Browsing by Subject "TSC-associated neuropsychiatric disorders"

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    The research landscape of tuberous sclerosis complex–associated neuropsychiatric disorders (TAND)—a comprehensive scoping review
    (2022-02-13) Vanclooster, Stephanie; Bissell, Stacey; van Eeghen, Agnies M; Chambers, Nola; De Waele, Liesbeth; Byars, Anna W; Capal, Jamie K; Cukier, Sebastián; Davis, Peter; Flinn, Jennifer; Gardner-Lubbe, Sugnet; Gipson, Tanjala; Heunis, Tosca-Marie; Hook, Dena; Kingswood, J C; Krueger, Darcy A; Kumm, Aubrey J; Sahin, Mustafa; Schoeters, Eva; Smith, Catherine; Srivastava, Shoba; Takei, Megumi; Waltereit, Robert; Jansen, Anna C; de Vries, Petrus J
    Background Tuberous sclerosis complex (TSC)–associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. Methods The study was conducted in accordance with stages outlined within the Arksey and O’Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. Results Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low–middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder–like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). Conclusions Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified.
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    Open Access
    TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study
    (BioMed Central, 2018-09-10) de Vries, Petrus J; Belousova, Elena; Benedik, Mirjana P; Carter, Tom; Cottin, Vincent; Curatolo, Paolo; Dahlin, Maria; D’Amato, Lisa; d’Augères, Guillaume B; Ferreira, José C; Feucht, Martha; Fladrowski, Carla; Hertzberg, Christoph; Jozwiak, Sergiusz; Kingswood, J. C; Lawson, John A; Macaya, Alfons; Marques, Ruben; Nabbout, Rima; O’Callaghan, Finbar; Qin, Jiong; Sander, Valentin; Sauter, Matthias; Shah, Seema; Takahashi, Yukitoshi; Touraine, Renaud; Youroukos, Sotiris; Zonnenberg, Bernard; Jansen, Anna C
    Abstract Background Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations. Results The study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015). The most common behavioural problems (reported in > 10% of participants) were overactivity, sleep difficulties, impulsivity, anxiety, mood swings, severe aggression, depressed mood, self-injury, and obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%), attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%), and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate, severe, and profound degrees of intellectual disability (ID) were observed in 28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in 58.6% of participants, and neuropsychological deficits (performance <5th percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity were observed in children and higher rates of anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations were observed in adults. Genotype-TAND correlations showed a higher frequency of self-injury, ASD, academic difficulties and neuropsychological deficits in TSC2. Those with no mutations identified (NMI) showed a mixed pattern of TAND manifestations. Children and those with TSC2 had significantly higher rates of intellectual disability, suggesting that age and genotype comparisons should be interpreted with caution. Conclusions These results emphasize the magnitude of TAND in TSC and the importance of evaluating for neuropsychiatric comorbidity in all children and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no mutations identified. However, the high rates of unreported or missing TAND data in this study underline the fact that, even in expert centres, TAND remains underdiagnosed and potentially undertreated.