Tackle your Tics, a brief intensive group-based exposure treatment for young people with tics: results of a randomised controlled trial.

Tics can have a serious impact on the quality of life of children and their families. Behavioural therapy is an evidence-based first line treatment for tic disorders. This randomised controlled trial studied the efficacy of a brief, condensed group-based programme for children with tics (Dutch Trial Registry NL8052, 27 September 2019). Tackle your Tics is a four-day group treatment, including exposure and response prevention and supporting components, delivered by therapists and 'experts by experience'. We collected outcome measures at baseline (T1), directly post-treatment (T2), and at three- and 6-months follow-up (T3, T4) including tic severity (primary outcome measure), tic-related impairment, quality of life, tic-related cognitions, emotional/behavioural functioning, family functioning, treatment satisfaction and adherence. Outcomes directly post-treatment improved in both the treatment group (n = 52) and waiting list (n = 54), but showed no statistically significant differences between the conditions (differential change over time T1-T2) on tic severity (Yale Global Tic Severity Scale), quality of life (Gilles de la Tourette Syndrome Quality of Life Scale), tic-related cognitions and family functioning. At longer term (T3), again no between-group difference was found on tic severity, but tic-related impairment, quality of life and emotional/behavioural functioning significantly improved in the treatment group compared to the waiting list. Mean treatment satisfaction scores were favourable for both children and parents. Directly posttreatment, Tackle your Tics showed no superior effect compared to waiting list. However, on longer term this brief four-day group treatment was effective in improving tic-related impairment, quality of life and emotional/behavioural functioning.

Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.

RATIONALE: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. OBJECTIVES: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. METHODS: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS-) were measured. RESULTS: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. CONCLUSIONS: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies.

[Visual hallucinations, misidentification and reduplication of time: a sense of distorted reality due to a cerebral metastasis]. / Visuele hallucinaties, misidentificaties en tijdsreduplicatie: verstoorde realiteitsbeleving door hersenmetastase.

We describe a 66-year-old female patient with no prior psychiatric history who presented with an unusual psychotic state, largely in accordance with Fregoli syndrome (misidentification of people). Further, the patient suffered from reduplication of time, scenic hallucinations and psychotic perceptions. Symptoms were the result of a brain metastasis originating from a lung carcinoma. We describe the performed (additional) diagnostics and discuss how to differentiate between organic and functional psychosis, as well as the given psychiatric treatment. Finally, potential pathophysiological explanations are discussed that might explain the (reduction of) symptoms in the patient.

[Routine outcome monitoring in anxiety disorders: diagnosis-specific versus generic assessment instruments]. / Routine outcome monitoring bij de behandeling van angststoornissen: diagnosespecifieke versus generieke meetinstrumenten.

BACKGROUND: Mental health institutions increasingly utilise routine outcome monitoring (rom) in order to assess treatment effectiveness. It remains unclear which instruments are more sensitive to change with regard to rom in patients with an anxiety disorder: diagnosis-specific or generic instruments.
AIM: To compare the sensitivity of diagnosis-specific versus generic rom-instruments in patients with an anxiety disorder.
METHOD: 160 adults with an anxiety disorder received cognitive behavioural therapy at the Altrecht Academic Anxiety Centre. Approximately half of the population also received medication. Patients completed an assessment both before and after treatment. This consisted of two generic instruments (Outcome Questionnaire (oq-45) and Brief Symptom Inventory (bsi)) and two diagnosis-specific instruments, determined by the main diagnosis.
RESULTS: The differences between pre- and post-treatment assessments were generally larger for the generic bsi and diagnosis-specific instruments than for the generic oq-45.
CONCLUSION: When assessed after cognitive behavioural therapy, the (generic) bsi and diagnosis-specific instruments indicated larger progress than the oq-45. The bsi might be a relatively diagnosis-specific measure for anxiety disorders. when selecting an instrument for assessment, both the intended goal of treatment (symptom reduction or improvement in quality of life) and other reasons for assessment should be taken into consideration. The bsi or diagnosis-specific instruments are preferred if the goal is to assess the change in specific anxiety symptoms.

Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

BACKGROUND: The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families. METHOD: OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed. RESULTS: EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders). CONCLUSIONS: Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

Heritability of tic disorders: a twin-family study.

BACKGROUND: Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. METHOD: In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. RESULTS: Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. CONCLUSIONS: Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

Functional jerks, tics, and paroxysmal movement disorders.

Functional jerks are among the most common functional movement disorders. The diagnosis of functional jerks is mainly based on neurologic examination revealing specific positive clinical signs. Differentiation from other jerky movements, such as tics, organic myoclonus, and primary paroxysmal dyskinesias, can be difficult. In support of a functional jerk are: acute onset in adulthood, precipitation by a physical event, variable, complex, and inconsistent phenomenology, suggestibility, distractibility, entrainment and a Bereitschaftspotential preceding the movement. Although functional jerks and tics share many similarities, characteristics differentiating tics from functional jerks are: urge preceding the tic, childhood onset, rostrocaudal development of the symptoms, a positive family history of tics, attention-deficit hyperactivity disorder or obsessive-compulsive symptoms, and response to dopamine antagonist medication. To differentiate functional jerks from organic myoclonus, localization of the movements can give direction. Further features in support of organic myoclonus include: insidious onset, simple and consistent phenomenology, and response to benzodiazepines or antiepileptic medication. Primary paroxysmal dyskinesias and functional jerks share a paroxysmal nature. Leading in the differentiation between the two are: a positive family history, in combination with video recordings revealing a consistent symptom pattern in primary paroxysmal dyskinesias. In this chapter functional jerks and their differential diagnoses will be discussed in terms of epidemiology, symptom characteristics, disease course, psychopathology, and supportive neurophysiologic tests.

Self-esteem treatment in anxiety: A randomized controlled crossover trial of Eye Movement Desensitization and Reprocessing (EMDR) versus Competitive Memory Training (COMET) in patients with anxiety disorders.

BACKGROUND AND PURPOSE: Little is known about treating low self-esteem in anxiety disorders. This study evaluated two treatments targeting different mechanisms: (1) Eye Movement Desensitization and Reprocessing (EMDR), which aims to desensitize negative memory representations that are proposed to maintain low self-esteem; and (2) Competitive Memory Training (COMET), which aims to activate positive representations for enhancing self-esteem. METHODS: A Randomized Controlled Trial (RCT) was used with a crossover design. Group 1 received six sessions EMDR first and then six sessions COMET; group 2 vice versa. Assessments were made at baseline (T0), end of first treatment (T1), and end of second treatment (T2). Main outcome was self-esteem. We included 47 patients and performed Linear Mixed Models. RESULTS: COMET showed more improvements in self-esteem than EMDR: effect-sizes 1.25 versus 0.46 post-treatment. Unexpectedly, when EMDR was given first, subsequent effects of COMET were significantly reduced in comparison to COMET as the first intervention. For EMDR, sequence made no difference. Reductions in anxiety and depression were mediated by better self-esteem. CONCLUSIONS: COMET was associated with significantly greater improvements in self-esteem than EMDR in patients with anxiety disorders. EMDR treatment reduced the effectiveness of subsequent COMET. Improved self-esteem mediated reductions in anxiety and depression symptoms.

Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs.

Variation in obsessive-compulsive symptoms (OCS) has a heritable basis, with genetic association studies starting to yield the first suggestive findings. We contribute to insights into the genetic basis of OCS by performing an extensive series of genetic analyses in a homogeneous, population-based sample from the Netherlands. First, phenotypic and genetic longitudinal correlations over a 6-year period were estimated by modeling OCS data from twins and siblings. Second, polygenic risk scores (PRS) for 6931 subjects with genotype and OCS data were calculated based on meta-analysis results from IOCDF-GC, to investigate their predictive value. Third, the contribution of measured single nucleotide polymorphisms (SNPs) to the heritability was estimated using random-effects modeling. Last, we performed an exploratory genome-wide association study (GWAS) of OCS, testing for SNP- and for gene-based associations. Stability in OCS (test-retest correlation 0.63) was mainly explained by genetic stability. The PRS based on clinical samples predicted OCS in our population-based twin-family sample. SNP-based heritability was estimated at 14%. GWAS revealed one SNP (rs8100480), located within the MEF2BNB gene, associated with OCS (P=2.56 × 10(-8)). Additional gene-based testing resulted in four significantly associated genes, which are located in the same chromosomal region on chromosome 19p13.11: MEF2BNB, RFXANK, MEF2BNB-MEF2B and MEF2B. Thus, common genetic variants explained a significant proportion of OCS trait variation. Genes significantly associated with OCS are expressed in the brain and involved in development and control of immune system functions (RFXANK) and regulation of gene expression of muscle-specific genes (MEF2BNB). MEF2BNB also showed a suggestive association with OCD in an independent case-control study, suggesting a role for this gene in the development of OCS.

Partitioning the etiology of hoarding and obsessive-compulsive symptoms.

BACKGROUND: Until recently, hoarding was considered an obsessive-compulsive symptom (OCS). However, current evidence suggests that these two phenotypes may be clinically, and perhaps etiologically, distinct. Both hoarding and OCS have a genetic etiology, but the degree of unique and shared genetic contributions to these phenotypes has not been well studied. METHOD: Prevalence rates were assessed for hoarding and OCS in a sample of adult twin pairs (n = 7906 twins) and their family members from The Netherlands Twin Register (total sample = 15,914). Using Mplus, genetic analyses using liability threshold models were conducted for both phenotypes, for their co-morbidity, and for specific hoarding symptoms (cluttering, discarding and acquiring). RESULTS: Of the total sample, 6.7% met criteria for clinically significant hoarding; endorsement of all three hoarding symptoms was > or = 79%. Men had slightly higher rates than women. Also, 5.7% met criteria for clinically significant OCS; rates were similar in males and females. Genetic factors accounted for 36% of the variance for hoarding and 40% of the variance for OCS. The genetic correlation between hoarding and OCS was 0.10. There was no evidence of sex-specific genetic contributions for hoarding or OCS. There was evidence for a genetic contribution to all hoarding symptom subtypes. Only cluttering showed evidence of a contribution from the shared environment. CONCLUSIONS: OCS and hoarding are common in this population-based sample, have prevalence rates similar to those previously reported, and show significant heritability. Genetic factors contributed to the co-morbidity of both traits, although the genetic correlation between them was low.

Genome-wide association study of Tourette's syndrome.

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.

[The characterisation of anxiety disorders: staging and profiling based on common sense]. / De karakterisering van angststoornissen: stageren en profileren met gezond verstand.

BACKGROUND: Clinicians need to be well informed about staging and profiling so that they can divide patients with anxiety disorders into groups according to the phase and severity of their illness. The group to which the patient is assigned determines the types of treatment he or she receives. AIM: To investigate ways in which clinicians can be helped to apply staging and profiling procedures to patients with anxiety disorders. METHOD: We searched the literature for articles about the staging and profiling of anxiety disorders. RESULTS: There seems to be practically no literature relating to the staging and profiling of anxiety disorders. However, in daily practice clinicians do attempt to classify their patients and use forms of staging when deciding on special types of treatment for their patients and when assessing the length of treatment required. The revised Dutch guidelines on anxiety disorders include a generalised form of staging, called 'stepped care’. These revisions have been made on the basis of consensus decisions reached by the guideline committee. CONCLUSION: The revised guidelines on anxiety disorders assist clinicians with the application of staging in their daily practice. However, because of the lack of scientific data, our article closes with the presentation of a research agenda.

[Obsessive compulsive disorder with tics: a new subtype?]. / Obsessieve-compulsieve stoornis met tics: een nieuw subtype?

BACKGROUND: Obsessive compulsive disorder (OCD) is a heterogeneous disorder. With the help of phenomenological research, attempts are being made to create more homogeneous subtypes. AIM: To search the literature in order to compare the symptoms of OCD patients with tics and without tics, and thereby determine whether OCD with tics can be distinguished clinically from OCD without tics. METHOD: Search terms were used in conjunction with PubMed and Psychinfo in order to locate studies in which OCD patients without tics were compared with OCD patients with tics. RESULTS: In the 26 studies found in our search 872 OCD patients out of a total of 2801 OCD patients (i.e. 31%) had a comorbid tic disorder. OCD patients with tics displayed similarities and differences at symptom level. OCD patients with tics were associated with male gender and early age of onset. Tic-like symptoms such as touching, twitching, repeating, symmetry behavior and rubbing were seen more frequently in OCD patients with tics. OCD patients without tics more often displayed contamination obsessions and engaged in compulsive washing. On the other hand, the obsessions of patients with tics and without tics were very similar. The goal-directedness of compulsions differed between OCD patients with tics and those without tics. By analogy with 'the premonitory urges' that often precede tics, OCD patients with tics more often reported 'just-right' perceptions prior to their compulsions. OCD patients without tics more often reported anxiety prior to their compulsions. Compulsions seemed to be aimed at reducing tension and feelings of anxiety. CONCLUSION: On the basis of the clinical symptoms OCD with tics does seem to be a subtype of OCD. However further research is needed into the aetiology, effective treatment and the course of the disorder before OCD with tics can be accepted conclusively as a subtype of OCD.

Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis.

BACKGROUND: Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). METHOD: The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. RESULTS: Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. CONCLUSIONS: Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

[Obsessive-compulsive disorder]. / Obsessieve-compulsieve stoornis.

Obsessive-compulsive disorder is a complex psychiatric disorder characterised by obsessions and/or compulsions. Obsessive-compulsive disorder has a relatively high prevalence and is a highly disabling disease. The disorder is associated with shame, which causes long delays in accessing treatment. Obsessive-compulsive disorder is caused by a complex interplay between genetic and environmental factors. Effective treatments exist in the form of either pharmacotherapy--clomipramine or selective serotonin reuptake inhibitors--or cognitive behaviour therapy.

[Antipsychotics in the treatment of Tourette disorder: a review]. / Antipsychotica in de behandeling van het syndroom van Gilles de la Tourette: een literatuuroverzicht.

BACKGROUND: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder, characterised by the presence of multiple motor and vocal tics. Some GTS patients need pharmacological treatment. Patients who have a moderate to severe tic syndrome are usually treated with antipsychotics. AIM: To provide a literature review of the use of typical and atypical antipsychotics as well as dopamine agonists in patients with GTS. METHOD: Publications in the Medline database from 1970 onwards were used, as well as literature references from books and book chapters. The following search terms were used: 'treatment', 'psychopharmaca', 'psychopharmacological treatment', 'medication', 'antipsychotics', 'D2 antagonists', 'D2 agonists' and 'atypical antipsychotics'. results A few controlled short-term studies had been performed on haloperidol, pimozide, risperidone and pergolide. These agents all appeared to be effective in the short term, with risperidone showing fewest side-effects. CONCLUSION: Surprisingly few controlled studies have been performed on antipsychotics in GTS. Future studies should focus on what the second step should be in the case of treatment-resistant patients, on comparisons between drug therapy and behavioural therapy and on identifying predictors of drug response.

Marital resemblance for obsessive-compulsive, anxious and depressive symptoms in a population-based sample.

BACKGROUND: Resemblance between spouses can be due to phenotypic assortment, social homogamy and/or marital interaction. A significant degree of assortment can have consequences for the genetic architecture of a population. We examined the existence and cause(s) of assortment for obsessive-compulsive (OC), anxious and depressive symptoms in a population-based twin-family sample. METHOD: OC, anxious and depressive symptoms were measured in around 1400 twin-spouse pairs and >850 parent pairs. Correlations of twins and their spouse, twin and co-twin's spouse, spouses of both twins and parents of twins were obtained to consider phenotypic assortment versus social homogamy as possible causes of marital resemblance. The association of length of relationship with marital resemblance was also investigated. Finally, we examined whether within-trait or cross-trait processes play a primarily role in marital resemblance. RESULTS: Small but significant within-trait correlations of between 0.1 and 0.2 were seen for spouse similarity in OC, anxious and depressive symptoms. Cross-correlations were significant but lower. There was no correlation between length of relationship and marital resemblance. From the pattern of correlations for twin-spouse, co-twin-spouse and spouses of both twins, phenotypic assortment could not be distinguished from social homogamy. Both within- and cross-assortment processes play a role in marital resemblance. CONCLUSIONS: Small within- and across-trait correlations exist for OC, anxious and depressive symptoms. No evidence for marital interaction was found. Spouse correlations are small, which makes it difficult to distinguish between social homogamy and phenotypic assortment. It is unlikely that correlations of this size will have a large impact on genetic studies.

Life events, anxious depression and personality: a prospective and genetic study.

BACKGROUND: The association between life events and anxious depression might be due to causality or to gene-environment correlation. We examined unidirectional and reciprocal causality and a gene-environment correlation model, in which genes that influence the vulnerability for anxious depression also increase the risk of exposure to life events. The effect of genes that influence environmental exposure might be mediated through personality and we therefore also examined the association between life events and personality (neuroticism and extraversion). METHOD: Information on life events, anxious depression, neuroticism and extraversion was collected in 5782 monozygotic (MZ) and dizygotic (DZ) twins who participated in a longitudinal survey study of the Netherlands Twin Register. To examine causality, data were analysed longitudinally. To examine gene-environment correlation, the co-twin control method was used. RESULTS: Anxious depression and, to a lesser extent, neuroticism scores increased after exposure to life events. Anxious depression and neuroticism also predicted the experience of life events. Prospectively, extraversion was not associated with life events. Anxious depression, neuroticism and extraversion scores did not differ between the non-exposed subjects of MZ and DZ twin pairs and unrelated subjects discordant for life events. CONCLUSIONS: Our findings suggest that reciprocal causation explains the relationship between life events and anxious depression and between life events and neuroticism. Extraversion is not related to life events. No evidence was found for gene-environment correlation, i.e. the genes that influence anxious depression, neuroticism or extraversion do not overlap with the genes that increase the risk of exposure to life events.

Genetic and clinical analysis of a large Dutch Gilles de la Tourette family.

Gilles de la Tourette syndrome is a complex neuropsychiatric disorder, which becomes evident in childhood between the ages of 2 and 15 years. Tourette syndrome is defined by the occurrence of a large range and variable number of unwanted repetitive simple or complex motor and vocal tics that start in childhood and follow a waxing and waning course. A major gene for this syndrome has not yet been identified, probably owing to both genetic and phenotypic heterogeneity of this disease. This article describes the clinical evaluation of patients and family members in a large Dutch Gilles de la Tourette Syndrome pedigree and the decisions encountered with respect to phenotyping. The importance of an accurate definition of the Tourette phenotype is discussed, which is highly important for reliable genetic linkage and association studies. Subsequent linkage analysis resulted in three linkage peaks on different chromosomes 3q, 9q, and 13q. Multipoint analysis resulted in a single linkage peak with logarithm of odds score 2.55 with marker D3S1311 on chromosome 3q.