Assessing Depressive Symptoms in Patients With Cancer Treated With Interleukin-2: A Comparison of 2 Measures.

BACKGROUND: High-dose interleukin-2 is a therapy available for individuals with renal cell carcinoma; however, it can produce adverse effects, specifically depressive symptoms. There is limited information regarding the trajectory of depressive symptoms and measurement-based care assessment of depressive symptoms. OBJECTIVE: The purpose was to describe the trajectory of depressive symptoms and compare 2 depression measures. METHODS: A descriptive, mixed-method case study approach was used to describe the longitudinal trajectory of depressive symptoms The qualitative assessment included a journal entry and an interview. The quantitative depression symptom severity measures included the 8-item self-report Patient-Reported Outcomes Measurement Information System Depression and the 30-item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C). RESULTS: Ten cases were enrolled. The maximum number of interleukin-2 doses that any patient received within a single hospitalization ranged from 4 to 12. Mean scores on the 8-item Patient-Reported Outcomes Measurement Information System Depression showed no changes in depressive symptoms from pretreatment to posttreatment, nor across hospitalizations. Mean total scores on the IDS-C increased from "normal" to "mild severity" depressive symptom range across all treatment cycles, suggesting transient depressive symptoms within hospitalizations. Qualitative data from the case supported the IDS-C increase, suggesting that the patient developed depressive symptoms pretreatment to posttreatment. CONCLUSIONS: Understanding the trajectory of depressive symptoms allows for the identification of critical time points when depressive symptoms present and change across treatment. It is critical to use measurement-based care using validated measures to assess for the presence and changes in depressive symptoms. IMPLICATIONS FOR PRACTICE: Validated self-report or clinician-rated depression symptom measures should be used to document the presence or absence of depressive symptoms in this population.

Impact of Depression and Nicotine Dependence on Executive Functioning in Rural Older Adult Smokers: A Brief Report (NCT02510716).

INTRODUCTION: Rural older adults are an underserved population with high rates of smoking and related morbidity and mortality. Age-related executive function deficits are common in older smokers; however, the association of depression and nicotine dependence on executive function has not been explored. This study addressed whether depression and nicotine dependence are related to executive dysfunction in rural older adult smokers. METHODS: The sample included 40 rural older adults recruited from two primary care clinics in North Carolina. Executive function was evaluated with the Behavioral Regulation Index (BRI), Metacognition Index, and Global Executive Composite (GEC) T scores from the Behavior Rating Inventory of Executive Function-Adult. Nicotine dependence and depression symptoms were assessed using the Fagerstrom Test and Center for Epidemiologic Depression Scale-10, respectively. Analysis of variance was used to explore whether depression and/or nicotine dependence influences executive function. Nondirectional tests were performed with significance set at .10. RESULTS: Smokers who screened positive for depression had significantly greater executive dysfunction than those who did not (BRI: p = .0003, Metacognition Index: p < .0001, GEC: p < .0001), and moderate/high dependence was associated with greater executive function deficits compared with those with mild dependence (BRI: p = .0942). Together, depression and nicotine dependence explained 50% of the variability of the GEC overall scores. CONCLUSIONS: Executive dysfunction is common in rural older adult smokers and associated with depression and nicotine dependence severity. Futures studies should test the relationship of executive function and smoking cessation in the older adult population as it may have implications for cessation in this population.

Brief cognitive screening instruments for electroconvulsive therapy: Which one should I use?

OBJECTIVES: To review brief cognitive screening instruments for routine clinical monitoring in electroconvulsive therapy. METHODS: Brief cognitive screening instruments specifically developed for electroconvulsive therapy and commonly used brief generalised cognitive screening instruments were reviewed with relative advantages and disadvantages highlighted. RESULTS: Several brief cognitive screening tests designed for use in electroconvulsive therapy have been found sensitive for monitoring electroconvulsive therapy-related cognitive side effects. The choice of a brief generalised cognitive screening instrument for use in an electroconvulsive therapy clinical context comes with several pertinent considerations. CONCLUSION: Electroconvulsive therapy is a highly effective treatment for pharmacoresistant and severe neuropsychiatric illness although cognitive side effects can be a barrier for treatment. Routine monitoring using brief cognitive screening instruments has advantages in busy clinical settings and can assist with optimising patient outcomes. More detailed neuropsychological assessment is recommended if the results from brief cognitive screening raise concerns.

TrkB activation by 7, 8-dihydroxyflavone increases synapse AMPA subunits and ameliorates spatial memory deficits in a mouse model of Alzheimer's disease.

We recently demonstrated that activation of tyrosine receptor kinase B (TrkB) by 7, 8-dihydroxyflavone (7, 8-DHF), the selective TrkB agonist, increased surface alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPARs) AMPA receptor subunit GluR1 (GluA1) subunit expression at the synapses of Fragile X Syndrome mutant mice. This present study investigated the effects of 7, 8-DHF on both memory function and synapse structure in relation to the synapse protein level of AMPARs in the Tg2576 Alzheimer's disease (AD) mouse model. The study found that chronic oral administration of 7, 8-DHF significantly improved spatial memory and minimized dendrite loss in the hippocampus of Tg2576 mice. A key feature of 7, 8-DHF action was the increased expression of both GluA1 and GluA2 at synapses. Interestingly, 7, 8-DHF had no effect on the attenuation of amyloid precursor protein or Aß exhibiting in the Tg2576 AD brains, yet it activated the phosphorylation of TrkB receptors and its downstream signals including CaMKII, Akt, Erk1/2, and cAMP-response element-binding protein. Importantly, cyclotraxin B (a TrkB inhibitor), U0126 (a Ras-ERK pathway inhibitor), Wortmannin (an Akt phosphorylation inhibitor), and KN-93 (a CaMKII inhibitor) counteracted the enhanced expression and phosphorylation of AMPAR subunits induced by 7, 8-DHF. Collectively, our results demonstrated that 7, 8-DHF acted on TrkB and resolved learning and memory impairments in the absence of reduced amyloid in amyloid precursor protein transgenic mice partially through improved synaptic structure and enhanced synaptic AMPARs. The findings suggest that the application of 7, 8-DHF may be a promising new approach to improve cognitive abilities in AD. We provided extensive data demonstrating that 7, 8-dihydroflavone, the TrkB agonist, improved Tg2576 mice spatial memory. This improvement is correlated with a reversion to normal values of GluA1 and GluA2 AMPA receptor subunits and dendritic spines in CA1. This work suggests that 7, 8-DHF is a suitable drug to potentiate in vivo Tropomyosin receptor kinase B (TrkB) signaling in the Alzheimer's disease mice model.

School Scoliosis Screenings: Family Experiences and Potential Anxiety After Orthopaedic Referral.

STUDY DESIGN: Cross-sequential study design that used data from Texas Scottish Rite Hospital for Children (TSRHC). OBJECTIVE: Examine anxiety symptoms and family experiences subsequent to school scoliosis screening (SSS) referrals. SUMMARY OF BACKGROUND DATA: Use of SSS remains controversial. Prior research suggested that SSS programs may result in anxiety for both children and parents. Unfortunately, no study has examined the SSS referral processes and anxiety in families. METHODS: Study consisted of 2 groups-patients/parents from TSRHC evaluated for Adolescent Idiopathic Scoliosis (AIS) (n = 27) and control participants/parents (n = 27) between ages 9 and 17. All participants completed the primary outcome measure (State-Trait Anxiety Inventory) before and after the scoliosis evaluation or controlled wait time. Parents also rated experience and satisfaction with SSS. RESULTS: Compared with the control group, children/parents in patient group experienced significantly elevated levels of state-anxiety at preappointment. Children/parents in the patient group not diagnosed with AIS experienced a significant decline in state-anxiety. Children/parents in the patient group diagnosed with AIS continued to report elevated levels of anxiety. The control group remained consistent, reporting of low levels of anxiety pre to post. More than half (55.5%) of families indicated they received no information from the school about scoliosis. A third of the families who received information indicated it did not adequately address their concerns. Nonetheless, most families reported overall satisfaction with SSS. CONCLUSION: This study suggested that children and parents referred through the SSS program experienced significantly elevated levels of state-anxiety. This supports the subjective concerns of anxiety experiences in families voiced by researchers previously. However, families deemed the costs of the SSS referral process as worth the benefits. Though challengers of SSS programs were accurate in observing anxiety in families, it may not constitute significant burden to eliminate SSS programs altogether. Improvements to the current system may be warranted. LEVEL OF EVIDENCE: 3.

Small molecules activating TrkB receptor for treating a variety of CNS disorders.

The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. Indeed, both have been implicated in the pathophysiology of numerous diseases. Although the remarkable therapeutic potential of BDNF has generated much research over the past decade, the poor pharmacokinetics and adverse side effect profile have limited its clinical usefulness of BDNF. Small compounds that mimic BDNF's neurotrophic signaling and overcome the pharmacokinetic and side effect barriers may have greater therapeutic potential. The purpose of this review is to provide a survey of the various strategies taken towards the development of small molecule mimetics for BDNF and the selective TrkB agonist. A particular focus was placed on TrkB agonist 7, 8-dihydroxyflavone, which modulates multiple functions and has demonstrated remarkable therapeutic efficacy in a variety of central nervous system disease models. Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB binding domains of BDNF, loop II-LM22A compounds that directly activate TrkB. These alternative molecules have shown promise in preclinical studies and may be included in prospective clinical investigations.

Assessing anxious features in depressed outpatients.

Both the 17-item Hamilton Rating Scale for Depression (HRSD(17)) and 30-item Inventory of Depressive Symptomatology - Clinician-rated (IDS-C(30) ) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSD(ANX) and IDS-C(ANX)) in a large sample (N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self-report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSD(ANX) and IDS-C(ANX) were highly correlated (r = 0.75) and both had moderate internal consistency given their limited number of items (HRSD(ANX) Cronbach's alpha = 0.48; IDS-C(ANX) Cronbach's alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSD(ANX) and seven or eight for the IDS-C(ANX) . It would seem beneficial to delete item 17 (loss of insight) from the HRSD(ANX) as it negatively correlated with the scale's total score. Both the HRSD(ANX) and IDS-C(ANX) subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes.

Neuropsychologic effects of neuromodulation techniques for treatment-resistant depression: a review.

Electroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies, including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions.