Brain development

A primary interest of the field of infant mental health is in the early conditions that place infants at risk for less than optimal development. The fundamental problem of what constitutes normal and abnormal development is now a focus of developmental psychology, infant psychiatry, and developmental neuroscience. In the second part of this sequential work, I present interdisciplinary data to more deeply forge the theoretical links between severe attachment failures, impairments of the early development of the right brain's stress coping systems, and maladaptive infant mental health. In the following, I offer thoughts on the negative impact of traumatic attachments on brain development and infant mental health, the neurobiology of infant trauma, the neuropsychology of a disorganized/disoriented attachment pattern associated with abuse and neglect, trauma-induced impairments of a regulatory system in the orbitofrontal cortex, the links between orbitofrontal dysfunction and a predisposition to posttraumatic stress disorders, the neurobiology of the dissociative defense, the etiology of dissociation and body-mind psychopathology, the effects of early relational trauma on enduring right hemispheric function, and some implications for models of early intervention. These findings suggest direct connections between traumatic attachment, inefficient right brain regulatory functions, and both maladaptive infant and adult mental health.

Anormal Psikoloji kitabı, ruhsal bozukluklar alanında çalışan tüm profesyoneller, psikiyatristler, klinik psikologlar, psikologlar, psikolojik danışmanlar, hekimler, sosyal hizmet uzmanları, psikiyatri hemşireleri ve bu alanlarda öğrenci yetiştiren akademisyenler ile eğitim alan öğrenciler için temel bir başvuru kitabıdır.
2013 yılının Mayısı ayında yayımlanan DSM-5 ölçütlerine göre ruhsal bozukluklarla ilgili sunulan bilgilerin güncellemesinin de yapıldığı bu kitap, tüm dünyada pek çok üniversitenin psikiyatri ve psikoloji bölümlerinde ders kitabı olarak okutulmaktadır.
Kitabın her bölümünde, ilk olarak ruhsal bozukluklarla ilgili vakalar sunulmakta, daha sonra bozuklukların klinik tanıları yapılmakta ve DSM-IV-TR’den farklı olan DSM-5’te yapılan değişikliklere yer verilmektedir. Ayrıca, DSM-5’teki tanı ölçütleri, bozuklukların etiyolojisi ve epidemiyolojisi, bozukluklar üzerinde kalıtımın ve çevrenin etkileri, biyolojik ve sosyal ve kültürel etkiler, en güncel araştırmalardan elde edilen verilerle harmanlanarak sunulmaktadır. Ruhsal bozuklukların tedavisinde etkili olacak terapi yaklaşımları ve ilaçla yapılan tedaviler hakkında da bilgiler veren kitap, sahip olduğu zengin içeriği ile eşsiz bir kaynaktır.
Anormal Psikoloji kitabının; profesyoneller ve öğrenciler için önemli bir rehber olacağına, yardıma ihtiyaç duyan insanların sorunlarının çözümüne, ruhsal bozuklukların tanı ve tedavisinde önemli katkılar sağlayacağına inanıyoruz.

Two angiotensin II (Ang II)–specific receptors, AGTR1 and AGTR2, are expressed in the mammalian brain. Ang II actions on blood pressure regulation, water electrolyte balance, and hormone secretion are primarily mediated by AGTR1. The function of AGTR2 remains unclear. Here, we show that expression of the AGTR2 gene was absent in a female patient with mental retardation (MR) who had a balanced X;7 chromosomal translocation. Additionally, 8 of 590 unrelated male patients with MR were found to have sequence changes in the AGTR2 gene, including one frameshift and three missense mutations. These findings indicate a role for AGTR2 in brain development and cognitive function.

Laboratory housing conditions have significant physiological and psychological effects on rodents, raising both scientific and humane concerns. Published studies of rats, mice and other rodents were reviewed to document behavioural and psychological problems attributable to predominant laboratory housing conditions. Studies indicate that rats and mice value opportunities to take cover, build nests, explore, gain social contact, and exercise some control over their social milieu, and that the inability to satisfy these needs is physically and psychologically detrimental, leading to impaired brain development and behavioural anomalies (e.g. stereotypies). To the extent that space is a means to gain access to such resources, spatial confinement likely exacerbates these deficits. Adding environmental 'enrichments' to small cages reduces but does not eliminate these problems, and I argue that substantial changes in housing and husbandry conditions would be needed to further reduce them.

The derivation of neural progenitor cells from human embryonic stem (ES) cells is of value both in the study of early human neurogenesis and in the creation of an unlimited source of donor cells for neural transplantation therapy. Here we report the generation of enriched and expandable preparations of proliferating neural progenitors from human ES cells. The neural progenitors could

MR image data can provide many features or measures although any single measure is unlikely to comprehensively characterize the underlying morphology. We present a framework in which multiple measures are used in manifold learning steps to generate coordinate embeddings which are then combined to give an improved single representation of the population. An application to neonatal brain MRI data shows that the use of shape and appearance measures in particular leads to biologically plausible and consistent representations correlating well with clinical data. Orthogonality among the correlations suggests the embedding components relate to comparatively independent morphological features. The rapid changes that occur in brain shape and in MR image appearance during neonatal brain development justify the use of shape measures (obtained from a deformation metric) and appearance measures (obtained from image similarity). The benefit of combining separate embeddings is demonstrated by improved correlations with clinical data and we illustrate the potential of the proposed framework in characterizing trajectories of brain development.

We report an 11-year-old girl who has paroxysmal nocturnal hemoglobinuria (PNH) and was admitted because of recurrent cerebrovascular accidents (CVA) and intermittent hemoglobinuria. Internal carotid angiography revealed bilateral typical moyamoya patterns. Although CVA due to arterial thrombosis may occur in PNH, the basal moyamoya vessels were never mentioned in case reports yet. The moyamoya syndrome has been reported in a variety of diseases and represents the nonspecific response to an impairment of arterial flow at specific sites in the brain. Our case discloses that PNH may present as moyamoya syndrome.

Longitudinal neuroimaging studies demonstrate that the adolescent brain continues to mature well into the 20s. This has prompted intense interest in linking neuromaturation to maturity of judgment. Public policy is struggling to keep up with burgeoning interest in cognitive neuroscience and neuroimaging. However, empirical evidence linking neurodevelopmental processes and adolescent real-world behavior remains sparse. Nonetheless, adolescent brain development research is already shaping public policy debates about when individuals should be considered mature for policy purposes. With this in mind, in this article we summarize what is known about adolescent brain development and what remains unknown, as well as what neuroscience can and cannot tell us about the adolescent brain and behavior. We suggest that a conceptual framework that situates brain science in the broader context of adolescent developmental research would help to facilitate research-topolicy translation. Furthermore, although contemporary discussions of adolescent maturity and the brain often use a deficit-based approach, there is enormous opportunity for brain science to illuminate the great strengths and potentialities of the adolescent brain. So, too, can this information inform policies that promote adolescent health and well-being.

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Prenatal and perinatal alcohol exposure caused by maternal alcohol intake during gestation and lactation periods can have long-lasting detrimental effects on the brain development and behaviour of offspring. Children diagnosed with Foetal Alcohol Spectrum Disorders (FASD) display a wide range of cognitive, emotional and motor deficits, together with characteristic morphological abnormalities. Maternal alcohol binge drinking is particularly harmful for foetal and early postnatal brain development, as it involves exposure to high levels of alcohol over short periods of time. However, little is known about the long-term effects of maternal alcohol binge drinking on brain function and behaviour. To address this issue, we used pregnant C57BL/6 female mice with time-limited access to a 20% v/v alcohol solution as a procedure to model alcohol binge drinking during gestation and lactational periods. Male offspring were behaviourally tested during adolescence (30 days) and adulthood (60 days), and baseline neural metabolic capacity of brain regions sensitive to alcohol effects were also evaluated in adult animals from both groups. Our results show that prenatal and postnatal alcohol exposure caused age-dependent changes in spontaneous locomotor activity, increased anxiety-like behaviour and attenuated alcohol-induced conditioned place preference in adults. Also, significant changes in neural metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry were found in the hippocampal dentate gyrus, the mammillary bodies, the ventral tegmental area, the lateral habenula and the central lobules of the cerebellum in adult mice with prenatal and postnatal alcohol exposure. In addition, the analysis of interregional CCO activity correlations in alcohol-exposed adult mice showed disrupted functional brain connectivity involving the limbic, brainstem, and cerebellar regions. Finally, increased neurogenesis was found in the dentate gyrus of the hippocampus of alcohol-exposed offspring, suggesting neuroadaptive effects due to early alcohol exposure. Our results demonstrate that maternal binge-like alcohol drinking causes long-lasting effects on motor and emotional-related behaviours associated with impaired neuronal metabolic capacity and altered functional brain connectivity.

Mapping regional brain development in terms of protein synthesis (PS) activity yields insight on specific spatio-temporal ontogenetic patterns. The biosynthetic activity of an individual brain nucleus is represented as a time-series object, and clustering of time-series contributes to the problem of inducing indicative patterns of brain developmental events and forming respective PS chronological maps. Clustering analysis of PS chronological maps, in comparison with epigenetic influences of ␣ 2 adrenoceptors treatment, reveals relationships between distantly located brain structures. Clustering is performed with a novel graph theoretic clustering approach (GTC). The approach is based on the weighted graph arrangement of the input objects and the iterative partitioning of the corresponding minimum spanning tree. The final result is a hierarchical clustering-tree organization of the input objects. Application of GTC on the PS patterns in developing brain revealed five main clusters that correspond to respective brain development indicative profiles. The induced profiles confirm experimental findings, and provide evidence for further experimental studies.

Interstitial deletions of the proximal short arm of chromosome 3 occurring as constitutional aberrations are rare and a defined clinical phenotype is not established yet. We report on a 30-months-old girl with distinct facial features (square facies, plagiocephaly, broad forehead, broad nasal bridge, long philtrum and low set ears) and psychomotor/speech delay associated with an interstitial deletion of 3p12 chromosomal band, del(3)(p12p12). Clinical manifestations of our child were compared with those of other eight patients with the same deletion previously described to further delineate the proximal 3p deletion syndrome.

In this pilot study the severity of autism spectrum disorders (ASD) was associated with alterations in white matter development. Children with ASD and without ASD were assessed by magnetic resonance imaging (MRI) for their myelination development on a regional basis. Measures were obtained in medial frontal cortex, temporal poles, and temporo-parietal junction in both left and right hemispheres. Children with ASD showed myelination that was greater than expected for their age in both left and right medial frontal cortex and showed myelination that was less than expected in left temporo-parietal junction. The severity of ASD symptoms, as assessed by the Autism Diagnostic Observation Schedule-Generic, was associated more with left hemisphere alterations than right hemisphere. ß 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 755-763, 2010.

Objective: To examine the utility of the Bayley Infant Neurodevelopmental Screener (BINS) for the neurodevelopmental follow up of high-risk preterms. Methods: The study group consisted of 122 preterm infants of the gestational ages between 26 and 37 weeks. Medical factors such as; mean birth weight, gestational age, gender, birth place and type, number of multiple pregnancy, days of hospitalization and oxygen therapy, use of antenatal steroids, and occurence of sepsis for each patient were evaluated. The neurodevelopmental examination and BINS administration was made at each visit to the patients whose ages were adjusted for prematurity. Results: At the corrected age of 7-10 months patients at 26-29 GA had significantly lower total means of BINS scores when compared to those of the other two groups at 30-32 and 33-37 GA (P!0.01 and P!0.001). At the corrected age of 3-4 months, the total means of the BINS scores of the patients at 30-32 GA were lower than that of the patients at 33-37 GA (P!0.009). at 7-10 months the scores of the items defining the expressive and cognitive functions of the patients at 26-29 GA were lower than those of the patients at 30-32 GA (P!0.05) and 33-37 GA (P!0.05). At 16-20 months the mean scores of the items of expressive functions were significantly lower in patients of the 26-29 GA compared to those of the patients of 33-37 GA (P!0.03). Conclusion: As data accumulates, BINS will turn out to be a quick way of determining infants at risk of developmental delay in many aspects of neurologically high risk conditions. q

The natural history of X-linked adrenoleukodystrophy (ALD) was investigated, using a nation-wide retrospective study based on a questionnaire survey. The data on 145 patients, including 46 patients with the childhood cerebral form, 39 with adrenomyeloneuropathy (AMN), 33 with the adult cerebral form, 14 with the adolescent form and 13 with the olivo-ponto-cerebellar (OPC) form, were analyzed. Initial symptoms of the childhood cerebral form were intellectual (nZ16) and visual (nZ11) disturbances, whereas those of AMN were gait (nZ37) and sensory (nZ3) disturbances; the adult cerebral form, psychic (nZ19) and gait (nZ11) disturbances; the adolescent form, visual nZ5) and gait (nZ4) disturbances; and the OPC form, gait (nZ9) disturbance. Patients with onset under the age of 8 years progressed more rapidly than those over 8 years old. Visual, hearing, gait and swallowing disturbances progressed more slowly in the older group. About half of AMN patients showed cerebral involvement about 10 years after onset. Patients with the OPC form also showed a similar progression. A Kaplan-Meier plot clarified the characteristic pattern of progression of neurological symptoms in each phenotype. These finding will improve the understanding of the natural history of X-linked ALD and will provide a basis for the evaluation of specific treatment for X-linked ALD. q 2004 Elsevier B.V. All rights reserved.

We here reported the clinical course and therapeutic details of a 16-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who had had five stroke-like episodes (two episodes were clinically mild, while the three subsequent episodes were severe). Among the three episodes, the symptoms improved earliest and magnetic resonance spectroscopy abnormality was minimal when given L-arginine in addition to prednisolone, glycerol and edalavone. L-arginine administration during the acute phase of MELAS might be a potential therapy to reduce brain damage due to mitochondrial dysfunction. q

This is the unusual case of a 17-year-old girl affected by Rett Syndrome (RS) who suffered acute abdominal distension and constipation for a week. Laparotomy showed massive gastric dilatation, with total necrosis and perforation. Total gastrectomy and Y-Roux esophagojejunostomy were performed. We believe the clinical status was caused by the mechanism of air swallowing, present in our patient and typical in RS. In fact, as reported, massive air bloat may result in a decrease of the intramural blood flow with consequential ischemia of the gastric wall. We stress the importance of early detection of the gastroenterological symptoms in these patients, with timely positioning of nasogastric tube and gastrostomy, to prevent serious complications potentially life-threatening as massive gastric necrosis. q

Autism is a neurodevelopmental disorder that severely disrupts social and cognitive functions. MRI is the method of choice for in vivo and non-invasively investigating human brain morphology in children and adolescents. The authors reviewed structural MRI studies that investigated structural brain anatomy and development in autistic patients. All original MRI research papers involving autistic patients, published from 1966 to May 2003, were reviewed in order to elucidate brain anatomy and development of autism and rated for completeness using a 12-item check-list. Increased total brain, parieto-temporal lobe, and cerebellar hemisphere volumes were the most replicated abnormalities in autism. Interestingly, recent findings suggested that the size of amygdala, hippocampus, and corpus callosum may also be abnormal. It is conceivable that abnormalities in neural network involving fronto-temporo-parietal cortex, limbic system, and cerebellum may underlie the pathophysiology of autism, and that such changes could result from abnormal brain development during early life. Nonetheless, available MRI studies were often conflicting and could have been limited by methodological issues. Future MRI investigations should include well-characterized groups of autistic and matched healthy individuals, while taking into consideration confounding factors such as IQ, and socioeconomic status.

Large medical image datasets form a rich source of anatomical descriptions for research into pathology and clinical biomarkers. Many features may be extracted from data such as MR images to provide, through manifold learning methods, new representations of the population's anatomy. However, the ability of any individual feature to fully capture all aspects morphology is limited. We propose a framework for deriving a representation from multiple features or measures which can be chosen to suit the application and are processed using separate manifold-learning steps. The results are then combined to give a single set of embedding coordinates for the data. We illustrate the framework in a population study of neonatal brain MR images and show how consistent representations, correlating well with clinical data, are given by measures of shape and of appearance. These particular measures were chosen as the developing neonatal brain undergoes rapid changes in shape and MR appearance and were derived from extracted cortical surfaces, non-rigid deformations and image similarities. Combined single embeddings show improved correlations demonstrating their benefit for further studies such as identifying patterns in the trajectories of brain development. The results also suggest a lasting effect of age at birth on brain morphology, coinciding with previous clinical studies.

To study the selectivity of visual perceptual impairment in children with early brain injury, eight visual perceptual tasks (L94), were administered to congenitally disabled children both with and without risk for cerebral visual impairment (CVI). The battery comprised six object-recognition and two visuoconstructive tasks. Seven tasks were newly designed. For these normative data are presented (age 2.75±6.50 years). Because the recognition tasks required object naming, each item included a canonical control drawing and visual perceptual ability was evaluated relative to the non-verbal intelligence level, instead of chronological age. In 22 multiple disabled children with no indications of CVI, the frequency of impairment did not exceed that in the reference sample for any L94 task. In contrast, in 57 5-year-old children who were at risk for CVI due to pre-maturity or birth asphyxia, a signi®cant increase in the frequency of impairment was seen on six L94 tasks (range 12±38%). However, only ®ve children had more than two impairments, indicating that the de®cits were selective, not pervasive. We conclude that early brain lesions interfere with the functioning of particular visual subsystems, yet leave other subsystems intact and functioning within the normal range. q

THE EXPLOSION OF KNOWLEDGE about the brain and its functions that occurred during the last two decades is informing psychosocial knowledge relevant to graduate and undergraduate social work education and to practice in several areas (Farmer, 2009; Garrett, 2003). These areas include, for instance, human development and behavior across the lifespan, cognition, memory, emotions, stress and trauma,

The maturational patterns of 'track alternant' (TA) and sleep spindles obtained from 16 early detected phenylketonuric (PKU) children during their first months of life were compared with others that were evaluated in recordings taken from 42 controls of the same age group. The TA maturation evolved significantly later in the PKU group than in the control group during the 5th-8th week (the TA score for the PKU group was 64% vs. 10% in the control group, P < 0.001). Afterwards, during the 9th-12th week the score for the PKU group was 27% vs. 0% in the controls (P < 0.002). The sleep spindle evolution score also matured significantly later in the PKU than the control group: the score was 31% in PKU children vs. 85% in controls for the 5th-8th week of age (P < O.Ol), and it was 66% vs. 96% for the 9th-12th week (P < 0.02). After the 12th week, TA pattern could not be detected, and spindles reached complete maturation in the PKU children as well. Our results show a consistent delay in the maturation of TA and spindle scores in PKU children. This trend of delay is parallel to the plasma phenylalanine normalization, but not necessarily dependent only on it. In conclusion, we suggest that studies on the critical maturational periods of different sleep components (TA and sleep spindles) might provide a sensitive tool for early diagnosis of neurophysiological brain alterations during the first trimester of life in a population of children 'at risk'.

Benign paroxysmal vertigo of childhood (BPV) is a paroxysmal, non-epileptic, recurrent event characterized by subjective or objective vertigo that occurs in neurologically intact children. We recorded the history and the clinical aspects of 19 cases presenting with neurological problems to the outpatient clinic at the Pediatrics Department of Padova University between 1987 and 1998 and re-examined in 1999. Details were collected on the characteristics of their vertigo: age at onset, mode of onset, trigger factors, duration, frequency and recurrence of episodes, duration of symptoms in time and age at disappearance. An attempt was also made to establish any family history of migraine and kinetosis and the most important data were compared, when possible, with those reported in the literature. Differential diagnosis and pathogenetic hypothesis were also reported. It is worth emphasizing that it is important for pediatricians to be aware of these benign events to ensure a correct diagnostic approach, avoiding the child and family any pointless anxiety or costly and sometimes invasive diagnostic procedures. q

Severe violent behavior is almost always the product of predisposing individual differences and precipitating situational factors (Huesmann, 1998). One important environmental experience that contributes both to predisposing a person to behave more violently in the long run and to precipitating violent behavior in the short run is exposure to violence. Psychological theories that have emerged over the past few decades now explain the short-term precipitating effects mostly in terms of priming, simple imitation, and excitation transfer. However, the long-term predisposing effects involve more complex processes of observational learning of cognitions and of emotional desensitization. In this chapter these theories are elaborated, and the compelling empirical evidence in support of these theories from experiments and longitudinal field studies is reviewed. We explain why the processes operate equally well from exposure to reallife violence or exposure to dramatic violence in the mass media. We focus particularly on the role of low emotional arousal and diminished emotional reactions to violence as consequences of exposure to violence and precursors of violent behavior. We argue that anticipated emotional responses play an important role in the cognitive processing that controls violent behavior. Abnormal violent behavior is not viewed as a consequence of "deficient" processing, but rather as a consequence of "different" processing.

Fungi share an ancient historical bond with humans which is completely fascinating.
The Strange History of Life
Humans have always been fascinated with life in all its forms, but thousands of years ago, we only classified life on Earth into two categories – plants and animals. We can thank Aristotle for that, and he further divided animals into those with and without blood, as well as those in the land, sea, and air. That rudimentary system remained in place until the 1600s. In the 18th century, Carolus Linnaeus divided life into the kingdoms of animals and plants, and then further began dividing those into different genera and species, which is why we have the two-part naming system in science (Homo sapiens, for example; Homo is the genus and sapiens is the species.

It wasn’t until the middle of the 19th century that single-celled organisms were finally given their due as a separate kingdom of life (Protista). Seventy years later, single-celled organisms were divided into eukaryotes and prokaryotes, so bacteria became the 4th kingdom of life. Although fungi had been recognized as a unique part of the animal kingdom, it was not separated into its own kingdom until 1969. This five-kingdom system remains the most widely accepted format for classifying life on Earth.
All classifications of life until recently, including the expansion from two kingdoms to five, were based on physical observations of how things looked, even under a microscope. This is how the closeness and relationships between species, genera, classes, orders and kingdoms were decided. Given that fact, it comes as no surprise that most people classified fungi as plants for so long. The similarity in appearance is pretty clear, like little red and white trees…

However, thanks to modern technology, the analysis of genetic relationships between species and organisms is now possible, and it shows something very interesting. By examining the genes of different species, both animal and fungi, the mutational changes can be observed, and genealogical relationships can be determined that go back millions of years.

As it turns out, animals and fungi share a common ancestor and branched away from plants at some point about 1.1 billion years ago. It was only later that animals and fungi separated on the genealogical tree of life, making mushrooms more closely related to humans than plants. Most likely, this common ancestor was a single-celled organism that had sperm-like characteristics (like an animal) and then a later developmental stage with a stronger cell wall (fungi).

Are mushrooms vegetables?
Simple answer? No, it’s not a vegetable. Mushrooms are fruiting bodies of macroscopic filamentous fungi. Earlier when mycology (the study of fungi) arose, it was a part of botany. This happened as fungi were considered to be primitive plants. The major difference between a plant (vegetable) and mushroom is how they acquire their food. In the case of plants, they possess chlorophyll and make their food via photosynthesis. Fungi, on the other hand, exist on decaying material in nature. Also the obvious structural differences, such as lack of leaves, roots, and seeds.So fungi now have their own kingdom on the basis of cellular organization.

However, this is the science side of things. Now let us take a look at the other side, the side of food! In terms of food and nutrition, mushrooms are often put in the category of vegetables. The reason for this lies in the nutritional value. Mushrooms and plants have similar nutritional attributes. The nutrients provided by mushroom are spread across various core food groups such as meat and grains. All this has made mushroom a valuable asset in the kitchen both for taste and nutrition.

The Connection Between Mushrooms and Men
Haven’t you ever noticed that eating a perfectly cooked portobello mushroom is closer to eating meat than a salad? Well, that isn’t exactly a scientific explanation of the connection, but this new revelation of our link to fungi does shed some light on the trouble we have with fungal infections in the body. It is notoriously difficult to treat fungal infections, rather than viral and bacterial pathogens, and this close genetic link may explain why.

Fungi and animals are both eukaryotes, with nuclei and other complex structures inside their cell membranes, whereas bacteria are much simpler – composed of just genetic material and a cell wall. Therefore, when we try to fight a bacterial infection, the body is able to easily differentiate and neutralize the threat. Unfortunately, with fungal infections, the body sometimes thinks that the infection is…. us. Drugs that are synthesized to fight the cells of fungal infections may also attack healthy human cells, as there is very little structural difference.

We report on five sibs affected by congenital microcephaly, growth retardation, sloping forehead, bitemporal grooving and micrognathia. Generalized tonic-clonic seizures started very early in life. Postnatal brain computerized tomography (CT) presented cortical band-like calcification, calcification of basal ganglia and brain stem while brain magnetic resonance imaging (MRI) revealed abnormal gyral pattern, marked loss of white matter, dysplastic ventricles, polymicrogyria, hypogenesis of corpus callosum and cerebellar hypoplasia. No abnormalities of the internal organs, eye, or skeleton were found to be associated with this syndrome. Fetal Magnetic resonance imaging helped reaching the diagnosis in utero in one patient. Three patients died in the first years of life while the others within days after birth preceded by high fever and status epilepticus. These patients present many overlapping features with pseudo TORCH syndrome, however, the imaging findings are quite different. We propose that the distinct pattern in these sibs constitutes genetic disorder of microcephaly, developmental brain malformation and intracranial calcification of likely autosomal recessive inheritance. © 2008 Wiley-Liss, Inc.

We describe two sisters affected by pontocerebellar hypoplasia type 2 associated with microcephaly, hypertonia, severe choreiform movements, an almost complete lack of psychomotor development, and generalized tonic-clonic seizures. Clinical and neuroradiological ®ndings ruled out other conditions associated with pontocerebellar hypoplasia, i.e. pontocerebellar hypoplasia type 1, carbohydrate-de®cient glycoprotein syndrome, and olivopontocerebellar hypoplasia/atrophy. q

Wide variability in patient selection, extent of callosal section and definition of successful outcome between studies make impact of corpus callosotomy on patients with medically refractory epilepsies difficult to interpret. Severe mental retardation is considered to be predictive of unfavorable seizure outcome after callosotomy. Very little attention has been paid on the influence of callosotomy on the psychosocial burden on the patients' families. We evaluated the seizure outcome, and parental perception about change in cognition and behavior of 17 children (median age 9.5 years, range 3.5-18 years) with severe mental retardation (IQ < 30 in all, except one) and injurious drop attacks, who have completed P1-year postoperative follow-up after callosotomy. Nearly two-thirds of our patients had P90% reduction in drop attacks and generalized tonic-clonic seizures. In the one-stage total callosotomy group, 9 of 11 (82%) patients had favorable outcome, compared to 2 of the 6 (33%) in the partial callosotomy group. Absence of generalized epileptiform discharges on the 1-year postoperative EEG was significantly associated with a favorable seizure outcome. The mean duration of epilepsy prior to callosotomy tended to be shorter among patients with favorable seizure outcome. Postoperative complications were trivial and transient. Nearly three-fourths of the parents appreciated improvements in behavior and attentiveness of their children and were satisfied with the outcome. We conclude that, in children with severe mental retardation and injurious drop attacks, total callosotomy can be undertaken as a one-stage procedure with insignificant morbidity and results in highly favorable seizure outcome.

There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the ''Biological Plausibility'' of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that vitamin D acts as a neurosteroid with direct effects on brain development. Crown

Adolescence is a period of development particularly vulnerable to the effects of alcohol use, with recent studies underscoring alcohol's effects on adolescent brain development. Despite the alarming rates and consequences of adolescent alcohol use, gifted adolescents are often overlooked as being at risk for early alcohol use. Although gifted adolescents may possess protective factors that likely inhibit the use of alcohol, some gifted youth may be vulnerable to initiating alcohol use during adolescence as experimenting with alcohol may be one way gifted youth choose to compensate for the social price (whether real or perceived) of their academic talents. To address the dearth of research on alcohol use among gifted adolescents the current study (a) examined the extent to which gifted adolescents use alcohol relative to their nongifted peers and (b) examined the adjustment profile of gifted adolescents who had tried alcohol relative to nongifted adolescents who tried alcohol as well as gifted and nongifted abstainers. More than 300 students in seventh grade (42.5% gifted) participated in the present study. Results indicated gifted students have, in fact, tried alcohol at rates that do not differ from nongifted students. Although trying alcohol was generally associated with negative adjustment, giftedness served as a moderating factor such that gifted students who had tried alcohol were less at risk than their nongifted peers. However, evidence also suggests that gifted adolescents who tried alcohol may be a part of a peer context that promotes substance use, which may place these youth at risk for adjustment difficulties in the future.

Electrical status epilepticus in sleep (ESES) is an electrographic pattern consisting of an almost continuous presence of spike-wave discharges in slow wave sleep. ESES is frequently encountered in pediatric syndromes associated with epilepsy or cognitive and language dysfunction. It can be present in various evolutionary stages of a spectrum of diseases, the prototypes of which are the`continuous spikes and waves during slow wave sleep' syndrome (CSWS), the Landau±Kleffner syndrome (LKS), as well as in patients initially presenting as benign childhood epilepsy with centrotemporal spikes (BECTS). The purpose of this article is to review the literature data on the semiology, electrographic ®ndings, prognosis, therapeutic options, as well as the current theories on the pathophysiology of these disorders. The frequent overlap of CSWS, LKS, and BECTS urges an increased level of awareness for the occasional transition from benign conditions such as BECTS to more devastating syndromes such as LKS and CSWS. Identi®cation of atypical signs and symptoms, such as high discharge rates, prolonged duration of ESES, neuropsychiatric and cognitive dysfunction, lack of responsiveness to medications, and pre-existing neurologic conditions is of paramount importance in order to initiate the appropriate diagnostic measures. Prolonged and if needed repetitive sleep electroencephalographs (EEGs) are warranted for proper diagnosis. q

During mammalian brain development, neurons are generated along the ventricle, migrate radially, and become aligned in defined patterns. These precise patterns of neuronal alignment are regulated by an extracellular matrix protein Reelin, and binding of Reelin to its receptors induces tyrosine phosphorylation of the intracellular adaptor protein disabled 1 (Dab1). We recently reported that Reelin molecules assemble to form a homomeric protein complex. Although the number of molecules in the full-length complex is unknown, recombinant N-terminal fragments, which contain the epitope for the function-blocking CR-50 antibody, assembled to form a complex of more than 40 monomers. When the N-terminus was deleted from Reelin, the truncated protein did not form a stable complex. To further characterize the Reelin assembly, we performed biochemical analysis of the full-length Reelin assembly in this study. Here, we report that a full-length Reelin forms a disulfide-linked homodimer. A chemic...

Chronic or repeated stress during human fetal brain development has been associated with various learning, behavioral, and/or mood disorders, including depression in later life. The mechanisms accounting for these effects of prenatal stress are not fully understood. The aim of this study was to investigate the effects of prenatal stress on early postnatal brain development, a disturbance of which may contribute to this increased vulnerability to psychopathology. We studied the effects of prenatal stress on fetal growth, stress-induced corticosterone secretion, brain cell proliferation, caspase-3-like activity and brain-derived neurotrophic factor protein content in newborn Fischer 344 rats. In addition to a slight reduction in birth weight, prenatal stress was associated with elevated corticosterone levels (33.8%) after 1 h of maternal deprivation on postnatal day 1, whereas by postnatal day 8 this pattern was reversed (؊46.5%). Further, prenatal stress resulted in an approximately 50% decrease in brain cell proliferation just after birth in both genders with a concomitant increase in caspase-3-like activity within the hippocampus at postnatal day 1 (36.1%) and at postnatal day 5 (females only; 20.1%). Finally, brainderived neurotrophic factor protein content was reduced in both the olfactory bulbs (؊24.6%) and hippocampus (؊28.2%) of prenatally stressed male offspring at postnatal days 1 and 5, respectively. These detrimental central changes observed may partly explain the increased susceptibility of prenatally stressed subjects to mood disorders including depression in later life.

Normal fetal brain maturation can be studied by in vivo magnetic resonance imaging (MRI) from the 18th gestational week (GW) to term, and relies primarily on T2-weighted and diffusion-weighted (DW) sequences. These maturational changes must be interpreted with a knowledge of the histological background and the temporal course of the respective developmental steps. In addition, MR presentation of developing and transient structures must be considered. Signal changes associated with maturational processes can mainly be ascribed to the following changes in tissue composition and organization, which occur at the histological level: (1) a decrease in water content and increasing cell-density can be recognized as a shortening of T1- and T2-relaxation times, leading to increased T1-weighted and decreased T2-weighted intensity, respectively; (2) the arrangement of microanatomical structures to create a symmetrical or asymmetrical environment, leading to structural differences that may be demonstrated by DW-anisotropy; (3) changes in non-structural qualities, such as the onset of a membrane potential in premyelinating axons. The latter process also influences the appearance of a structure on DW sequences. Thus, we will review the in vivo MR appearance of different maturational states of the fetal brain and relate these maturational states to anatomical, histological, and in vitro MRI data. Then, the development of the cerebral cortex, white matter, temporal lobe, and cerebellum will be reviewed, and the MR appearance of transient structures of the fetal brain will be shown. Emphasis will be placed on the appearance of the different structures with the various sequences. In addition, the possible utility of dynamic fetal sequences in assessing spontaneous fetal movements is discussed.

Carrier detection for 12 women and prenatal diagnosis for six fetuses in Japanese families with a patient with Menkes disease (MNK) were performed by gene analysis and/or measurement of the copper concentration in cultured cells. Six out of eight mothers of MNK patients were carriers while two (25%) were not carriers. Two unrelated patients showed the same mutation (R986X): one patient's mother was a carrier while the other was not. One male and three female fetuses did not have the same mutant allele as the respective MNK proband and have been healthy since birth. One female fetus had the same mutant allele as her affected brother. Gene analysis is very useful and reliable, although such examination is only indicated in families in which a mutation has been identified. In one family in which a mutation in ATP7A was not found, cultured amniocytes from a male fetus had a high copper concentration. Thus after his birth, the biochemical findings confirmed the presence of MNK and early treatment was started. As his early treatment with parenteral copper-histidine prevented the neurological disorders effectively, prenatal diagnosis is very important. q