How does Tourette syndrome impact adolescents' daily living? A text mining study.

Tourette syndrome is a neurodevelopmental disease in which clinical manifestations are essentially present during childhood and adolescence, corresponding to one of the critical development phases. However, its consequences on the daily lives of young patients have been insufficiently investigated. Here, we aimed to investigate this using a statistical text mining approach, allowing for the analysis of a large volume of free textual data. Sixty-two adolescents with Tourette syndrome participated in an interview in which they discussed their daily life (i) in school, (ii) at home, and (iii) with strangers, (iv) the aspect of Tourette syndrome which caused the most difficulty, and (v) their thoughts regarding their future as adults. Following data pre-processing, these corpora were analyzed separately using the IRAMUTEQ software through factorial correspondence analysis to identify the most commonly recurring topics of each corpus, and their relations with clinical features. The main difficulty corpus was directly related to comorbidities of Tourette syndrome. Daily life at home was correlated with executive functioning. Difficulties at school were related to a higher severity of tics. Thoughts regarding future daily life were worst for the youngest patients and were correlated with executive functioning and a higher depression score. Taken altogether, our results highlighted that social stigma was a pervasive topic among our corpora. From a clinical standpoint, tic severity was especially related to difficulties at school, while comorbidities had a high impact on social daily living and cost for managing both tics and symptoms of comorbidities. TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04179435.

Decision-making under risk and ambiguity in adults with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) as well as its most common comorbidities are associated with a higher propensity for risky behaviour in everyday life. However, it is unclear whether this increased risk propensity in real-life contexts translates into a generally increased attitude towards risk. We aimed to assess decision-making under risk and ambiguity based on prospect theory by considering the effects of comorbidities and medication. METHODS: Fifty-four individuals with TS and 32 healthy controls performed risk and ambiguity decision-making tasks under both gains and losses conditions. Behavioural and computational parameters were evaluated using (i) univariate analysis to determine parameters difference taking independently; (ii) supervised multivariate analysis to evaluate whether our parameters could jointly account for between-group differences (iii) unsupervised multivariate analysis to explore the potential presence of sub-groups. RESULTS: Except for general 'noisier' (less consistent) decisions in TS, we showed no specific risk-taking behaviour in TS or any relation with tics severity or antipsychotic medication. However, the presence of comorbidities was associated with distortion of decision-making. Specifically, TS with obsessive-compulsive disorder comorbidity was associated with a higher risk-taking profile to increase gain and a higher risk-averse profile to decrease loss. TS with attention-deficit hyperactivity disorder comorbidity was associated with risk-seeking in the ambiguity context to reduce a potential loss. CONCLUSIONS: Impaired valuation of risk and ambiguity was not related to TS per se. Our findings are important for clinical practice: the involvement of individuals with TS in real-life risky situations may actually rather result from other factors such as psychiatric comorbidities.

Structural and functional abnormalities within sensori-motor and limbic networks underpin intermittent explosive symptoms in Tourette disorder.

BACKGROUND: Intermittent explosive outbursts (IEO), manifesting as sudden episodes of verbal or physical aggression, are frequently present in patients with Tourette disorder (TD) and considered as one of the most disabling symptoms by patients and families. The neuronal correlates of these behaviours are poorly understood, and this was the primary objective of the present study. METHODS: We assessed the presence of IEO in 55 patients with TD and then compared the subgroup of the patients with IEO to those without these manifestations using a multimodal neuroimaging approach. RESULTS: 47% of TD patients presented IEO, which was frequently associated with attention deficit hyperactivity disorder (ADHD). TD patients (without ADHD) with IEO compared to TD without IEO, showed structural changes in the right supplementary motor area as well as in the right hippocampus (increased fractional anisotropy), and in the left orbitofrontal cortex (decreased mean diffusivity). Using these three nodes as seeds for resting state functional connectivity, we showed a lower connectivity within the sensori-motor cortico-basal ganglia network, and an altered connectivity pattern among the orbito-frontal cortex, amygdala and hippocampus. CONCLUSIONS: Overall, our results indicate that TD with IEO is associated with brain dysfunction related to a less efficient top-down control on action selection, and impairments related to emotional regulation, impulse control and aggressive behaviours.

Disentangling Tourette syndrome heterogeneity through hierarchical ascendant clustering.

AIM: To explore the heterogeneity of Tourette syndrome as part of a neurodevelopmental spectrum. METHOD: Using hierarchical ascendant clustering based on tic symptoms, developmental milestones, and neurodevelopmental comorbidities, we analyzed the heterogeneity of Tourette syndrome phenotypes in a sample of 174 children and adolescents with Tourette syndrome referred to a tertiary university clinic. RESULTS: The model yielded three distinct clusters characterized as follows. In cluster 1, we found many neurodevelopmental comorbidities (including intellectual disabilities, autism spectrum disorder, attention-deficit-hyperactivity disorder [ADHD], and learning disabilities) and academic impairments. In cluster 2, patients had no other neurodevelopmental comorbidities. In cluster 3, patients had higher intelligence, a high frequency of attentional impairment, school problems related to both ADHD and unspecific attention difficulties, and handwriting problems related to the tics themselves. Interestingly, clusters did not differ in terms of family history or anxious-depressive comorbidities. The only other differences that emerged were related to prenatal or perinatal risk factors (more represented in cluster 1) and treatment profiles (higher rates of stimulants in cluster 1). INTERPRETATION: We conclude that from a phenotypical perspective, Tourette syndrome is a heterogeneous syndrome with at least three main clusters that may help in addressing the etiological basis of Tourette syndrome and specific rehabilitative and therapeutic approaches. WHAT THIS PAPER ADDS: The clustering of Tourette syndrome based on comorbidity with other neurodevelopmental conditions reveals three clusters. A group of patients with Tourette syndrome show school difficulties related to non-specific attention and writing problems. Analysing only children and adolescents helps to distinguish between developmental comorbid conditions and coexistent disorders.

Tourette syndrome and other neurodevelopmental disorders: a comprehensive review.

Gilles de la Tourette syndrome (TS) is a complex developmental neuropsychiatric condition in which motor manifestations are often accompanied by comorbid conditions that impact the patient's quality of life. In the DSM-5, TS belongs to the "neurodevelopmental disorders" group, together with other neurodevelopmental conditions, frequently co-occurring. In this study, we searched the PubMed database using a combination of keywords associating TS and all neurodevelopmental diagnoses. From 1009 original reports, we identified 36 studies addressing TS and neurodevelopmental comorbidities. The available evidence suggests the following: (1) neurodevelopmental comorbidities in TS are the rule, rather than the exception; (2) attention deficit/hyperactivity disorder (ADHD) is the most frequent; (3) there is a continuum from a simple (TS + ADHD or/and learning disorder) to a more complex phenotype (TS + autism spectrum disorder). We conclude that a prompt diagnosis and a detailed description of TS comorbidities are necessary not only to understand the aetiological basis of neurodevelopmental disorders but also to address specific rehabilitative and therapeutic approaches.

Impact of Perceived Stress, Anxiety-Depression and Social Support on Coping Strategies of Parents Having A Child With Gilles de la Tourette Syndrome.

PURPOSE: Previous reports have indicated that raising a child with Gilles de la Tourette syndrome (GTS) could be considered a stressful experience. Thus our study aimed to assess the impact of perceived stress (i.e. parental cognitive perception of their child's disorder) and social support (number of people surrounding the subject providing support) on coping strategies-defined as processes of restoring balance between excessive demands and inadequate resources-of parents having a child with GTS. METHODS: Twenty-eight parents of 21 patients with GTS (aged 6 to 16years) completed questionnaires on perceived stress (ALE Scale), social support (SSQ6), coping strategies (WCC-R) and anxiety-depression (HAD). RESULTS: Principal component analysis showed a negative correlation between social support on one side and perceived stress and anxiety/depression on the other. Problem- and emotion-focused coping both correlated with social support, all of them being independent from perceived stress and anxiety/depression. Hierarchical ascendant classification showed three clusters of individuals in our parents' groups: i) those having high scores in perceived stress and anxiety-depression; ii) those having high scores in social support associated with low scores in perceived stress; iii) parents having lower than average scores on both problem- and emotion- focused coping and social support. CONCLUSION: Our results reinforce the need for developing training programs for parents with GTS children to better understand and tolerate the disorder to decrease their stress.

Diagnostic transition towards schizophrenia in adolescents with severe bipolar disorder type I: an 8-year follow-up study.

BACKGROUND: The diagnosis of bipolar disorder-I (BD-I) is currently well-established. However, more studies exploring diagnostic stability and psychosocial adaptation during follow-up in adulthood are needed. OBJECTIVES: We assessed factors at follow-up (FU): (1) the diagnostic stability of manic/mixed episodes from adolescence to adulthood, (2) psychosocial adaptation, and (3) factors associated with psychosocial adaptation. METHODS: A sample of 80 adolescents hospitalized in a university hospital between 1993 and 2004 for a manic or mixed episode were contacted for an FU assessment on average 8 years after the index episode. Assessments included socio-demographic data, mortality, lifetime psychiatric diagnosis, the Social Adaptation Scale, negative life events and insight. RESULTS: Of the 64 patients with available information, one patient died from a heart attack. Of the 55 patients available for an FU assessment, 35 (63.6%) still presented a diagnosis of BD-I at FU, whereas 20 (36.4%) had changed diagnosis towards a schizophrenia spectrum disorder. Psychosocial adaptation was moderate to poor for most patients, and 91% of the patients had at least one relapse. A low socio-economic status, intellectual disability, negative life events, a history of sexual abuse, and treatment with classical antipsychotics at FU were significantly associated with poorer psychosocial adaptation. In contrast, better insight, a family history of depression and a diagnosis of BD-I at FU were associated with better psychosocial adaptation. CONCLUSION: BD-I in adolescent inpatients can lead to important morbidity and mortality during outcome. Diagnostic stability is high, but a high proportion of patients also show a transition towards a schizophrenia spectrum disorder.

Psychosocial and Clinical Correlates of Substance use Disorder in an Adolescent Inpatient Psychiatric Population.

OBJECTIVE: This study aimed at exploring the psychosocial and clinical correlates of substance use disorder in an adolescent inpatient psychiatric population. METHOD: During the period from 2006-2007, all subjects were systematically screened for substance use disorder (SUD) and were assessed for SUD characteristics by an independent support team using the RECAP (Joint Report on Drug Addiction and Treatment). Each SUD case was matched for age, gender, unit, and admission week, so as to compare a consumer sample (cases) with a non-consumer sample (controls). We retrospectively extracted data (socio-demographic and clinical characteristics) from charts to realize a case-control comparison. To assess Axis II borderline psychopathology, the child retro-DIB (Diagnosis Interview for Borderline) was used. RESULTS: The sample included 30 cases and 30 controls between 14 and 17 years of age. SUD was significantly associated with maltreatment (p=0.038), loss of a first-degree relative (p=0.039), school absenteeism (p=0.035) and suicide attempts (p=0.02). Regarding psychopathology, significant co-occurrence was observed between SUD and conduct disorder (p=0.019), all personality disorders (p=0.003) and borderline personality disorder specifically (p=0.021). CONCLUSION: Adolescent inpatients with SUD possess differential psychosocial and clinical characteristics and particular correlates that justify adopting a specific multidisciplinary approach to this high-risk clinical subgroup.

Predictors of placebo response in randomized controlled trials of psychotropic drugs for children and adolescents with internalizing disorders.

OBJECTIVE: The aim of this study was to assess predictors of placebo response in all available short-term, placebo-controlled trials of psychotropic drugs for children and adolescents with internalizing disorders, major depressive disorder (MDD), obsessive compulsive disorder (OCD,) and anxiety disorders (ANX) exclusive of OCD and posttraumatic stress disorder (PTSD). METHOD: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalizing disorders, restricting our review to double-blind studies including a placebo arm. Placebo response, defined according to each trial's primary response outcome variable and Clinical Global Impressions-Improvement, when available, and potential predictive variables were extracted from 40 studies. RESULTS: From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication involving youth with MDD, 7 pertaining to youths with OCD, and 10 pertaining to youths with ANX (N = 2,533 patients in placebo arms). For all internalizing disorders combined, predictors of nonresponse to placebo were the percentage of Caucasian patients included in the study and the duration of the disorder: Both variables were negatively correlated with the percent of placebo responders. The type of disorder was found to predict the robustness of placebo response: (OCD < ANX < MDD). For a subset of MDD studies, we found that baseline illness severity tended to be negatively correlated with placebo response. Finally, trial "success" was significantly associated with lower placebo response rate. CONCLUSION: Predictors of placebo response in internalizing disorders of youths parallel those in adult studies, with the exception of race. These predictors should be considered when designing placebo-controlled trials in youths to enhance findings of true drug-placebo differences.

Medication use in adolescents treated in a French psychiatric setting for acute manic or mixed episode.

OBJECTIVE: In the absence of recommendations from drug regulatory agencies for most medications to treat severe manic or mixed episode in adolescence, this study aims to (i) describe the pharmacological treatment prescribed in an inpatient setting for acute manic or mixed episodes in adolescents; (ii) determine whether type of episode, duration of stay, improvement, and psychotic features were associated with the nature of the given treatment; (iii) compare the results with evidence-based data. METHOD: From 1993 to 2003, we received 80 subjects, aged 12 to 20 years, consecutively hospitalized for a manic or mixed episode. Socio-demographic, clinical and treatment data were extracted by reviewing patients' charts. Treatment data were available for 75 subjects. RESULTS: Most patients received a combination treatment including mood stabilizer (82.6%), classical antipsychotic (AP) (86.6%) and atypical AP (24%). Despite prolonged hospitalisation (minimum stay = 17 days), 69 (86.2%) patients were scored very much or much improved at discharge. Secondary therapeutic options occurred in 15 subjects because of poor therapeutic response (N=13), severe adverse effects (N=5) or both. Two patients had electroconvulsive therapy as third therapeutic option. Adolescents with psychotic symptoms were significantly more frequently treated by lithium (Fisher exact test: p=0,0052). No other variable was associated with treatment. CONCLUSIONS: This study reported on patterns of medication use that mainly followed treatment recommendations and evidence-based data existing in adults. However, the presence of psychotic features appeared to favour the use of lithium in this French sample.

Phenomenology, socio-demographic factors and outcome upon discharge of manic and mixed episodes in hospitalized adolescents: a chart review.

BACKGROUND: The existence of bipolar disorder type I (BD-I) during adolescence is now clearly established whereas there are still some controversies on BD-II and BD-NOS diagnosis, mainly in Europe (O'Dowd in Br Med J 29, 2006). Little is known on the phenomenology and potential short-term prognosis factors of bipolar episodes in this age population. In particular, very few studies examine this issue on inpatients in the European context of free access to care. OBJECTIVE: To describe the phenomenology of acute manic and mixed episodes in hospitalized adolescents and to analyse potential predictive factors associated with clinical improvement at discharge and length of hospitalization. METHODS: A total of 80 subjects, aged 12-20 years, consecutively hospitalized for a manic or mixed episode. Socio-demographic and clinical data were extracted by reviewing patients' charts. We used a multivariate analysis to evaluate short-term outcome predictors. RESULTS: The sample was characterized by severe impairment, high rates of psychotic features (N = 50, 62.5%), a long duration of stay (mean 80.4 days), and an overall good improvement (86% very much or much improved). Thirty-three (41.3 %) patients had a history of depressive episodes, 13 (16.3%) had manic or brief psychotic episodes but only 3 (3.7%) had a history of attention deficit/hyperactivity disorders. More manic episodes than mixed episodes were identified in subjects with mental retardation (MR) and in subjects from migrant and/or low socio-economic families. Overall severity and female gender predicted better improvement in GAF scores. Poor insight and the existence of psychotic features predicted longer duration of stay. CONCLUSION: These results suggest that severe manic and mixed episodes in adolescents with BD-I need prolonged inpatient care to improve and that socio-cultural factors and MR should be examined more closely in youth with BD.

Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials.

BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD), obsessive compulsive disorder (OCD) and other anxiety disorders (AD-non-OCD). METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD), age (adolescent vs. child), and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants) involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms). As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002). Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.

[Drug treatment of early-onset schizophrenia]. / Traitement médicamenteux des schizophrénies à début précoce.

The earlier the onset of schizophrenia, the more severe the disease. Atypical antipsychotics are the first-line treatment of choice in children as in adults. Nonetheless, most of these drugs have not been approved for use in patients younger than 15 years. In children and adolescents, the atypical antipsychotics have fewer adverse effects than first-generation antipsychotics do, but are nonetheless not tolerated as well as in adults. Among the notable adverse effects are weight gain, sedation, and hyperprolactinemia. The most recent data suggest the need for prevention and attentive monitoring of the components of the metabolic syndrome (elevation of blood pressure, waist circumference, HDL cholesterol, blood glucose, and triglycerides).