The Human Hypothalamus

Neuropsychiatric Disorders

1st Edition - July 7, 2021

Editors: Dick F. Swaab, Ruud M. Buijs, Felix Kreier, Paul J. Lucassen, Ahmad Salehi

Hardback ISBN:

9 7 8 - 0 - 1 2 - 8 1 9 9 7 3 - 2

eBook ISBN:

9 7 8 - 0 - 1 2 - 8 1 9 9 7 4 - 9

The Human Hypothalamus: Neuropsychiatric Disorders, Volume 181 in the Handbook of Clinical Neurology series, provides comprehensive summaries of recent research on the brain and… Read more

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The Human Hypothalamus: Neuropsychiatric Disorders, Volume 181 in the Handbook of Clinical Neurology series, provides comprehensive summaries of recent research on the brain and nervous system as they relate to clinical neurology. This volume identifies the neurobiology and neurophysiology of disorders relating to the hypothalamus and provides treatment information for these disorders. Disorders covered include neuropsychiatric, neurodegenerative, periodic, and autoimmune disorders. Coverage includes Alzheimer’s, Parkinson’s, epilepsy, sleep, pain, depression, anxiety, OCD, PTSD, schizophrenia, autism, aggressions, addiction, and more.

Cover image
Title page
Table of Contents
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
The HCN volumes on the Human Hypothalamus
Contributors
Contents of related volumes
Chapter 1: Introduction: The human hypothalamus and neuropsychiatric disorders
Section 21: Trauma and Iatrogenic Disorders
Section 22: Neurobehavioral Disorders
Section 23: Epilepsy
Section 24: Neurodegenerative Disorders
Section 25: Olfactory System
Section 26: Autonomic and Sleep Disorders
Section 27: Addiction and Pain
Section 28: Critical Care and Brain Death
Section 21: Trauma and iatrogenic disorders
Chapter 2: Chronic traumatic encephalopathy and the nucleus basalis of Meynert
Abstract
Introduction
Pathologic Features of CTE
CTE Tau Pathological Staging
Nucleus Basalis of Meynert in CTE
Cholinergic Basal Forebrain Subfields
Cholinergic nbM Dysfunction in CTE
Tau NFT Pathology Within the nbM in CTE
Amyloid Pathology in the nbM in CTE
nbM Cortical Cholinergic Disconnection in CTE
White Matter Disruption of nbM Axons in CTE
Transcript Expression in CTE
Cholinergic Transcript Dysregulation in Tau-Containing nbM Neurons in CTE
Clinical Consequences of nbM Pathobiology in CTE
Conclusions
Acknowledgments
Section 22: Neurobehavioral disorders
Chapter 3: Hypothalamic stress systems in mood disorders
Abstract
Stress System Dysfunction in Mood Disorders
Translation of Neuropeptide Pharmacology Into Novel Medicines
Conclusion
Chapter 4: Light therapy for mood disorders
Abstract
Introduction
Pathophysiology of (Peripartum) Mood Disorders
Working Mechanisms of Light Therapy
Clinical Studies of Light Therapy
Conclusions
Chapter 5: Neurobiology of peripartum mental illness
Abstract
Introduction to the Parental Brain
Peripartum Mental Illness Occurs in One in Seven Women
Neurobiology of Peripartum Mental Illness
Other Factors Influencing Peripartum Mental Illness
Concluding Remarks and Future Directions
Acknowledgments
Chapter 6: The hypothalamo–pituitary–adrenal axis and the autonomic nervous system in burnout
Abstract
Introduction
Hypothalamo–Pituitary–Adrenal Axis in Burnout
Autonomic System in Burnout
Methodologic Aspects
Summary
Chapter 7: Posterior hypothalamus as a target in the treatment of aggression: From lesioning to deep brain stimulation
Abstract
Introduction
Clinical Correlates of Aggression
Laboratory Experiences: Roots of Surgical Approach for Aggressive Disorders
At the Dawn of Surgery for Aggressive Disorders: The Lesional Era
A Step Into Brain Stimulation: The DBS Era
From the Target to the Circuit
Conclusions
Chapter 8: The implications of hypothalamic abnormalities for schizophrenia
Abstract
Introduction
Hypothalamic Gross Anatomic Pathology in Schizophrenia
Hypothalamic Cell Pathology in Schizophrenia
Concentrations of Classical Neurotransmitters and Their Metabolites
Changes in Hypothalamic Neurosecretory Neurons
Alterations of Hypothalamic-Releasing and Inhibiting Factors Which Regulate Hormonal Axes
Alteration of Peptide Hormones Regulating Food Intake, Appetite, and Satiety
Alteration of Hypothalamic Opioid Peptides: POMC, Endorphins, and Enkephalins
Alterations in the Expression of Susceptibility Genes for Schizophrenia
Role of the Hypothalamus in Sleep Disturbances in Schizophrenia
Disease-Related Neuroinflammatory and Neuroimmune Disturbances and the Impact of the Hypothalamus
Conclusions
Chapter 9: The promiscuity of the oxytocin–vasopressin systems and their involvement in autism spectrum disorder
Abstract
Introduction: Oxytocin and Vasopressin Synthesis, Gene Structure, and Function
Evolutionary History of Oxytocin and Vasopressin Ligands and Receptors
Oxytocin and Vasopressin Ligand and Receptor Distribution in the Human and Mouse Brain
Oxytocin and Vasopressin Regulate Social Behaviors
Oxytocinergic and Vasopressinergic Systems Are Impaired in ASD and Related Animal Models
Treatments for ASD Targeting the Oxytocinergic and Vasopressinergic Systems
Conclusion
Section 23: Epilepsy
Chapter 10: Gelastic seizures and the hypothalamic hamartoma syndrome: Epileptogenesis beyond the lesion?
Abstract
Introduction
MRI-Based Classification of HH With Regard to Clinical Phenotypes
Seizure Semiology in Epilepsy With HH
Epilepsy with HH as a Model of Secondary Epileptogenesis
Secondary Epileptogenesis and the Concept of Epileptogenic Networks
Conclusions
Chapter 11: The interactions between reproductive hormones and epilepsy
Abstract
Introduction
The Effects of Hormones on Epilepsy
The Effects of Epilepsy on Reproductive Endocrine Function
Antiepileptic Drug-Related Mechanisms
Concluding Remarks
Section 24: Neurodegenerative disorders
Chapter 12: Alternative splicing in aging and Alzheimer's disease: Highlighting the role of tau and estrogen receptor α isoforms in the hypothalamus
Abstract
Alternative Splicing
Alternative Splicing in the Brain
Alternative Splicing Regulators in the Brain
Alternative Splicing in the Human Brain in Aging
Alternative Splicing in the Human Brain in Neurodegenerative Disorders
Alzheimer's Disease
Tau Splicing in AD and Other Neurodegenerative Disorders
Tau Gene Alternative Splicing Regulation in AD and Other Neurodegenerative Disorders
Alternative Splicing Changes in Other AD-Related Genes
Relationship Between Estrogens, Estrogen Receptor α, and Alzheimer's Disease
ERα in the Human Brain in Aging and in AD
ERα Alternative Splicing Regulation
Conclusions
Chapter 13: Cholinergic neurodegeneration in Alzheimer disease mouse models
Abstract
The Cholinergic System: Contributions of the Hypothalamus
The Cholinergic System in Alzheimer's Disease
The Amyloid Cascade and Animal Models of AD
Early APP Models
Presenilin-1 and Double Transgenic Models: The 5xFAD Mouse
APP and Down Syndrome: The Ts65Dn Mouse
Tau Pathology in AD Mouse Models
Future Directions: The APP Knock-In Mouse and Other Alternatives
Conclusions
Declarations of interest
Chapter 14: Autonomic disorders in Parkinson disease: Disrupted hypothalamic connectivity as revealed from resting-state functional magnetic resonance imaging
Abstract
Introduction
Autonomic Dysfunction in Parkinson's Disease
Lewy Bodies and Neurodegeneration in the Hypothalamus
Alterations in Neurotransmitter Systems in the Hypothalamus Demonstrated In Vivo
Hypothalamic Connectivity and Autonomic Dysfunction in PD
Micro- and Macrostructural Alterations in the Hypothalamus in PD
The Role of the Hypothalamus in Atypical Parkinsonism Disorders
Hypothalamic Neuroimaging as a Tool in Clinical Trials
Future Research Directions
Chapter 15: Hypothalamic α-synuclein and its relation to autonomic symptoms and neuroendocrine abnormalities in Parkinson disease
Abstract
Introduction
Nonmotor Symptoms and Hypothalamic Dysfunction in Parkinson's Disease
Clinico-Pathologic Correlations in Parkinson's Disease and Hypothalamic Neuropathologic Involvement by Lewy Pathology
Future Directions
Chapter 16: Lewy bodies in the olfactory system and the hypothalamus
Abstract
Introduction
The Olfactory System
Hypothalamus
Conclusions
Chapter 17: Hypothalamic pathology in Huntington disease
Abstract
Introduction
Clinical Evidence of Hypothalamic Involvement in HD Patients
Rodent Models of HD Used to Study Hypothalamic Pathology and Their Comparison to HD Patients
The Hypothalamic Effects of Mutant Huntingtin
Hypothalamic Pathology in Huntington's Disease
Other Hypothalamic Nuclei
Therapeutic Opportunities
Conclusions
Chapter 18: Endocrine dysfunction in adrenoleukodystrophy
Abstract
Introduction and Historical Perspective
Pathology of Adrenoleukodystrophy
Biochemistry and Genetics of Adrenoleukodystrophy
Diagnosing Adrenoleukodystrophy
Clinical Features of Adrenoleukodystrophy
Treatment of ALD
Prognosis of ALD
Conclusions
Chapter 19: Hypothalamic symptoms of frontotemporal dementia disorders
Abstract
Introduction
FTD Pathology
Amyotrophic Lateral Sclerosis—Frontotemporal Dementia Overlap
Acknowledgments
Section 25: Olfactory system
Chapter 20: The vomeronasal organ: History, development, morphology, and functional neuroanatomy
Abstract
Introduction
Gross Morphology
Histology
Electron Microscopy
Neuroanatomy and Connections to the Hypothalamus
Function
Role in Social Behavior
Role in Some Pathological Processes
Malignancies
Future Directions
Acknowledgments
Chapter 21: Pheromone effects on the human hypothalamus in relation to sexual orientation and gender
Abstract
Introduction
Neural Coding of Mammalian Pheromones
Human Chemosensory Communication
Neural Responses to Human Chemosignals
Concluding Remarks
Chapter 22: Kallmann syndrome and idiopathic hypogonadotropic hypogonadism: The role of semaphorin signaling on GnRH neurons
Abstract
Introduction
The Role of Semaphorins and their Receptors/Coreceptors in GnRH Neuronal Ontogeny and Mammalian Reproduction
Conclusions
Chapter 23: Olfaction as an early marker of Parkinson's disease and Alzheimer's disease
Abstract
Introduction
Testing of Olfaction
Pathology in the Olfactory System in PD
Pathology in the Olfactory System in AD
Neurotransmitter Changes Associated with Olfactory Dysfunction in PD and AD
Vulnerability of the Olfactory System in PD and AD
Olfaction in the Differential Diagnosis of PD
Olfaction in the Differential Diagnosis of AD
Olfaction in the Premotor Diagnosis of PD
Olfaction as an Early Predictor of AD
Conclusions
Acknowledgments
Section 26: Autonomic and sleep disorders
Chapter 24: The hypothalamus and its role in hypertension
Abstract
Introduction
Hypothalamic Alteration in Hypertension
Clinical Relevance
Acknowledgments
Chapter 25: The heart is lost without the hypothalamus
Abstract
Introduction
The PVN—Reflex Circuitry
Excitatory–Inhibitory Neurotransmitter Interaction
Neuroinflammation
Neuronal Nitric Oxide—Nitric Oxide Bioavailability
NMDA—Hypoxia
Summary
Chapter 26: Sleep disorders and the hypothalamus
Abstract
General Introduction
Narcolepsy
Symptomatic Narcolepsy
Kleine–Levin Syndrome
Hypothalamic Syndromes With Prominent Sleep Involvement
Sleep in Endocrine Disorders
Section 27: Addiction and pain
Chapter 27: Molecular genetics of neurotransmitters and neuropeptides involved in Internet use disorders including first insights on a potential role of hypothalamus’ oxytocin hormone
Abstract
Internet Use Disorders
Neurotransmitters, Neuropeptides, and Internet Use Disorders
Twin Studies—Are Internet Use Disorders Heritable?
Initial Molecular Genetic Findings in the Light of Internet Use Disorders
Conclusion
Chapter 28: The neurobiology of cluster headache
Abstract
Introduction
Epidemiology
Genetics
Clinical Aspects
The Pain and the Trigeminal Nerve
The Hypothalamus
Calcitonin Gene-Related Peptide and Cluster Headache
Section 28: Critical care and brain-death
Chapter 29: Endocrine interventions in the intensive care unit
Abstract
Introduction
The Hypothalamic–Pituitary Cross-Talk, the Orchestrator of the Hormonal Stress Responses to Critical Illness
Alterations Within the Five Main Neuroendocrine Axes in Response to Critical Illness
Clinical Relevance and Implications
Chapter 30: Hypothalamic function in patients diagnosed as brain dead and its practical consequences
Abstract
Introduction
Basic Pathophysiology of Brain Death and Diagnostic Testing
Hypothalamic Function in Patients Diagnosed as Brain Dead
Discussion and Implications
Conclusion
Index

Dick F. Swaab

Dick Swaab (1944) earned his medical and doctoral degrees at the University of Amsterdam, where he became involved in brain research during his third year of medical school. He was Director of the Netherlands Institute for Brain Research from 1978 to 2005. Since 1979 he is Professor of Neurobiology at the Medical Faculty, University of Amsterdam.

In 1985, Dr. Swaab founded the Netherlands Brain Bank (NBB) to serve as a source of clinically and neuropathologically well-documented research tissue. Since its founding, the Brain Bank has provided samples from more than 4,000 autopsies to 500 research groups in 25 countries. He was director of the NBB until 2005.

He is Leader Research team Neuropsychiatric Disorders, Neth. Inst for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences (KNAW). Swaab is also appointed for 2011-2017 Chao Kuang Piu Chair of Zhejiang University, Hangzhou, P.R. China.

His major research interests focus on, sexual differentiation of the human brain in relation to gender identity and sexual orientation, aging of the brain, Alzheimer’s disease, the neurobiological basis of depression, suicide and eating disorders. He has published over 540 papers in SCI journals, authored more than 200 chapters in books, and edited more than 60 books. Swaab mentored 84 PhD students from which 16 are now full professor. He is “Companion in the Order of the Dutch Lion”, bestowed by her Royal Majesty Queen Beatrix of the Netherlands. In 2008 Swaab obtained the Academy medal for his role in national and international neuroscience.

Dick Swaab is author of the 2 volume monograph The Human Hypothalamus that appeared in the Handbook of Clinical Neurology series, Elsevier, Amsterdam (1000 pp) and the Dutch best seller We are our Brains (450.000 copies sold), that is translated in 14 languages. A children's version of the book (You are your brains) has also appeared in Dutch in 2013 and Russian (2014). Swaab's H-factor is 76.

Affiliations and expertise

Netherlands Institute for Brain Research, University of Amsterdam, Amsterdam, The Netherlands

Ruud M. Buijs

Dr. Ruud M. Buijs is head of the Physiology department of the I.I.Biomedicas at the UNAM university and leader of the group Hypothalamic Integration Mechanisms. In that group, the scientists study how the brain and body interact with each other, and hereby the attention is focussed on autonomic and hormonal regulation of body functions under the influence of the biological clock of the brain.

Affiliations and expertise

Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Mexico D.F.

Felix Kreier

Felix Kreier is a pediatrician and affiliated with OLVG Hospitals in Amsterdam, The Netherlands.

Affiliations and expertise

OLVG Hospitals, Amsterdam, The Netherlands

Paul J. Lucassen

Paul J. Lucassen did his PhD in 1995 on Alzheimer’s Disease at the Netherlands Institute for Brain Research in Amsterdam. After a.o. a postdoc in Leiden, he became Full Professor of Brain Plasticity in 2011 at the Swammerdam Institute for Life Sciences (SILS) of the University of Amsterdam, The Netherlands. His group studies molecular, nutritional, pharmacological and environmental regulation of brain plasticity. They combine molecular tools, in vitro/vivo model systems, human brain tissue, cohort studies and brain imaging. A major focus is on adult neurogenesis and cognition in relation to; (early life) stress, exercise, enrichment, depression, brain insults and dementia.

Affiliations and expertise

Swammerdam Institute for Life Sciences (SILS) - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands

Ahmad Salehi

Ahmad Salehi is affiliated with Stanford Medical School, Department of Psychiatry & Behavioral Sciences, in Palo Alto, CA, United States.

Affiliations and expertise

Stanford Medical School, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, United States