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Table of Contents
Intro
Sex Differences in Neurology and Psychiatry
Copyright
Available titles
Foreword
Preface
Contributors
Contents
Section I: Sex differences in neuroanatomy and neurophysiology
Chapter 1: Structural differences between male and female brains
Why Sex Matters: Searching for Differences Between Male and Female Brains
A Short Detour Into the World (of Human Brain Mapping): Global, Regional, and Local
A Mixed Bag: A Multitude of (Conflicting) Findings Based on Structural MRI
Global measures
Regional measures
Some general observations
A specific consideration: The corpus callosum
Local measures
Voxel-wise gray matter volume
Vertex-wise cortical thickness
Point-wise cortical gyrification
Why Size Matters: The Possible Confounding Impact of Total Brain Volume
Conclusions
Acknowledgments
References
Chapter 2: Beyond sex differences and a male-female continuum: Mosaic brains in a multidimensional space
The Basis of the Mosaic Hypothesis: Studies in Laboratory Animals
Testing the Mosaic Hypothesis
Mosaic in human brain structure and connectivity as revealed by magnetic resonance imaging (MRI)
Mosaic in brain connectivity
Mosaic in neuronal numbers in the post-mortem human hypothalamus
Mosaic in structural changes following exposure to severe real-life stress
A Comment on the Source of Differences Between Women and Men
Typical and Rare Brain ``Types ́́
Criticism of the Mosaic Hypothesis
Questioning the analytical method used to test the mosaic hypothesis
The question of prediction
The straw-man criticism of the mosaic hypothesis
Moving from a Male-Female Continuum to a Multidimension Space
Conclusions
References
Chapter 3: Sex differences and brain development during puberty and adolescence
Introduction.
Sex Effects on Anatomical Brain Changes Across Childhood and Adolescence
Anatomical brain changes
Cerebral cortex
Subcortical structures
White matter
Sex effects on anatomical brain development
Cerebral cortex
Subcortical structures
White matter
Greater male variability in brain structure and development
Behavioral and Functional Brain Changes and Sex Effects
Behavioral changes and brain functioning
Social and affective functioning
Social relationships
Emotion processing and amygdala responsiveness
Behavioral control, risk-taking, and cognitive development
Sex effects in adolescent functional brain changes and behavior
Sex effects in affective brain functioning
Sex effects in behavioral control, risk-taking, and cognitive functioning
Sex steroid hormones at puberty and adolescence
Gender Identity Development
Gender incongruence
Sexual orientation
Effects of puberty suppression and gender-affirming hormones on brain and cognition
Concluding Remarks
Acknowledgments
References
Chapter 4: Hypothalamic-pituitary-adrenal axis and stress
Introduction1
Animal Models
Human Studies
Comparison Between Preclinical and Clinical Studies
Conclusions
References
Chapter 5: Spatial skills
Introduction
Types of Spatial Skills Underlying Navigation
Mental object transformations
Object location memory
Spatial visualization and perception
Spatial Navigation
Navigation, development and aging
Cognitive and Neural Models
Neural models of spatial navigation
Cognitive styles and spatial orientation
Conclusions
References
Chapter 6: Gender differences in language are small but matter for disorders
Why Should Neuroscientists Care about Language?
Gender, Evolution and Language
Essentialist ``sex ́́model.
Experientialist ``gender ́́model
Language and Gender in the Normal Population
Primary language acquisition
Language development (4-12 years)
Adolescent and adult language
Voice
Speaking and talkativeness
Word use
Verbal comprehension and vocabulary
Reading
Verbal fluency
Language and brain lateralization
Language and Gender in Disorders and in the Diseased Brain
Language in sex chromosome aneuploidies
Developmental disorders
Developmental language disorder
Autism spectrum disorder
Childhood-onset fluency disorder (stuttering)
Specific learning disorder with reading impairment (dyslexia)
Neurodegenerative Disorders
Huntington's disease
Parkinson's disease
Dementia
Alzheimer's dementia
Primary progressive aphasia
Acquired Neurologic Deficits
Stroke and aphasia
Aphasia severity and prevalence
Types of aphasia
Aphasia recovery
Category-specific deficits
Psychiatric Disorders
Depression
Schizophrenia
Summary and Synthesis
References
Chapter 7: Sex differences in cognition and aging and the influence of sex hormones
Introduction
Sex Differences in Adult Cognition
Visual-spatial abilities
Attention
Verbal fluency
Verbal working memory and verbal memory
Summary: Sex differences in cognition
Sex Hormones and Cognition Across the Lifespan: Prenatal Androgen Exposure, Puberty and Adulthood
Sex Hormones and Cognition Across the Lifespan: Menopause
Sex Hormones and Cognition Across the Lifespan: Aging
Hormone Treatments for Cognitive Decline
Overall Conclusion
References
Chapter 8: Sex and the serotonergic underpinnings of depression and migraine
Introduction
The Human Serotonin System and Its Assessment Using PET
Serotonin synthesis
Serotonin degradation
Serotonin receptors
5-HT1 receptors.
5-HT2 receptors
5-HT3 receptors
5-HT4 receptors
5-HT5 receptors
5-HT6 receptors
5-HT7 receptors
Serotonin transporter
Sex, Sex Hormones, and Serotonin Neurotransmission: Animal Research
Serotonin synthesis
Serotonin degradation
Serotonin receptors
5-HT1 receptors
5-HT2 receptors
5-HT3 receptors
5-HT4, 5-HT5, 5-HT6, 5-HT7 receptors
Serotonin transporter
Sex, Sex Hormones, and Serotonin Neurotransmission: Human Studies
Serotonin synthesis
Serotonin degradation
Serotonin receptors
5-HT1 receptors
5-HT2 receptors
5-HT4 receptors
Serotonin transporter
Migraine, the Serotonergic System, and Sex Hormones
Migraine-A brief overview
Migraine pathophysiology and the serotonergic system
Migraine in males and females
Sex steroids and migraine
Pharmacotherapy of migraine and the influence of sex hormones
CGRP, migraine, and female sex hormones
5-HT, migraine, and sex hormones
Conclusion
References
Chapter 9: Sex and the dopaminergic system: Insights from addiction studies
IntroductionCo-first authorship.
Why study sex differences in dopamine?
Dopamine Neurobiology
Investigating dopamine neurobiology in humans
Sex differences in dopamine neurobiology
Dopamine D2/3R levels
DAT availability
Dopamine synthesis capacity
Evoked dopamine release
Dopamine and Sex Hormones
Testosterone
Estrogen
Progesterone
Menstrual cycle phase
Menopause
Dopamine and Genetics
Dopamine and Cognition
Working memory
Decision-making
Executive control
Dopamine and Addiction
Discussion
Funding
Author Contributions
Conflicts of Interest
References
Chapter 10: Sex and the noradrenergic system
The Locus Coeruleus as a Sexually Dimorphic Regulator of Central Nervous System Function.
Sex Differences in Locus Coeruleus Anatomy and Morphology
Impact of Ovarian Hormones on Locus Coeruleus Physiology and Function
Sex-Biased Regulation of Locus Coeruleus Neurons by Stress and Corticotropin Releasing Hormone
Sex Biased Corticotropin Releasing Hormone Signaling and Its Potential Link to Alzheimer's Disease
Clinical Evidence for Human Sex Differences in Locus Coeruleus Structure and Function
Indirect Evidence for the Contribution of Locus Coeruleus Sex Differences to Sex-Biased Disease
Conclusions
References
Section II: Genes, hormones and epigenetic mechanisms
Chapter 11: Genetics of sex differences in neuroanatomy and function
Introduction
Classic vs Emerging Views on Sex Differences
Hormones vs Sex Chromosomes
Candidate Sex Chromosomal Genes Influencing Sex Differences in the Brain
Steroid Receptor Genes
Neurochemistry
Genetic Sex Differences in Neurologic and Psychiatric Disorders
Alternative Approaches to Study Genetic Mechanisms of Sex Differences
Conclusions
References
Chapter 12: Sex hormones and human brain function
Introduction
Sex hormones and the brain
Methods to Study the Effects of Sex Hormones
Criteria for inclusion of studies
Estradiol and Progesterone
Cognition
Language
Visuospatial skills
Memory
Emotion processing
Passive viewing of emotional content
Emotion recognition and reactivity
Reward processing
Reward processing
Response inhibition
Testosterone
Cognition
Language
Visuospatial skills
Memory
Emotion processing
Passive viewing of emotional content
Emotion recognition and reactivity
Reward processing
Reward processing
Response inhibition
Decision making
Conclusion
References
Chapter 13: Environmental epigenetics of sex differences in the brain
Introduction.
Epigenetics of Developmental Sex Differences: Hormones and Beyond.
Sex Differences in Neurology and Psychiatry
Copyright
Available titles
Foreword
Preface
Contributors
Contents
Section I: Sex differences in neuroanatomy and neurophysiology
Chapter 1: Structural differences between male and female brains
Why Sex Matters: Searching for Differences Between Male and Female Brains
A Short Detour Into the World (of Human Brain Mapping): Global, Regional, and Local
A Mixed Bag: A Multitude of (Conflicting) Findings Based on Structural MRI
Global measures
Regional measures
Some general observations
A specific consideration: The corpus callosum
Local measures
Voxel-wise gray matter volume
Vertex-wise cortical thickness
Point-wise cortical gyrification
Why Size Matters: The Possible Confounding Impact of Total Brain Volume
Conclusions
Acknowledgments
References
Chapter 2: Beyond sex differences and a male-female continuum: Mosaic brains in a multidimensional space
The Basis of the Mosaic Hypothesis: Studies in Laboratory Animals
Testing the Mosaic Hypothesis
Mosaic in human brain structure and connectivity as revealed by magnetic resonance imaging (MRI)
Mosaic in brain connectivity
Mosaic in neuronal numbers in the post-mortem human hypothalamus
Mosaic in structural changes following exposure to severe real-life stress
A Comment on the Source of Differences Between Women and Men
Typical and Rare Brain ``Types ́́
Criticism of the Mosaic Hypothesis
Questioning the analytical method used to test the mosaic hypothesis
The question of prediction
The straw-man criticism of the mosaic hypothesis
Moving from a Male-Female Continuum to a Multidimension Space
Conclusions
References
Chapter 3: Sex differences and brain development during puberty and adolescence
Introduction.
Sex Effects on Anatomical Brain Changes Across Childhood and Adolescence
Anatomical brain changes
Cerebral cortex
Subcortical structures
White matter
Sex effects on anatomical brain development
Cerebral cortex
Subcortical structures
White matter
Greater male variability in brain structure and development
Behavioral and Functional Brain Changes and Sex Effects
Behavioral changes and brain functioning
Social and affective functioning
Social relationships
Emotion processing and amygdala responsiveness
Behavioral control, risk-taking, and cognitive development
Sex effects in adolescent functional brain changes and behavior
Sex effects in affective brain functioning
Sex effects in behavioral control, risk-taking, and cognitive functioning
Sex steroid hormones at puberty and adolescence
Gender Identity Development
Gender incongruence
Sexual orientation
Effects of puberty suppression and gender-affirming hormones on brain and cognition
Concluding Remarks
Acknowledgments
References
Chapter 4: Hypothalamic-pituitary-adrenal axis and stress
Introduction1
Animal Models
Human Studies
Comparison Between Preclinical and Clinical Studies
Conclusions
References
Chapter 5: Spatial skills
Introduction
Types of Spatial Skills Underlying Navigation
Mental object transformations
Object location memory
Spatial visualization and perception
Spatial Navigation
Navigation, development and aging
Cognitive and Neural Models
Neural models of spatial navigation
Cognitive styles and spatial orientation
Conclusions
References
Chapter 6: Gender differences in language are small but matter for disorders
Why Should Neuroscientists Care about Language?
Gender, Evolution and Language
Essentialist ``sex ́́model.
Experientialist ``gender ́́model
Language and Gender in the Normal Population
Primary language acquisition
Language development (4-12 years)
Adolescent and adult language
Voice
Speaking and talkativeness
Word use
Verbal comprehension and vocabulary
Reading
Verbal fluency
Language and brain lateralization
Language and Gender in Disorders and in the Diseased Brain
Language in sex chromosome aneuploidies
Developmental disorders
Developmental language disorder
Autism spectrum disorder
Childhood-onset fluency disorder (stuttering)
Specific learning disorder with reading impairment (dyslexia)
Neurodegenerative Disorders
Huntington's disease
Parkinson's disease
Dementia
Alzheimer's dementia
Primary progressive aphasia
Acquired Neurologic Deficits
Stroke and aphasia
Aphasia severity and prevalence
Types of aphasia
Aphasia recovery
Category-specific deficits
Psychiatric Disorders
Depression
Schizophrenia
Summary and Synthesis
References
Chapter 7: Sex differences in cognition and aging and the influence of sex hormones
Introduction
Sex Differences in Adult Cognition
Visual-spatial abilities
Attention
Verbal fluency
Verbal working memory and verbal memory
Summary: Sex differences in cognition
Sex Hormones and Cognition Across the Lifespan: Prenatal Androgen Exposure, Puberty and Adulthood
Sex Hormones and Cognition Across the Lifespan: Menopause
Sex Hormones and Cognition Across the Lifespan: Aging
Hormone Treatments for Cognitive Decline
Overall Conclusion
References
Chapter 8: Sex and the serotonergic underpinnings of depression and migraine
Introduction
The Human Serotonin System and Its Assessment Using PET
Serotonin synthesis
Serotonin degradation
Serotonin receptors
5-HT1 receptors.
5-HT2 receptors
5-HT3 receptors
5-HT4 receptors
5-HT5 receptors
5-HT6 receptors
5-HT7 receptors
Serotonin transporter
Sex, Sex Hormones, and Serotonin Neurotransmission: Animal Research
Serotonin synthesis
Serotonin degradation
Serotonin receptors
5-HT1 receptors
5-HT2 receptors
5-HT3 receptors
5-HT4, 5-HT5, 5-HT6, 5-HT7 receptors
Serotonin transporter
Sex, Sex Hormones, and Serotonin Neurotransmission: Human Studies
Serotonin synthesis
Serotonin degradation
Serotonin receptors
5-HT1 receptors
5-HT2 receptors
5-HT4 receptors
Serotonin transporter
Migraine, the Serotonergic System, and Sex Hormones
Migraine-A brief overview
Migraine pathophysiology and the serotonergic system
Migraine in males and females
Sex steroids and migraine
Pharmacotherapy of migraine and the influence of sex hormones
CGRP, migraine, and female sex hormones
5-HT, migraine, and sex hormones
Conclusion
References
Chapter 9: Sex and the dopaminergic system: Insights from addiction studies
IntroductionCo-first authorship.
Why study sex differences in dopamine?
Dopamine Neurobiology
Investigating dopamine neurobiology in humans
Sex differences in dopamine neurobiology
Dopamine D2/3R levels
DAT availability
Dopamine synthesis capacity
Evoked dopamine release
Dopamine and Sex Hormones
Testosterone
Estrogen
Progesterone
Menstrual cycle phase
Menopause
Dopamine and Genetics
Dopamine and Cognition
Working memory
Decision-making
Executive control
Dopamine and Addiction
Discussion
Funding
Author Contributions
Conflicts of Interest
References
Chapter 10: Sex and the noradrenergic system
The Locus Coeruleus as a Sexually Dimorphic Regulator of Central Nervous System Function.
Sex Differences in Locus Coeruleus Anatomy and Morphology
Impact of Ovarian Hormones on Locus Coeruleus Physiology and Function
Sex-Biased Regulation of Locus Coeruleus Neurons by Stress and Corticotropin Releasing Hormone
Sex Biased Corticotropin Releasing Hormone Signaling and Its Potential Link to Alzheimer's Disease
Clinical Evidence for Human Sex Differences in Locus Coeruleus Structure and Function
Indirect Evidence for the Contribution of Locus Coeruleus Sex Differences to Sex-Biased Disease
Conclusions
References
Section II: Genes, hormones and epigenetic mechanisms
Chapter 11: Genetics of sex differences in neuroanatomy and function
Introduction
Classic vs Emerging Views on Sex Differences
Hormones vs Sex Chromosomes
Candidate Sex Chromosomal Genes Influencing Sex Differences in the Brain
Steroid Receptor Genes
Neurochemistry
Genetic Sex Differences in Neurologic and Psychiatric Disorders
Alternative Approaches to Study Genetic Mechanisms of Sex Differences
Conclusions
References
Chapter 12: Sex hormones and human brain function
Introduction
Sex hormones and the brain
Methods to Study the Effects of Sex Hormones
Criteria for inclusion of studies
Estradiol and Progesterone
Cognition
Language
Visuospatial skills
Memory
Emotion processing
Passive viewing of emotional content
Emotion recognition and reactivity
Reward processing
Reward processing
Response inhibition
Testosterone
Cognition
Language
Visuospatial skills
Memory
Emotion processing
Passive viewing of emotional content
Emotion recognition and reactivity
Reward processing
Reward processing
Response inhibition
Decision making
Conclusion
References
Chapter 13: Environmental epigenetics of sex differences in the brain
Introduction.
Epigenetics of Developmental Sex Differences: Hormones and Beyond.