From early intervention in psychosis to youth mental health reform: a review of the evolution and transformation of mental health services for young people.

PURPOSE: The objective of this review is to report on recent developments in youth mental health incorporating all levels of severity of mental disorders encouraged by progress in the field of early intervention in psychotic disorders, research in deficiencies in the current system and social advocacy. METHODS: The authors have briefly reviewed the relevant current state of knowledge, challenges and the service and research response across four countries (Australia, Ireland, the UK and Canada) currently active in the youth mental health field. RESULTS: Here we present information on response to principal challenges associated with improving youth mental services in each country. Australia has developed a model comprised of a distinct front-line youth mental health service (Headspace) to be implemented across the country and initially stimulated by success in early intervention in psychosis; in Ireland, Headstrong has been driven primarily through advocacy and philanthropy resulting in front-line services (Jigsaw) which are being implemented across different jurisdictions; in the UK, a limited regional response has addressed mostly problems with transition from child-adolescent to adult mental health services; and in Canada, a national multi-site research initiative involving transformation of youth mental health services has been launched with public and philanthropic funding, with the expectation that results of this study will inform implementation of a transformed model of service across the country including indigenous peoples. CONCLUSIONS: There is evidence that several countries are now engaged in transformation of youth mental health services and in evaluation of these initiatives.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00127-015-1165-

Polymorphism of the 5-HT2A Receptor Gene: Association with Stress-Related Indices in Healthy Middle-Aged Adults

Past research has concentrated on the stress system and personality in order to explain the variance found in cognitive performance in old age. A growing body of research is starting to focus on genetic polymorphism as an individual difference factor to explain the observed heterogeneity in cognitive function. While the functional mechanism is still under investigation, polymorphism of the 5-HT2A receptor gene (−1438A/G) has been linked to certain behavioral and physiological outcomes, including cortisol secretion, the expression of certain personality traits, and memory performance. It was the goal of the present study to investigate the association between the −1438A/G polymorphism and stress hormone secretion, stress-related psychological measures, and cognitive performance in a group of adults between the ages of 50 and 65. To examine these associations, 101 middle-aged adults were recruited, completed a battery of psychological questionnaires and were administered a battery of cognitive tasks that assess frontal lobe and hippocampal function. Basal and stress-reactive salivary cortisol levels were collected, at home and in the laboratory. Analyses on psychological measures showed that participants with the GG genotype reported significantly higher levels of neuroticism compared to the AG group and higher levels of depression and more emotion-based coping strategies compared to both the AG and AA group. In terms of cortisol secretion, the AA genotype was related to a significantly higher awakening cortisol response (ACR) compared to the AG and GG group and the GG genotype group displayed a greater increase in cortisol secretion following a psychosocial stressor compared to the two other groups. On measures of cognitive performance, the AA genotype group performed significantly better on a test of declarative memory and selective attention compared to the other two groups. Together, these results suggest that carriers of the GG genotype are more susceptible to low mood and display a greater potential for an overactive stress system, which may influence cognitive function in later years

Rai1 frees mice from the repression of active wake behaviors by light.

Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka 'masking') mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output

The quantification of mRNA in cerebellum tissue: diagnosis, genotype, methylation and expression

Background: The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val(158)Met polymorphism. Method: In this study we examined the expression levels of COMT mRNA using quantitative RTPCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. Results: We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val(158)met (rs165688; Val allele) rs737865 ( G allele) and rs165599 ( G allele) all showed reduced expression ( P <0.05). Finally, we observe a strong sexual dimorphism in COMT expression, with females exhibiting significantly greater levels of COMT mRNA. Conclusion: The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gen

Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects

Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutatio n manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients.National Institute of Mental Health (U.S.) (Grant 5R01MH097104)National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institutes of Health (U.S.) (Grant R01-NS 07312401

Investigating subjective cognitive complaints in psychosis:Introducing the brief scale to Investigate cognition in schizophrenia (SSTICS-Brief)

Background: Cognitive difficulties are a core deficit for people with schizophrenia and are generally assessed with neuropsychological tests. Self-report assessments are also useful in understanding difficulties from the service user’s perspective. This study aims to introduce and test the shorter version of the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) to improve its acceptability and comprehensibility. Methods: In consultation with service users and clinicians, we identified items from the original 21-item SSTICS that were found difficult and these were excluded. The reduced scale was explored with Confirmatory Factor Analysis (CFA) in two independent samples in the UK and Canada. Convergent validity with symptoms and IQ was assessed and compared between the original and the reduced scale. Results: Six-hundred and seven people with schizophrenia and first-episode psychosis took part in this study. Seven items were removed to produce the SSTICS-Brief. This had good reliability and the CFA confirmed a unidimensional structure. Convergent validity with symptoms and IQ were optimal between the long and short versions. Conclusions: The SSTICS-B has better acceptability than its longer form and could be administered in less time. The resulting measure is likely to be a valuable short self-assessment of cognitive complaints for people with schizophrenia.</p

OA Lal 2023 Digital health innovation to prevent relapse and support recovery in young people with first-episode psychosis : A pilot study of Horyzons-Canada

Digital health innovations may help to improve access to psychosocial therapy and peer support; however, the existence of evidence-based digital health interventions for individuals recovering from a first-episode psychosis (FEP) remains limited. This study aims to investigate the feasibility, acceptability, safety, and pre-post outcomes of Horyzons-Canada (HoryzonsCa), a Canadian adaptation of a digital mental health intervention consisting of psychosocial interventions, online social networking, and clinical and peer support moderation. Using a convergent mixed-methods research design, we recruited participants from a specialized early intervention clinic for FEP in Montreal, Canada. Twenty-three participants (mean age = 26.8) completed baseline assessments, and 20 completed follow-up assessments after 8 weeks of intervention access. Most participants provided positive feedback on general experience (85%, 17/20) and the utility of Horyzons for identifying their strengths (70%, 14/20). Almost all perceived the platform as easy to use (95%, 19/20) and felt safe using it (90%, 18/20). There were no adverse events related to the intervention. Participants used HoryzonsCa to learn about their illness and how to get better (65%, 13/20), receive support (60%, 12/20), and access social networking (35%, 7/20) and peer support (30%, 6/20). Regarding adoption, 65% (13/20) logged in at least 4 times over 8 weeks. There was a nonsignificant increase in social functioning and no deterioration on the Clinical Global Impression Scale. Overall, HoryzonsCa was feasible to implement and perceived as safe and acceptable. More research is needed with larger sample sizes and using in-depth qualitative methods to better understand the implementation and impact of HoryzonsCa

Association study of the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia

BACKGROUND: Brahma (BRM) is a key component of the multisubunit SWI/SNF complex, a complex which uses the energy of ATP hydrolysis to remodel chromatin. BRM contains an N-terminal polyglutamine domain, encoded by a polymorphic trinucleotide (CAA/CAG) repeat, the only known polymorphism in the coding region of the gene (SMARCA2). We have examined the association of this polymorphism with schizophrenia in a family-based and case/control study. SMARCA2 was chosen as a candidate gene because of its specific role in developmental pathways, its high expression level in the brain and some evidence of its association with schizophrenia spectrum disorder from genome-wide linkage analysis. RESULTS: Family-based analysis with 281 complete and incomplete triads showed that there is no significant preferential transmission of any of the alleles to the affected offspring. Also, in the case/control analysis, similar allele and genotype distributions were observed between affected cases (n = 289) and unaffected controls (n = 273) in each of three Caucasian populations studied: French Canadian, Tunisian and other Caucasians of European origin. CONCLUSION: Results from our family-based and case-control association study suggest that there is no association between the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia