Susanne Steinlechner

Primary focal dystonia: evidence for distinct neuropsychiatric and personality profiles

Background: Primary focal dystonia (PFD) is characterised by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. In this study, prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of patients with PFD were evaluated. Methods: Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared with a population based sample (n = 3943) using a multiple regression approach. Furthermore, participants were evaluated for personality traits with the 5 Factor Personality Inventory. Results: Lifetime prevalence for any psychiatric or personality disorder was 70.9%. More specifically, axis I disorders occurred at a 4.5-fold increased chance. Highest odds ratios were found for social phobia (OR 21.6), agoraphobia (OR 16.7) and panic disorder (OR 11.5). Furthermore, an increased prevalence rate of 32.6% for anxious personality disorders comprising obsessive–compulsive (22.1%) and avoidant personality disorders (16.3%) were found. Except for social phobia, psychiatric disorders manifested prior to the occurrence of dystonia symptoms. In the self-rating of personality traits, PFD patients demonstrated pronounced agreeableness, conscientiousness and reduced openness. Conclusions: Patients with PFD show distinct neuropsychiatric and personality profiles of the anxiety spectrum. PFD should therefore be viewed as a neuropsychiatric disorder rather than a pure movement disorder.

Co-occurrence of affective and schizophrenia spectrum disorders with PINK1 mutations

Objective: To investigate a possible association of mutations in the PTEN-induced putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with monogenic parkinsonism. Method: 20 members of a family (4 homozygous, 11 heterozygous and 5 non-mutation carriers) were investigated for the presence of psychiatric disorders using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); information on three additional heterozygous mutation carriers was obtained according to the family history research diagnostic criteria. Results: We found predominantly affective and schizophrenia spectrum disorders in 11 (61%) of the 18 mutation carriers and in 1 (20%) of the 5 mutation-negative cases. Conclusions: First, affective and psychotic symptoms may be part of the phenotypic spectrum or even the sole manifestation of PINK1 mutations. Second, patients with familial movement disorders associated with psychiatric conditions may serve as a valuable study population to explore (genetic) causes of neuropsychiatric disease.

Limbic and Frontal Cortical Degeneration Is Associated with Psychiatric Symptoms in PINK1 Mutation Carriers

BACKGROUND Mutations in the PINK1 gene can cause Parkinsons disease and are frequently associated with psychiatric symptoms that might even precede motor signs. METHODS To determine whether specific gray matter degeneration of limbic and frontal structures might be liable to different psychiatric symptoms in PINK1 mutation carriers, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 14 PINK1 mutation carriers from a large German family and 14 age- and gender-matched healthy control subjects. RESULTS Psychiatric diagnoses in PINK1 mutation carriers comprised major depression without psychotic symptoms and schizophrenia-spectrum, panic, adjustment, and obsessive-compulsive personality disorders. As hypothesized, the categorical comparison between all PINK1 mutation carriers and control subjects demonstrated atrophy of limbic structures, especially the hippocampus and parahippocampus. More specifically, multiple regression analysis considering all psychiatric subscores simultaneously displayed different frontal (prefrontal, dorsolateral, and premotor cortex) and limbic (parahippocampus and cingulate) degeneration patterns. The duration of the psychiatric disease was also correlated with the extent of limbic and frontal gray matter volume decrease. CONCLUSIONS Our results support the hypothesis that limbic and frontal gray matter alterations could explain various psychiatric symptoms observed in PINK1 mutation carriers. Factors determining individual susceptibility to degeneration of certain brain areas remain to be elucidated in future studies.

Altered Velocity Processing in Schizophrenia during Pursuit Eye Tracking

Smooth pursuit eye movements (SPEM) are needed to keep the retinal image of slowly moving objects within the fovea. Depending on the task, about 50%–80% of patients with schizophrenia have difficulties in maintaining SPEM. We designed a study that comprised different target velocities as well as testing for internal (extraretinal) guidance of SPEM in the absence of a visual target. We applied event-related fMRI by presenting four velocities (5, 10, 15, 20°/s) both with and without intervals of target blanking. 17 patients and 16 healthy participants were included. Eye movements were registered during scanning sessions. Statistical analysis included mixed ANOVAs and regression analyses of the target velocity on the Blood Oxygen Level Dependency (BOLD) signal. The main effect group and the interaction of velocity×group revealed reduced activation in V5 and putamen but increased activation of cerebellar regions in patients. Regression analysis showed that activation in supplementary eye field, putamen, and cerebellum was not correlated to target velocity in patients in contrast to controls. Furthermore, activation in V5 and in intraparietal sulcus (putative LIP) bilaterally was less strongly correlated to target velocity in patients than controls. Altered correlation of target velocity and neural activation in the cortical network supporting SPEM (V5, SEF, LIP, putamen) implies impaired transformation of the visual motion signal into an adequate motor command in patients. Cerebellar regions seem to be involved in compensatory mechanisms although cerebellar activity in patients was not related to target velocity.

Personality profiles are different in musician's dystonia and other isolated focal dystonias

Psychological abnormalities have been reported in patients with musicians dystonia. To further differentiate these abnormalities, we evaluated personality traits in musicians dystonia and compared them to those in other isolated focal dystonias. Therefore patients with musicians dystonia (n = 101) and other isolated focal dystonias (n = 85) underwent the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). Women with musicians dystonia had higher NEO-FFI neuroticism scores, and men significantly higher openness scores compared to women and men with other isolated focal dystonias, respectively. There were negative correlations in men with musicians dystonia between duration of dystonia and the NEO-FFI openness and extraversion scores and between age and extraversion scores. Women with other isolated focal dystonias showed correlations between age and agreeableness and conscientiousness scores. Patients with musicians dystonia are characterized by a specific personality profile with increased neuroticism and openness compared to other isolated focal dystonias. Whether this profile can be traced back to specific underlying disease mechanisms should be further investigated.