Cross-cultural perspectives on coping with the risks of maternal phenylketonuria

Abstract

Maternal phenylketonuria (PKU) refers to the deleterious effects on a fetus due to high maternal phenylalanine levels. Prevention of these effects requires that women with PKU reduce their blood phenylalanine levels prior to and throughout pregnancy which means that they plan their regnancies and adhere to a phenylalanine restricted diet. According to a psycho-social model of maternal PKU, a first necessary step in preventing the effects of maternal PKU is prevention of unplanned pregnancies i.e.: using effective family planning practices. In the present study, findings are presented on seventy-five phenylketonuric women (60 from the United States and 15 from Israel) who participate in a prospective longitudinal study, to reveal the reasons why the proportion of pregnancies treated prior to conception has consistently been higher in Israel than in the United States. The two groups were interviewed and administered a battery of tests and questionnaires measuring a wide range of variables associated with family planning. Subjects in the United States were found to have more knowledge about fertility, contraception and maternal PKU. Israeli subjects held more negative attitudes towards and were less engaged in premarital sexual relationships, more frequently used oral contraceptives, had stronger motivation to have their own children, and perceived their disease to have a more negative effect on their lives. These findings suggest that the issues in maternal PKU are cultural as well as medical and psychosocial.     

Developmental Timing of Exposure to Elevated Levels of Phenylalanine Is Associated with ADHD Symptom Expression

This study addresses attention deficit hyperactivity disorder (ADHD), with a focus on how the timing of a known biological insult affects ADHD symptom expression. The sample consists of children exposed to elevated levels of phenylalanine, either postnatally as in Phenylketonuria (PKU; n = 46) or prenatally as in Maternal PKU (MPKU; n = 15). Non-hyperphenylalaninemic siblings of children with PKU (n = 18) serve as controls. Results indicate that elevated levels of phenylalanine are associated with ADHD symptoms. The manifestations of the symptom expression are dependent on exposure timing: prenatal exposure is associated with a higher likelihood of expressing hyperactive/impulsive symptoms and postnatal exposure is associated with a higher likelihood of expressing inattentive symptoms. This toxicity is dose-dependent and higher levels of phenylalanine appear more detrimental.     

Meta-Analysis of Neuropsychological Symptoms of Adolescents and Adults with PKU

Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive inborn error of phenylanaline metabolism. PKU is characterized by deficient or defective phenylalanine hydroxylase activity and persistantly increased levels of the essential amino acid phenylalanine in the circulation. The present article examines current understanding of the etiology of PKU, along with a meta-analysis examining neuropsychological and intellectual presentations in continuously treated adolescents and adults. Patients with PKU differed significantly from controls on Full-Scale IQ, processing speed, attention, inhibition, and motor control. Future research utilizing an integrative approach and detailed analysis of specific cognitive domains will assist both the scientist and clinician, and ultimately the patient.     

“I Feel Lucky” – Gratitude Among Young Adults with Phenylketonuria (PKU)

If persons with phenylketonuria (PKU) do not start a protein restricted diet in early infancy, they will suffer severe brain damage. Previous qualitative research on adults and adolescents with PKU has identified stigmatization, uncertain risk perceptions, considerable time spent on preparing food, and incongruence between the PKU diet and certain lifestyle demands. The aim of this study was to explore young and early treated Norwegian adults’ experiences, by conducting in-depth interviews in 2011 with 11 adults with PKU, aged 20–30. Being the first qualitative study on people with PKU in Norway, the process was inspired by grounded theory. All participants reflected on their own health and existence by expressing positive counterfactual thoughts. They considered themselves lucky to have had parents who had managed the diet, they were grateful for the time and place they were born, and for information and treatment availability, although the results also show some ambiguous attitudes towards the hospital which provided the treatment. The expression of gratitude in association with having PKU suggests a major positive coping strategy. It contributes to a more holistic understanding of the experiences and attitudes of young, Norwegian adults with PKU, as it provides a counterweight to the negative experiences.     

Parenting a Child with Phenylketonuria (PKU): an Interpretative Phenomenological Analysis (IPA) of the Experience of Parents

Phenylketonuria (PKU) is a rare inherited metabolic disorder which can cause neurological damage if left untreated. PKU is identified through newborn screening in developed countries, and treatment begins immediately to prevent these severe consequences. When a child is diagnosed, parents must assume immediate responsibility for the management of PKU and prevention of neurological damage. Quantitative studies have identified significant psychosocial stressors for parents, but little is known about how the parents experience this process. This study aimed to explore the experiences of parents of children with PKU under the age of two. It is the first study to examine these experiences in this way. Seven parents were interviewed about their experiences, and interpretative phenomenological analysis was used to analyse the data. Three main themes were identified: control, striving for normality and acceptance of PKU as a continuum. Links between the themes and processes underpinning the results were explored with relation to existing literature and theories from a clinical psychology perspective. The role of acceptance of PKU was central to the parent’s experiences. Clinical implications and suggestions for further research are discussed.     

Weigh(t)ing for Awareness

We wished to learn if weight perception can be extinguished by studying two patients with right hemisphere brain damage. When lifting weights simultaneously, a patient with right frontal damage was not biased in her judgments of which weight was heavier. By contrast, a patient with right parietal damage reported left-sided weights as being lighter than those on the right. Psychophysical power functions revealed that her awareness of increasing weights on the left was dampened compared to the right when lifting weights individually on each side. Strikingly, her awareness of weight changes on the left was completely abolished when she lifted weights in both hands simultaneously. She demonstrated an unusual split in awareness, being motorically aware of and actively engaged with left-sided weights while being unaware of their incremental changes.     

Thought translation, tennis and Turing tests in the vegetative state

Brain damage can cause massive changes in consciousness levels. From a clinical and ethical point of view it is desirable to assess the level of residual consciousness in unresponsive patients. However, no direct measure of consciousness exists, so we run into the philosophical problem of other minds. Neurologists often make implicit use of a Turing test-like procedure in an attempt to gain access to damaged minds, by monitoring and interpreting neurobehavioral responses. New brain imaging techniques are now being developed that permit communication with unresponsive patients, using their brain signals as carriers of messages relating to their mental states.     

Perceptual, cognitive and linguistic development after early hemispherectomy: two case studies.

Longitudinal data on perceptual-motor, cognitive, and linguistic functioning is reported for two children: one with right hemispherectomy and one with left hemispherectomy. Both levels of functioning and specific profiles of abilities within an area of function are evaluated. The subjects both show effects from damage to the brain: shortened memory span, general perceptual and motor disabilities, and somewhat depressed general intellectual functioning. Areas of comparative strength and weakness in functioning in the two subjects are suggestive of adult patterns of hemispheric specialization, despite the young age of the subjects at the time of brain damage.     

Regional brain catecholamines and memory: effects of footshock, amygdala implantation, and stimulation

Previous findings have revealed a correlation between post-training release of whole brain norepinephrine (NE) and later retention performance. The present experiment examined changes after a training footshock in NE levels, as well as the levels of the major central NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine (DA), and epinephrine (EPI) in eight brain regions. Brain levels of these amines and the metabolite were assessed 10 min after training in a one-trial inhibitory (passive) avoidance task. The results indicate that NE levels decreased significantly in neocortex, neostriatum, hypothalamus, frontal pole, septum, and brainstem, but not in hippocampus or thalamus. The decreases in NE levels were generally accompanied by increases in MHPG; the MHPG/NE ratio increased significantly in all areas in which decreases in NE were observed. DA levels decreased in neostriatum and increased in neocortex and brainstem. Epinephrine levels decreased only in the brainstem sample. Thus, the effects of training on NE are widespread, probably reflecting the release of the amine in most brain regions. Such findings are consistent with the view that posttraining release of brain NE may modulate the storage of new information in many brain regions. One especially potent treatment for modulating memory storage is electrical stimulation of the amygdala. Therefore, we also examined the effects of amygdala implantation and stimulation on brain catecholamine levels to determine whether such changes might be correlated with the effects of amygdala stimulation on memory. The results indicate that electrode implantation into the amygdala results in pervasive changes in NE levels in most brain regions tested. Against this modified baseline, the results of training and electrical stimulation were region specific and very difficult to interpret. The major conclusion which can be derived from this portion of the experiment is that the amygdala damage produced by electrode implantation produces a brain which is substantially different from that of intact animals.     

Discrimination by rhesus monkeys of diets containing supplemental amino acids.

Following an opportunity to demonstrate a preference for water with or without the addition of the amino acid isoleucine, methionine, phenylalanine, or tryptophan at a concentration proportional to that in whole egg protein, 9 monkeys were subjected on 4 occasions to a 7-day experimental week when they received an isocaloric diet containing only one-fourth the amount of protein of their normal diet. An identical low-protein diet supplemented with one of the above amino acids, again at a concentration proportional to that in egg, was presented for an equivalent period during the experimental week and the amounts consumed of each diet were compared. Ss failed to exhibit a preference or an aversion for water supplemented with any of the amino acids; however, all low-protein diets supplemented with an amino acid were consumed in greater quantities than a low-protein diet lacking a supplement. On Days 6 and 7 of the experimental weeks when protein depletion was most severe, Ss significantly (p less than .05) preferred the diet supplemented with isoleucine to a diet lacking the supplement.     

Cerebral palsy in very preterm infants: new epidemiological insights

The focus of this review is on new insights from recent epidemiological research on cerebral palsy in preterm infants. These include: 1) a better understanding of issues related to diagnosis and classification; 2) new information about the brain abnormalities underlying cerebral palsy in preterm infants; and 3) a better understanding of biological mechanisms that may underlie previously described epidemiological associations. Ongoing efforts to improve the diagnosis and classification of cerebral palsy have been enhanced by findings from serial examinations of cohorts of very preterm infants. Cranial ultrasonography through the anterior fontanelle of very preterm infants has provided information about grossly evident brain damage, found in about one-half of preterm infants who develop cerebral palsy. Insights into the pathophysiologic basis for certain epidemiologic associations have come from studies of experimental brain damage in animals and clinical studies of neurologic disorders in adults. Much of the current epidemiological research into the causes of cerebral palsy in preterm infants has focused on two potential mechanisms of brain damage. One mechanism involves insufficient cerebral perfusion; the other, cytokine-mediated damage, potentially triggered by events such as maternal infection (e.g., intrauterine or periodontal infection), neonatal infection (e.g., sepsis and necrotizing enterocolitis), and neonatal oxygen- or ventilator-induced lung injury. In addition to the preterm infant's increased exposure to such damaging factors, the high frequency of cerebral palsy in these infants might be due, in part, to insufficient levels of developmentally regulated protective substances, such as thyroid hormone and glucocorticoids. Models of causation currently are being investigated using recently developed methods for quantifying, with small quantities of blood, biomolecules that are suspected to either promote or protect against brain damage in the neonate. Clinical investigations now under way can be expected to identify strategies to be tested in clinical trials that could lower the risk of cerebral palsy in very preterm infants.     

Brain catecholamines and memory modulation: effects of footshock, amygdala implantation, and stimulation

The results of previous studies indicate that the extent of a transient decline in brain norepinephrine (NE) levels shortly after training and administration of any of several memory modulating treatments is correlated with later retention performance. The present experiment assessed such changes after one-trial inhibitory (passive) avoidance training and, in addition, measured concentration changes in 3-methoxy-4-hydroxyphenylglycol (MHPG), the major metabolite of brain NE, as well as dopamine (DA) and epinephrine (EPI) levels. The results indicate that the decreases in brain NE after footshock are accompanied by an increase in MHPG, thus providing additional evidence that brain NE is released after training. DA levels were unchanged after training; brainstem EPI levels increased after the training footshock, but forebrain EPI levels were unchanged. A second experiment examined brain catecholamine levels in animals which received post-training electrical stimulation of the amygdala. The findings of this experiment indicate that the amygdala damage which accompanies electrode implantation apparently results in a chronic change in whole brain NE levels and metabolism. After amygdala, NE concentrations in both brainstem and forebrain samples were reduced by 20% and MHPG was increased by 22-34%. Furthermore, NE levels were not responsive to training in implanted animals. Thus, brain NE levels after training were not predictive of retention performance in amygdala-implanted or -stimulated animals. However, the significance of such findings for understanding the possible role of central NE in memory storage is complicated by the severe modification of the dynamics of brain aminergic systems in animals bearing amygdala electrodes.     

Adrenalectomy Causes Oxidative Damage and Monoamine Increase in the Brain of Rats and Enhances Immobilization Stress-Induced Oxidative Damage and Neurotransmitter Changes

The paradox that increased levels of glucocorticoids can either enhance or suppress the organism's defense against stress, has been an obstacle to formulating a unified picture of glucocorticoid function. To clarify the glucocorticoid paradox, we examined male Sprague-Dawley rats exposed to immobilization stress and/or bilateral adrenalectomy (ADX), and measured oxidative damage to lipid, protein, and DNA, as well as monoamine neurotransmitter turnover. ADX, which is similar to stress, induces an increase in lipid peroxidation and protein oxidation, accompanied by increased monoamine neurotransmitter turnover in several regions of the brain of rats. The effect of ADX is greater than that induced by short-term immobilization stress. In addition, ADX enhances stress-induced oxidative damage and increase of monoamine neurotransmitter turnover. These results, together with our previous finding that long-term stress causes oxidative damage to the brain, suggest that stress levels of glucocorticoids, or levels lower than basal, cause oxidative damage. However, basal levels of glucocorticoids appear to buffer against oxidative damage. These findings provide possible mechanisms to understand the glucocorticoid paradox, and support the stress-oxidative hypothesis of aging acceleration.     

Sleep and dream suppression following a lateral medullary infarct: a first-person account

Consciousness can be studied only if subjective experience is documented and quantified, yet first-person accounts of the effects of brain injury on conscious experience are as rare as they are potentially useful. This report documents the alterations in waking, sleeping, and dreaming caused by a lateral medullary infarct. Total insomnia and the initial suppression of dreaming was followed by the gradual recovery of both functions. A visual hallucinosis during waking that was associated with the initial period of sleep and dream suppression is described in detail. Since the changes in sleep and their recovery are comparable to results of animal experiments, it can be concluded that damage to the medullary brain stem causes extreme but short-lived alterations in conscious state and that substantial recovery occurs even though the damage to the brain stem endures.     

Involvement of reactive oxygen species in emotional stress: A hypothesis based on the immobilization stress-induced oxidative damage and antioxidant defense changes in rat brain,and the effect of antioxidant treatment with reduced glutathione

We examined the oxidative damage and antioxidant defense changes with immobilization-induced emotional stress in the rat brain. Though superoxide dismutase activity remained unchanged, brain peroxidation was significantly accelerated by the immobilization stress. Membrane fluidity study with spin labeling in brain cortical membrane showed that immobilization stress induced an increase in microviscosity of membrane layer near the surface and in the ordering of membrane proteins but a decrease in microviscosity at the core of the membrane bilayer. The Na, K-ATPase activity decreased whereas the levels of some monoamines and their metabolites increased along with their metabolic rate. The administration of reduced glutathione showed a protective effect on the immobilization stress-induced stomach bleeding, oxidative damage and abnormal changes in the brain antioxidant defenses. Based on these results and on previous reports, we hypothesize that immobilization stress may induce the formation of reactive oxygen species which weakens the brain antioxidant defenses and induces oxidative damage. The antioxidant administration of reduced glutathione provides further evidence to support the above hypothesis, and also may provide clues in the search for a rational therapy to emotional stress. A possible correlation of emotional stress to aging is also discussed.     

Locating volition

In this paper, it is examined how neuroscience can help to understand the nature of volition by addressing the question whether volitions can be localized in the brain. Volitions, as acts of the will, are special mental events or activities by which an agent consciously and actively exercises her agency to voluntarily direct her thoughts and actions. If we can pinpoint when and where volitional events or activities occur in the brain and find out their neural underpinnings, this can substantively aid to demystify the concept of volition. After first discussing some methodological issues regarding whether it is possible to locate volition in the brain, various approaches by which neuroscientists and psychologists explore the neural correlates and substrates of volition are examined. Although different psychological conceptualizations of volition shape different perspectives toward understanding the functions of volition, the explorations of the neural basis of volition converge on certain common brain areas and structures. A unifying conception of volition that helps to make better sense of recent empirical findings is then suggested.     

Using the Impact of Event Scale to Evaluate Psychological Response to Being a Phenylketonuria Gene Carrier

The birth of a child with phenylketonuria (PKU) is almost always a shock to the parents, who are faced with the realities of caring for a child with special needs and the need to cope with the realization that they are obligate carriers of the responsible gene. The Impact of Event Scale (IES) was used to assess the psychological impact of being a PKU gene carrier on 83 parents of children with PKU. IES scores decreased significantly from the time of initial diagnosis of PKU to the current time. The magnitude of the psychological impact did not correlate with the age of the parent, the number of years since the diagnosis of PKU, or the health or development of the child. As more tests become available for detecting the presence of disease-related genes, instruments such as the IES may prove useful in the evaluation of psychological responses to genetic information.     

Moral Competence, Moral Blame, and Protest

I argue that wrongdoers may be open to moral blame even if they lacked the capacity to respond to the moral considerations that counted against their behavior. My initial argument turns on the suggestion that even an agent who cannot respond to specific moral considerations may still guide her behavior by her judgments about reasons. I argue that this explanation of a wrongdoer’s behavior can qualify her for blame even if her capacity for moral understanding is impaired. A second argument is based on the observation that even when a blameworthy wrongdoer could have responded to moral considerations, this is often not relevant to her blameworthiness. Finally, I argue against the view that because blame communicates moral demands, only agents who can be reached by such communication are properly blamed. I contend that a person victimized by a wrongdoer with an impaired capacity for moral understanding may protest her victimization in a way that counts as a form of moral blame even though it does not primarily express a moral demand or attempt to initiate moral dialogue.     

Use of virtual reality distraction to reduce claustrophobia symptoms during a mock magnetic resonance imaging brain scan: a case report.

The present case series with two patients explored whether virtual reality (VR) distraction could reduce claustrophobia symptoms during a mock magnetic resonance imaging (MRI) brain scan. Two patients who met DSM-IV criteria for specific phobia, situational type (i.e., claustrophobia) reported high levels of anxiety during a mock 10-min MRI procedure with no VR, and asked to terminate the scan early. The patients were randomly assigned to receive either VR or music distraction for their second scan attempt. When immersed in an illusory three-dimensional (3D) virtual world named SnowWorld, patient 1 was able to complete a 10-min mock scan with low anxiety and reported an increase in self-efficacy afterwards. Patient 2 received "music only" distraction during her second scan but was still not able to complete a 10-min scan and asked to terminate her second scan early. These results suggest that immersive VR may prove effective at temporarily reducing claustrophobia symptoms during MRI scans and music may prove less effective.     

It's Not a Story

This writing presents a firsthand account of living with the certain knowledge that you can't rely on your brain the way you used to. Epilepsy, multiple sclerosis, brain tumor—what do these words really mean day by day, moment by moment? The author blends poetry and prose in her account of forging a new relationship with her own brain. Activities that were once routine are now difficult and even dangerous. No longer is her brain a silent partner as she navigates the debilitating, embarrassing, and occasionally humiliating symptoms of her disease. Can I really get through this shower? How much help do we need today, Brain? Mindfulness practice helps the author become more aware of her moment-by-moment experience. Her therapist prods her to dig into her own story, but the author resists. She resists and yet she shares her story that may not be a story.