Chapter
2 Brain development in healthy children and adolescents: magnetic resonance imaging studies
3 Cognitive development: functional magnetic resonance imaging studies
Brain and cognitive maturation
Functional magnetic resonance imaging
Changes in brain function supporting cognitive development
Development of brain function supporting language
Attention-deficit hyperactivity disorder
Pediatric fMRI studies of schizophrenia
Challenges to pediatric neuroimaging
Differences in performance
4 Cognitive development in adolescence: cerebral underpinnings, neural trajectories, and the impact of aberrations
Brain development during adolescence
Links between the emergence of cognitive skills and cerebral development
Aberrations in development that impact on adolescence
Conclusions and future directions
5 Brain plasticity and long-term function after early cerebral insult: the example of very preterm birth
A brief history of plasticity
Plasticity after brain injury
The example of very preterm birth
The University College Hospital London study
Patterns of perinatal brain injury
Can the sequelae of preterm birth still be seen in the brains of adolescents?
What are the consequences of persisting brain abnormality?
The link between brain structure and brain function
Possible mechanisms of brain reorganization and sparing of function
At the level of neural networks
At the level of connectivity
The limits of brain plasticity
Part II Etiological factors
6 Do degenerative changes operate across diagnostic boundaries? The case for glucocorticoid involvement in major psychiatric disorders
Evidence for a common neuropathology in major depression, bipolar disorder, and schizophrenia
A role for glucocorticoids in the neuronal changes of mood disorders and schizophrenia?
Hypothalamic-pituitary-adrenal axis abnormalities in major depression
Hypothalamic-pituitary-adrenal axis abnormalities in schizophrenia
Cortisol: hero or villain?
7 Velocardiofacial syndrome (deletion 22q11.2): a homogeneous neurodevelopmental model for schizophrenia
Cognitive and behavioral phenotype in childhood developmental delays
Childhood behavioral phenotype
Psychiatric presentation in adulthood
8 Can structural magnetic resonance imaging provide an alternative phenotype for genetic studies of schizophrenia?
The heritability of brain structure
Brain structure and schizophrenia
Brain abnormalities in unaffected relatives
9 Nutritional factors and schizophrenia
Nutrition in brain and behavioral development and maintenance
Nutritional factors and schizophrenia
Essential polyunsaturated fatty acids and schizophrenia
Altered fatty acid metabolism in schizophrenia
Precursors of brain phospholipids and neurodevelopment in schizophrenia
Membrane signal transduction
Other physiological roles of phospholipid precursors relevant to schizophrenia
Factors affecting membrane polyunsaturated fatty acid metabolism in schizophrenia
Intake of polyunsaturated fatty acids
Oxidative breakdown of polyunsaturated fatty acids
Strategies to address nutritional deficits in schizophrenia
Factors influencing supplementation
Preferred supplementation components
When and what should be treated with antioxidants and essential polyunsaturated fatty acids'77
10 Schizophrenia, neurodevelopment, and epigenetics
The basics of epigenetics
Relevance of epigenetics to schizophrenia
Epigenetics and development
The synthesis: epigenetics, development, and schizophrenia
11 Early environmental risk factors for schizophrenia
Prenatal risk factors for schizophrenia
Prenatal rubella and other prenatal infections
Neonatal and early childhood infection
Prenatal exposure to stress
Perinatal risk factors: obstetric complications
Neonatal risk factors: early rearing environment
12 Transcriptomes in schizophrenia: assessing altered gene expression with microarrays
Assessing transcriptomes with microarrays
Experimental design in microarray studies
Microarray data analysis and interpretation
Gene expression changes associated with schizophrenia
Conclusions and future directions
13 Is there a role for social factors in a comprehensive developmental model for schizophrenia
Animal models of isolation rearing and social stress
Mother-child relationship
Family communication deviance
Dysfunctional family environment
Social drift and social residue theories
Moving schools in adolescence
Migration and ethnic minority status
African-Caribbeans in the UK
Socioeconomic factors, deprivation, and inequality
Interaction between social and other etiological factors
Gene-environment interaction
Social factors and cognitive processing
Social causation versus social selection
14 How does drug abuse interact with familial and developmental factors in the etiology of schizophrenia
Association of drug abuse and psychosis
Direction of the association
Drug abuse as a cause of psychosis
Amphetamine-induced psychosis
Cannabis-induced psychosis:
Phencyclidine-induced psychosis
Lysergic acid diethylamide-induced psychosis
Individual differences in liability to developing drug-related psychosis
Childhood development and personality
Molecular genetic studies of substance-associated psychosis
Animal models of the interaction of drugs with perinatal brain damage
15 Developmental dysregulation of the dopamine system and the pathophysiology of schizophrenia
Role in the pathophysiology of schizophrenia
Role in stress and emotional reactivity
Developmental models of schizophrenia
Possible origins of the delayed onset of schizophrenia
Pathophysiological impact on dopamine transmission
16 The development of miswired limbic lobe circuitry in schizophrenia and bipolar disorder
Postmortem findings in schizophrenia and bipolar disorder
The gamma-aminobutyric acid system
The role of the amygdala in limbic lobe changes
Postnatal maturation of limbic lobe circuitry
The development of the gamma-aminobutyric acid system
Late maturation of dopamine projections
The ingrowth of amygdalar fibers into the anterior cingulate cortex
A model for how a "mis-wired" circuit might lead to decompensation
17 Development of thalamocortical circuitry and the pathophysiology of schizophrenia
Function and development of the circuitry of the mediodorsal nucleus and dorsolateral prefrontal cortex
Organization of thalamocortical circuitry
Development of thalamocortical circuitry
Dysfunction of thalamocortical circuitry in schizophrenia
Conclusions and future directions
18 X chromosome, estrogen, and brain development: implications for schizophrenia
Sex differences in epidemiology and clinical features of schizophrenia
Anatomical differences between men and women with schizophrenia
Normal brain development and aging
Development and aging of the serotonergic and dopaminergic systems
The role of estrogen in brain development and aging
19 Premorbid structural abnormalities in schizophrenia
The neuroanatomy of schizophrenia
Prospective studies of high-risk populations
Edinburgh High Risk Study
Melbourne High Risk Study
Structural imaging and risk factors for schizophrenia
Neurodevelopment and premorbid adjustment
20 Neurodegenerative models of schizophrenia
Clinical psychopathology and neurocognition
Postmortem neuropathology
Functional and spectroscopic studies
Correlation between neuroimaging data and clinical outcome
Potential mechanisms underlying neurodegeneration
21 Does disordered brain development occur across diagnostic boundaries?
Neuroimaging and the pathological trajectory of psychiatric disorders
Attention-deficit hyperactivity disorder
Obsessive--compulsive disorder
Major depressive disorder and bipolar disorder
Other factors that may occur across psychiatric disorders
Part IV Clinical implications
22 Can one identify preschizophrenia children?
Neurointegrative predictors
Archival--observational studies
Neuropsychological predictors
Archival--observational studies
23 Highrisk studies, brain development, and schizophrenia
General population cohort studies
Follow-back and retrospective studies
Genetic high-risk studies
"Neurobehavioral" high-risk strategies
Clinical high-risk strategies
"Enhanced" high-risk strategies
Reliability of parental diagnoses
Specificity to schizophrenia
Generalizability to schizophrenia
Predictive and outcome measures
Critical periods of development
24 Developmental models and hypothesis-driven early interventions in schizophrenia
Clinical "facts" about the early course of schizophrenia
The premorbid phase is characterized by cognitive impairments
The prodromal phase is characterized by emergence of subthreshold symptoms
Early psychosis may be associated with further functional decline
Clinical observations can inform us about pathophysiology
The "early" developmental model and premorbid alterations
The "late" developmental model and the peri-adolescent beginning of illness
The neurodegenerative model and deterioration after the onset of illness
Pathophysiology may be explained by an integrative neurochemical model
Toward an understanding of etiological factors
Strategies for preventive intervention suggested by current pathophysiological models
Premorbid phase: primary (universal or selective) prevention efforts
Prodromal phase: secondary (indicated) prevention strategies
Strategies after onset of schizophrenia: toward tertiary prevention
Neurodevelopment and Schizophrenia
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