Unraveling the molecular basis of cannabidiolic acid methyl Ester's anti-depressive effects in a rat model of treatment-resistant depression.

Major depressive disorder (MDD) stands as a significant cause of disability globally. Cannabidiolic Acid-Methyl Ester (CBDA-ME) (EPM-301, HU-580), a derivative of Cannabidiol, demonstrates immediate antidepressant-like effects, yet it has undergone only minimal evaluation in psychopharmacology. Our goal was to investigate the behavioral and potential molecular mechanisms associated with the chronic oral administration of this compound in the Wistar Kyoto (WKY) genetic model of treatment-resistant depression. Male WKY rats were subjected to behavioral assessments before and after receiving chronic (14-day) oral doses of CBDA-ME (0.5 mg/kg), 15 mg/kg of imipramine or vehicle. At the end of the study, plasma corticosterone levels and mRNA expression of various genes in the medial Prefrontal Cortex and Hippocampus were measured. Behavioral outcomes from CBDA-ME treatment indicated an antidepressant-like effect similar to imipramine, as oral ingestion reduced immobility and increased swimming duration in the Forced Swim Test. Neither treatment influenced locomotion in the Open Field Test nor preference in the Saccharin Preference Test. The behavioral impact in WKY rats coincided with reduced corticosterone serum levels, upregulated mRNA expression of Cannabinoid receptor 1, Fatty Acid Amide Hydrolase, and Corticotropin-Releasing Hormone Receptor 1, alongside downregulation of the Serotonin Transporter in the hippocampus. Additionally, there was an upregulation of CB1 mRNA expression and downregulation of Brain-Derived Neurotrophic Factor in the mPFC. These findings contribute to our limited understanding of the antidepressant effects of CBDA-ME and shed light on its potential psychopharmacological mechanisms. This discovery opens up possibilities for utilizing cannabinoids in the treatment of major depressive disorder and related conditions.

Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression.

BACKGROUND AND PURPOSE: Cannabidiolic acid methyl ester (HU-580) was recently shown to reduce stress-induced anxiety-like behavior in rats. The aim of this study was to examine the antidepressant effect of HU-580 in two different rat models of depression. EXPERIMENTAL APPROACH: Using the forced swim test (FST), we evaluated the effect of HU-580 in 43 Wistar-Kyoto (WKY) and 23 Flinders Sensitive Line (FSL) adult male rats. KEY RESULTS: 1 mg/kg HU-580 reduced immobility and increased swimming in WKY rats, compared to vehicle-treated controls (p < 0.05). This dose exerted similar effects in FSL rats (p < 0.05). CONCLUSION AND IMPLICATIONS: This is the first report of antidepressant efficacy of HU-580. These findings expand the very limited existent results, suggesting that HU-580 is a potent anxiolytic agent. Taken together with its chemical stability, HU-580 emerges as a candidate for a future antidepressant medication.

Non-suicidal self-injury within the school context: Multilevel analysis of teachers' support and peer climate.

BACKGROUND: Recent studies regarding non-suicidal self-injury (NSSI) among adolescents have focused primarily on individual characteristics (e.g., depressive symptoms) and background factors (e.g., parental relationship), whereas less emphasis has been given to the role of school-related factors in NSSI. Therefore, the purpose of the current study was to explore the relationships between teachers' support, peer climate, and NSSI within the school context. METHODS: The sample consisted of 594 high school students nested within 27 regular classes (54.4% boys; mean age 14.96, SD=1.33 years). The students were evaluated for NSSI behaviors, perception of teacher support, peer climate, relationships with mothers, and depressive symptoms using validated scales. RESULTS: The primary analysis used hierarchical linear modeling (HLM), controlling for gender and age. The main findings indicated that teacher support was positively associated with NSSI at the classroom-level (OR=6.15, 95% CI=2.05-18.5) but negatively associated at the student-level (OR=0.66, 95% CI=0.49-0.89). There was a trend toward an association between positive peer climate and NSSI at the classroom-level (OR=0.43, 95% CI=0.18-1.05), while negative peer climate was associated with NSSI at the student-level (OR=1.37, 95% CI=1.00-1.87). CONCLUSIONS: School-related factors are associated with NSSI behaviors among students. Teachers and educators should focus on both individual-level and classroom-level perceptions of school context. Students who feel supported by their teachers and who are exposed to a positive peer climate are less likely to engage in NSSI.

Psychological autopsy of seventy high school suicides: Combined qualitative/quantitative approach.

OBJECTIVE: Suicide is the leading cause of death among Israeli youths but data on causes are scarce. This study used psychological autopsies of 70 Israeli school students who committed suicide during 2004-2011, attempting to determine the causes. METHODS: Four narratives of the self were identified (qualitative analysis) and compared (quantitative analysis): (1) regressive: functioning and mood deteriorated continuously (45%); (2) tragic: doing well until rapid decline around suicidal crisis (20%); (3) unstable: peaks and crises throughout life (20%); and (4) stable: long lasting state of adverse living circumstances (15%). Functioning, mental disorders, stressful life events and substance abuse were examined. RESULTS: A representative profile of the suicide-completer emerged. Suicidality in the tragic narrative involved shorter crisis, fewer risk factors and less psychopathology than the other narratives, also better general functioning and better school performance. Though decrease in functioning was evident in all groups, in the tragic group it tended to be disregarded. CONCLUSION: This study presents an in-depth analysis of a unique suicide population of high school students. A combined methodology of qualitative and quantitative analyses reveals a distinct subpopulation of suicidal adolescents with little or no overt psychopathology that poses a challenge to suicide prevention strategies.

Dynamic occupation assessment of executive function in adolescents with schizophrenia spectrum disorders: An initial report.

OBJECTIVE: This study presents an initial evaluation of the psychometric properties of the Dynamic Occupation Assessment of Executive Function (DOAEF), a new tool designed to assess adolescents' executive function (EF) in daily situations and offering two levels of mediation through the administration process. METHOD: In the preliminary study, we tested 22 healthy adolescents. In the advanced stage, the instrument was administered to 105 healthy adolescents and to another 92 adolescents diagnosed with schizophrenia spectrum disorders. Information regarding EF was assessed by the DOAEF and Wisconsin Card Sorting Computer Version Test (WCST-CV-64). RESULTS: Inter-rater, test-retest and internal consistency indices were found to be satisfactory. Correlation between the DOAEF and the WCST-CV-64 scores supports the DOAEF's convergent validity. Significant differences were found between the healthy participants and the adolescents diagnosed with schizophrenia spectrum disorders, thus supporting the DOAEF's criterion validity. CONCLUSION: The DOAEF may be useful in assessing the level of mediation, which patients need for the comprehension of daily situations in which EFs are required.

Insight and satisfaction with life among adolescents with mental disorders: assessing associations with self-stigma and parental insight.

OBJECTIVE: The purpose of the current study was to assess the associations of illness perception-related variables with satisfaction with life (SwL) among adolescents with mental disorders. METHODS: Insight into mental disorder (SAI-E), Internalized stigma of mental illness (ISMI) and Multidimensional Students' Life Satisfaction Scale (MSLSS) were administrated to 30 adolescent patients. Adapted version for parents of the SAI-E was also administrated to 37 of their parents. RESULTS: Significant positive correlations were found between insight into the illness, self-stigma and parental insight. Insight and self-stigma were significantly negatively related to the total score of SwL and few of its dimensions while parental insight was significantly associated only with the SwL dimensions of school and self. Regression models revealed main negative effects of insight and self-stigma on SwL and no interaction effect. CONCLUSIONS: The possible independent contribution of insight and self-stigma to SwL should be addressed in interventions designed for family and adolescents coping with mental illness. Special attention should be given to the possible negative implications that insight possesses. In lack of support of the moderation role of self-stigma, reported in studies among adults with mental illness, future studies should trace other variables in order to further understand the insight paradox among adolescents.

Religiosity is a protective factor against self-injurious thoughts and behaviors in Jewish adolescents: findings from a nationally representative survey.

PURPOSE: Few studies have investigated the association between religiosity and self-injurious thoughts and behaviors specifically in adolescents, yielding inconsistent results. To date, no study has examined this relationship in a Jewish adolescent cohort. METHODS: Self-injurious thoughts and behaviors, as well as depression, were assessed in a nationally representative sample of Jewish adolescents (n=620) and their mothers, using the Development and Well-Being Assessment Inventory (DAWBA) structured interview. Degree of religiosity was obtained by a self-report measure. RESULTS: Using multivariate analysis, level of religiosity was inversely associated with self-injurious thoughts and behaviors (Wald χ(2)=3.95, P=0.047), decreasing the likelihood of occurrence by 55% (OR=0.45, 95% CI 0.2-0.99), after adjusting for depression and socio-demographic factors. This model (adjusted R(2)=0.164; likelihood ratio χ(2)=7.59; df=1; P<0.047) was able to correctly classify 95.6% of the patients as belonging either to the high or low risk groups. CONCLUSION: This is the first study demonstrating religiosity to have a direct independent protective effect against self-injurious thoughts and behaviors in Jewish adolescents. This finding has clinical implications regarding risk assessment and suicide prevention. Further research can potentially elucidate the complex relationship between religiosity, self-injury and suicide in this population.

The use of mental health services by adolescent smokers: a nationwide Israeli study.

In this study, we aimed to evaluate the utilization of mental health services by adolescent smokers, the presence of untreated mental disorders in this young population and the associated emotional and behavioral difficulties. We performed a nationwide survey study of an Israeli representative sample of 906 adolescents and their mothers. Mental disorders were assessed using the Development and Well-Being Assessment (DAWBA) Inventory. Emotional and behavioral difficulties were evaluated using the Strengths and Difficulties Questionnaire (SDQ). Mental health services use and smoking habits were evaluated by relevant questionnaires. Adolescent smokers were using significantly more mental health services than non-smokers (79% vs. 63%, respectively, P<0.001), independently of their mental health status or ethnic group. Adolescent smokers also reported more emotional and behavioral difficulties in most areas (P<0.001), which are consistent with their mothers' reports, except in the area of peer relationships. The treatment gap for the smoking adolescents was 53% compared to 69% in the non-smokers (P<0.001). This is the first study characterizing the use of mental health services and the related emotional and behavioral difficulties in a nationally-representative sample of adolescents. The findings of a wide treatment gap and the rates of the associated emotional and behavioral difficulties are highly relevant to the psychiatric assessment and national treatment plans of adolescent smokers.

Self versus maternal reports of emotional and behavioral difficulties in suicidal and non-suicidal adolescents: an Israeli nationwide survey.

UNLABELLED: There is relatively little research addressing parent-adolescent agreement as regards to reporting on adolescent suicidal behavior in general and their behavioral and emotional difficulties in particular. The objective of this study was to compare maternal and adolescents' reports on behavioral and emotional difficulties among adolescents with and without suicidal behavior. This nationally-representative sample included 906 adolescents and their mothers. The mothers and adolescents were interviewed and evaluated separately using the Development and Well-Being Assessment Inventory (DAWBA) and the Strengths and Difficulties Questionnaire (SDQ). Self-rated SDQ scores of the suicidal adolescents were significantly higher in all SDQ problem scales compared to the non-suicidal participants. In contrast, maternal-rated SDQ assessments failed to discriminate between these groups, except the Hyperactivity scale. We demonstrated that mothers of suicidal adolescents in the community hardly recognize the emotional and behavioral difficulties of their offsprings. CONCLUSION: The mental examination of the adolescent patient should be maintained as the central and most reliable source of information regarding the suicidal adolescent. Mental health services planning of national suicide prevention programs should take into account these poor mother-adolescent agreement findings.

Gender differences in emotional and behavioral disorders and service use among adolescent smokers: a nationwide Israeli study.

Marked gender differences have been identified in cigarette smoking. In this study, we aimed to identify the gender-specific emotional and behavioral disorders among adolescent smokers and their consequent utilization of mental health services. We performed a nationwide survey study of an Israeli representative sample of 906 adolescents and their mothers. Mental disorders were assessed using the Development and Well-Being Assessment (DAWBA) Inventory. Levels of emotional and behavioral difficulties were evaluated using the Strengths and Difficulties Questionnaire (SDQ). Mental health services use and smoking habits were also assessed. Among non-smoker adolescents there were significant gender differences in almost all SDQ scales: emotional problems, pro-social, hyperactivity/inattention and conduct problems, whereas in the smoker group there was a difference only in the SDQ emotional problems scale (both self- and maternal-rated, P<0.001 and P=0.002, respectively). Only marginal difference was noted between males and females in help-seeking for emotional or behavioral problems. Over 50% of both male and female smokers in the study had untreated mental disorders (non-significant gender difference). The well-established gender differences in psychiatric symptomatology narrowed markedly in adolescent smokers; the typical gender difference in disruptive behaviors was lost in the adolescent smoking population. The implications of these findings are particularly relevant to developing more effective gender-specific programs to prevent youth smoking, to facilitate quitting and prepare primary care practitioners to identify mental disorders and behavioral problems in adolescents with a smoking history.

Parental bonding in severely suicidal adolescent inpatients.

Family environment has a clear role in suicidal behavior of adolescents. We assessed the relationship between parental bonding and suicidal behavior in suicidal (n=53) and non-suicidal (n=47) adolescent inpatients. Two dimensions of parental bonding: care and overprotection, were assessed with the Parental Bonding Instrument. Results showed that adolescents with severe suicidal behavior tended to perceive their mothers as less caring and more overprotective compared to those with mild or no suicidal behavior. A discriminant analysis distinguished significantly between adolescents with high suicidality and those with low suicidality [χ2 (5) = 15.54; p=0.01] in 71% of the cases. The perception of the quality of maternal bonding may be an important correlate of suicidal behavior in adolescence and may guide therapeutic strategies and prevention.