Sharon L. Naismith

A Systematic Review of the Impact of Adherence on the Effectiveness of e-Therapies

Background As the popularity of e-therapies grows, so too has the body of literature supporting their effectiveness. However, these interventions are often plagued by high attrition rates and varying levels of user adherence. Understanding the role of adherence may be crucial to understanding how program usage influences the effectiveness of e-therapy interventions. Objective The aim of this study was to systematically review the e-therapy literature to (1) describe the methods used to assess adherence and (2) evaluate the association of adherence with outcome of these interventions. Methods A systematic review of e-therapy interventions was conducted across disease states and behavioral targets. Data were collected on adherence measures, outcomes, and analyses exploring the relationship between adherence measures and outcomes. Results Of 69 studies that reported an adherence measure, only 33 (48%) examined the relationship between adherence and outcomes. The number of logins was the most commonly reported measure of adherence, followed by the number of modules completed. The heterogeneity of adherence and outcome measures limited analysis. However, logins appeared to be the measure of adherence most consistently related to outcomes in physical health interventions, while module completion was found to be most related to outcomes in psychological health interventions. Conclusions There is large variation in the reporting of adherence and the association of adherence with outcomes. A lack of agreement about how best to measure adherence is likely to contribute to the variation in findings. Physical and psychological outcomes seem influenced by different types of adherence. A composite measure encompassing time online, activity completion, and active engagements with the intervention may be the best measure of adherence. Further research is required to establish a consensus for measuring adherence and to understand the role of adherence in influencing outcomes.

The neurobiology of depression in later-life: Clinical, neuropsychological, neuroimaging and pathophysiological features

As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.

The specific contributions of set-shifting to freezing of gait in Parkinson's disease†

Freezing of gait (FOG) in Parkinsons disease (PD) is common and the pathophysiology of FOG is poorly understood. It has been hypothesized to reflect complementary yet competing frontostriatal pathways that reduce the ability to keep different tasks (motor or cognitive) on‐line. This inability to “set‐shift” has been proposed to trigger a freezing episode. If correct, this hypothesis would predict a differential pattern of executive dysfunction with FOG being most specifically related to attentional set‐shifting. In this study, 31 patients with a range of self‐reported FOG symptom severities were administered tests of executive functioning. The results demonstrate that FOG symptoms were selectively correlated with poorer performance on tasks of set‐shifting, but not with a range of other executive tasks. This was apparent even after controlling for slowed processing speed, disease stage and depressive symptoms. The results support the recently proposed hypothesis for the pathophysiology underlying FOG in PD.

Neuropsychological Performance in Patients With Depression is Associated With Clinical, Etiological and Genetic Risk Factors

The present study explores neuropsychological functioning in patients with depression with reference to key clinical, etiological and genetic features. In comparison to healthy volunteers, patients with severe depression demonstrated poorer performance on all neuropsychological tests except for WAIS-R Vocabulary and a 64-item computerized version of the Wisconsin Card Sorting Test. On average, patients exhibited significant impairments (greater than –2 standard deviation units) on tests of simple reaction time, Part B of the Trail Making Test and Raven’s Colored Progressive Matrices. When performance decrements were analyzed with reference to key clinical features, patients with melancholia performed more poorly on WAIS-R Vocabulary, semantic fluency and choice reaction time than those with nonmelancholic depression. After controlling for age, those patients with late-onset depression (i.e., age of onset =50 years) exhibited poorer performance on a computerized version of the Tower of London test in comparison to those with an early onset. While there was no relationship between neuropsychological test scores and summed vascular risk factors or apolipoprotein E genotypes, presence of the methylenetetrahydrofolate reductase gene mutation was associated with slowed reaction time. The differential relationships between clinical, etiological and genetic risks and neuropsychological performance supports the presence of unique pathophysiological mechanisms in distinct subgroups of patients. These findings underscore the need to consider subtypes when investigating neuropsychological deficits in patients with depression.

Neurobehavioral functioning in obstructive sleep apnea: differential effects of sleep quality, hypoxemia and subjective sleepiness

This study evaluated the relationship between neuropsychological and affective functioning, subjective sleepiness and sleep-disordered breathing in 100 patients with obstructive sleep apnea (OSA). Using principal components analysis, three indices of sleep-disordered breathing were identified from polysomnography: sleep disturbance, extent of nocturnal hypoxemia, and sleep quality. Poorer sleep quality was related to slower processing speed, somatic symptomatology and tension-anxiety levels. Nocturnal hypoxemia was related to visuconstructional abilities, processing speed and mental flexibility. Patients who had high levels of subjective sleepiness had poorer performances on a complex task of executive functioning and higher levels of tension-anxiety. These results imply a differential effect of sleep-disordered breathing on domains of neuropsychological functioning. Additionally, they suggest that a patient’s subjective level of sleepiness is a good predictor of certain aspects of neurobehavioral functioning.

Late-onset depression: genetic, vascular and clinical contributions.

BACKGROUND Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. METHODS Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 549 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). RESULTS Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. CONCLUSIONS Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Impaired MMN/P3a complex in first-episode psychosis: Cognitive and psychosocial associations

Mismatch negativity (MMN) is a neurophysiological indicator of the brains ability to extract relevant information from an irrelevant background. The P3a orienting response often accompanies MMN in deviance detection paradigms. Both MMN and P3a have been described as reliable biomarkers of schizophrenia. MMN/P3a impairments are associated with deficits in verbal memory and attentional switching, reflecting dysfunctions in the temporal and frontal systems, respectively. It remains unresolved whether MMN/P3a are robust biomarkers of psychosis in first-episode patients. Thirty-four young people (18 to 30years) were assessed in this study; 17 first-episode psychosis (FEP) patients were compared to 17 healthy controls. To elicit MMN/P3a, a two-tone passive auditory oddball paradigm with 8% duration deviants was used; event-related potentials were recorded at frontal, central and temporal (mastoid) sites. Neuropsychological assessments included processing speed, attentional switching, simple attention, and verbal learning and memory. Social functioning and quality of life measures were also obtained. The FEP group showed significantly reduced MMN amplitudes compared to controls. The FEP group also showed significantly reduced P3a amplitudes at frontal and central sites compared with controls. As expected, the FEP group also showed significant deficits in attention and verbal learning/memory. Correlational analyses found strong associations between fronto-central MMN/P3a peak amplitude and cognitive/psychosocial functioning. This study provides evidence of early neurobiological markers in young people with FEP. These findings suggest that MMN/P3a impairments are present at early stages of psychosis and that fundamental pre-attentive/deviance detection deficits may mark the beginning of progressive underlying changes with illness onset. Such deficits in FEP appear to have important links with higher-order cognitive and psychosocial functioning.

Freezing of gait in Parkinson’s disease is associated with functional decoupling between the cognitive control network and the basal ganglia

Recent neuroimaging evidence has led to the proposal that freezing of gait in Parkinsons disease is due to dysfunctional interactions between frontoparietal cortical regions and subcortical structures, such as the striatum. However, to date, no study has employed task-based functional connectivity analyses to explore this hypothesis. In this study, we used a data-driven multivariate approach to explore the impaired communication between distributed neuronal networks in 10 patients with Parkinsons disease and freezing of gait, and 10 matched patients with no clinical history of freezing behaviour. Patients performed a virtual reality gait task on two separate occasions (once ON and once OFF their regular dopaminergic medication) while functional magnetic resonance imaging data were collected. Group-level independent component analysis was used to extract the subject-specific time courses associated with five well-known neuronal networks: the motor network, the right- and left cognitive control networks, the ventral attention network and the basal ganglia network. We subsequently analysed both the activation and connectivity of these neuronal networks between the two groups with respect to dopaminergic state and cognitive load while performing the virtual reality gait task. During task performance, all patients used the left cognitive control network and the ventral attention network and in addition, showed increased connectivity between the bilateral cognitive control networks. However, patients with freezing demonstrated functional decoupling between the basal ganglia network and the cognitive control network in each hemisphere. This decoupling was also associated with paroxysmal motor arrests. These results support the hypothesis that freezing behaviour in Parkinsons disease is because of impaired communication between complimentary yet competing neural networks.

Delayed sleep phase in young people with unipolar or bipolar affective disorders

BACKGROUND Circadian disturbances may play a key role in the pathogenesis of some forms of mood disorders. Despite marked changes in circadian rhythms during the normal course of adolescence and young adulthood, less is known about changes in the 24-h sleep-wake cycle in young persons with mood disorders. METHODS Seventy-five young participants with mood disorders (unipolar: n=46, 20.1 ± 4.7 years old; bipolar I or II: n=29, 23.2 ± 4.3) and 20 healthy participants (24.8 ± 2.5 years old) underwent actigraphy monitoring during a depressive phase over seven consecutive days and nights. Sleep phase delay was defined as mean sleep onset ≥ 1:30 am and/or sleep offset ≥ 1 0:00 am. RESULTS A delayed sleep phase was found in 62% of participants with bipolar disorders when depressed, compared with 30% of those with unipolar depression (χ(2)=6.0, p=0.014) and 10% of control participants (χ(2)=11.2, p<0.001). Sleep offset times were significantly later in subjects with mood disorders compared to the control group, and later in those with bipolar as compared with unipolar disorders (all p ≤ 0.043). LIMITATIONS This study was cross-sectional and the depressed groups were somewhat younger compared to the healthy controls. Longitudinal studies are required to determine the predictive significance of these findings. CONCLUSIONS Young patients with mood disorders, especially those with bipolar disorders, are particularly likely to have a delayed sleep phase. Therapies focused on advancing sleep phase may be of specific benefit to these young persons.

Targeted primary care-based mental health services for young Australians

Objective: To assess the extent to which youth‐specific, mental health care centres engage young people (12–25 years of age) in treatment, and to report the degree of psychological distress, and the diagnostic type, stage of illness, and psychosocial and vocational impairment evident in these young people.