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ItemThe Anorexia Nervosa Genetics Initiative (ANGI): overview and methods(Elsevier, 2018-10-01) Thornton, Laura M; Munn-Chernoff, Melissa A; Baker, Jessica H; Jureus, Anders; Parker, Richard; Henders, Anjali K; Larsen, Janne T; Petersen, Liselotte; Watson, Hunna J; Yilmaz, Zeynep; Kirk, Katherine M; Gordon, Scott; Leppa, Virpi M; Martin, Felicity C; Whiteman, David C; Olsen, Catherine M; Werge, Thomas M; Pedersen, Nancy L; Kaye, Walter; Bergen, Andrew W; Halmi, Katherine A; Strober, Michael; Kaplan, Allan S; Woodside, D Blake; Mitchell, James; Johnson, Craig L; Brandt, Harry; Crawford, Steven; Horwood, L John; Boden, Joseph M; Pearson, John F; Duncan, Laramie E; Grove, Jakob; Mattheisen, Manuel; Jordan, Jennifer; Kennedy, Martin A; Birgegard, Andreas; Lichtenstein, Paul; Norring, Claes; Wade, Tracey Diane; Montgomery, Grant W; Martin, Nicholas G; Landen, Mikael; Mortensen, Preben Bo; Sullivan, Patrick F; Bulik, Cynthia MBackground Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. Methods ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. Results Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. Conclusions Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ItemAssociations between health-related self-efficacy and suicidality(BioMed Central, 2018-05-10) Isaac, Vivian; Wu, Chia-Yi; McLachlan, Craig S; Lee, Ming-BeenAbstract Background Few studies have focused on exploring the association of self-efficacy and suicidal behaviour. In this study, we aim to investigate the association between health-related self-efficacy and suicidality outcomes, including lifetime/recent suicidal ideation, suicidal attempts and future intent of suicide. Methods A computer-assisted telephone interview (CATI) system was used to draw potential respondents aged over 15 in Taiwan via telephone numbers, which were selected by a stratified proportional randomization method according to the distribution of population size in different geographic areas of Taiwan. We obtained available information on suicide behaviours for the analysis of 2110 participants. Logistic regression was applied to investigate the independent effect of health-related self-efficacy on life-time suicidal thoughts and attempts. Results Suicidality measured as suicide ideation and attempted suicide was reported as 12.6 and 2.7% respectively in the sample. Among those with suicide ideation, 9.8% had thoughts of future suicide intent. Female gender, low education, people living alone or separated, history of psychiatric disorders, substance abuse, poor self-rated mental health and physical health were associated with suicidality factors. Low health-related self-efficacy was associated with lifetime suicide ideation, prior suicide attempt and future suicidal intent. Among those with recent suicidal ideation, low health self-efficacy was independently associated with future suicide intent after adjustment of gender, age, education, marital status, substance abuse, psychological distress, poor mental and physical health. Conclusion Health-related self-efficacy was associated with suicide risks across different time points from prior ideation to future intention. Evaluation of the progress of self-efficacy in health may be long-term targets of intervention in suicide prevention strategies. ItemNeuropsychiatric aspects of frontal lobe meningioma(Elsevier, 2017-07-14) Tibrewal, Prashant; Loo, Yi Jia; Dhillon, Rohan; Bastiampillai, Tarun; Parthasarathy, Bhargava RamanBrain tumours are known to typically present with neurological signs. Rarely, psychiatric symptoms can be the only manifestation of a brain tumour (Madhusoodanan et al., 2015). Though it is not uncommon for patients to present with psychiatric symptoms as the first clinical manifestation of a brain tumour, they are often non-specific and do not assist in localising the lesion. With the limited available research, it is found that neuropsychiatric disturbances are more frequently associated with frontal and temporolimbic lesions (Filley and Kleinschmidt-DeMasters, 1995). We present a case of a woman with frontal lobe meningioma who presented with a neuropsychiatric syndrome. Ms S is a 50 years old woman with chronic schizophrenia that was stable for several years on a combination of 4 mg of Risperidone and 50 mg of Quetiapine. In early April, she presented with abrupt onset of fever, tremors, generalised weakness, lethargy, confusion, vomiting and loose bowels. On examination, she was noted to have a body temperature of 37.8 °C with borderline tachycardia, bradykinesia, cogwheel rigidity and increased deep tendon reflexes. She did not have diaphoresis or autonomic instability. Laboratory tests showed elevated Creatine Kinase (CK) of 1800 U/L and neutrophilia. With clinical suspicion for NMS, her antipsychotic medications were ceased leading to a decrease in her CK to 60. She was discharged after being commenced on Olanzapine 2.5 mg daily, with positive effect for her psychotic symptoms. Nine days following discharge Ms S presented again with some symptoms of NMS such as worsening tremors, two episodes of fever, rigidity, bradykinesia and was disoriented to time. Her CK and white cell count, however, were within normal levels. She also had catatonic features such as increasingly withdrawn behaviour, mutism and negativism. On hospital presentation, she was afebrile and septic screen was negative, and she was admitted to the psychiatric unit for further investigation. Whilst assessment by the emergency physician suggested that the etiology of her symptoms were related to psychotropic drugs, the psychiatrist opined that it was more likely to be delirium and also considered a differential diagnosis of organic catatonia. CT head was done following the recommendation of the psychiatrist and it showed left frontal lobe meningioma with 12 cm midline shift with surrounding oedema. Ms S then was referred to the neurosurgery department and underwent surgical resection of the meningioma, which was successful. Ms S was a patient with a stable psychiatric illness, who presented with overlapping features of NMS and catatonia but no overt psychotic symptoms. Her neuropsychiatric symptoms were likely to be the pressure effect of a left frontal meningioma. The nature of her presentation made the process of diagnosis challenging, especially with the initial absence of neuroimaging, which resulted in a delay in diagnosis and appropriate treatment. Frontal lobe tumours have higher chances of producing mental status and personality changes with left sided lesions being more associated with inhibition of motor activity, impairment in motor and initiative aspect of speech, diminished generalization ability and general inertia of mental processes as seen in Ms S (Belyi, 1987). Given the absence of frank neurological symptoms to help localise the lesion, a high degree of clinical suspicion is usually required for early diagnosis. In patients suffering from schizophrenia, these symptoms can be explained by the illness itself and the side effects of the medications, thereby increasing the chances of missing the organic pathology due to diagnostic overshadowing of the primary psychiatric illness. Neuroimaging should be considered in patients with atypical psychiatric symptoms, new-onset psychosis, recurrence of previously well-controlled psychiatric symptoms, and if they become refractory to psychiatric treatment (Madhusoodanan et al., 2015). Clinical suspicion must be raised when these symptoms are vague, rare, non-specific, with no clear cause or trigger and are associated with several causative etiologies. Despite the many studies that have been done to correlate clinical presentation to the location of brain lesions, symptoms are still extremely unreliable diagnostic tools, and neuroimaging should be done when there is high suspicion index for organic pathology. ItemREM sleep fragmentation associated with depressive symptoms and genetic risk for depression in a community-based sample of adolescents(Elsevier, 2018-11-11) Pesonen, Anu-Katriina; Gradisar, Michael Shane; Kuula, Liisa; Short, Michelle; Merikanto, Ilona; Tark, Riin; Raikkonen, Katri; Lahti, JariIntroduction Fragmented REM sleep may impede overnight resolution of distress and increase depressive symptoms. Furthermore, both fragmented REM and depressive symptoms may share a common genetic factor. We explored the associations between REM sleep fragmentation, depressive symptoms, and a polygenic risk score (PRS) for depression among adolescents. Methods About 161 adolescents (mean age 16.9 ± 0.1 years) from a birth cohort underwent a sleep EEG and completed the Beck Depression Inventory-II the same day. We calculated PRSes for depressive symptoms with PRSice 1.25 software using weights from a recent genome-wide association study for dimensions of depressive symptoms (negative emotion, lack of positive emotion and somatic complaints). REM fragmentation in relation to entire REM duration was manually calculated from all REM epochs. REM latency and density were derived using SomnoMedics DOMINO software. Results PRSes for somatic complaints and lack of positive emotions were associated with higher REM fragmentation percent. A higher level of depressive symptoms was associated with increased percent of REM fragmentation and higher REM density, independently of the genetic risks. Belonging to the highest decile in depressive symptoms was associated with a 2.9- and 7.6-fold risk of belonging to the highest tertile in REM fragmentation and density. In addition, higher PRS for somatic complaints had an independent, additive effect on increased REM fragmentation. Limitation A single night's sleep EEG was measured, thus the night-to-night stability of the REM fragmentation-depressive symptom link is unclear. Conclusion Depressive symptoms and genetic risk score for somatic complaints are independently associated with more fragmented REM sleep. This offers new insights on the quality of sleep and its relation to adolescents’ mood. ItemWeb-based intervention to improve quality of life in late stage bipolar disorder (ORBIT): randomised controlled trial protocol(2018-07-13) Fletcher, Kathryn; Foley, Fiona; Thomas, Neil; Michalak, Erin; Berk, Lesley; Berk, Michael; Bowe, Steve; Cotton, Sue; Engel, Lidia; Johnson, Sheri L; Jones, Steven; Kyrios, Michael; Lapsley, Sara; Mihalopoulos, Cathrine; Perich, Tania; Murray, GregBackground The primary objective of this randomised controlled trial (RCT) is to establish the effectiveness of a novel online quality of life (QoL) intervention tailored for people with late stage (≥ 10 episodes) bipolar disorder (BD) compared with psychoeducation. Relative to early stage individuals, this late stage group may not benefit as much from existing psychosocial treatments. The intervention is a guided self-help, mindfulness based intervention (MBI) developed in consultation with consumers, designed specifically for web-based delivery, with email coaching support. Methods/design This international RCT will involve a comparison of the effectiveness and cost-effectiveness of two 5-week adjunctive online self-management interventions: Mindfulness for Bipolar 2.0 and an active control (Psychoeducation for Bipolar). A total of 300 participants will be recruited primarily via social media channels. Main inclusion criteria are: a diagnosis of BD (confirmed via a phone-administered structured diagnostic interview), no current mood episode, history of 10 or more mood episodes, no current psychotic features or active suicidality, under the care of a medical practitioner. Block randomisation will be used for allocation to the interventions, and participants will retain access to the program for 6 months. Evaluations will be conducted at pre- and post- treatment, and at 3- and 6- months follow-up. The primary outcome measure will be the Brief Quality of Life in Bipolar Disorder Scale (Brief QoL.BD), collected immediately post-intervention at 5 weeks (T1). Secondary measures include BD-related symptoms (mania, depression, anxiety, stress), time to first relapse, functioning, sleep quality, social rhythm stability and resource use. Measurements will be collected online and via telephone assessments at baseline (T0), 5 weeks (T1), three months (T2) and six months (T3). Candidate moderators (diagnosis, anxiety or substance comorbidities, demographics and current treatments) will be investigated as will putative therapeutic mechanisms including mindfulness, emotion regulation and self-compassion. A cost-effectiveness analysis will be conducted. Acceptability and any unwanted events (including adverse treatment reactions) will be documented and explored. Discussion This definitive trial will test the effectiveness and cost-effectiveness of a novel QoL focused, mindfulness based, online guided self-help intervention for late stage BD, and investigate its putative mechanisms of therapeutic action.