Background Deficient cerebral inhibition is a pathophysiological brain deficit related to poor sensory gating and attention in schizophrenia and other disorders. Cerebral inhibition develops perinatally, influenced by genetic and in utero factors. Amniotic choline activates fetal α7-nicotinic acetylcholine receptors and facilitates development of cerebral inhibition. Increasing this activation may protect infants from future illness by promoting normal brain development. Methods A randomized placebo-controlled clinical trial of dietary phosphatidylcholine supplementation was conducted with 100 healthy pregnant women, who consented to the study at second trimester. Supplementation to twice normal dietary levels for mother or newborn continued through the third postnatal month. All women received dietary advice regardless of treatment. Infants’ electroencephalographic recordings of inhibition of the P50 component of the cerebral evoked response to paired sounds were analyzed. Criterion for inhibition was suppression of the amplitude of the second P50 response by at least half, compared to the first response. Results No adverse effects of choline were observed in maternal health and delivery, birth, or infant development. More choline-treated infants (76%) suppressed the P50 response, compared to placebo-treated infants (43%) at the fifth postnatal week (effect size 0.7). There was no difference at the 13th week. A CHRNA7 genotype associated with schizophrenia diminished P50 inhibition in the placebo-treated infants, but not in the choline-treated infants. Conclusion Neonatal developmental delay in inhibition is associated with attentional problems as the child matures. Perinatal choline activates timely development of cerebral inhibition, even in the presence of gene mutations that otherwise delay it.

The effect of attention to a focal stimulus on 14, 20 and 26-week-old infant's peripheral stimulus localization with eye and head movements was examined in this study. Fixation was engaged on a stimulus in the central visual field and a stimulus was presented in the periphery immediately or after a delay. Peripheral stimulus localization occurred less frequently near the beginning of fixation and when a significant heart rate deceleration had occurred (sustained attention), compared with when no focal stimulus was present or after heart rate had returned to prestimulus level (attention termination). Localization was accompanied by head movements on more than two-thirds of the trials, and the likelihood of head movements was positively associated with stimulus eccentricity. The saccades to localize the peripheral stimulus had unusually high velocities in the attention conditions for the two older aged groups relative to their saccades in inattentive conditions. There were unusual "localizing head movements" in the attention conditions in the absence of localizing saccades or changes in fixation for the two older age groups. Infant attention modulates eye movement characteristics of infants. These data also support the hypothesis that eye and head movement systems are relatively independent in the infant, and that eye-head relations during infant attention may be different from during inattention.

Objective α7-Nicotinic receptors are involved in the final maturation of GABA inhibitory synapses before birth. Choline at levels found in the amniotic fluid is an agonist at α7-nicotinic receptors. The authors conducted a double-blind placebo-controlled trial to assess whether high-dose oral phosphatidylcholine supplementation during pregnancy to increase maternal amniotic fluid choline levels would enhance fetal development of cerebral inhibition and, as a result, decrease childhood behavior problems associated with later mental illness. Method The authors previously reported that newborns in the phosphatidylcholine treatment group have increased suppression of the cerebral evoked response to repeated auditory stimuli. In this follow-up, they report parental assessments of the children’s behavior at 40 months of age, using the Child Behavior Checklist. Results At 40 months, parent ratings of children in the phosphatidylcholine group (N=23) indicated fewer attention problems and less social withdrawal compared with the placebo group (N=26). The improvement is comparable in magnitude to similar deficits at this age associated with later schizophrenia. The children’s behavior is moderated by CHRNA7 variants associated with later mental illness and is related to their enhanced cerebral inhibition as newborns. Conclusions CHRNA7, the α7-nicotinic acetylcholine receptor gene, has been associated with schizophrenia, autism, and attention deficit hyperactivity disorder. Maternal phosphatidylcholine treatment may, by increasing activation of the α7-nicotinic acetylcholine receptor, alter the development of behavior problems in early childhood that can presage later mental illness.

Diminished inhibitory gating of cerebral auditory evoked responses is transmitted in families with psychoses as an endophenotype related to the genetic risk for these illnesses. To assess whether the endophenotype is already expressed in infants of parents with psychotic illness and to assess effects of other known risk factors for schizophrenia, ie, maternal cigarette smoking and depression, inhibitory gating of cerebral auditory evoked responses was evaluated by comparing the P1 evoked responses to the first and second of paired auditory stimuli. Cerebral evoked responses were recorded during active sleep from 22 infants with a parent diagnosed with a psychotic illness and 129 infants with parents with no such history. Of these infants, 25 were prenatally exposed to nicotine (16 from the comparison group and 9 from the group with parental psychosis). Mothers of 35 infants had diagnoses of major depressive disorder. Parental psychosis (P = .032) and exposure to maternal smoking (P = .012) both resulted in diminished inhibitory gating in infant offspring. Compared to infants of mothers who did not smoke and who had neither parental psychosis nor maternal depression, diminished inhibitory gating was observed in infants with parental psychosis (P = .027) and in infants with maternal depression (P = .049). Diminished inhibitory gating of auditory evoked response in infants who have risk factors for schizophrenia mirrors reports of its familial transmission in adults. The results further indicate that the phenotypic expression of familial genetic and environmental risks for psychosis is already manifest very early in development.

PurposeIn 1997, Vogelzang et al. reported that 61 % of patients with cancer indicated fatigue impacted daily life more than pain, and only 37 % of oncologists shared this perception. We provide an update to this study, which can help prioritize symptom assessment and management in the clinic. Study aims were to determine and compare perceptions of patients with cancer and health care providers (HCPs) of the impact of fatigue and pain.MethodsA random sample of patients with cancer was recruited in the USA by Harris Poll Online and Schlesinger Associates. Oncology HCPs were recruited by Food and Drug Research, Inc. and Toluna, Inc.ResultsFrom June to November 2012, 550 of 1122 eligible patients (49 %), 400 of 533 eligible oncologists (75 %), and 400 of 617 eligible oncology nurses (65 %) completed a survey. Of patients, 58 % reported that fatigue affected their daily lives more than pain while undergoing treatment with chemotherapy versus 29 % of oncologists and 25 % of oncology nurses that had this perception. Ninety-eight percent of patients reported experiencing fatigue, whereas 72 % of oncologists and 84 % of oncology nurses thought this was the case. Eighty-six percent of patients reported pain while undergoing treatment with chemotherapy, whereas 36 % of oncologists and 51 % of oncology nurses believed this occurred. Nausea and vomiting felt by HCPs were the most concerning symptoms for patients (88 %).ConclusionsThis study shows the importance of assessing symptoms by direct patient report during chemotherapy treatment. HCPs continue to underestimate the prevalence and importance of fatigue and pain for patients with cancer, a finding that may alter the management of treatment-related symptoms and may influence the development of patient symptom management plans.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-016-3275-2) contains supplementary material, which is available to authorized users.