Tic disorders can have a significant emotional and social impact on children and their families. There is increasing support for the use of parenting programmes in childhood conditions; however research into the applicability of such programmes in tic disorders is limited. This thesis therefore aimed to investigate the topic of parenting interventions in tic disorders. The thesis presents five chapters, written as a series of self-contained papers and prepared in accordance with selected journal submission guidance. Paper 1 is a systematic literature review of the implementation and effectiveness of behavioural parent training programmes across neurodevelopmental disorders. Twenty-two randomised controlled studies were included in the review. Neurodevelopmental disorders included attention deficit hyperactivity disorder, autistic spectrum conditions, intellectual difficulties and developmental disorders and tic disorders. Training programmes included Triple P, Barkley’s Defiant Children, Parent Child Interaction Therapy, New Forest Parenting, Parenting your Hyperactive Preschooler, Parents Plus Children, Preschoolers with Autism, Incredible Years and an idiosyncratic programme. Effects of interventions on child outcomes were examined alongside intervention characteristics and content. Results indicated robust evidence for effects of parent training on attention-deficit/hyperactivity difficulties and externalising difficulties, across neurodevelopmental disorders and training programmes. Evidence to support the effect of parent training on internalising, social and global difficulties across disorders was less robust, with fewer and inconsistent outcomes reported. Clinical and research implications resulting from the findings are discussed. Papers 2 and 3 present empirical studies. Both studies are Q-methodological investigations into opinions on parenting interventions in tic disorders. Q-methodology is a technique which enables participants’ subjective viewpoints to be grouped using by-person factor analysis. Views on the acceptability, effectiveness, feasibility and utility of parenting interventions were explored across parents of children with tic disorders (Paper 2) and professionals (Paper 3). Across both studies, seven main factors were identified (parents four, professionals three). Findings highlighted that interventions were generally considered acceptable, justified and perceived as needed. However, important differences in opinions were found within and between parent and professional groups, highlighting key clinical considerations for possible intervention format, delivery and content. Paper 4 provides a commentary of the clinical implications of these findings when the two studies are considered together, and provides guidance to further develop and implement interventions. Paper 5 presents a critical review, including discussion of the strengths, limitations and implications of the findings, alongside personal reflections on the research process.

This study aimed to characterize and assess the subjective impact of the COVID- 19 pandemic on symptom severity and psychosocial experiences of youth with chronic tic disorders (CTD), obsessive-compulsive disorder (OCD), and co-occurring tic and OCD (Tics+OCD) through the use of Likert scales and validated measures. Children and adolescents aged 6 to 18 and their parents were asked to complete an online survey from July 2020 to April 2021. Overall, youth in the study reported negative pandemic-related impact on several domains, particularly after-school activities, relationships with friends, and family and community gatherings. Though limited by the small sample size of the group, youth with OCD appeared to report more negative impact compared to the other diagnostic subgroups. The median screen use for youth in this study was 3-8 hours a day; youth who reported >8 hours of screen time per day on weekends trended towards a 13x greater odds of depression compared to those with <8 hours per day although not statistically significant. If future public health emergencies were to ensue, supports aimed at helping these particularly vulnerable youth navigate the impact of those restrictions would be welcome and important to their mental health and general well-being.

Introdução: O Transtorno Obsessivo-Compulsivo (TOC) é reconhecido como um transtorno heterogêneo. Esta heterogeneidade dificulta a interpretação dos resultados dos estudos. A descrição de grupos de pacientes mais homogêneos pode facilitar a identificação desta busca, já que pode identificar fenótipos que sejam hereditários e válidos do ponto de vista genético. A abordagem categorial e dimensional são estratégias reconhecidas para a identificação de subgrupos mais homogêneos de pacientes. Dentro da abordagem categorial, o subgrupo de pacientes com início precoce dos sintomas obsessivo-compulsivo (SOC), e o subgrupo de TOC associado a transtorno de tiques apresentam características clínicas semelhantes, com evidências de sobreposição destas características entre os dois grupos. Os objetivos deste estudo foram: investigar características demográficas e clínicas dos pacientes com TOC de início precoce (GP) e TOC de início tardio (GT); e pesquisar características demográficas e clínicas dos pacientes com TOC de início precoce (GP) com tiques e pacientes com TOC de início precoce (GP) sem tiques. Metodologia: Trezentos e trinta pacientes com diagnóstico de TOC de acordo com o DSM-IV foram avaliados diretamente com os seguintes instrumentos: Entrevista Clínica Estruturada para o DSM-IV - Transtornos do Eixo I; Escala Yale-Brown de Sintomas Obsessivo-Compulsivos - Y-BOCS; Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos DY-BOCS; Escala de Avaliação Global de Tiques desenvolvida pelo Yale Child Study Center - YGTSS. Foi considerado TOC de início precoce se os sintomas dos pacientes tiveram início até os 10 anos de idade (160 pacientes). Os pacientes com início de sintomas entre 11 e 17 anos (95 pacientes) foram denominados grupo intermediário, enquanto aqueles após os 17 anos foram chamados grupo de início tardio (75 pacientes). Resultados: os pacientes do GP se diferenciaram dos pacientes do GT por apresentar maior freqüência do sexo masculino; maior freqüência de história familiar de SOC em familiares de primeiro grau; maiores escores da escala Y-BOCS para compulsões e Y-BOCS total; maior chance de ter obsessões de contaminação; maior chance de ter compulsões de repetição, colecionismo, diversas e compulsões do tipo tic-like; menor chance de ter compulsões de contagem; maior chance de apresentar sintomas da dimensão de \"colecionismo\"; maior gravidade nas dimensões de \"agressão/violência\", \"diversas\" e escore global da escala DY-BOCS; maior número médio de comorbidades; maior probabilidade de ocorrência de transtorno de ansiedade de separação, fobia social, transtorno dismórfico corporal e transtorno de tiques; menor chance de apresentar transtorno de estress pós-traumático; e maior chance de ter redução de 35% dos sintomas na escala Y-BOCS. O GP com tiques se diferenciou do GP sem tiques por apresentar maior prevalência de fenômenos sensoriais; menor chance e menor gravidade de ter a dimensão de \"contaminação/limpeza\" e menor gravidade no escore global da escala DY-BOCS; menor chance de apresentar transtorno de humor, transtorno unipolar, transtornos ansiosos, fobia social e skin picking, e maior a chance de apresentar diminuição de 35% dos sintomas na escala Y-BOCS. Os resultados sugeriram que as diferenças encontradas entre os grupos precoce, intermediário e tardio foram devidas à própria idade de início, e outras diferenças foram devidas à presença de tiques. / Introduction: Obsessive-compulsive disorder (OCD) is recognized as a heterogeneous condition. This heterogeneity obscures the interpretation of the results of the studies. The description of more homogeneous groups of patients can facilitate the identification of this search, since it can identify phenotypes that are hereditary and valid to the genetic point of view. Categorical and dimensional approaches are recognized strategies for the identification of more homogeneous subgroups of patients. Regarding the categorical approach, the subgroup of patients with early age at onset of the obsessive-compulsive symptoms (OCS), and the tic-related-OCD subgroup present similar clinical characteristics, with evidences of an overlap of these characteristics between the two groups. The aims of this study were: to investigate clinical and demographic characteristics of the early age at onset subgroup (EO), compared to the late onset subgroup (LO); and to investigate demographic and clinical characteristics of early age at onset OCD patients, with and without comorbid tic disorders. Methodology: Three hundred and thirty patients with the diagnosis of OCD according to the DSM-IV were directly assessed with the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition - SCID-I/P; Yale-Brown Obsessive-Compulsive Scale - Y-BOCS; Dimensional Yale-Brown Obsessive-Compulsive Scale - DY-BOCS and Yale Global Tics Severity Scale - YGTSS. We considered early age at onset when OCS began before the age of 10 (160 patients). Patients with age at onset between 11 and 17 years old were termed intermediate group (95 patients), whereas those with age at onset after 17 years old were designated as late onset OCD (75 patients). Results: EO patients differed from LO patients in terms of presenting higher frequency of the male gender; higher frequency of a family history of OCS; higher Y-BOCS for compulsions and total Y-BOCS scores; higher chance of presenting contamination obsessions, repeating, hoarding, miscellaneous and tic-like compulsions; lower chance of having counting compulsions; higher probability of presenting symptoms of \"hoarding\" dimension; higher severity in \"aggression/violence\" and \"miscellaneous\" dimensions and global DY-BOCS scale score; higher mean number of comorbidities; higher probability of presenting separation anxiety disorder, social phobia, body dysmorphic disorder and tic disorders; lower chance of presenting posttraumatic stress disorder; and a higher chance of having a 35% reduction on the Y-BOCS scale. The EO subgroup with tic disorders differed from the EO without tics for presenting higher chance of having sensory phenomena, somatic obsessions; lower chance and lower score in the DY-BOCS scale; lower chance of presenting mood disorder, depressive disorder, anxiety disorders, social phobia and skin picking; higher chance of having a 35% reduction on the Y-BOCS scale. Results suggested that the differences found among early, intermediated and late onset groups with early onset were secondary to the own age at onset, and other differences were secondary to the presence of tics.

No description available.

Introdução: O Transtorno Obsessivo-Compulsivo (TOC) é reconhecido como um transtorno heterogêneo. Esta heterogeneidade dificulta a interpretação dos resultados dos estudos. A descrição de grupos de pacientes mais homogêneos pode facilitar a identificação desta busca, já que pode identificar fenótipos que sejam hereditários e válidos do ponto de vista genético. A abordagem categorial e dimensional são estratégias reconhecidas para a identificação de subgrupos mais homogêneos de pacientes. Dentro da abordagem categorial, o subgrupo de pacientes com início precoce dos sintomas obsessivo-compulsivo (SOC), e o subgrupo de TOC associado a transtorno de tiques apresentam características clínicas semelhantes, com evidências de sobreposição destas características entre os dois grupos. Os objetivos deste estudo foram: investigar características demográficas e clínicas dos pacientes com TOC de início precoce (GP) e TOC de início tardio (GT); e pesquisar características demográficas e clínicas dos pacientes com TOC de início precoce (GP) com tiques e pacientes com TOC de início precoce (GP) sem tiques. Metodologia: Trezentos e trinta pacientes com diagnóstico de TOC de acordo com o DSM-IV foram avaliados diretamente com os seguintes instrumentos: Entrevista Clínica Estruturada para o DSM-IV - Transtornos do Eixo I; Escala Yale-Brown de Sintomas Obsessivo-Compulsivos - Y-BOCS; Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos DY-BOCS; Escala de Avaliação Global de Tiques desenvolvida pelo Yale Child Study Center - YGTSS. Foi considerado TOC de início precoce se os sintomas dos pacientes tiveram início até os 10 anos de idade (160 pacientes). Os pacientes com início de sintomas entre 11 e 17 anos (95 pacientes) foram denominados grupo intermediário, enquanto aqueles após os 17 anos foram chamados grupo de início tardio (75 pacientes). Resultados: os pacientes do GP se diferenciaram dos pacientes do GT por apresentar maior freqüência do sexo masculino; maior freqüência de história familiar de SOC em familiares de primeiro grau; maiores escores da escala Y-BOCS para compulsões e Y-BOCS total; maior chance de ter obsessões de contaminação; maior chance de ter compulsões de repetição, colecionismo, diversas e compulsões do tipo tic-like; menor chance de ter compulsões de contagem; maior chance de apresentar sintomas da dimensão de \"colecionismo\"; maior gravidade nas dimensões de \"agressão/violência\", \"diversas\" e escore global da escala DY-BOCS; maior número médio de comorbidades; maior probabilidade de ocorrência de transtorno de ansiedade de separação, fobia social, transtorno dismórfico corporal e transtorno de tiques; menor chance de apresentar transtorno de estress pós-traumático; e maior chance de ter redução de 35% dos sintomas na escala Y-BOCS. O GP com tiques se diferenciou do GP sem tiques por apresentar maior prevalência de fenômenos sensoriais; menor chance e menor gravidade de ter a dimensão de \"contaminação/limpeza\" e menor gravidade no escore global da escala DY-BOCS; menor chance de apresentar transtorno de humor, transtorno unipolar, transtornos ansiosos, fobia social e skin picking, e maior a chance de apresentar diminuição de 35% dos sintomas na escala Y-BOCS. Os resultados sugeriram que as diferenças encontradas entre os grupos precoce, intermediário e tardio foram devidas à própria idade de início, e outras diferenças foram devidas à presença de tiques. / Introduction: Obsessive-compulsive disorder (OCD) is recognized as a heterogeneous condition. This heterogeneity obscures the interpretation of the results of the studies. The description of more homogeneous groups of patients can facilitate the identification of this search, since it can identify phenotypes that are hereditary and valid to the genetic point of view. Categorical and dimensional approaches are recognized strategies for the identification of more homogeneous subgroups of patients. Regarding the categorical approach, the subgroup of patients with early age at onset of the obsessive-compulsive symptoms (OCS), and the tic-related-OCD subgroup present similar clinical characteristics, with evidences of an overlap of these characteristics between the two groups. The aims of this study were: to investigate clinical and demographic characteristics of the early age at onset subgroup (EO), compared to the late onset subgroup (LO); and to investigate demographic and clinical characteristics of early age at onset OCD patients, with and without comorbid tic disorders. Methodology: Three hundred and thirty patients with the diagnosis of OCD according to the DSM-IV were directly assessed with the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition - SCID-I/P; Yale-Brown Obsessive-Compulsive Scale - Y-BOCS; Dimensional Yale-Brown Obsessive-Compulsive Scale - DY-BOCS and Yale Global Tics Severity Scale - YGTSS. We considered early age at onset when OCS began before the age of 10 (160 patients). Patients with age at onset between 11 and 17 years old were termed intermediate group (95 patients), whereas those with age at onset after 17 years old were designated as late onset OCD (75 patients). Results: EO patients differed from LO patients in terms of presenting higher frequency of the male gender; higher frequency of a family history of OCS; higher Y-BOCS for compulsions and total Y-BOCS scores; higher chance of presenting contamination obsessions, repeating, hoarding, miscellaneous and tic-like compulsions; lower chance of having counting compulsions; higher probability of presenting symptoms of \"hoarding\" dimension; higher severity in \"aggression/violence\" and \"miscellaneous\" dimensions and global DY-BOCS scale score; higher mean number of comorbidities; higher probability of presenting separation anxiety disorder, social phobia, body dysmorphic disorder and tic disorders; lower chance of presenting posttraumatic stress disorder; and a higher chance of having a 35% reduction on the Y-BOCS scale. The EO subgroup with tic disorders differed from the EO without tics for presenting higher chance of having sensory phenomena, somatic obsessions; lower chance and lower score in the DY-BOCS scale; lower chance of presenting mood disorder, depressive disorder, anxiety disorders, social phobia and skin picking; higher chance of having a 35% reduction on the Y-BOCS scale. Results suggested that the differences found among early, intermediated and late onset groups with early onset were secondary to the own age at onset, and other differences were secondary to the presence of tics.

Le terme « tiqueur » est utilisé pour alléger le texte, et ce, sans préjudice. / Les tics sont des manifestations motrices ou phoniques, involontaires, soudaines, rapides, stéréotypées, non rythmiques et répétitives (Bloch & Leckman, 2009). Selon la cinquième version du manuel diagnostique et statistique des troubles mentaux (DSM-5), le Syndrome Gilles de la Tourette (SGT) inclut la présence de tics moteurs multiples associés à au moins un tic phonique se manifestant plusieurs fois par jour, depuis plus d'un an (APA, 2013). Lorsqu’au moins un tic moteur ou phonique existe de façon isolée depuis au moins un an, le diagnostic de Trouble de tics chroniques est plutôt envisagé (TTC). Plusieurs études ont permis de montrer une similarité entre le SGT et le TTC du point de vue des comorbidités, ainsi que des variables neuropsychologiques et psychosociales associées (Spencer & al., 1995; Shapiro & Shapiro, 1982). Ainsi, plusieurs auteurs suggèrent que le TTC constitue une forme moins sévère du SGT (Jedynak, 2004). Les effets néfastes associés aux tics chroniques sur la vie sociale, scolaire ou professionnelle sont suffisamment bien documentés dans la littérature scientifique (Cavanna, Servo, Monaco & Robertson, 2009; Robertson, 2006; Thibert, Day & Sandor, 1995). Les thérapies cognitivo-comportementales (TCC) représentent une bonne alternative à la médication dont les effets secondaires peuvent parfois être très incommodants. Toutefois, ces dernières montrent un taux d’efficacité très variable, de 30 % à 67 % selon les études (Verdellen, Van de Griendt, Hartmann & Murphy, 2011; Piacentini & al., 2010; O’Connor et al., 2015, 2008, 2005a, 2005b, 2001, 1997a, 1997b, 1997c). Pour cette raison, plusieurs auteurs ont tenté de prédire le taux de réussite thérapeutique associé à une TCC par une série de facteurs neuropsychologiques afin de trouver un élément d’explication à ces variations. La plupart s’accordent pour dire que le taux de réussite d’une TCC dépend du fonctionnement exécutif, et notamment des capacités d’inhibition et de flexibilité cognitive. Les participants ciblés par cette étude sont des adultes âgés entre 18 et 50 ans souffrants d’un SGT ou d’un Trouble de tics chroniques (n = 92), comparés à des participants sans problème psychiatrique ou neurologique (n = 56). La cueillette de données s’est effectuée au Centre d’Étude sur les Troubles Obsessionnel-Compulsif et les Tics (CÉTOCT), entre 2003 et 2013. L’objectif du premier volet de cette étude visait à comparer les capacités d’inhibition et de flexibilité cognitive chez un groupe de participants atteints de tics chroniques et un groupe de participants neurotypiques (groupe témoin). D’autre part, l’objectif du deuxième volet visait à mesurer les capacités d’inhibition et de flexibilité cognitive chez deux sous-groupes de participants : un sous-groupe ayant fortement réussi une Thérapie Cognitivo-Comportementale (TCC) pour les tics chroniques et un autre ayant faiblement réussi. Les résultats obtenus montrent que les participants atteints de tics chroniques présentent, de façon significative, de plus faibles capacités d’inhibition et de flexibilité cognitive qu’un groupe témoin. Toutefois, seules les capacités de flexibilité cognitive permettent de prédire significativement le taux de réussite thérapeutique associé à une TCC pour les tics chroniques. / Tics are involuntary motor movements or vocalizations which are sudden, rapid, stereotyped, non-rhythmic and repetitive (Bloch & Leckman, 2009). According to the fifth edition of the Diagnostic and statistical manual of mental disorders (DSM-5), Tourette’s Disorder (TD) includes multiple motor tics and at least one vocal tic that can be observed multiple times every day for more than a year (APA, 2013). When at least one motor or vocal tic can be observed for at least a year, Chronic Tic Disorder (CTD) is diagnosed instead. Multiple studies show similarities between TD and CTD for comorbidities as well as associated neuropsychological and psychosocial variables (Spencer & al., 1995; Shapiro & Shapiro, 1982). Many authors suggest that CTD is actually a milder form of TD (Jedynak, 2004). The harmful effects of chronic tics on social, academic or professional life are extensively documented in the scientific literature (Cavanna, Servo, Monaco & Robertson, 2009; Robertson, 2006; Thibert, Day & Sandor, 1995). Cognitive-behavioral therapies (CBT) represent an alternative to medications whose side effects can sometimes be incapacitating. However, their success rate is highly variable, from 30% to 67% depending on the study (Verdellen, Van de Griendt, Hartmann & Murphy, 2011; Piacentini & al., 2010; O’Connor et al., 2015, 2008, 2005a, 2005b, 2001, 1997a, 1997b, 1997c). For this reason, many authors tried to predict the therapeutic success rate by using a series of neuropsychological factors in order to explain these variations. The general consensus is that the success rate of a CBT depends on executive functioning, notably on inhibition and cognitive flexibility. Participants in this study are adults aged 18 to 50 suffering from TD or CTD (n = 92) who are compared to participants without a diagnosed psychiatric or neurological disorder (n = 56). The data was collected at the Centre d’Étude sur les Troubles Obsessionnels-Compulsifs et les Tics (CÉTOCT) between 2003 and 2013. The objective of the first part of this study was to compare the inhibition and cognitive flexibility of a group of participants with chronic tics and a group of neurotypical participants (control group). On the other hand, the aim of the second component was to measure inhibition and cognitive flexibility in two subgroups of participants : a subgroup that strongly succeeded in Cognitive Behavioral Therapy (CBT) for chronic tics and another with weak success. The results showed that participants with chronic tics had significantly lower inhibition and cognitive flexibility than a control group. However, only cognitive flexibility can significantly predict the therapeutic success rate associated with CBT for chronic tics.

No description available.

Le syndrome de Gilles de la Tourette (SGT) est une condition neuropsychiatrique qui se caractérise par la présence de tics moteurs et vocaux. Au-delà des tics, le SGT s’accompagne souvent de troubles concomitants, tels que le trouble de déficit de l’attention avec ou sans hyperactivité et le trouble obsessionnel compulsif. Plusieurs études ont rapporté que les adultes atteints du SGT sont plus susceptibles de souffrir de dépression et de troubles anxieux comorbides que les personnes neurotypiques. Bien que les tics soient la caractéristique déterminante du SGT, les comorbidités engendrent de multiples conséquences psychologiques, sociales et comportementales, en plus d’avoir un impact considérable sur la qualité de vie des personnes qui en souffre. Jusqu'à présent, les études neuropsychologiques auprès de cette population ont révélé des résultats parfois conflictuels quant à leurs performances cognitives, notamment au niveau de l’inhibition, des processus moteurs et des capacités visuospatiales. Ces disparités peuvent être attribuées à divers facteurs, y compris la présence de comorbidités. L’objectif général de ce mémoire est d’apporter une meilleure compréhension du profil neuropsychologique des individus atteints du SGT, en tenant compte de la comorbidité anxiodépressive. Notre échantillon est composé de 128 participants divisés en trois groupes : un groupe SGT+ présentant une comorbidité anxieuse et/ou dépressive (n = 21), un groupe clinique SGT- sans comorbidité significative (n = 37) et un groupe contrôle neurotypique (n = 70). Ils ont été soumis à des mesures neuropsychologiques, dont le Stroop Color-Word Test (SCWT), le Purdue Pegboard Test (PPT) et la figure complexe de Rey-Osterrieth (ROCF). Concernant les capacités d’inhibition, aucune différence n'a été observée entre les groupes cliniques et les neurotypiques. Les patients SGT- et SGT+ ont tous deux montré une dextérité motrice supérieure. Toutefois, seuls les participants atteints de SGT+ ont présenté des déficits au niveau des fonctions visuoconstructives et de la mémoire non verbale. Les résultats suggèrent que les individus atteints du SGT avec une comorbidité anxiodépressive pourraient présenter des déficits supplémentaires dans certains domaines spécifiques. Néanmoins, des recherches supplémentaires axées sur ces conditions comorbides sont nécessaires pour tirer des conclusions robustes. / Tourette's syndrome (TS) is a neuropsychiatric condition characterized by the presence of motor and vocal tics. Beyond tics, TS is often accompanied by co-occurring disorders, such as attention deficit disorder with or without hyperactivity and obsessive-compulsive disorder. Several studies have reported that adults with TS are more likely to suffer from depression and comorbid anxiety disorders than neurotypical people. Although tics are the defining characteristic of TS, comorbidities have multiple psychological, social, and behavioural consequences, and they considerably impact the quality of life of those who suffer from them. So far, neuropsychological studies in this population have revealed sometimes conflicting results regarding their cognitive performance, particularly in inhibition, motor processes and visuospatial abilities. These disparities can be attributed to a variety of factors, including the presence of comorbidities. The general objective of this thesis is to provide a better understanding of the neuropsychological profile of individuals with TS, considering anxiodepressive comorbidity. Our sample consisted of 128 participants divided into three groups: a TS+ group with an anxiety and/or depressive comorbidity (n = 21), a clinical group TS- without significant comorbidity (n = 37) and a neurotypical control group (n = 70). They were subjected to neuropsychological measures, including the Stroop Color- Word Test (SCWT), the Purdue Pegboard Test (PPT), and the Rey-Osterrieth Complex Figure (ROCF). Regarding inhibition abilities, no differences were observed between clinical and neurotypical groups. Both TS- and TS+ patients showed superior motor dexterity. However, only participants with TS+ had deficits in visuoconstructive function and nonverbal memory. The results suggest that individuals with TS with an anxiodepressive comorbidity may have additional deficits in some specific areas. Nevertheless, further research focused on these comorbid conditions is needed to draw robust conclusions.