Scholarly literature review: management of neurocognitive late effects with stimulant medication

OBJECTIVE: To examine the extant literature on stimulant drug therapy for survivors of childhood cancer during the late-effects period. METHODS: A review of literature is provided on the mechanism of and cognitive toxicities for children and adolescents treated for acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) as well as the pharmacotherapy of stimulant medications, with a specific review of literature on the efficacy and safety of the stimulants for children with ALL and BT. RESULTS: Only four studies were found that have examined the effects of stimulant medication on the cognitive toxicities of childhood survivors of cancer during the late-effects period and only two of these investigations were controlled clinical trials. Findings suggest efficacy of the stimulants on parent and teacher ratings of attention and putative tasks of attention and executive functioning. CONCLUSIONS: Although there is some preliminary support for the efficacy and safety of the stimulants for survivors of ALL and BT, more research is needed concerning the long-term effects of the stimulants among cancer survivors.     

Lateralized cerebral dysfunction in schizophrenia and depression: gender and medication effects.

The neuropsychological functioning of 52 schizophrenic and 39 major depressive patients was examined using the four Luria-Nebraska Neuropsychological Battery lateralization scales, with the effects of gender and medication status examined alone and in interaction with diagnosis and laterality variables. Comparisons between the diagnostic groups revealed that gender influences some aspects of neuropsychological performance, particularly those involving bilateral complex cognitive-perceptual rather than sensorimotor skills. This effect was more distinct for depressives than schizophrenics when cerebral lateralization differences were present. There was no significant left hemisphere disadvantage for schizophrenics which was gender-related. Medication status revealed no appreciable effects for depressives, although both male and female schizophrenics receiving neuroleptics showed a greater degree of complex perceptual-cognitive dysfunction compared to unmedicated schizophrenics. Level of cerebral impairment was equivalent for the right and left hemispheres for both groups. Consequently, these data are not consistent with other findings demonstrating differential hemispheric disadvantages between schizophrenia and depression.     

Messages of medication: effects of actual versus informed medication status on hyperactive boys' expectancies and self-evaluations

After 15 boys with attention-deficit hyperactivity disorder (ADHD) were informed that they had taken either medication or placebo, they completed computer tasks, self-assessments, and causal judgments. The boys predicted better performance when told they were on medication versus placebo. For self-evaluations, medication status and information interacted, with boys actually taking placebo rating themselves more positively when told they had taken medication versus placebo. These effects were more apparent following failure than success. Both ADHD and comparison boys overestimated future classroom performance, with the former more unrealistic. Discussion focused on difficulties in assessing children's causal reasoning and the need to monitor emanative effects of pharmacotherapy on self-cognitions.     

Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach.

BACKGROUND: The aim of this study was to assess visual information processing and cognitive functions in unaffected siblings of patients with schizophrenia, bipolar disorder and control subjects with a negative family history. METHODS: The siblings of patients with schizophrenia (N = 25), bipolar disorder (N = 20) and the controls subjects (N = 20) were matched for age, education, IQ, and psychosocial functioning, as indexed by the Global Assessment of Functioning scale. Visual information processing was measured using two visual backward masking (VBM) tests (target location and target identification). The evaluation of higher cognitive functions included spatial and verbal working memory, Wisconsin Card Sorting Test, letter fluency, short/long delay verbal recall and recognition. RESULTS: The relatives of schizophrenia patients were impaired in the VBM procedure, more pronouncedly at short interstimulus intervals (14, 28, 42 ms) and in the target location task. Marked dysfunctions were also found in the spatial working memory task and in the long delay verbal recall test. In contrast, the siblings of patients with bipolar disorder exhibited spared performances with the exception of a deficit in the long delay recall task. CONCLUSIONS: Dysfunctions of sensory-perceptual analysis (VBM) and working memory for spatial information distinguished the siblings of schizophrenia patients from the siblings of individuals with bipolar disorder. Verbal recall deficit was present in both groups, suggesting a common impairment of the fronto-hippocampal system.     

Effects of neurocognitive enhancement therapy in schizophrenia: Normalisation of memory performance

Introduction. A preponderance of research indicates that cognitive function in schizophrenia can be improved through cognitive remediation. However, few studies have attempted to characterise the extent of improvement relative to nonpsychiatric controls.

Method. Cognitive performance on reaction time, digit recall, and word recall of 58 schizophrenia patients at baseline and after 6 months of cognitive remediation was compared to the performance on these tasks of 39 community controls. Schizophrenia patients participated in Neurocognitive Enhancement Therapy (NET) and received hierarchical training on the memory tasks, but not on the reaction time task, which was only administered at intake and follow‐up.

Results. The schizophrenia sample showed significantly poorer performances than the community control sample on all three tasks at baseline. NET led to significant improvements in performance on trained memory tasks, but not the untrained reaction time task. There was a significant increase in the proportion of schizophrenia patients who achieved normal range performance on the memory tasks.

Conclusions. 52% of schizophrenia patients who were impaired on at least one of the memory tasks normalised their performance on at least one of those tasks as a result of cognitive training. Results suggest that clinically meaningful improvement may be possible using cognitive remediation.     

Olanzapine counteracts reduction of brain-derived neurotrophic factor and TrkB receptors in rat hippocampus produced by haloperidol

Recently, we have reported studies in rats showing that the atypical antipsychotic olanzapine (OLZ), in contrast to haloperidol (HAL), was not associated with reduction of markers of central cholinergic neurons as well as decrements in cognitive performance after chronic exposure. We compared the effect of 45 day chronic exposure of HAL (2 mg/kg per day) to OLZ (10 mg/kg per day) on brain-derived neurotrophic factor (BDNF)) and its high affinity receptor TrkB in rat hippocampus. Since the use of OLZ is presently preferred over HAL in patients, effects of its post-treatment on HAL-induced changes in the expression of BDNF and its TrkB receptor were also investigated. OLZ was administered after 45 days of HAL exposure. HAL, but not OLZ, significantly reduced the levels of BDNF in hippocampus. These changes in BDNF paralleled the levels of TrkB receptors. Furthermore, post-treatment with OLZ markedly restored the HAL treatment associated reductions in both BDNF and TrkB receptors in hippocampus.     

Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat

Iron deficiency (ID) is a common nutrient deficiency worldwide. This condition is linked to changes in myelin formation, dopaminergic function, and energy metabolism. Early ID results in persistent long-term cognitive and behavioral disturbances in children, despite a return to normal iron status. The present study assesses formerly ID adult rats on maze learning tasks that depend on specific brain regions related to learning, specifically the hippocampus, striatum, and amygdala. Rat dams were fed ID chow starting on gestational Day 2 through postnatal Day 7, and behavioral testing began at postnatal Day 65--following a return to normal iron status. Formerly ID rats exhibited delayed acquisition of the hippocampus-dependant task and no differences from controls on the striatum- and amygdala-dependent tasks. These findings likely reflect long-term reduction in but not abolition of hippocampus-dependent learning and preserved function in other brain structures (e.g., striatum and amygdala).     

Articulatory rehearsal in verbal working memory: a possible neurocognitive endophenotype that differentiates between schizophrenia and schizoaffective disorder

Recent fMRI studies have identified brain systems underlying different components of working memory in healthy individuals. The aim of this study was to compare the functional integrity of these neural networks in terms of behavioural performance in patients with schizophrenia, schizoaffective disorder and healthy controls. In order to detect specific working memory deficits based on dysfunctions of underlying brain circuits we used the same verbal and visuospatial Sternberg item-recognition tasks as in previous neuroimaging studies. Clinical and performance data from matched groups consisting of 14 subjects each were statistically analyzed. Schizophrenic patients exhibited pronounced impairments of both verbal and visuospatial working memory, whereas verbal working memory performance was preserved in schizoaffective patients. The findings provide first evidence that dysfunction of a brain system subserving articulatory rehearsal could represent a biological marker which differentiates between schizophrenia and schizoaffective disorder.     

Observation learning versus physical practice leads to different consolidation outcomes in a movement timing task

Motor learning is a process that extends beyond training sessions. Specifically, physical practice triggers a series of physiological changes in the CNS that are regrouped under the term “consolidation” (Stickgold and Walker 2007). These changes can result in between-session improvement or performance stabilization (Walker 2005). In a series of three experiments, we tested whether consolidation also occurs following observation. In Experiment 1, participants observed an expert model perform a sequence of arm movements. Although we found evidence of observation learning, no significant difference was revealed between participants asked to reproduce the observed sequence either 5 min or 24 h later (no between-session improvement). In Experiment 2, two groups of participants observed an expert model perform two distinct movement sequences (A and B) either 10 min or 8 h apart; participants then physically performed both sequences after a 24-h break. Participants in the 8-h group performed Sequence B less accurately compared to participants in the 5-min group, suggesting that the memory representation of the first sequence had been stabilized and that it interfered with the learning of the second sequence. Finally, in Experiment 3, the initial observation phase was replaced by a physical practice phase. In contrast with the results of Experiment 2, participants in the 8-h group performed Sequence B significantly more accurately compared to participants in the 5-min group. Together, our results suggest that the memory representation of a skill learned through observation undergoes consolidation. However, consolidation of an observed motor skill leads to distinct behavioural outcomes in comparison with physical practice.     

Predictors of medical student interest in Indigenous health learning and clinical practice: a Canadian case study

Background

Including content on Indigenous health in medical school curricula has become a widely-acknowledged prerequisite to reducing the health disparities experienced by Indigenous peoples in Canada. However, little is known about what levels of awareness and interest medical students have about Indigenous peoples when they enter medical school. Additionally, it is unclear whether current Indigenous health curricula ultimately improve students’ beliefs and behaviours.

Methods

A total of 129 students completed a 43-item questionnaire that was sent to three cohorts of first-year medical students (in 2013, 2014, 2015) at one undergraduate medical school in Canada. This survey included items to evaluate students’ sociopolitical attitudes towards Indigenous people, knowledge of colonization and its links to Indigenous health inequities, knowledge of Indigenous health inequities, and self-rated educational preparedness to work with Indigenous patients. The survey also assessed students’ perceived importance of learning about Indigenous peoples in medical school, and their interest in working in an Indigenous community, which were examined as outcomes. Using principal component analysis, survey items were grouped into five independent factors and outcomes were modelled using staged multivariate regression analyses.

Results

Generally, students reported strong interest in Indigenous health but did not believe themselves adequately educated or prepared to work in an Indigenous community. When controlling for age and gender, the strongest predictors of perceived importance of learning about Indigenous health were positive sociopolitical attitudes about Indigenous peoples and knowledge about colonization and its links to Indigenous health inequities. Significant predictors for interest in working in an Indigenous community were positive sociopolitical attitudes about Indigenous peoples. Knowledge about Indigenous health inequities was negatively associated with interest in working in an Indigenous community.

Conclusions

Students’ positive sociopolitical attitudes about Indigenous peoples is the strongest predictor of both perceived importance of learning about Indigenous health and interest in working in Indigenous communities. In addition to teaching students about the links between colonization, health inequities and other knowledge-based concepts, medical educators must consider the importance of attitude change in designing Indigenous health curricula and include opportunities for experiential learning to shape students’ future behaviours and ultimately improve physician relationships with Indigenous patients.

     

Chlamydial cervicitis: a research study from general practice

Chlamydia trachomatis was isolated from the cervix in five out of 294 women at routine cervical cytology screening. Significant sera antibody titres were obtained from six out of 115 isolate-negative women similarly screened. The antibody response increased in proportion to the past frequency and severity of cervical pathology and sexually transmitted disease.

It is suggested that the true incidence of chlamydial genital infection in general practice will be five times as high as the current cervical isolation rate.

     

Family treatment and medication dosage reduction in schizophrenia: effects on patient social functioning, family attitudes, and burden

The effects of 2 family intervention programs (supportive family management [SFM], including monthly support groups for 2 years; or applied family management [AFM], including 1 year of behavioral family therapy plus support groups for 2 years), and 3 different neuroleptic dosage strategies (standard, low, targeted) on social functioning of patients with schizophrenia. their relatives' attitudes, and family burden were examined. AFM was associated with lower rejecting attitudes by relatives toward patients and less friction in the family perceived by patients. Patients in both AFM and SFM improved in social functioning but did not differ, whereas family burden was unchanged. Medication strategy had few effects, nor did it interact with family intervention. The addition of time-limited behavioral family therapy to monthly support groups improved family atmosphere, but did not influence patient social functioning or family burden.     

Antihypertensive medication versus health promotion for improving metabolic syndrome in preventing cardiovascular events: a success rate-oriented simulation study

Background  

In practice, it is difficult to compare the effectiveness of traditional antihypertensive treatment with that of health promotion in reducing incidence rate of cardiovascular disease (IR_CVD, events/year). This simulation study compared the effectiveness of two approaches to reducing IR_CVD in a sample population: a traditional approach, in which high-risk patients are treated with conventional antihypertensive medications, and a population-based approach, in which subjects participate in a health promotion program.