Trajectories of brain development: point of vulnerability or window of opportunity?
Section snippets
Background and theoretical framework
Nearly 22.1% of the adult population of the United States has a diagnosable mental illness. Differences in diagnostic issues may slightly influence this statistic, but the World Health Organization estimates that mental disorders are on the rise [94]. Depression, for example, is projected to become the second leading disorder by 2020 [94]. Despite the complete mapping of the human genome, the genetic culprits that underlie the most prevalent psychiatric disorders in our society remain elusive.
Normal brain development
The trajectory of brain development occurs in multiple stages as reviewed below. Schematically, this timeline is found in Fig. 1. Within the timeline, different brain regions have a unique course of ontogeny. Late developing structures, including the cortex, hippocampus and the cerebellum [77], [103], [107], set the stage for differential periods of vulnerability in a regionally specific manner.
Intrinsic factors of brain development
A number of functional changes occur during the maturation of the brain that serve as important regulators or stabilizers of programmed development [101]. In addition to the structure–function relationships described above, age-dependent changes in intrinsic factors are integral for determining set points in synaptic activity that further define a developmental trajectory. Four categories exist: (1) neurotransmitters serve as trophic factors that directly guide innervation; (2)
Extrinsic factors of brain development
The sculpting of the immature brain is an interactive process between genetic programming, cell function, and the environment. The result of this process is an endophenotype, which refers to heritable traits that increase the risk to develop or manifest a given disease [39], and offers a new approach to elucidating the underlying mechanisms of action of common symptoms across disorders [3]. For example, the endophenotypes of ADHD consist of aberrancies in temporal processing or delay gradients
Extrinsic factors known to influence the vulnerability to insult
This section will highlight supportive data regarding the importance of a number of factors that influence the appearance of any early insult.
Conclusions
The relationship between early insult and resulting psychopathology is still in its infancy. Waves of overproduction and elimination of synapses, receptors, and function may serve as a neural guide or stabilization mechanism during adolescence [101]. Thus, the key to understanding the impact of various risk factors on the emergence of psychopathology is the time course of development of the underlying brain structures and function. In this regard, we know very little about how the brain matures
Acknowledgements
The author wishes to thank Carryl P. Navalta and Kai C. Sonntag for valuable comments and Martin H. Teicher for his continued support (MH-43474). The financial support of the Scottish Rite Schizophrenia Research Program, the Tourettes Syndrome Association, and NARSAD (SLA) is also gratefully acknowledged.
References (233)
Changes in the second messenger cyclic AMP during development may underlie motoric symptoms in attention deficit/hyperactivity disorder (ADHD)
Behav Brain Res
(2002)- et al.
Pubertal changes in gonadal hormones do not underlie adolescent dopamine receptor overproduction
Psychoneuroendocrinology
(2002) - et al.
The development of D2 autoreceptor-mediated modulation of K(+)-evoked dopamine release in the neostriatum
Brain Res Dev Brain Res
(1994) - et al.
Sex differences in dopamine receptors and their relevance to ADHD
Neurosci Biobehav Rev
(2000) - et al.
Synchronous development of pyramidal neuron dendritic spines and parvalbumine-immunoreactive chandelier neuron axon terminals in layer III of monkey prefrontal cortex
Neuroscience
(1995) - et al.
Stressed-out, or in (utero)?
Trends Neurosci
(2002) - et al.
Functional magnetic resonance imaging of facial affect recognition in children and adolescents
J Am Acad Child Adolesc Psychiatry
(1999) - et al.
Glutamate recognition sites in human fetal brain
Neurosci Lett
(1988) - et al.
A rheostat model for a rapid and reversible form of imprinting-dependent evolution
Am J Hum Genet
(2002) - et al.
The influence of estrogen on nigrostriatal dopamine activity: behavioral and neurochemical evidence for both pre- and postsynaptic components
Behav Brain Res
(1986)
Sex differences and estrous cycle variations in amphetamine elicited rotational behavior
Eur J Pharmacol
Estradiol TRH and striatal dopaminergic mechanisms
Prog Neuropsychopharmacol Biol Psychiatry
The role of stress and dopamine–GABA interactions in the vulnerability for schizophrenia
J Psychiatr Res
Emerging principles of altered neural circuitry in schizophrenia
Brain Res Brain Res Rev
Actions of (+/−)-7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) on dopamine synthesis in limbic and extrapyramidal regions of rat brain
Brain Res
Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats
Neuropsychopharmacology
Postnatal development of striatal dopamine function. I. An examination of D1 and D2 receptors, adenylate cyclase regulation and presynaptic dopamine markers
Brain Res Dev Brain Res
Structural and functional brain development and its relation to cognitive development
Biol Psychol
Regulation of class I MHC gene expression in the developing and mature CNS by neural activity
Neuron
Transient expression of 5-HT1A receptor binding sites in some areas of the rat CNS during postnatal development
Int J Dev Neurosci
Differential ontogeny of functional dopamine and muscarinic receptors mediating presynaptic inhibition of neurotransmitter release and postsynaptic regulation of adenylate cyclase activity in rat striatum
Brain Res Dev Brain Res
Early deprivation and behavioral and physiological responses to social separation/novelty in the marmoset
Pharmacol Biochem Behav
Neurite branch development of an identified serotonergic neuron from embryonic Helisoma: evidence for autoregulation by serotonin
Dev Biol
Regulation of white adipocyte guanin nucleotide binding proteins Gs alpha and Gi alpha 1–2 by testosterone in vivo: influence of regional fat distribution
Biochim Biophys Acta
The serotonin innervation of the basal forebrain shows a transient phase during development
Brain Res Dev Brain Res
Preweaning cocaine administration alters the adult response to quipazine: comparison with fluoxetine
Neurotoxicol Teratol
Sexual dimorphism in the brain metabolic response to prenatal cocaine exposure
Brain Res Dev Brain Res
The effect of seizures and kindling on reproductive hormones in the rat
Neurosci Biobehav Rev
The nature and heritability of attention-deficit/hyperactivity disorder
Child Adolesc Psychiatr Clin N Am
Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence?
J Psychiatr Res
Critical period control in sensory cortex
Curr Opin Neurobiol
Dopamine D1 receptor development depends on endogenous dopamine
Brain Res Dev Brain Res
Postnatal development of dopamine D1 and D2 receptor sites in rat striatum
Brain Res
A quantitative MRI study of the corpus callosum in children and adolescents
Brain Res Dev Brain Res
Postnatal development of monoamine content and synthesis in the cerebral cortex of rhesus monkeys
Brain Res
Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs
Trends Neurosci
Sex steroid hormones change the differential distribution of the isoforms of the D2 dopamine receptor messenger RNA in the rat brain
Neuroscience
Direct striatothalamic projections in the neonatal rat
Brain Res Dev Brain Res
Androgens and puberty
Best Pract Res Clin Endocrinol Metab
Alterations in the spontaneous release of dopamine and the density of the DA D2 receptor mRNA after chronic postnatal exposure to cocaine
Brain Res Bull
Early exploration of the visual cortex
Neuron
Sexual orientation and the size of the anterior commissure in the human brain
Proc Natl Acad Sci USA
Prenatal and perinatal influences on risk for psychopathology in childhood and adolescence
Dev Psychopathol
Endophenotypes as quantitative risk factors for psychiatric disease: rationale and study design
Am J Med Genet
Differences in behavior and monoamine laterality following neonatal clomipramine treatment
Dev Psychobiol
Altered responsiveness to cocaine in rats exposed to methylphenidate during development
Nat Neurosci
Developmental differences in dopamine synthesis inhibition by 7-OHDPAT
Naunyn Schmiedeberg's Arch Pharmacol
The ontogeny of apomorphine-induced alterations in dopamine release: I. Effects on spontaneous release
J Neurochem
Effects of (−) sulpiride on dopamine release in striatum of developing rats: degree of depolarization influences responsiveness
J Neurochem
Maturational increases in c-fos expression in the ascending dopamine systems
Synapse
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