Kava and St. John's wort : current evidence for use in mood and anxiety disorders

Background: Mood and anxiety disorders pose significant health burdens on the community. Kava and St John’s wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively. Objectives: To conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in Major Depressive Disorder (MDD), Bipolar Disorder (BP), Seasonal Affective Disorder (SAD), Generalized Anxiety Disorder (GAD), Social Phobia (SP), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), and Post Traumatic Stress Disorder (PTSD). Methods: A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St John’s wort, Hypericum perforatum, hypericin and hyperforin. Additional search criteria for safety, pharmacodynamics , and pharmacokinetics was employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search. Results: Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD or SP. These disorders constitute potential applications that warrant exploration. Conclusions: Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.

The relationship of meta-worry and intolerance of uncertainty with pathological worry, anxiety, and depression

This study explored how meta-worry and intolerance of uncertainty relate to pathological worry, generalised anxiety, obsessive compulsive disorder, social phobia, and depression. University students (n = 253) completed a questionnaire battery. A series of regression analyses were conducted. The results indicated that meta-worry was associated with GAD, social phobia, obsessive compulsive, and depressive symptoms. Intolerance of uncertainty was related to GAD, social phobia, and obsessive compulsive symptoms, but not depressive symptoms. The importance of meta-worry and intolerance of uncertainty as predictors of pathological worry, GAD, social phobia, obsessive compulsive and depressive symptoms was also examined. Even though both factors significantly predicted the aforementioned symptoms, meta-worry emerged as a stronger predictor of GAD and obsessive compulsive symptoms than did intolerance of uncertainty. Intolerance of uncertainty, compared with meta-worry, appeared as a stronger predictor of social phobia symptoms. Findings emphasise the importance of addressing meta-worry and/or intolerance of uncertainty not only for the assessment and treatment of generalised anxiety disorder (GAD), but also obsessive compulsive disorder, social phobia, and depression.

Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults

The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain.To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6. ±. 2.2. years; range: 20-29. years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity.FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=. 0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

An imagery-based road map to tackle maladaptive motivation in clinical disorders

There is now a widespread recognition of the importance of mental imagery in a range of clinical disorders (1). This provides the potential for a transdiagnostic route to integrate some aspects of these disorders and their treatment within a common framework. This opinion piece argues that we need to understand why imagery is such a central and recurring feature, if we are to progress theories of the origin and maintenance of disorders. This will aid us in identifying therapeutic techniques that are not simply targeting imagery as a symptom, but as a manifestation of an underlying problem. As papers in this issue highlight, imagery is a central feature across many clinical disorders, but has been ascribed varying roles. For example, the involuntary occurrence of traumatic memories is a diagnostic criterion for PTSD (2), and it has been suggested that multisensory imagery of traumatic events normally serves a functional role in allowing the individual to reappraise the situation (3), but that this re-appraisal is disabled by extreme affective responses. In contrast to the disabling flashbacks associated with PTSD, depressed adults who experience suicidal ideation often report “flash forward” imagery related to suicidal acts (4), motivating them to self-harm. Socially anxious individuals who engage in visual imagery about giving a talk in public become more anxious and make more negative predictions about future performance than others who engage in more abstract, semantic processing of the past event (5). People with Obsessive Compulsive Disorder (OCD) frequently report imagery of past adverse events, and imagery seems to be associated with severity (6). The content of intrusive imagery has been related to psychotic symptoms (7), including visual images of the catastrophic fears associated with paranoia and persecution. Imagery has been argued (8) to play a role in the maintenance of psychosis through negative appraisals of imagined voices, misattribution of sensations to external sources, by the induction of negative mood states that trigger voices, and through maintenance of negative schemas. In addiction and substance dependence, Elaborated Intrusion (EI) Theory (9, 10) emphasizes the causal role that imagery plays in substance use, through its role in motivating an individual to pursue goals directed toward achieving the pleasurable outcomes associated with substance use...

How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment.

BACKGROUND: Most information about the lifetime prevalence of mental disorders comes from retrospective surveys, but how much these surveys have undercounted due to recall failure is unknown. We compared results from a prospective study with those from retrospective studies. METHOD: The representative 1972-1973 Dunedin New Zealand birth cohort (n=1037) was followed to age 32 years with 96% retention, and compared to the national New Zealand Mental Health Survey (NZMHS) and two US National Comorbidity Surveys (NCS and NCS-R). Measures were research diagnoses of anxiety, depression, alcohol dependence and cannabis dependence from ages 18 to 32 years. RESULTS: The prevalence of lifetime disorder to age 32 was approximately doubled in prospective as compared to retrospective data for all four disorder types. Moreover, across disorders, prospective measurement yielded a mean past-year-to-lifetime ratio of 38% whereas retrospective measurement yielded higher mean past-year-to-lifetime ratios of 57% (NZMHS, NCS-R) and 65% (NCS). CONCLUSIONS: Prospective longitudinal studies complement retrospective surveys by providing unique information about lifetime prevalence. The experience of at least one episode of DSM-defined disorder during a lifetime may be far more common in the population than previously thought. Research should ask what this means for etiological theory, construct validity of the DSM approach, public perception of stigma, estimates of the burden of disease and public health policy.

Serotonin synthesis, release and reuptake in terminals: a mathematical model.

BACKGROUND: Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. METHODS: We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. RESULTS: We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine. CONCLUSIONS: Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.

Habit reversal training as a treatment for refractory OCD - A case study

Nearly 4 million American men and women from all geographic, ethnic, or economic backgrounds are diagnosed with obsessive-compulsive disorder (OCD). While a combination of cognitive behaviour therapy (CBT) and psycho-pharmaca seems successful for 50% to 60% of patients, for intractable cases the typical recommendation is more medication or more CBT, however there is little evidence that the intensified treatment regimen is successful. In this paper, habit reversal training, including awareness training, competing/other response training, self-monitoring, social support, and generalisation, was implemented with a long-term treatment-refractory OCD patient. Treatment gains and long-term maintenance indicate the potential of habit reversal procedures with these patients.

Alternative Factor Models and Heritability of the Short Leyton Obsessional Inventory-Children's Version

An alternative models framework was used to test three confirmatory factor analytic models for the Short Leyton Obsessional Inventory-Children's Version (Short LOI-CV) in a general population sample of 517 young adolescent twins (11-16 years). A one-factor model as implicit in current classification systems of Obsessive-Compulsive Disorder (OCD), a two-factor obsessions and compulsions model, and a multidimensional model corresponding to the three proposed subscales of the Short LOI-CV (labelled Obsessions/Incompleteness, Numbers/Luck and Cleanliness) were considered. The three-factor model was the only model to provide an adequate explanation of the data. Twin analyses suggested significant quantitative sex differences in heritability for both the Obsessions/Incompleteness and Numbers/Luck dimensions with these being significantly heritable in males only (heritability of 60% and 65% respectively). The correlation between the additive genetic effects for these two dimensions in males was 0.95 suggesting they largely share the same genetic risk factors.

Shame, intimacy and self-definition: An assessment of the emotional foundation and intimate relationship consequences of an introjective personality orientation.

The current study sought to elaborate and test a theoretical proposition that introjective personality functioning, which has been implicated in various psychological difficulties (e.g., self-critical depression, obsessive-compulsive disorder), has an emotional foundation in the self-conscious emotion of shame and is supported by dissociation. Moreover, introjective functioning was predicted to be associated with reduced interpersonal intimacy. To test the model, a Web-based survey design using path analysis was used. Three hundred and fifteen university students were assessed with measures of self-conscious emotions (i.e., shame, guilt, and embarrassment), introjective (self-definition) and anaclitic (relational) personality style, pathological dissociation, and interpersonal intimacy. Introjective personality was found to be associated with increased shame and reduced interpersonal intimacy. However, the path between pathological dissociation and introjective functioning was not significant. The results are discussed with reference to the moderating influence of introjective functioning between shame and reduced interpersonal intimacy.

Dynamics of serotonergic neurons revealed by fiber photometry

This work was developed in the context of the MIT Portugal Program, area of Bioengineering Systems, in collaboration with the Champalimaud Research Programme, Champalimaud Center for the Unknown, Lisbon, Portugal. The project entitled Dynamics of serotonergic neurons revealed by fiber photometry was carried out at Instituto Gulbenkian de Ciência, Oeiras, Portugal and at the Champalimaud Research Programme, Champalimaud Center for the Unknown, Lisbon, Portugal

Using fuction-based CBT with parent involvement to treat OCD in two school-age children with high-functioning autism

Obsessive Compulsive Disorder (OCD) involves excessive worry coupled with engaging in rituals that are believed to help alleviate the worry. Pervasive Developmental Disorders (PODs) are characterized by impairments in social interaction, communication, and the presence of repetitive and/or restrictive behaviours (American Psychiatric Association, 2000). Research suggests that as many as 81% of children with a POD also meet criteria for a diagnosis ofOCD. Currently, only a handful of studies have investigated the use of Cognitive Behavioural Therapy (CBT) in treating OCD in children with autism (Reaven & Hepburn, 2003 ; Sze & Wood, 2007; Lehmkuhl, Storch, Bodtish & Geflken, 2008). In these case studies. the use of a multi-modal CBT treatment package was successful in alleviating OCD behaviours. The current study used function-based CBT with parent involvement and behavioural supplements to treat 2 children with POD and OCD. Using a multiple baseline design across behaviours and participants, parents reported that their child 's anxiety was alleviated and these gains were maintained at 6-month follow-up. According to results of the Children 's Yale-Brown Obsessive Compulsive Scale (Goodman, Price, Rasmussen, Riddle, & Rapoport, 1986) from preto post-test, OCD behaviours of the children decreased II"om the severe to the mild range. In addition, the parents rated the family's level of interference related to their child 's OCD as substantially lower. Last, the CBT treatment received high ratings of consumer satisfaction.

Évaluation gastro-intestinale chez des chiens présentant un comportement de léchage excessif de surface

L’objectif de cette étude était de démontrer que le léchage excessif de surface (LES) chez le chien représente un signe clinique d’un trouble digestif sous-jacent plutôt qu’un trouble obsessionnel compulsif. Vingt chiens présentés pour LES (groupe L) ont été divisés en 2 sous-groupes de 10 chiens chacun : L0, sans, et LD, avec des signes cliniques digestifs concomitants. Dix chiens en santé ont été assignés à un groupe contrôle (groupe C). Une évaluation comportementale complète, un examen physique et neurologique ont été réalisés avant un bilan diagnostic gastro-intestinal (GI) complet (hématologie, biochimie, analyse urinaire, mesure des acides biliaires pré et post-prandiaux et de l’immunoréactivité spécifique de la lipase pancréatique canine, flottaison fécale au sulfate de zinc, culture de selles, échographie abdominale et endoscopie GI haute avec prise de biopsies). En fonction des résultats, un interniste recommandait un traitement approprié. Les chiens étaient suivis pendant 90 jours durant lesquels le comportement de léchage était enregistré. Des troubles GI ont été identifiés chez 14/20 chiens du groupe L. Ces troubles GI sous-jacents incluaient une infiltration éosinophilique du tractus GI, une infiltration lymphoplasmocytaire du tractus GI, un retard de vidange gastrique, un syndrome du côlon irritable, une pancréatite chronique, un corps étranger gastrique et une giardiose. Une amélioration >50% en fréquence ou en durée par rapport au comportement de léchage initial a été observée chez une majorité de chiens (56%). La moitié des chiens ont complètement cessé le LES. En dehors du LES, il n’y avait pas de différence significative de comportement (p.ex. anxiété), entre les chiens L et les chiens C. Les troubles GI doivent être considérés dans le diagnostic différentiel du LES chez le chien.

Étude des intrusions cognitives et des croyances dysfonctionnelles reliées au trouble obsessionnel-compulsif

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Électrophysiologie cognitive et motrice du syndrome Gilles de la Tourette

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal