Blunted reward responsiveness in remitted depression

Major depressive disorder has been associated with blunted responsiveness to rewards, but inconsistencies exist whether such abnormalities persist after complete remission. To address this issue, across two independent studies, 47 adults with remitted major depressive disorder (rMDD) and 37 healthy controls completed a Probabilistic Reward Task, which used a differential reinforcement schedule of social or monetary feedback to examine reward responsiveness (i.e., ability to modulate behavior as a function of reinforcement history). Relative to controls, adults with rMDD showed blunted reward responsiveness. Importantly, a history of depression predicted reduced reward learning above and beyond residual depressive (including anhedonic) symptoms and perceived stress. Findings indicate that blunted reward responsiveness endures even when adults are in remission and might be a trait-related abnormality in MDD. More research is warranted to investigate if blunted reward responsiveness may predict future depressive episodes and whether targeting reward-related deficits may prevent the re-occurrence of the disorder.     

Cost analysis of risperidone long-acting injection in the treatment of schizophrenia and schizoaffective disorders in Hong Kong: An approach using generalised estimating equations

Schizophrenia is one of the most expensive psychiatric illnesses. This study compared retrospectively health-care resources consumed 12 months before and 24 months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A mirror-image analysis was conducted using data (N=191) from three public hospitals in Hong Kong from 2003 to 2007. The main outcome measure was hospitalisation cost. Other secondary outcomes such as hospitalisation episodes, outpatient visits and adverse events were also compared. A predictive model was established using linear regression based on generalised estimating equations. Analysis showed that RLAI was associated with a reduction in hospitalisation cost by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value <0.05). Days of hospitalisation were reduced by 1538 days (10.1%) (15,271 vs. 13,733; P-value <0.05). The predictive model estimated that the hospitalisation cost of patients using RLAI was only 11.1% (3.1–3.93%, 95% confidence interval (CI)) compared to those receiving conventional antipsychotics combined with oral risperidone. Cost of hospitalisation was significantly reduced after RLAI therapy. However, results should be considered as indicative or suggestive only, due to potential channelling bias where certain drug regimens are preferentially prescribed to patients with particular conditions. The findings from our study may be useful in health-care decision making considering treatment options for schizophrenia in resource-limited settings.     

When nouns and verbs degrade: Facilitating communication in semantic dementia

Background: Little is known about how to maintain communicative effectiveness in semantic dementia as the disease progresses from impairment in word retrieval to a loss of conceptual knowledge.

Aim: The purpose of this study is twofold. The first objective is to characterise communicative effectiveness using a modified framework derived from Chapman and Ulatowska (1997 Chapman, S. B. and Ulatowska, H. K. 1997. “Discourse in dementia: Consideration of consciousness.”. In Language structure, discourse and the access to consciousness, Edited by: Stamenov, M. I. 155–188. Philadelphia: John Benjamin Publishing Company.  [Google Scholar]) that integrates two components: codification of ideas (falling on a continuum from verbal to nonverbal and generative to automatic forms) and functions of communication (imaginative, heuristic, informative, personal, interactional, regulatory, and instrumental). The second objective is to outline principles of a discourse intervention that focuses on communicative effectiveness.

Method & Procedures: The participant was Mr Bobby V, a man with semantic dementia. His communication abilities were characterised at diagnosis and 24 months later using the framework of communicative effectiveness, based on discourse samples, clinical observation, and caregiver report. From the time of diagnosis, Bobby V received discourse intervention, which focused on maintaining his communication abilities using all available communication resources. We outline principles of discourse intervention in semantic dementia based on our experience of delivering individual and group intervention to Bobby V.

Outcomes and Results: The communicative effectiveness framework described here could be used to characterise communication skills, set therapy goals, and monitor progress in semantic dementia. Discourse intervention likely facilitated Bobby V's continued success in maintaining communication despite progressive loss of nouns and verbs.

Conclusions: Targeting conversational effectiveness in terms of communicative functions offers a promising and ecologically valuable intervention for people with semantic dementia, as it allows individuals with this form of dementia to connect meaningfully with people in their immediate surroundings well into the later stages of the disease.     

Surgical treatment of complex spinal cord lipomas

Purpose

This paper shows the long-term benefits of total/near-total resection of complex spinal cord lipomas and meticulous reconstruction of the neural placode, and specifically, its advantage over partial resection, and over non-surgical treatment for the subset of children with asymptomatic virgin lipomas.

Methods

The technique of total resection and placode reconstruction, together with technical nuances, are described in detail. We added 77 patients with complex lipomas to our original lipoma series published in 2009 and 2010, to a total of 315 patients who had had total or near-total resection and followed for a span of 20 years. Long-term outcome is measured by overall progression-free survival (PFS) with the Kaplan–Meier analysis, and by subgroup Cox proportional recurrence hazard analysis for the influence on outcome of 4 predictor variables of lipoma type, presence of symptoms, prior surgery, and post-operative cord–sac ratio. These results are compared to an age-matched, lesion-matched series of 116 patients who underwent partial lipoma resection over 11 years. The results for total resection is also compared to two large published series of asymptomatic lipomas followed without surgery over 9 to 10 years, to determine whether prophylactic total resection confers better long-term protection over conservative treatment for children with asymptomatic lipomas..

Results

The PFS after total resection for all lipoma types and clinical subgroups is 88.1 % over 20 years versus 34.6 % for partial resection at 10.5 years (p?<?0.0001). Culling only the asymptomatic patients with virgin (previously unoperated) lipomas, the PFS for prophylactic total resection for this subgroup rose to 98.8 % over 20 years, versus 67 % at 9 years for one group of non-surgical treatment and 60 % at 10 years for another group of conservative treatment. Our own as well as other published results of partial resection also compare poorly to non-surgical treatment for the subset of asymptomatic virgin lipomas. Multivariate subgroup analyses show that cord–sac ratio is the only independent variable that predicts outcome, with a 96.9 % PFS for ratio <30 % (loosest sac), 86.2 % for ratio between 30 and 50 %, and 78.3 % for ratio >50 % (tightest sac), and a threefold increase in recurrence hazard for high ratios (p?=?0.0009). Pre-operative patient profiling using multiple correspondence analysis shows the ideal patient for total resection is a child less than 2 years old with a virgin asymptomatic lipoma, who, with a PFS of 99.2 %, is virtually cured by total resection.

Conclusion

Total/near-total resection of complex lipomas and complete reconstruction of the neural placode achieves far better long-term protection against symptomatic recurrence than partial resection for all lesions; and for the subset of asymptomatic virgin lipomas, also better than non-surgical treatment. Partial resection in many cases produces worse outcome than conservative treatment for asymptomatic lesions.     

Efficacy of therapeutic play for pediatric brain tumor patients during external beam radiotherapy

Objective

External beam radiotherapy (EBRT) is frequently used to improve disease control for pediatric brain tumor patients. However, to facilitate the radiotherapy (RT) procedure, “forced” type interventions including conscious sedation or general anesthesia are frequently used to manage patients’ fear and anxiety. The aim of this study was to investigate the effects of therapeutic play (TP) in reducing anxiety for pediatric brain tumor patients treated by EBRT.

Methods

Between April 1st and September 30th, 2009, 19 young brain tumor patients, aged 3–15 years and recommended for RT, were recruited: ten to a control group and nine to the study intervention group. The study group was introduced with TP during EBRT. The Beck Youth Anxiety Inventory and the Faces Anxiety Scale were used to evaluate patients’ psychological levels of anxiety. The heart rate variability and salivary cortisol concentrations were used to indicate the patients’ physical levels of anxiety. Both the psychological and physiological tests were administered to all subjects before and after the RT procedure.

Results

The study group had significantly lower anxiety scores and expressed fewer negative emotions than did the control group before EBRT.

Conclusions

TP can not only improve the quality of medical services but can also reduce costs and staffing demands. In addition, it can help lower young patients’ anxiety and fear during medical procedures. As a result, it further decreases the potential negative impacts of hospitalization on these young patients.     

The interface between phonetic and lexical abilities in early Cantonese language development

Data from the Cantonese Communicative Development Inventory (CCDI) is used to review the phonological preferences of younger (16–22 months) and older (23–30 month) groups of children in the lexical items they are reported to be able to say. Analogous results to those found for English emerge from the Cantonese data: the younger group display selectivity in the initial consonants of words they say, and their preferences accord with developmental tendencies in Cantonese phonology. From children whose scores fell below the tenth percentile of the CCDI, a subset were followed up 1 year later and their linguistic progress evaluated. Only a proportion of these children were below still below the tenth percentile for vocabulary at follow‐up. Their lexical immaturities were accompanied by limited phonetic abilities. The implications of the findings are discussed.     

Estrogen‐related receptor β deletion modulates whole‐body energy balance via estrogen‐related receptor γ and attenuates neuropeptide Y gene expression

Estrogen‐related receptors (ERRs) α, β and γ are orphan nuclear hormone receptors with no known ligands. Little is known concerning the role of ERRβ in energy homeostasis, as complete ERRβ‐null mice die mid‐gestation. We generated two viable conditional ERRβ‐null mouse models to address its metabolic function. Whole‐body deletion of ERRβ in Sox2‐Cre:ERRβ^lox/lox mice resulted in major alterations in body composition, metabolic rate, meal patterns and voluntary physical activity levels. Nestin‐Cre:ERRβ^lox/lox mice exhibited decreased expression of ERRβ in hindbrain neurons, the predominant site of expression, decreased neuropeptide Y (NPY) gene expression in the hindbrain, increased lean body mass, insulin sensitivity, increased energy expenditure, decreased satiety and decreased time between meals. In the absence of ERRβ, increased ERRγ signaling decreased satiety and the duration of time between meals, similar to meal patterns observed for both the Sox2‐Cre:ERRβ^lox/lox and Nestin‐Cre:ERRβ^lox/lox strains of mice. Central and/or peripheral ERRγ signaling may modulate these phenotypes by decreasing NPY gene expression. Overall, the relative expression ratio between ERRβ and ERRγ may be important in modulating ingestive behavior, specifically satiety, gene expression, as well as whole‐body energy balance.     

Canonical transient receptor potential channel subtype 3‐mediated hair cell Ca2+ entry regulates sound transduction and auditory neurotransmission

The physiological significance of canonical transient receptor potential (TRPC) ion channels in sensory systems is rapidly emerging. Heterologous expression studies show that TRPC3 is a significant Ca²⁺ entry pathway, with dual activation via G protein‐coupled receptor (GPCR)–phospholipase C–diacylglycerol second messenger signaling, and through negative feedback, whereby a fall in cytosolic Ca²⁺ releases Ca²⁺–calmodulin channel block. We hypothesised that the latter process contributes to cochlear hair cell cytosolic Ca²⁺ homeostasis. Confocal microfluorimetry with the Ca²⁺ indicator Fluo‐4 acetoxymethylester showed that, when cytosolic Ca²⁺ was depleted, Ca²⁺ re‐entry was significantly impaired in mature TRPC3^?/? inner and outer hair cells. The impact of this disrupted Ca²⁺ homeostasis on sound transduction was assessed with the use of distortion product otoacoustic emissions (DPOAEs), which constitute a direct measure of the outer hair cell transduction that underlies hearing sensitivity and frequency selectivity. TRPC3^?/? mice showed significantly stronger DPOAE (2f₁ ? f₂) growth functions than wild‐type (WT) littermates within the frequency range of best hearing acuity. This translated to hyperacusis (decreased threshold) measured by the auditory brainstem response (ABR). TRPC3^?/? and WT mice did not differ in the levels of temporary and permanent threshold shift arising from noise exposure, indicating that potential GPCR signaling via TRPC3 is not pronounced. Overall, these data suggest that the Ca²⁺ set‐point in the hair cell, and hence membrane conductance, is modulated by TRPC3s through their function as a negative feedback‐regulated Ca²⁺ entry pathway. This TPRC3‐regulated Ca²⁺ homeostasis shapes the sound transduction input–output function and auditory neurotransmission.