Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette's

Background  

Excessive sequential stereotypy of behavioral patterns (sequential super-stereotypy) in Tourette's syndrome and obsessive compulsive disorder (OCD) is thought to involve dysfunction in nigrostriatal dopamine systems. In sequential super-stereotypy, patients become trapped in overly rigid sequential patterns of action, language, or thought. Some instinctive behavioral patterns of animals, such as the syntactic grooming chain pattern of rodents, have sufficiently complex and stereotyped serial structure to detect potential production of overly-rigid sequential patterns. A syntactic grooming chain is a fixed action pattern that serially links up to 25 grooming movements into 4 predictable phases that follow 1 syntactic rule. New mutant mouse models allow gene-based manipulation of brain function relevant to sequential patterns, but no current animal model of spontaneous OCD-like behaviors has so far been reported to exhibit sequential super-stereotypy in the sense of a whole complex serial pattern that becomes stronger and excessively rigid. Here we used a hyper-dopaminergic mutant mouse to examine whether an OCD-like behavioral sequence in animals shows sequential super-stereotypy. Knockdown mutation of the dopamine transporter gene (DAT) causes extracellular dopamine levels in the neostriatum of these adult mutant mice to rise to 170% of wild-type control levels.     

CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder

Gilles de la Tourette syndrome (GTS) is a sporadic or inherited complex neuropsychiatric disorder characterized by involuntary motor and vocal tics. There is comorbidity with disorders like obsessive compulsive disorder and attention deficit hyperactivity disorder. Until now linkage analysis has pointed to a number of chromosomal locations, but has failed to identify a clear candidate gene(s). We have investigated a GTS family with a complex chromosomal insertion/translocation involving chromosomes 2 and 7. The affected father [46,XY,inv(2) (p23q22),ins(7;2) (q35-q36;p21p23)] and two affected children [46,XX,der(7)ins(7;2)(q35-q36;p21p23) and 46,XY,der(7)ins(7;2)(q35-q36;p213p23)] share a chromosome 2p21-p23 insertion on chromosome 7q35-q36, thereby interrupting the contactin-associated protein 2 gene (CNTNAP2). This gene encodes a membrane protein located in a specific compartment at the nodes of Ranvier of axons. We hypothesize that disruption or decreased expression of CNTNAP2 could lead to a disturbed distribution of the K(+) channels in the nervous system, thereby influencing conduction and/or repolarization of action potentials, causing unwanted actions or movements in GTS.     

Dream and blog content analysis of a long term diary of a video game player with obsessive compulsive disorder.

A case study of a young man who is an avid video game player and designer is the focus of this paper. His online Website offers over 800 dreams, of which over half were content analyzed using the Hall and Van de Castle system. Also available were daily blogs. Thus, several research questions could be addressed. Did the diary evidence consistency across time? Did the dreams evidence incorporation of activities discussed in the daily blogs from the day before the dream? Did this one individual's dream diary echo former research into the dreams of video game players? A final question was addressed because of the diagnosis of the diarist as having Obsessive Compulsive Disorder (OCD). Did the dreams of this young man echo previous research into dreams of OCD sufferers? The findings were that the diary was consistent across time and there was incorporation of some elements of the daily blog into subsequent dreams. Some aspects of his dreams echoed previous video game players' dream findings, like more dead and imaginary characters. Finally, the OCD analysis only partly replicated the previous research into the dreams of those with OCD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Relationship of self-mutilative behaviour with history of childhood trauma and adult ADHD symptoms in a sample of inpatients with alcohol use disorder

The aim of the present study was to evaluate relationship of self-mutilative behaviour (SMB) with the severity of childhood trauma and adult attention-deficit/hyperactivity disorder (ADHD) symptoms in a sample of inpatients with alcohol use disorder (AUD). Participants included 188 inpatients with AUD. Participants were evaluated with the Self-mutilative Behaviour Questionnaire, the Childhood Trauma Questionnaire (CTQ-28) and the Adult ADD/ADHD DSM-IV Based Diagnostic Screening and Rating Scale (Adult ADHD Scale). Among inpatients with AUD those who have a history of SMB constituted the SMB group (n = 57, 30.3%), and those without a history of SMB constituted the group without SMB (n = 131, 69.7%). Risk of high ADHD risk was 2.5 times higher among those with SMB. Adult ADHD Scale and CTQ-28 scores were also higher in the group with SMB. In the first backward logistic regression model, the severity of ADHD symptoms predicted the presence of SMB, together with the severity of childhood trauma, whereas in the second model, physical neglect and inattentive (IN) dimension of ADHD predicted the presence of SMB. These findings suggest that the higher severity of physical neglect and adult IN dimension of ADHD may be related to SMB among inpatients with AUD.     

Migration Watch: an Internet survey to monitor spring migration in Britain and Ireland

The arrival patterns of summer visitors to Britain and Ireland were monitored from 2002 to 2004 using large numbers of birdwatching lists collected by Migration Watch, an Internet-based survey. Records were only accepted from registered observers, and procedures for data validation were implemented. We show here how data on the frequency of occurrence from birdwatching lists can be analysed to estimate the timing and duration of the migration period. Aerial insectivores showed clear species-specific arrival patterns, with sand martins arriving first, followed in succession by swallows, house martins and finally swifts. Wheatears showed two peaks of arrivals, one for the British population and one for passage migrants from Greenland. The progression of arrivals from south to north and variation in arrival timing between years were also demonstrated. The method offers considerable potential for studying migration phenology at large spatial scales, and within Britain and Ireland it is now being applied throughout the year within the BTO/RSPB/BWI BirdTrack project. It could potentially be implemented at a continental scale, at which it would provide an important tool for measuring the growing impacts of global climate change on bird populations.     

Factors predicting treatment adherence in patients with adult attention-deficit/hyperactivity disorder: a preliminary study

This study aimed to elicit patient- and treatment-related factors that can potentially predict treatment adherence in adult ADHD. Subjects who were over 18 and received a diagnosis of ADHD were included in the study. Chart review data of 102 subjects regarding demographics, medications, comorbidities, concomitant medications and domains of functional impairment were collected, and predictors were assessed using a binominal logistical regression model. One hundred and two patients (78.4 % male) with a mean age of 28.8 (SD = 9.8, range = 18–55) years were enrolled in the study. Childhood diagnosis of ADHD, agents used for treatment (MPH or atomoxetine), individual domains of dysfunction and use of additional psychotropic drugs were not found to be related to treatment adherence. Patients with a university education and those referred for family history of ADHD were more likely to adhere to treatment (p = 0.05 and 0.03, respectively). On the other hand, reasons for referral other than ADHD were significantly more frequently related to non-adherence (p = 0.02). Treatment noncompliance remains a significant problem despite therapeutic effects of medications. Identification of predictors of non-adherence can lead to heightened awareness of special populations at risk. We have found that prior awareness on ADHD (via past history/media/friends) leading to self/clinician referral to rule out ADHD and pervasiveness of symptoms across functional domains led to better compliance in our sample. Future research with prospective design utilizing objective tools for adherence is required.     

Emerging experience with selected new categories in the ICD‐11: complex PTSD,prolonged grief disorder,gaming disorder,and compulsive sexual behaviour disorder

Among the important changes in the ICD‐11 is the addition of 21 new mental disorders. New categories are typically proposed to: a) improve the usefulness of morbidity statistics; b) facilitate recognition of a clinically important but poorly classified mental disorder in order to provide appropriate management; and c) stimulate research into more effective treatments. Given the major implications for the field and for World Health Organization (WHO) member states, it is important to examine the impact of these new categories during the early phase of the ICD‐11 implementation. This paper focuses on four disorders: complex post‐traumatic stress disorder, prolonged grief disorder, gaming disorder, and compulsive sexual behaviour disorder. These categories were selected because they have been the focus of considerable activity and/or controversy and because their inclusion in the ICD‐11 represents a different decision than was made for the DSM‐5. The lead authors invited experts on each of these disorders to provide insight into why it was considered important to add it to the ICD‐11, implications for care of not having that diagnostic category, important controversies about adding the disorder, and a review of the evidence generated and other developments related to the category since the WHO signaled its intention to include it in the ICD‐11. Each of the four diagnostic categories appears to describe a population with clinically important and distinctive features that had previously gone unrecognized as well as specific treatment needs that would otherwise likely go unmet. The introduction of these categories in the ICD‐11 has been followed by a substantial expansion of research in each area, which has generally supported their validity and utility, and by a significant increase in the availability of appropriate services.     

The relationship between quality of life, binge-eating disorder, and obesity status in an ethnically diverse sample

This study examined the relationship between obesity status, binge-eating disorder (BED), and quality of life (QOL) in a large, ethnically diverse community sample of adult men and women. Using data from the Collaborative Psychiatric Epidemiological Surveys (N = 20,013), individuals were categorized into four groups: nonobese with BED (n = 142), nonobese without BED (n = 14,301), obese with BED (n = 136), and obese without BED (n = 4,863). Results indicated obese individuals with BED consistently reported the poorest QOL. Findings suggested that obesity status was more strongly related to physical health-related QOL variables (e.g., number of physical conditions, mobility impairment) whereas diagnostic status was more predictive of mental health and social functioning QOL variables (e.g., cognitive impairment, social interaction impairment, time out of role). The degree to which lifetime BED diagnosis was associated with impairment in social interaction differed across ethnic groups. For black individuals, the number of physical health conditions was associated with BED presence moreso than weight status.     

Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment.

OBJECTIVES--To assess women''s preferences for, and the acceptability of, medical abortion and vacuum aspiration in the early first trimester. DESIGN--Patient centred, partially randomised trial. Medical abortion was performed with mifepristone 600 mg followed 48 hours later by gemeprost 1 mg vaginal pessary. Vacuum aspiration was performed under general anaesthesia. SETTING--Teaching hospital in Scotland. PATIENTS--363 women undergoing legal induced abortion at less than nine weeks'' gestation. MAIN OUTCOME MEASURES--Women''s preferences for method of abortion before abortion; acceptability judged two weeks after abortion by recording the method women would opt to undergo in future and by semantic differential rating technique. RESULTS--73 (20%) women preferred to undergo medical abortion, and 95 (26%) vacuum aspiration; 195 (54%) were willing to undergo either method, and were allocated at random. Both procedures were highly acceptable to women with preferences. Gestation had a definite effect on acceptability in randomised women; at less than 50 days there were no differences, but between 50 and 63 days vacuum aspiration was significantly more acceptable. CONCLUSIONS--Women who wish to use a particular method should be allowed their choice, regardless of gestation. Women of 50-63 days'' gestation without preferences for a particular method are likely to find vacuum aspiration more acceptable. A patient centred, partially randomised trial design may be a useful tool in pragmatic research.     

Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: provider knowledge and acceptability

Malaria in pregnancy (MiP) is associated with increased risks of maternal and foetal complications. The WHO recommends a package of interventions including intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), insecticide-treated nets and effective case management. However, with increasing SP resistance, the effectiveness of SP-IPT has been questioned. Intermittent screening and treatment (IST) has recently been shown in Ghana to be as efficacious as SP-IPT. This study investigates two important requirements for effective delivery of IST and SP-IPT: antenatal care (ANC) provider knowledge, and acceptance of the different strategies. Structured interviews with 134 ANC providers at 67 public health facilities in Ashanti Region, Ghana collected information on knowledge of the risks and preventative and curative interventions against MiP. Composite indicators of knowledge of SP-IPT, and case management of MiP were developed. Log binomial regression of predictors of provider knowledge was explored. Qualitative data were collected through in-depth interviews with fourteen ANC providers with some knowledge of IST to gain an indication of the factors influencing acceptance of the IST approach. 88.1% of providers knew all elements of the SP-IPT policy, compared to 20.1% and 41.8% who knew the treatment policy for malaria in the first or second/third trimesters, respectively. Workshop attendance was a univariate predictor of each knowledge indicator. Qualitative findings suggest preference for prevention over cure, and increased workload may be barriers to IST implementation. However, a change in strategy in the face of SP resistance is likely to be supported; health of pregnant women is a strong motivation for ANC provider practice. If IST was to be introduced as part of routine ANC activities, attention would need to be given to improving the knowledge and practices of ANC staff in relation to appropriate treatment of MiP. Health worker support for any MiP intervention delivered through ANC clinics is critical.     

The clinical characterization of the adult patient with bipolar disorder aimed at personalization of management

Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal­ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical “multi‐omic” measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point‐of‐care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features – especially during depressive episodes – and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally‐oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point‐of‐care.