Ph2CS to give the disulfido compound [η5-1,2,4-(Me3Si)3C5H2]2U(S2CPh2) (5). The imido moiety also promotes deprotonation reactions as illustrated in the reactions with the amide PhCONH(p-tolyl), the nitrile PhCH2CN and the imine (p-tolyl)2CNH to form the bis-amidate [η5-1,2,4-(Me3Si)3C5H2]2U[OC(Ph)N(p-tolyl)]2 (7), and the iminato complexes [η5-1,2,4-(Me3Si)3C5H2]2U[N(p-tolyl)C(CH2Ph)NH](NCCHPh) (8) and [η5-1,2,4-(Me3Si)3C5H2]2U[NH(p-tolyl)][NC(p-tolyl)2] (9), respectively. Addition of PhSiH2Cl to 1 yields [η5-1,2,4-(Me3Si)3C5H2]2U(Cl)[N(p-tolyl)SiH2Ph] (10). In contrast, the uranium(V) imido complexes [η5-1,2,4-(Me3Si)3C5H2]2UN(p-tolyl)(I) (11) and [η5-1,2,4-(Me3Si)3C5H2]2UN(p-tolyl)(SPh) (12), may be isolated upon addition of CuI or Ph2S2 to 1, respectively. Uranium(VI) bis-imido metallocenes [η5-1,2,4-(Me3Si)3C5H2]2UN(p-tolyl)(NR) (R = p-tolyl (13), mesityl (14)) and [η5-1,2,4-(Me3Si)3C5H2]2UN(p-tolyl)[NN(9-C13H8)] (15) are accessible from 1 on exposure to RN3 (R = p-tolyl, mesityl) and 9-diazofluorene, respectively. Complexes 2, 3, 5, and 7-15 were characterized by various spectroscopic techniques and, in addition, compounds 2, 3, 5, and 7-13 were structurally authenticated by single-crystal X-ray diffraction analyses.

Exercise Addiction and Major Depressive Disorder - Clinical Diagnoses and Longitudinal Course.

Background: People at risk of exercise addiction report increased symptoms of psychopathology. The aim of this study was to clinically assess the lifetime prevalence of depressive disorders in individuals at risk of exercise addiction and to determine whether depressive symptoms tend to precede or follow excessive exercising. Methods: Based on the Exercise Dependence Scale-21, a total of 31 individuals categorized at risk of exercise addiction underwent the Structured Clinical Interview for DSM-5 to assess major depressive disorder (MDD). Findings: The results showed 16 of the 31 participants suffered from MDD. The onset of MMD occurred in 10 participants after excessive exercising and in 5 before excessive exercising. In one participant, the symptom onset was unclear. Conclusion: MDD is far more prevalent in patients with exercise addiction compared to the general population and develops more often after the beginning of exercise addiction. Caution in the use of exercise to treat depression may be warranted.

A Comprehensive Study Concerning the Synthesis, Structure, and Reactivity of Terminal Uranium Oxido, Sulfido, and Selenido Metallocenes.

Terminal uranium oxido, sulfido, and selenido metallocenes were synthesized, and their reactivity was comprehensively studied. Heating of an equimolar mixture of [η5-1,2,4-(Me3Si)3C5H2]2UMe2 (2) and [η5-1,2,4-(Me3Si)3C5H2]2U(NH-p-tolyl)2 (3) in the presence of 4-dimethylaminopyridine (dmap) in refluxing toluene forms [η5-1,2,4-(Me3Si)3C5H2]2U═N(p-tolyl)(dmap) (4), which is a useful precursor for the preparation of the terminal uranium oxido, sulfido, and selenido metallocenes [η5-1,2,4-(Me3Si)3C5H2]2U═E(dmap) (E = O (5), S (6), Se (7)) employing a cycloaddition-elimination methodology with Ph2C═E (E = O, S) or (p-MeOPh)2CSe, respectively. Metallocenes 5-7 are inert toward alkynes, but they act as nucleophiles in the presence of alkylsilyl halides. The oxido and sulfido metallocenes 5 and 6 undergo [2 + 2] cycloadditions with isothiocyanate PhNCS or CS2, while the selenido derivative 7 does not. The experimental studies are complemented by density functional theory (DFT) computations.

Cannabis Consumers' View of Regulated Access to Recreational Cannabis: A Multisite Survey in Switzerland.

INTRODUCTION: There is considerable effort in legalizing recreational use of cannabis globally. The successful implementation of a program of regulated access to recreational cannabis (PRAC) depends on the consumers' engagement. The aim of this study was to examine the acceptability of twelve different regulatory aspects by cannabis users including those obtaining cannabis from the illicit market and vulnerable populations such as young adults and problematic users. METHODS: The current study is a multisite online survey conducted in Switzerland. A total of 3,132 adult Swiss residents who consumed cannabis within the previous 30 days represented the studied population. Mean age was 30.5 years, 80.5% were men, and 64.2% of the participants stated that they always or often obtain cannabis from the illicit market. We described consumers' acceptability of twelve regulatory aspects concerning THC content control, disclosure of sensitive personal data, security aspects, and follow-up procedures by applying descriptive statistics and multiple regression models. RESULTS: THC content regulation showed most discrepancy with 89.4% of the participants stating to engage in a PRAC if five different THC contents were available as compared to 54% if only 12% THC was available. The least accepted regulatory aspect was disposal of contact details with an acceptability rate of 18.1%. Consumers mainly obtaining cannabis from the illicit market, young adults, and problematic users showed similar acceptability patterns. Participants obtaining cannabis from the illicit market were more likely to engage in a PRAC if five different THC contents were available as compared to participants obtaining cannabis from other sources (OR 1.94, 95% CI: 1.53-2.46). CONCLUSION: A carefully designed PRAC that takes into account the consumers' perspective is likely to transfer them to the regulated market and to engage vulnerable populations. We cannot recommend the distribution of cannabis with only 12% THC content as this is unlikely to engage the target population.

Transdiagnostic brain correlates of self-reported trait impulsivity: A dimensional structure-symptom investigation.

Impulsivity transcends psychiatric diagnoses and is often related to anhedonia. This ad hoc cross-sectional investigation explored 1) whether self-reported trait impulsivity mapped onto a common structural brain substrate across healthy controls (HCs) and psychiatric patients, and 2) in a more exploratory fashion, whether impulsivity and anhedonia were related to each other and shared overlapping brain correlates. Structural magnetic resonance imaging (sMRI) datasets from 234 participants including HCs (n = 109) and patients with opioid use disorder (OUD, n = 22), cocaine use disorder (CUD, n = 43), borderline personality disorder (BPD, n = 45) and schizophrenia (SZ, n = 15) were included. Trait impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11) and anhedonia with a subscore of the Beck Depression Inventory (BDI). BIS-11 global score data were available for the entire sample, while data on the BIS-11 2nd order factors attentional, motor and non-planning were additionally in hand for a subsample consisting of HCs, OUD and BPD patients (n = 116). Voxel-based morphometry analyses were conducted for identifying dimensional associations between grey matter volume and impulsivity/anhedonia. Partial correlations were further performed to exploratory test the relationships between impulsivity and anhedonia and their corresponding volumetric brain substrates. Volume of the left opercular part of the inferior frontal gyrus (IFG) was negatively related to global impulsivity across the entire sample and specifically to motor impulsivity in the subsample of HCs, OUD and BPD patients. Across patients anhedonia expression was negatively correlated with left putamen volume. Although there was no relationship between global impulsivity and anhedonia across all patients, only across OUD and BPD patients anhedonia was positively associated with attentional impulsivity. Finally, also across OUD and BPD patients, motor impulsivity associated left IFG volume was positively linked with anhedonia-associated volume in the left putamen. Our findings suggest a critical role of left IFG volume in self-reported global impulsivity across healthy participants and patients with substance use disorder, BPD and SZ. Preliminary findings in OUD and BPD patients further suggests associations between impulsivity and anhedonia that are related to grey matter reductions in the left IFG and putamen.

Effects of cannabis regulation in Switzerland: Study protocol of a randomized controlled trial.

Background: Cannabis is the most widely used illicit substance. Various countries have legalized cannabis for recreational use. Evidence on the health effects of cannabis regulation remains unclear and is mainly based on observational studies. To date, there is no randomized controlled study evaluating the impact of cannabis regulation for recreational use compared to the illicit market on relevant health indicators. The present study ("Weed Care") is the first to evaluate the impact of regulated cannabis access in pharmacies versus a waiting list control group representing the illicit market on problematic cannabis use as well as on mental and physical health. Methods: The study is divided into two parts-a randomized controlled study of 6 months followed by an observational study of 2 years. Participants (N = 374) are randomly assigned to either the experimental group with access to legal cannabis in pharmacies or to the waiting list control group representing the current legal framework in Switzerland, namely the illicit market. After 6 months, all participants will have access to legal cannabis for the following 2 years (observational study). The primary outcome is problematic cannabis use as measured with the Cannabis Use Disorders Identification Test-Revised (CUDIT-R). Secondary outcomes are cannabis use patterns, mental disorders (e.g., depression, anxiety, and psychosis) and physical health (e.g., respiratory symptoms). Primary and secondary outcomes will be assessed online every 6 months. The study is approved by the responsible ethics committee as well as by the Swiss Federal Office of Public Health. Discussion: Findings from this study may provide a scientific basis for future discussions about addiction medicine and cannabis policy in Switzerland. Clinical Trial Registration: ClinicalTrials.gov (NCT05522205). https://clinicaltrials.gov/ct2/show/NCT05522205.

Psychotherapy for Chronic In- and Outpatients with Common Mental Disorders: The "Choose Change" Effectiveness Trial.

INTRODUCTION: Treatment non-response occurs regularly, but psychotherapy is seldom examined for such patients. Existing studies targeted single diagnoses, were relatively small, and paid little attention to treatment under real-world conditions. OBJECTIVE: The Choose Change trial tested whether psychotherapy was effective in treating chronic patients with treatment non-response in a transdiagnostic sample of common mental disorders across two variants of treatment delivery (inpatient and outpatient). METHODS: The controlled nonrandomized effectiveness trial was conducted between May 2016 and May 2021. The study took place in two psychiatric clinics with N = 200 patients (n = 108 inpatients and n = 92 outpatients). Treatment variants were integrated inpatient care versus outpatient care based on acceptance and commitment therapy (ACT) for approximately 12 weeks. Therapists delivered individualized and non-manualized ACT. Main outcome measures were symptoms (Brief Symptom Checklist [BSCL]); well-being (Mental Health Continuum-Short Form [MHC-SF]), and functioning (WHO Disability Assessment Schedule [WHO-DAS]). RESULTS: Both inpatients and outpatients showed decreases in symptomatology (i.e., BSCL: d = 0.68) and increases in well-being and functioning (MHC-SF: d = 0.60 and WHO-DAS: d = 0.70), with more improvement in the inpatients during treatment. Both groups maintained gains 1 year following treatment, and the groups did not significantly differ from each other at this timepoint. Psychological flexibility moderated impact of stress on outcomes. CONCLUSIONS: Psychotherapy as practiced under routine conditions is effective for a sample of patients with common mental disorders, a long history of treatment experience and burden of disease, in both inpatient and outpatient settings. TRIAL REGISTRATION: This study was registered in the ISRCTN registry on May 20, 2016, with the registration number ISRCTN11209732.

Skeletal muscle and intermuscular adipose tissue gene expression profiling identifies new biomarkers with prognostic significance for insulin resistance progression and intervention response.

AIMS/HYPOTHESIS: Although insulin resistance often leads to type 2 diabetes mellitus, its early stages are often unrecognised, thus reducing the probability of successful prevention and intervention. Moreover, treatment efficacy is affected by the genetics of the individual. We used gene expression profiles from a cross-sectional study to identify potential candidate genes for the prediction of diabetes risk and intervention response. METHODS: Using a multivariate regression model, we linked gene expression profiles of human skeletal muscle and intermuscular adipose tissue (IMAT) to fasting glucose levels and glucose infusion rate. Based on the expression patterns of the top predictive genes, we characterised and compared individual gene expression with clinical classifications using k-nearest neighbour clustering. The predictive potential of the candidate genes identified was validated using muscle gene expression data from a longitudinal intervention study. RESULTS: We found that genes with a strong association with clinical measures clustered into three distinct expression patterns. Their predictive values for insulin resistance varied substantially between skeletal muscle and IMAT. Moreover, we discovered that individual gene expression-based classifications may differ from classifications based predominantly on clinical variables, indicating that participant stratification may be imprecise if only clinical variables are used for classification. Of the 15 top candidate genes, ST3GAL2, AASS, ARF1 and the transcription factor SIN3A are novel candidates for predicting a refined diabetes risk and intervention response. CONCLUSION/INTERPRETATION: Our results confirm that disease progression and successful intervention depend on individual gene expression states. We anticipate that our findings may lead to a better understanding and prediction of individual diabetes risk and may help to develop individualised intervention strategies.

Dimensional personality impairment is associated with disruptions in intrinsic intralimbic functional connectivity.

BACKGROUND: Recently proposed alternative dimensional models of personality disorder (PD) place the severity of impairments in self and interpersonal functioning at the core of personality pathology. However, associations of these impairments with disturbances in social, cognitive, and affective brain networks remain uninvestigated. METHODS: The present study examined patterns of resting-state functional connectivity (rsFC) in a sample of 74 age- and sex-matched participants (45 inpatients with PD and 29 healthy controls). At a minimum, PD patients carried a diagnosis of borderline PD, although the majority of the sample had one or more additional PDs. rsFC patterns in the following networks were compared between groups and in association with dimensional personality impairments: default mode network (DMN)/core mentalization, frontolimbic, salience, and central executive. Further, the extent to which variation in rsFC was explained by levels of personality impairment as compared to typology-specific borderline PD symptom severity was explored. RESULTS: Relative to controls, the PD group showed disruptions in rsFC within the DMN/core mentalization and frontolimbic networks. Among PD patients, greater severity of dimensional self-interpersonal impairment was associated with stronger intralimbic rsFC. In contrast, severity of borderline PD-specific typology was not associated with any rsFC patterns. CONCLUSIONS: Disruptions in core mentalization and affective networks are present in PD. Higher intralimbic functional connectivity may underlie self-interpersonal personality impairment in PD regardless of diagnostic typology-specific PD symptoms, providing initial neurobiological evidence supporting alternative dimensional conceptualizations of personality pathology.

Striatal resting-state connectivity after long-term diacetylmorphine treatment in opioid-dependent patients.

New treatment approaches for opioid-dependent patients include injectable opioid agonist treatment with diacetylmorphine. While evidence has shown beneficial clinical effects of diacetylmorphine, it is still not clear how long-term diacetylmorphine treatment affects the brain and whether functional brain changes are accompanied by clinical improvements. Therefore, this prospective case-control study focuses on long-term effects of diacetylmorphine on resting-state functional connectivity. We included opioid-dependent patients (N = 22, age range 33-58, 16 males) treated with diacetylmorphine and healthy controls (N = 9, age range 27-55, 5 males) that underwent two MRI assessments approximately nine years apart. For the patients, the assessments took part shortly after the diacetylmorphine intake to be able to explore changes in resting-state functional connectivity in brain regions related to the stage of binge and intoxication (caudate, putamen, nucleus accumbens). A cluster in the right superior frontal gyrus was detected, showing over nine years an increase in functional connectivity originating from the left caudate and the left accumbens in patients but not in healthy controls. These connectivity changes in patients were related to the duration of the diacetylmorphine treatment at the follow-up, indicating smaller increases in functional connectivity with longer treatment duration (r = 0.63, P < 0.01). These results suggest that long-term diacetylmorphine treatment in opioid-dependent patients increases fronto-striatal connections, an effect that is linked to the duration of the treatment duration. Future research needs to further address the wide-ranging effects of diacetylmorphine on brain functioning and deepen the understanding of their clinical relevance.

Low-Coordinate Iron(II) Amido Half-Sandwich Complexes with Large Internal Magnetic Hyperfine Fields.

The half-sandwich complex [Cp'Fe{N(dipp)(SiMe3)}] (Fe-dipp; Cp' = 1,2,4-tri-tert-butylcyclopentadienyl and dipp = 2,6-diisopropylphenyl) and the mixed metallocene [Cp'Fe{(η5-C6H3iPr2)═N(SiMe3)}] (Fe-chd) formed in the reaction between [{Cp'Fe(µ-I)}2] and [Li{N(dipp)(SiMe3)}]2 were characterized by NMR spectroscopy and X-ray diffraction analysis. Fe-dipp complements the series of low-coordinate, quasi-linear iron amido half-sandwich complexes [Cp'Fe{N(tBu)(SiMe3)}] (Fe-tBu) and [Cp'Fe{N(SiMe3)2}] (Fe-tms) reported earlier, and all three compounds were characterized in the solid state by zero-field 57Fe Mössbauer spectroscopy and magnetic susceptibility measurements, confirming their S = 2 electronic ground state. Moreover, the Mössbauer absorption spectra reveal slow paramagnetic relaxation at low temperatures with large internal magnetic hyperfine fields of Bhf = 96.4 T (Fe-dipp, 20 K), Bhf = 101.3 T (Fe-tBu, 15 K), and Bhf = 96.9 T (Fe-tms, 20 K). The magnetic measurements further confirm that the presence of significant axial zero-field splitting and slow relaxation of magnetization is detected, which is revealed even in the absence of a static magnetic field in the case of Fe-tBu. Supplementary ab initio and density functional theory calculations were performed and support the experimental data.