Stressful Newborn Memories: Pre-Conceptual, In Utero, and Postnatal Events

Early-life stressful experiences are critical for plasticity and development, shaping adult neuroendocrine response and future health. Stress response is mediated by the autonomous nervous system and the hypothalamic–pituitary–adrenal (HPA) axis while various environmental stimuli are encoded via epigenetic marks. The stress response system maintains homeostasis by regulating adaptation to the environmental changes. Pre-conceptual and in utero stressors form the fetal epigenetic profile together with the individual genetic profile, providing the background for individual stress response, vulnerability, or resilience. Postnatal and adult stressful experiences may act as the definitive switch. This review addresses the issue of how preconceptual in utero and postnatal events, together with individual differences, shape future stress responses. Putative markers of early-life adverse effects such as prematurity and low birth weight are emphasized, and the epigenetic, mitochondrial, and genomic architecture regulation of such events are discussed

Ο Christfried Jakob πάνω στο φλοιό των εγκεφαλικών ημισφαιρίων: νευροβιολογικές, νευροφιλοσοφικές και νευροεκπαιδευτικές έννοιες

The present dissertation examines the culmination of Christfried‟s Jakob neurobiological, neurophilosophical and neuroeducational ideas from 1890 to 1949. His work numbers 30 books and 200 articles on developmental, evolutionary, anatomical and pathological issues in neurobiology and it further includes pioneering contributions in modern scientific fields such as educational neuroscience and neurophilosophy. We have divided Jakob‟s work into three periods. During the „early‟ period (1890–1912), Jakob mostly carried out anatomical work. In his „middle period‟ (1913–1935), he elaborated psychobiological ideas. In the „late‟ period (1936–1949), he came up with synthetic neurobiological and neurophilosophical theories. His works were written in German and Spanish and a couple of papers in French. Thus, they had scarce diffusion in the English literature. Given that Jakob‟s works still provide meaningful clues on the riddle of the human brain, an objective of this study was to render his legacy accessible by a wider audience. Accordingly, an aim of my dissertation consisted in crediting Jakob for the formulation of original ideas in evolutionary, behavioral, cognitive, affective and educational neuroscience as well as in neurophilosophy. In a broad framework, I retraced the evolution of Jakob‟s avant garde thought and bridged his still timely works with the modern literature

Ο Christfried Jakob πάνω στο φλοιό των εγκεφαλικών ημισφαιρίων: νευροβιολογικές, νευροφιλοσοφικές και νευροεκαπαιδευτικές έννοιες.

Η βιβλιοθήκη διαθέτει αντίτυπο της διατριβής σε έντυπη μορφή.Διατριβή (Διδακτορική)--Πανεπιστήμιο Μακεδονίας, Θεσσαλονίκη, 2011.Περιλαμβάνει βιβλιογραφικές αναφορές (σ. 114-139).016/2011The present dissertation examines the culmination of Christfried's Jakob neurobiological, neurophilosophical and neuroeducational ideas from 1890 to 1949. His work numbers 30 books and 200 articles on developmental, evolutionary, anatomical and pathological issues in neurobiology and it further includes pioneering contributions in modern scientific fields such as educational neuroscience and neurophilosophy. We have divided Jakob's work into three periods. During the 'early' period (1890-1912), Jakob mostly carried out anatomical work. In his 'middle period' (1913-1935), he elaborated psychobiological ideas. In the 'late' period (1936-1949), he came up with synthetic neurobiological and neurophilosophical theories. His works were written in German and Spanish and a couple of papers in French. Thus, they had scarce diffusion in the English literature. Given that Jakob's works still provide meaningful clues on the riddle of the human brain, an objective of this study was to render his legacy accessible by a wider audience. Accordingly, an aim of my dissertation consisted in crediting Jakob for the formulation of original ideas in evolutionary, behavioral, cognitive, affective and educational neuroscience as well as in neurophilosophy. In a broad framework, I retraced the evolution of Jakob's avant garde thought and bridged his still timely works with the modern literature.Η παρούσα διδακτορική διατριβή πραγματεύεται τη συνεισφορά του Christfried Jakob (1866-1956) στις νευροεπιστήμες, δίνοντας ιδιαίτερη έμφαση στις νευροβιολογικές, τις νευροφιλοσοφικές και τις νευροεκπαιδευτικές του ιδέες. Ο σκοπός της διατριβής συνίσταται στην ανάσυρση και ανάδειξη του πρωτότυπου έργου του Jakob διαμέσου της συστηματικής μελέτης των έργων που δημοσίευσε από το 1890 ως το 1949. Η εξέλιξη της σκέψης του Jakob εξετάζεται μέσα στο ιστορικό πλαίσιο και κάτω από το πρίσμα της προόδου που συντελέστηκε στις νευροεπιστήμες τα τελευταία χρόνια Ο Jakob άφησε μία παρακαταθήκη από έργα η μελέτη των οποίων θα μπορούσε να ρίξει φως στη λειτουργία του ανθρώπινου εγκεφάλου. Πέρα από τη συμβολή του Jakob στα επιμέρους επιστημονικά πεδία, το έργο του αποτελεί ένα υπόδειγμα διεπιστημονικότητας που έχει νόημα να ληφθεί υπόψη στη σύγχρονη αναζήτηση απαντήσεων για το γρίφο του εγκεφάλου

Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)

We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4–14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2), succinic semialdehyde dehydrogenase (SSADH) deficiency (2), and phenylketonuria (1) (2.7%). Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b) production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet (KD). Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated non-specific MRI pathology, while 25/187 had abnormal electroencephalogram (EEG) findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology) and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA) and novel treatment approaches in ASD patients. Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b) in 7% (13/187) of patients for whom biotin supplementation or institution of a KD resulted in mild to significant clinical improvement in autistic features

Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)

We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4-14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2), succinic semialdehyde dehydrogenase (SSADH) deficiency (2), and phenylketonuria (1) (2.7%). Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b) production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet (KD). Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated non-specific MRI pathology, while 25/187 had abnormal electroencephalogram (EEG) findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology) and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA) and novel treatment approaches in ASD patients. Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b) in 7% (13/187) of patients for whom biotin supplementation or institution of a KD resulted in mild to significant clinical improvement in autistic features