Temporomandibular Disorders and Headache in Adolescents

13-16-vuotiaiden purentaelimistön toimintahäiriöt ja päänsärky Tutkimuksen tarkoituksena oli selvittää purentaelimistön toimintahäiriöihin (TMD) liittyvien oireiden ja kliinisten löydösten esiintyvyyttä ja muutosta kolmen vuoden seurannan aikana päänsärystä kärsivillä nuorilla ja heidän verrokeillaan, TMD-löydösten yhteyttä eri tyyppisiin päänsärkyihin ja päänsärkyyn liittyviin tekijöihin, TMD-löydöksiä ennustavia tekijöitä sekä perhetaustan osuutta TMD-löydösten esiintyvyyteen. Tutkimus perustui kahteen laajaan koululaismateriaaliin Turun seudulla. Ensimmäinen 13-vuotiaiden nuorten ryhmä (n = 311) osallistui myös 16-vuotiaana seuranta-tutkimukseen. Toisen 13-vuotiaiden nuorten ryhmän (n = 154) äidit (n = 154) osallistuivat myös tutkimukseen, jossa selvitettiin tapaus-verrokkiasetelmassa TMD-löydösten ja päänsärkyjen esiintyvyyttä kahdessa sukupolvessa. Nuoret jaettiin päänsärkyryhmiin ja terveisiin kontrolleihin IHS (1988) päänsärky-kriteerien mukaisesti kyselykaavakkeen ja lääkärin suorittaman haastattelun ja kliinisen tutkimuksen antamien tietojen perusteella. Lääkäri määritteli äitien päänsärkydiagnoosin kyselykaavakkeen tietojen perusteella. Kaikki nuoret ja heidän äitinsä haastateltiin ja heille tehtiin kliininen purentafysiologinen tutkimus sokkoutetusti. Tutkimuksen tulokset osoittivat, että tytöillä esiintyi TMD-löydöksiä selvästi enemmän kuin pojilla sekä ennen puberteettia että sen jälkeen. Tutkimuksessa havaittiin selkeä yhteys TMD-löydösten ja molempien päänsärkytyyppien, migreenin ja episodisen tensiotyyppisen päänsäryn, välillä. Kolmen vuoden seurannan aikana TMD-löydöksissä havaittiin runsasta muutosta ja iän myötä vähenemistä, mutta TMD-oireiden kohdalla ei vastaavaa muutosta todettu. TMD-löydösten ja niska-hartiaseudun lihaskipujen välillä havaittiin yhteys 13-vuotiailla nuorilla. Mikään päänsärkyyn liittyvistä tekijöistä 13-vuotiailla ei osoittautunut ennustavaksi taustatekijäksi myöhemmille TMD-löydöksille. TMD-löydösten suhteen ei todettu perheyhteyttä. Päänsäryistä kärsivillä nuorilla on enemmän myös muita kiputiloja, kuten purentaelimistön toimintahäiriöitä ja niska-hartiaseudun kipuja, kuin heidän terveillä verrokeillaan. 1316 vuoden iässä nämä löydökset ovat valtaosaltaan lieviä ja vaihtelevia.

Subtypes of adolescents with substance use disorders and psychiatric comorbidity using cluster and discriminant analysis of MMPI-A profiles

The main aim of this study was to replicate and extend previous results on subtypes of adolescents with substance use disorders (SUD), according to their Minnesota Multiphasic Personality Inventory for adolescents (MMPI-A) profiles. Sixty patients with SUD and psychiatric comorbidity (41.7% male, mean age = 15.9 years old) completed the MMPI-A, the Teen Addiction Severity Index (T-ASI), the Child Behaviour Checklist (CBCL), and were interviewed in order to determine DSMIV diagnoses and level of substance use. Mean MMPI-A personality profile showed moderate peaks in Psychopathic Deviate, Depression and Hysteria scales. Hierarchical cluster analysis revealed four profiles (acting-out, 35% of the sample; disorganized-conflictive, 15%; normative-impulsive, 15%; and deceptive-concealed, 35%). External correlates were found between cluster 1, CBCL externalizing symptoms at a clinical level and conduct disorders, and between cluster 2 and mixed CBCL internalized/externalized symptoms at a clinical level. Discriminant analysis showed that Depression, Psychopathic Deviate and Psychasthenia MMPI-A scales correctly classified 90% of the patients into the clusters obtained.

New genes for focal epilepsies with speech and language disorders.

The last 2 years have seen exciting advances in the genetics of Landau-Kleffner syndrome and related disorders, encompassed within the epilepsy-aphasia spectrum (EAS). The striking finding of mutations in the N-methyl-D-aspartate (NMDA) receptor subunit gene GRIN2A as the first monogenic cause in up to 20 % of patients with EAS suggests that excitatory glutamate receptors play a key role in these disorders. Patients with GRIN2A mutations have a recognizable speech and language phenotype that may assist with diagnosis. Other molecules involved in RNA binding and cell adhesion have been implicated in EAS; copy number variations are also found. The emerging picture highlights the overlap between the genetic determinants of EAS with speech and language disorders, intellectual disability, autism spectrum disorders and more complex developmental phenotypes.

Apple biological and physiological disorders in the orchard and in postharvest according to production system

The study aimed to evaluate the incidence of biological and physiological disorders in the field and postharvested apples cvs. Gala, Fuji and Catarina grown in four production systems: conventional, organic transition, integrated and organic. Apples were evaluated for damages related to biological and physiological disorders in the orchard and after harvest. The greatest damages were attributed to pests, especially Anastrepha fraterculus in the organic system and Grapholita molesta in the organic transition. Apples produced in organic orchards had higher damage levels caused by postharvest physiological disorders than those grown in other production systems. For apples becoming from organic orchards most of the damage was due to lenticels breakdown and degeneration ('Gala'), and bitter pit ('Fuji' and 'Catarina'). The incidence of postharvest rot was not influenced by apple production system.

Review of quantitative phase-digital holographic microscopy: promising novel imaging technique to resolve neuronal network activity and identify cellular biomarkers of psychiatric disorders.

Quantitative phase microscopy (QPM) has recently emerged as a new powerful quantitative imaging technique well suited to noninvasively explore a transparent specimen with a nanometric axial sensitivity. In this review, we expose the recent developments of quantitative phase-digital holographic microscopy (QP-DHM). Quantitative phase-digital holographic microscopy (QP-DHM) represents an important and efficient quantitative phase method to explore cell structure and dynamics. In a second part, the most relevant QPM applications in the field of cell biology are summarized. A particular emphasis is placed on the original biological information, which can be derived from the quantitative phase signal. In a third part, recent applications obtained, with QP-DHM in the field of cellular neuroscience, namely the possibility to optically resolve neuronal network activity and spine dynamics, are presented. Furthermore, potential applications of QPM related to psychiatry through the identification of new and original cell biomarkers that, when combined with a range of other biomarkers, could significantly contribute to the determination of high risk developmental trajectories for psychiatric disorders, are discussed.

EAACI IG Biologicals task force paper on the use of biologic agents in allergic disorders.

Biologic agents (also termed biologicals or biologics) are therapeutics that are synthesized by living organisms and directed against a specific determinant, for example, a cytokine or receptor. In inflammatory and autoimmune diseases, biologicals have revolutionized the treatment of several immune-mediated disorders. Biologicals have also been tested in allergic disorders. These include agents targeting IgE; T helper 2 (Th2)-type and Th2-promoting cytokines, including interleukin-4 (IL-4), IL-5, IL-9, IL-13, IL-31, and thymic stromal lymphopoietin (TSLP); pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17A, IL-17F, IL-23, and tumor necrosis factor (TNF); chemokine receptor CCR4; and lymphocyte surface and adhesion molecules, including CD2, CD11a, CD20, CD25, CD52, and OX40 ligand. In this task force paper of the Interest Group on Biologicals of the European Academy of Allergy and Clinical Immunology, we review biologicals that are currently available or tested for the use in various allergic and urticarial pathologies, by providing an overview on their state of development, area of use, adverse events, and future research directions.

Mood disorders in eating disorder patients: Prevalence and chronology of ONSET.

OBJECTIVES: In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control group matched for age and gender. METHOD: The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. RESULTS: Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. LIMITATIONS: Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. CONCLUSION: Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders.

Childhood adversities as specific contributors to the co-occurrence of posttraumatic stress and alcohol use disorders.

There is much evidence that alcohol use disorders (AUD) often co-occur with posttraumatic stress disorders (PTSD), and that the comorbid condition is associated with a more severe clinical profile than that of PTSD without AUD. However, little is known about the role of childhood adversities as specific risk factors for the development of AUD in individuals presenting with PTSD. The aim of the study was to explore whether specific stressors from the spectrum of trauma and childhood adversities contribute to the development of AUD among subjects with PTSD. From a large community sample, of N=140 individuals with PTSD, N=24 (17.14%) received an additional diagnosis of AUD with an onset after the onset of PTSD. Those with comorbid PTSD/AUD and those with PTSD only were compared regarding type and features of their trauma, childhood adversities and psychiatric comorbidity. Compared to PTSD alone, PTSD/AUD was associated with higher levels of stress in terms of childhood adversities; in particular, sexual abuse below the age of 16, but also with having been brought up in a foster home. PTSD/AUD was also associated with an earlier age of adverse events. Treatment of AUD should include standardized assessments of trauma, especially of trauma experienced during childhood.

Posttraumatic stress avoidance symptoms as mediators in the development of alcohol use disorders after exposure to childhood sexual abuse in a Swiss community sample.

This study examined the role of posttraumatic stress disorder (PTSD) symptoms of re-experience, avoidance, and hyperarousal in the relationship between different types of trauma and alcohol use disorders (AUD). We used data from 731 trauma-exposed individuals who participated in the first wave of the PsyCoLaus-study. Trauma characteristics were assessed relatively to the occurrence of lifetime PTSD symptoms and AUD. The results suggest that lifetime and childhood sexual abuse as well as overall childhood trauma were directly linked to AUD and PTSD symptoms, in particular to avoidance symptoms. From single symptom clusters PTSD avoidance was found to specifically mediate the trauma-AUD pathway. Both childhood and sexual trauma strongly contribute to the comorbidity of PTSD and AUD and avoidance-type symptoms appear to play a central role in maintaining this association. Hence, the alleviation of avoidance symptoms might be an important target for therapeutic intervention among victims of sexual abuse before specific addiction treatment is initiated.

Psychotherapy for Personality Disorders in a Natural Setting: A Pilot Study over Two Years of Treatment.

Long-term assessment of the effects of psychotherapy for personality disorders (PDs) in a natural environment is an important task. Such research contributes to enlarge the practice-based evidence, embedded in broad collaborations between clinicians and researchers in psychotherapy for PDs. The present pilot study used rigorous assessment procedures and incorporated feedback loops of outcome information to the therapists in demonstrating the effects of psychotherapy for PD in a natural setting. The number of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for any PD was the primary outcome (along with psychological distress, depression, impulsiveness, and quality of life as secondary measures), assessed at intake, 6, 12, 18, and 24 months of psychotherapy for N = 13 patients with PD. Data were analyzed using hierarchical linear modeling. Results demonstrated a large pre-post effect (d = 2.22) for the observer-rated measure (primary outcome), and small to medium effects for the secondary outcomes; these results were corroborated by a steady decrease of symptoms over all five time points, which was significant for several outcomes. These results add a piece to the literature by demonstrating the effects of long-term psychotherapy for PDs in increasingly diverse contexts and suggest that practice-oriented research can be carried out in a collaborative and systematic manner.

Discrepancies between clinical needs and helpseeking behaviors in co-occurring posttraumatic stress and alcohol use disorders.

OBJECTIVE: The aim of the study was to compare subjects dually diagnosed with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) to those with only one or none of these conditions regarding helpseeking needs and behaviors. METHOD: Data from a large community sample (N=3694) were used to assess the associations among lifetime PTSD and AUD, other psychiatric disorders, clinical characteristics and lifetime helpseeking behaviors derived from a semi-structured interview. RESULTS: Comorbid individuals had more severe clinical profiles and were more impaired than individuals with either PTSD or AUD alone or those with no/other psychiatric conditions. However, they did not differ in overall helpseeking behavior from any other group. Those with comorbid PTSD/AUD were even less likely than the other groups to seek help for depression and anxiety disorders through specific treatment facilities or the use of prescribed psychotropic drugs. CONCLUSIONS: Despite a greater need for treatment the comorbid group did not seek more help than the others. Their lower use of prescribed drugs supports the self-medication hypothesis, suggesting that those individuals relieve their symptoms through higher alcohol use instead. Our findings underline the need for health care facilities to encourage helpseeking behavior in the aftermath of stressful life events.

Clinically meaningful parameters of progression and long-term outcome of Parkinson disease: An international consensus statement.

Parkinson disease (PD) is associated with a clinical course of variable duration, severity, and a combination of motor and non-motor features. Recent PD research has focused primarily on etiology rather than clinical progression and long-term outcomes. For the PD patient, caregivers, and clinicians, information on expected clinical progression and long-term outcomes is of great importance. Today, it remains largely unknown what factors influence long-term clinical progression and outcomes in PD; recent data indicate that the factors that increase the risk to develop PD differ, at least partly, from those that accelerate clinical progression and lead to worse outcomes. Prospective studies will be required to identify factors that influence progression and outcome. We suggest that data for such studies is collected during routine office visits in order to guarantee high external validity of such research. We report here the results of a consensus meeting of international movement disorder experts from the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium, who convened to define which long-term outcomes are of interest to patients, caregivers and clinicians, and what is presently known about environmental or genetic factors influencing clinical progression or long-term outcomes in PD. We propose a panel of rating scales that collects a significant amount of phenotypic information, can be performed in the routine office visit and allows international standardization. Research into the progression and long-term outcomes of PD aims at providing individual prognostic information early, adapting treatment choices, and taking specific measures to provide care optimized to the individual patient's needs.

The 16p11.2 rearrangments genetic paradigms for obesity and neurodevelopmental disorders.

Recent discoveries of recurrent and reciprocal Copy Number Variants (CNVs) using genome- wide studies have led to a new understanding of the etiology of neuropsychiatric disorders. CNVs represent loss (deletion) or gain (duplication) of genomic material. This thesis work is focused on CNVs at the 16p11.2 BP4-BP5 locus, which are among the most frequent etiologies of neurodevelopmental disorders and have been associated with Autism Spectrum Disorders (ASD), schizophrenia, cognitive impairment, alterations of brain size as well as obesity and underweight. Because deletion and duplication of the 16p11.2 locus occur frequently and recurrently (with the same breakpoints), CNVs at this locus represent a powerful paradigm to understand how a genomic region may modulate cognitive and behavioral traits as well as the relationship and shared mechanisms between distinct psychiatric diagnoses such as ASD and schizophrenia. The present dissertation includes three studies: 1) The first project aims at identifying structural brain-imaging endophenotypes in 16p11.2 CNVs carriers at risk for ASD and schizophrenia. The results show that gene dosage at the 16p11.2 locus modulates global brain volumes and neural circuitry, including the reward system, language and social cognition circuits. 2) The second investigates the neuropsychological profile in 16p11.2 deletion and duplication carriers. While deletion carriers show specific deficits in language and inhibition, the profile of duplication carriers is devoid of specific weaknesses and presents enhanced performance in a verbal memory task. 3) The third study on food-related behaviors in 16p11.2 deletion and duplication carriers shows that alterations of the reponse to satiety are present in CNV carriers before the onset of obesity, pointing toward a potential mechanism driving the Body Mass Index increase in deletion carriers. Dysfunctions in the reward system and dopaminergic circuitries could represent a common mechanism playing a role in the phenotype and could be investigated in future studies. Our data strongly suggest that complex cognitive traits correlate to gene dosage in humans. Larger studies including expression data would allow elucidating the contribution of specific genes to these different gene dosage effects. In conclusion, a systematic and careful investigation of cognitive, behavioral and intermediate phenotypes using a gene dosage paradigm has allowed us to advance our understanding of the 16p11.2 BP4-BP5 locus and its effects on neurodevelopment. -- La récente découverte de variations du nombre de copies (CNVs pour 'copy number variants') dans le génome humain a amélioré nos connaissances sur l'étiologie des troubles neuropsychiatriques. Un CNV représente une perte (délétion) ou un gain (duplication) de matériel génétique sur un segment chromosomique. Ce travail de thèse est focalisé sur les CNVs réciproques (délétion et duplication) dans la région 16p11.2 BP4-BP5. Ces CNVs sont une cause fréquente de troubles neurodéveloppementaux et ont été associés à des phénotypes « en miroir » tels que obésité/sous-poids ou macro/microcéphalie mais aussi aux troubles du spectre autistique (TSA), à la schizophrénie et au retard de développement/déficience intellectuelle. La fréquence et la récurrence de la délétion et de la duplication aux mêmes points de cassure font de ces CNVs un paradigme unique pour étudier la relation entre dosage génique et les traits cognitifs et comportementaux, ainsi que les mécanismes partagés par des troubles psychiatriques apparemment distincts tels que les TSA et la schizophrénie. Ce travail de thèse comporte trois études distinctes : 1) l'étude en neuroimagerie structurelle identifie les endophénotypes chez les porteurs de la délétion ou de la duplication. Les résultats montrent une influence du dosage génique sur le volume cérébral total et certaines structures dans les systèmes de récompense, du langage et de la cognition sociale. 2) L'étude des profils neuropsychologiques chez les porteurs de la délétion ou de la duplication montre que la délétion est associée à des troubles spécifiques du langage et de l'inhibition alors que les porteurs de la duplication ne montrent pas de faiblesse spécifique mais des performances mnésiques verbales supérieures à leur niveau cognitif global. 3) L'étude sur les comportements alimentaires met en évidence une altération de la réponse à la satiété qui est présente avant l'apparition de l'obésité. Un dysfonctionnement dans le système de récompense et les circuits dopaminergiques pourrait représenter un mécanisme commun aux différents phénotypes observés chez ces individus porteurs de CNVs au locus 16p11.2. En conclusion, l'utilisation du dosage génique comme outil d'investigation des phénotypes cliniques et endophénotypes nous a permis de mieux comprendre le rôle de la région 16p11.2 BP4-BP5 dans le neurodéveloppement.

The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders.

BACKGROUND: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. METHODS: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. RESULTS: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LIMITATIONS: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. CONCLUSIONS: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD.