Activation therapy for the treatment of inpatients with depression - protocol for a randomised control trial compared to treatment as usual.

BACKGROUND: Inpatients with depression have a poor long term outcome with high rates of suicide, high levels of morbidity and frequent re-admission. Current treatment often relies on pharmacological intervention and focuses on observation to maintain safety. There is significant neurocognitive deficit which is linked to poor functional outcomes. As a consequence, there is a need for novel psychotherapeutic interventions that seek to address these concerns. METHODS: We combined cognitive activation and behavioural activation to create activation therapy (AT) for the treatment of inpatient depression and conducted a small open label study which demonstrated acceptability and feasibility. We propose a randomised controlled trial which will compare treatment as usual (TAU) with TAU plus activation therapy for adult inpatients with a major depressive episode. The behavioural activation component involves therapist guided re-engagement with previously or potentially rewarding activities. The cognitive activation aspect utilises computer based exercises which have been shown to improve cognitive function. DISCUSSION: The proposed randomised controlled trial will examine whether or not the addition of this therapy to TAU will result in a reduced re-hospitalisation rate at 12 weeks post discharge. Subjective change in activation and objectively measured change in activity levels will be rated, and the extent of change to neurocognition will be assessed. TRIAL REGISTRATION: Unique trial number: U1111-1190-9517. Australian New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12617000024347p .

Parkinson's disease across ethnicities: A nationwide study in New Zealand.

BACKGROUND: New Zealand is an ethnically diverse country with a unified national prescribing system. This provides a good framework to use drug-tracing methodology to establish the prevalence and incidence of Parkinson's disease across different ethnic groups. The objective of this study was to determine the prevalence and incidence of Parkinson's disease in the major ethnic groups in New Zealand. METHODS: Information on Parkinson's disease-related medications was extracted from the national Pharmaceutical Collection of community-dispensed medications for the period January 1, 2005, to December 31, 2014. Diagnoses for a large subset of individuals were independently determined through national mortality and hospital admissions data sets. We used a Bayesian model, accommodating uncertainty and bias, to estimate the number of people with Parkinson's disease. RESULTS: We found the highest rate of Parkinson's disease in the European ethnic group and the lowest rate in the indigenous Maori. The 2006-2013 age-standardized incidence (per 100,000 population per year) was European, 33; Asian, 28; Pasifika, 27; Maori, 20. The 2013 age-standardized prevalence (per 100,000 population) was European, 223; Asian, 174; Pasifika, 160; Maori, 114. CONCLUSIONS: There is a differential occurrence of Parkinson's disease across the major ethnic groups within the New Zealand population, with indigenous Maori showing the lowest incidence. Varying susceptibility profiles, gene-environment interactions, and inequalities in accessing health care may play a role in the variation in rates of Parkinson's disease in New Zealand. © 2018 International Parkinson and Movement Disorder Society.

Clinical response to treatment in inpatients with depression correlates with changes in activity levels and psychomotor speed.

BACKGROUND: Monitoring clinical response to treatment in depressed inpatients, particularly identifying early improvement, may be sub-optimal. This may impact adversely on patients through longer admissions and sub-optimal pharmacotherapy. Psychomotor speed is a prominent neuropsychological function which changes as recovery occurs. This study examines simple techniques used to quantify psychomotor change and their potential to contribute to monitoring recovery. METHODS: Activity levels were continuously monitored in patients diagnosed with a major depressive episode from four acute psychiatric wards using two actigraphs (commercial and scientific) for 3 weeks and linear regression used to calculate a gradient to express rate of change. Psychomotor speed was assessed using the simple Coin Rotation Task. Mood and functioning were rated using the Quick Inventory of Depressive Symptoms, Clinical Global Impression Scale and Functioning Assessment Short Test. The assessments were completed at baseline and follow-up (3 weeks), and correlations were calculated for all change measures. RESULTS: In all, 24 inpatients were recruited but not all completed baseline and follow-up measures. Change in activity count ( N = 16) and psychomotor speed ( N = 13) correlated significantly with improvement in clinical measures of depressive symptoms. Actigraphs were acceptable to hospital inpatients. LIMITATIONS: The limited size of this pilot study precludes the analysis of predictive power or the influence of other variables such as depression subtypes, age, gender or variations related to medications. CONCLUSION: Early change in simple activity and psychomotor speed warrant further investigation for utility in measuring treatment response in depressed inpatients.

What factors contribute to the risk of depression in epilepsy?--Tasmanian Epilepsy Register Mood Study (TERMS).

OBJECTIVE: To model the factors associated with depression in a community sample of people with epilepsy. The factors investigated were derived from proposed risk factors for depression from patients with epilepsy, other chronic illness, and the general population. METHODS: Multivariate analysis using general linear regression models of factors associated with depression in the Tasmanian Epilepsy Register Mood Study (TERMS), a cross-sectional community sample of 440 patients with epilepsy. RESULTS: A model with acceptable fit was created that explained 66% of the variance of depression. Associated factors included in this model were neuroticism, physical functioning, social support, past history of depression, and stressful life events. SIGNIFICANCE: In this cross-sectional study designed specifically to investigate depression in epilepsy, we showed that general risk factors for depression in other illness and in the general population are also important in patients with epilepsy, with little support for disease-related risk factors.

Risk factors for depression in community-treated epilepsy: systematic review.

OBJECTIVE: Depression is one of the most common psychiatric comorbidities in epilepsy; however, the factors contributing to this association remain unclear. There is a growing consensus that methodological limitations, particularly selection bias, affect many of the original studies. A systematic review focussed on community-based studies offers an alternative approach for the identification of the risk factors for depression. METHODS: Searches were performed in MEDLINE (Ovid), 2000 to 31 December 2013, EMBASE, and Google Scholar to identify studies examining risk factors for depression in epilepsy. Community-based studies of adults with epilepsy that reported at least one risk factor for depression were included. RESULTS: The search identified 17 studies that met selection criteria, representing a combined total of 12,212 people with epilepsy with a mean sample size of 718. The most consistent risk factors for depression were sociodemographic factors, despite the fact that most studies focus on epilepsy-related factors. SIGNIFICANCE: Most studies lacked a systematic conceptual approach to investigating depression, and few risk factors were consistently well studied. Future community-based studies require a detailed systematic approach to improve the ability to detect risk factors for depression in epilepsy. Psychological factors were rarely studied in community-based samples with epilepsy, although the consistent association with depression in the few studies that did suggests this warrants further examination.

Serotonin transporter gene × environment and risk of depression in community-treated epilepsy.

OBJECTIVES: This study aimed to test whether a specific serotonin transporter (5HTT) gene polymorphism interacting with life stress increased the risk of depression in patients with epilepsy. METHODS: The Tasmanian Epilepsy Register Mood Study (TERMS) used a cross-sectional study design of a community sample of patients with epilepsy previously recruited into the Tasmanian Epilepsy Register. It employed a mailed self-complete questionnaire and saliva DNA collection. Depression was assessed using the Center for Epidemiologic Studies Depression Scale. Environmental measures were selected to cover recent stressful events, epilepsy-related stress, current social support, and early life stress. RESULTS: Of 820 eligible participants, 553 (67%) participants completed the study. Experience of at least one stressful life event was very common, with a significant association between depression and the stressful life events (F=26.2, df=3, p<0.001). There was no association between serotonin transporter genotype and level of depressive symptoms reported (F=0.421, df=2, p=0.7). There was no evidence of any adverse life experiences interacting with serotonin transporter genotype to moderate the risk of depression. SIGNIFICANCE: The failure to demonstrate a main effect of genotype on depression or a gene × environment interaction differs from several studies of patients with other chronic diseases. However, it is consistent with larger general population studies.

Risk factors for psychological distress in community-treated epilepsy.

The study aimed to determine risk factors for psychological distress in a community-treated sample of patients with epilepsy. This study investigated the Tasmanian Epilepsy Register participants. Participants included were as follows: aged 13 years and over, able to complete the individual computer-assisted participant interview, and diagnosed with epilepsy following an epilepsy specialist review of the diagnostic epilepsy interview, which was interpreted using standardized diagnostic guidelines. Psychological distress was assessed with the Kessler-10 questionnaire. Risk factors were grouped into four domains: sociodemographic factors, disease-related factors, psychological factors, and treatment-related factors. High or very high levels of psychological distress were reported by 22% of the participants, with 7.8% having very high distress. The regression model showed that psychological distress was significantly associated with female gender (F=18.1, p<0.001), diabetes mellitus (F=8.7, p=0.003), intellectual disability (F=7.1, p=0.06), and not receiving phenytoin (F=5.1, p=0.02). While the model was significant (F=5.78, p<0.001), only 11% of the variance of the K-10 score was explained by these factors (adjusted R-squared=0.11). This study identifies female gender and comorbid medical conditions as risk factors for psychological distress and the use of phenytoin as a protective factor. The few factors identified and the limited variance explained suggest that a focus on epilepsy-related variables is unlikely to explain key influences underlying psychiatric comorbidity in patients with epilepsy.

Community treatment orders: the experiences of Non-Maori and Maori within mainstream and Maori mental health services.

PURPOSE: Community treatment orders (CTOs) are sometimes used to coerce patients into treatment on the basis that such treatment is in their best interest. The experiences of Maori, New Zealand's indigenous ethnic minority are less well known and this paper compares the views of Maori and non-Maori about CTOs. METHODS: Patients with experience of CTOs for greater than 6 months participated. Self-report measures were used to identify patients' views of compulsory treatment. Demographic data, heath service characteristics, the experience of coercion, views of compulsory community treatment, satisfaction with care, social functioning, and psychopathology were assessed. RESULTS: There were few differences in demographic or clinical characteristics between Maori and non-Maori. There were no differences in the views of Maori compared to non-Maori patients with respect to compulsory community treatment. There were no differences in the views of Maori cared for by mainstream compared to culturally specialist Maori mental health service. CONCLUSIONS: In a well-established system of compulsory treatment, there is no evidence of greater negative impact of CTOs in an indigenous minority population. The opportunity for Maori to self-select between mainstream and specialist Maori mental health services may minimize the negative aspects of compulsory community treatment for Maori.

Psychiatric comorbidity and impact on health service utilization in a community sample of patients with epilepsy.

We aimed to determine the level of psychological distress in community-treated patients with epilepsy and to determine if this distress is associated with increased health service use. The Australian National prescription database was used to recruit patients with epilepsy onto the Tasmanian Epilepsy Register (TER). Psychological distress was measured using the K10 in the TER patients and compared to the Tasmanian population using the National Health Survey 2004-5. Of the 1,180 on the TER, 43 withdrew, 36 died, and 262 were excluded. Of 839 patients, 652 completed the K10 (78%). High-very high levels of psychological distress were observed in patients with epilepsy compared with the general population [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.79-2.56]. Patients with high-very high psychological distress had increased attendance at general practitioners (p < 0.001), specialists (p = 0.02), and emergency departments (p = 0.004). Psychological distress is increased in community-treated patients with epilepsy compared to the general population, and is associated with increased health service use.

Comparing the variants of takotsubo syndrome: an observational study of the ECG and structural changes from a New Zealand tertiary hospital.

OBJECTIVES: In takotsubo syndrome, QTc prolongation is a measure of risk of potentially fatal arrhythmia. It is not known how this risk, or derangement of other markers, differs across the echo variants of takotsubo syndrome. Therefore, we sought to explore whether apical takotsubo syndrome differs from the variants of the syndrome in more ways than just regional wall motion pattern. As the region of affected myocardium is usually larger, we hypothesised that patients with the classic apical ballooning form of takotsubo syndrome would have more severe derangement of their markers. DESIGN: Observational study of patients gathered from a prospective database (2010-2018) and by retrospective review (2006-2009). SETTING: The sole tertiary hospital from a New Zealand region in which case clusters of takotsubo syndrome were precipitated by large earthquakes in 2010, 2011 and 2016. PARTICIPANTS: A total of 222 patients who met a modified version of the Mayo criteria for takotsubo syndrome were included. All patients had digitally archived echocardiograms that were over-read by a second echocardiologist blinded to the clinical report. PRIMARY OUTCOME MEASURES: Ejection fraction, peak troponin and QTc interval. RESULTS: Patients with the apical form were older (p=0.011), had a lower initial left ventricular ejection fraction (35% vs 44%, p<0.0001) and a higher peak high-sensitivity troponin I (hsTnI) (p=0.01) than those with variant forms. There was no difference in the electrical abnormalities between the variants (QTc interval, heart rate, PR interval, QRS duration or T-wave axis). There was also no correlation between any of peak hsTnI, peak QTc and ejection fraction. QTc interval increased on day 2 and peaked on day 3 before falling steeply (p<0.0001). CONCLUSIONS: The variants of takotsubo syndrome differ in more ways than just their echo pattern but do not differ in their electrical abnormalities. There is a dissociation between the structural and electrical abnormalities. QTc peaks on day 3 and then falls steeply.

Drug Burden Index and Its Association With Hip Fracture Among Older Adults: A National Population-Based Study.

BACKGROUND: The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study was to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors. METHODS: A competing-risks regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (International Resident Assessment Instrument) assessment between September 1, 2012, and October 31, 2015, the study's end date. Outcome measures were survival status and hip fracture, with time-varying DBI exposure derived from 90-day time intervals. The multivariable competing-risks regression model was adjusted for a large number of medical comorbidities and activities of daily living. RESULTS: Among 70,553 adults assessed, 2,249 (3.2%) experienced at least one hip fracture, 20,194 (28.6%) died without experiencing a fracture, and 48,110 (68.2%) survived without a fracture. The mean follow-up time was 14.9 months (range: 1 day, 37.9 months). The overall DBI distribution was highly skewed, with median time-varying DBI exposure ranging from 0.93 (Q1 = 0.0, Q3 = 1.84) to 0.96 (Q1 = 0.0, Q3 = 1.90). DBI was significantly related to fracture incidence in unadjusted (p < .001) and adjusted (p < .001) analyses. The estimated subhazard ratio was 1.52 (95% confidence interval: 1.28-1.81) for those with DBI > 3 compared with those with DBI = 0 in the adjusted analysis. CONCLUSIONS: In this study, increasing DBI was associated with a higher likelihood of fractures after accounting for the competing risk of mortality and adjusting for confounders. The results of this unique study are important in validating the DBI as a guide for medication management and it could help reduce the risk of hip fractures in older adults.

Obsessive-compulsive disorder with mitochondrial disease.

BACKGROUND: Mitochondrial diseases are among the most common genetic disorders, and they have been associated with several psychiatric syndromes. METHOD: The authors present two cases of obsessive-compulsive disorder (OCD) occurring in patients with MELAS (the A3243G mutation). RESULTS: Their clinical course and response to standard OCD treatment strategies was poor. DISCUSSION: Possible mechanisms for OCD symptoms are suggested by animal models and neuropathological findings. It remains unclear whether different types of mitochondrial disorders are associated with particular neuropsychiatric symptoms. Psychiatric symptoms may predate the diagnosis of mitochondrial disorder; thus, psychiatrists should consider mitochondrial disorders in the presence of common physical signs that are typically associated with these disorders.

Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy.

The pathophysiology of stress cardiomyopathy (SCM), also known as takotsubo syndrome, is poorly understood. SCM usually occurs sporadically, often in association with a stressful event, but clusters of cases are reported after major natural disasters. There is some evidence that this is a familial condition. We have examined three possible models for an underlying genetic predisposition to SCM. Our primary study cohort consists of 28 women who suffered SCM as a result of two devastating earthquakes that struck the city of Christchurch, New Zealand, in 2010 and 2011. To seek possible underlying genetic factors we carried out exome analysis, genotyping array analysis, and array comparative genomic hybridization on these subjects. The most striking finding was the observation of a markedly elevated rate of rare, heterogeneous copy number variants (CNV) of uncertain clinical significance (in 12/28 subjects). Several of these CNVs impacted on genes of cardiac relevance including RBFOX1, GPC5, KCNRG, CHODL, and GPBP1L1. There is no physical overlap between the CNVs, and the genes they impact do not appear to be functionally related. The recognition that SCM predisposition may be associated with a high rate of rare CNVs offers a novel perspective on this enigmatic condition.