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Small longitudinal study of serum anticholinergic activity and cognitive change in community-dwelling older adults

Kashyap M, Mulsant BH, Tannenbaum C

Am J Geriatr Psychiatry, 2015 Mar;23(3):326-9.
PMID: 25450763 DOI: 10.1016/j.jagp.2014.09.009

The discriminative ability of serum anticholinergic activity (SAA) to differentiate between older individuals with stable versus deteriorating cognition remains undetermined. We examined the relationship between SAA changes, the presence or absence of a mild neurocognitive disorder, age and anticholinergic medication over a one-year time period.
Fulltext Feasibility of remotely supervised transcranial direct current stimulation and cognitive remediation: A systematic review

Gough N, Brkan L, Subramaniam P, Chiuccariello L, De Petrillo A, Mulsant BH, et al.

PLoS One, 2020;15(2):e0223029.
PMID: 32092069 DOI: 10.1371/journal.pone.0223029

With technological advancements and an aging population, there is growing interest in delivering interventions at home. Transcranial Direct Current Stimulation (tDCS) and Cognitive Remediation (CR) as well as Cognitive Training (CT) have been widely studied, but mainly in laboratories or hospitals. Thus, the objectives of this review are to examine feasibility and the interventions components to support the domiciliary administration of tDCS and CR. We performed a systematic search of electronic databases, websites and reference lists of included articles from the first date available until October 31, 2018. Articles included had to meet the following criteria: original work published in English using human subjects, majority of tDCS or CR intervention administered remotely. A total of 39 studies were identified (16 tDCS, 23 CR/CT, 5 using both tDCS & CT). Four studies were single case studies and two were multiple case studies. The remaining 33 studies had a range of 9-135 participants. Five tDCS and nine CR/CT studies were double blind randomized controlled trials. Most studies focused on schizophrenia (8/39) and multiple sclerosis (8/39). Literature examined suggests the feasibility of delivering tDCS or CR/CT remotely with the support of information and communication technologies.
Fulltext The Impact of Anticholinergic Burden on Functional Capacity in Persons With Schizophrenia Across the Adult Life Span

Khan WU, Ghazala Z, Brooks HJ, Subramaniam P, Mulsant BH, Kumar S, et al.

Schizophr Bull, 2021 Jan 23;47(1):249-257.
PMID: 32619225 DOI: 10.1093/schbul/sbaa093

Anticholinergic burden (ACB) from medications impairs cognition in schizophrenia. Cognition is a predictor of functional capacity; however, little is known about ACB effect on functional capacity in this population. This study assesses the relationship between ACB and functional capacity across the life span in individuals with schizophrenia after controlling for ACB effect on cognition. A cross-sectional analysis was performed with data collected from 6 academic tertiary health centers. Two hundred and twenty-three community-dwelling participants with schizophrenia or schizoaffective disorder were included in this study. Main variables were ACB, antipsychotic olanzapine equivalents, functional capacity, cognition, and negative symptoms. Simultaneous linear regression analyses were performed to assess the association between ACB, functional capacity, and cognition and then between ACB and cognition. A mediation analysis was then performed to examine whether cognition mediated ACB effect on functional capacity if there was an association between ACB and cognition. Mean age of participants was 49.0 years (SD = 13.1, range 19-79), and 63.7% of participants had severe ACB, ie, a total score of 3 or above. Regression analyses revealed that ACB, age, education, and cognition independently predicted functional capacity and that ACB predicted cognition among those aged 55 years and older. Mediation analysis showed that cognition did partially mediate the effect of ACB on functional capacity in this older cohort. In conclusion, people with schizophrenia are exposed to severe ACB that can have a direct negative impact on functional capacity after controlling for its impact on cognition. Reducing ACB could improve functional capacity and potentially real-world function in schizophrenia.
Fulltext Identifying the Common Genetic Basis of Antidepressant Response

Pain O, Hodgson K, Trubetskoy V, Ripke S, Marshe VS, Adams MJ, et al.

Biol Psychiatry Glob Open Sci, 2022 Apr;2(2):115-126.
PMID: 35712048 DOI: 10.1016/j.bpsgos.2021.07.008

BACKGROUND: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction.
METHODS: Genome-wide analysis of remission (n remit = 1852, n nonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism-based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA.
RESULTS: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism-based heritability was significantly different from zero for remission (h 2 = 0.132, SE = 0.056) but not for percentage improvement (h 2 = -0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response.
CONCLUSIONS: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.