CRITICAL PERIOD GENE-ENVIRONMENT INTERACTIONS AND THE DEVELOPMENT OF A VULNERABILITY TO PSYCHOPATHOLOGY
“The development, in the first two years of life, of a right hemispheric dynamic system that adaptively regulates psychobiological states is a product of the interaction of genetic systems and early experience…. The onset and offset of sensitive periods, “unique windows of organism-environment interaction,” are attributed to the activation and expression of families of programmed genes which synchronously turn on and off during infancy, thereby controlling the transient enhanced expression of enzymes of biosynthetic pathways which allow for growth in particular brain regions. (Schore/ad/112)”
“..early postnatal development represents an experiential shaping of genetic potential (Kendler & Eaves, 1986)…. (Schore/ad/112)”
“…visual experience regulates gene expression in the developing cortex (Neve & Bear, 1989)…. (Schore/ad/112)”
“…I suggest that gene-environment mechanisms are embedded within face-to-face visuoaffective interactions. (Schore/ad/112)”
“These socioemotional interactions thus directly impact the growth of limbic regions. The right cerebral cortex, densely interconnected into limbic structures, is specifically impacted by early social experiences, is primarily involved in attachment experiences, and is more vulnerable to early negative environmental influences than the left. (Schore/ad/112)”
“…during sensitive periods of right hemispheric growth less than optimal early environments in interaction with genetic factors are important forces in compromised brain organization and the pathogenesis of disorders of affect regulation. (Schore/ad/112)”
“The brain growth spurt spans from the end of prenatal life through the end of infancy, a time period when the right hemisphere is rapidly expanding. (Schore/ad/112)”
“During this exact interval the total amount of DNA in the cerebral cortex increases dramatically and then levels off…. It is in this period that timed gene action systems, which program the structural growth and connections of the higher structures of the limbic system, are activated. (Schore/ad/112)”
“Although it is established that these hereditary expressions require transactions with the environment, the question arises as to what mechanism embedded in the early caregiver-infant relationship could act to experientially shape genetic potential? (Schore/ad/112)”
“Hofer’s (1990) research showed that the mother acts as a “hidden” regulator of not only infant brain
catecholamines, agents that activate the hexose monophosphate shunt and ribonucleic acid synthesis (Cummins, Loreck, & McCanless, 1985),
but also of ornithine decarboxylase,
a key enzyme in (Schore/ad/112) the control of nucleic acid synthesis in the developing brain….
These events influence not only catecholaminergic-driven maturation of the amygdala, but
also later-maturing paralimbic areas in the temporal pole and then orbitofrontal cortices. (Schore/ad/113)”
“There is an increasing amount of evidence indicating that the underlying genetic defect in psychiatric disorders is in the hereditary systems involved in the synthesis and catabolism of biogenic amines which trophically regulate maturation in subcortical and cortical information processing centers, and that such mutations can lead to a disruption of normal synaptogenesis and circuit formation. The genes that encode the production of bioamines and their receptors continue to be activated postnatally, causing a dramatic expansion of these systems over the stages of human infancy. Aminergic neuromodulators regulate both the responsiveness of the developing cortex to environmental stimulation and the organization of cortical circuitry, and because their activity is highly heritable (Clarke et al., 1995), altered genetic systems that program the key enzymes in their biosynthesis are now considered to represent potential contributors to high-risk scenarios (Mallet, 1996). (Schore/ad/113)”
“”Indeed, the genes for tyrosine hydroxylase, the rate-limiting enzyme in both dopamine and noradrenaline production, are essential to both fetal development and postnatal survival (Zhou, Quaife, & Palmiter, 1995). Alterations in the genetic systems that program bioamines and their receptors, agents that directly influence morphogenesis, would thus negatively effect the critical period organization and functioning of ventral tegmental dopaminergic and lateral tegmental noradrenergic neurons that regulate the metabolic capacities of their corticolimbic terminal fields. (Schore/ad/113)”
“…the construction of modular circuits in critical periods is associated with linkages between areas of high activity of the energy generating enzyme cytochrome oxidase. This implies that early mitochondrial pathology would underlie defective brain circuitry. Nuclear and mitochondrial genes that encode cytochrome oxidase…, especially in bioaminergic (and hypothalamic neuroendocrine) systems and their receptors, may turn out to be an important locus for the development of “faulty” circuit wirings that mediate a predisposition to later forming psychiatric disorders. (Schore/ad/113)”
“In fact, brain mitochondrial abnormalities are implicated in the etiology of a childhood neurological disorder of the right frontal lobe (Rett syndrome) that shows socialization deficits at 9 months and onset of autistic-appearing regression of interpersonal interaction at 18 months (bunch of refs). Alterations of oxidative metabolism due to mutations of genes that encode isoforms of cytochrome oxidase are being explored in the pathogenesis of the schizophrenic brain (bunch of regs). (Schore/ad/113)”
“Mitochondrial gene expression is involved in “the mechanisms by which mammalian cells adapt to the changing energetic demands in response to functional, developmental and pathological factors” (Attardi et al, 1990, p. 509). The genetic system encoded in mitochondrial DNA is maternally inherited, is (Schore/ad/113) governed by non-Mendelian mechanisms, and has a mutagenicity rate ten times that of nuclear DNA. A mutation of these genes may occur in utero, but the amplification of mitochondrial DNA (which occurs from infancy onward; Simonetti, Chen, DiMauro, & Schon, 1992) during a critical period of rapid mitochondrial proliferation in actively growing brain regions represents a mechanism by which the number of local genetic mutations could increase. It is now thought that once the mutant mitochondrial DNAs reach a critical level, cellular phenotype changes rapidly from normal to abnormal, and the resultant impairment of oxidative phosphorylation and ATP production leads to disease expression. (Schore/ad/113)”
So this is like the boss genes that tell the “worker” genes what to do – like a queen bee in a hive of workers – tells them where to go, what their purpose is, how to do their job, how to build the regions of the brain – these queen bee genes are inherited through the mother and are 10 times more vulnerable to damage and mutation than are the rest of the genes.
She is the only one who knows how the “genetic system” is supposed to come about. She is the one with the vision and the wisdom, the knowledge and the expertise, to orchestrate the evolution, birth, development of the brain. She has the experience and she has the blue print.
These genes are the “mitochondrial mothers,” the mitochondrial matriarchs. Once enough of these mothers are damaged, then there will be a massive shift change in the nature of the worker bees themselves. What was normal becomes abnormal from the top down.
In other words, the early brain developmental environment is a matriarchy.
And what do they know about how this gene damage is passed down? Once these genes are altered that form the brain, are they stored or mutated in genetic codes that are stored in the body and passed down, or are they only localized to the person who is themselves experiencing the consequences of these alterations?
“Models of the genetic analysis of complex diseases prescribe an interaction between a susceptibility gene with a predisposing environmental agent. In these studies, “environmental” usually refers to factors in the physical environment, but I propose that in the case of the transmission of psychiatric diseases stressors in the social environment interact with genetic mechanisms to amplify a genetic predisposition and create a vulnerability to later forming mental illness. I further suggest that these interactions occur between the developing organism and the “nonshared” [What does this mean, “nonshared?” Is this where the individual is SEPARATE? Meaning that it is at the point where the individual no longer shares its environment with its mother that it becomes at risk? Taking this a step further, it would mean that at whatever point the mother, during crucial growth stages of the infant outside of the womb, becomes unavailable and separate and distanced from the infant, risk comes into play.] (Plomin et al., 1991) environment with which it interacts, responding first to the environmental signals provided by the internal body of the mother, and then after birth, to the environmental signals provided by the external body of the mother. The brain growth spurt, from the last trimester of pregnancy through the second year, spans both of these periods, emphasizing the principle that the genes that program its regional organization are expressed in two very different environments: first, a total anaerobic environment and then an increasingly aerobic cellular environment. Gene expression is regulated by oxygen levels in the cell as well as by neurohormones and bioaminergic neuromodulators. (Schore/ad/114)”
He is not talking, I don’t think, about what the individual genes carry, only about how internally created toxins can mutate them.
“During critical periods of regional maturation, prolonged perturbations in the social environment lead to dysregulated levels of stress-responsive catecholamines, thereby altering gene-environment interactions and providing for potential sites of pathomorphogenesis. Dopamine, acting at excitatory glutamatergic NMDA and D1 receptors triggers c-fos immediate-early genes…that turn on other genes within the cell, ultimately leading to long-term structural changes associated with early imprinting experiences. But dopamine increases under stress…, and can induce neurotoxic inhibition of mitochondrial respiration and defective energy metabolism…and DNA mutations in brain tissue…. An early stressful environment thus detrimentally and irreversibly impacts the genetic systems of catecholaminergic neurons and their receptors (including receptors on astroglial and endothelial cells, near dendritic spines) that trophically regulate the critical period growth and metabolism of widespread corticolimbic areas. (Schore/ad/114)”
“Indeed, animal studies show that early postnatal stress, such as maternal deprivation, produces permanent changes in dopamine receptor function…, especially in cortical areas, as well as a significant reduction in the number of dopaminergic neurons in the ventral tegmental area, long-lasting effects that result in “abnormalities of social and affective function”…and a reduced capacity to respond to aversive experiences in adulthood…. It is well established that postnatally maturing dopaminergic projections are potential sites of developmental defects. In light of the principle that “developing mesencephalic dopamine neurons may display varying subpopulation specific vulnerability to outside pathological influences over the course of postnatal ontogeny” (Wang & Pitts, 1994, p. 27), genetic systems, both nuclear and mitochondrial DNA, of the dopamine neurons within the ventral tegmental area, particularly the medial, rostral linear nucleus (as opposed to other mesencephalic dopaminergic subnuclei that innervate mesolimbic areas) would be particularly important, because these project collaterals to the cortex, including the ventral prefrontal area…. (Schore/ad/115)”
“In addition, early social experiences play a significant role in the development of the other catecholamines, noradrenaline. Attachment stress induces alterations in mammalian infant noradrenaline levels…that become permanent…. The enduring changes in noradrenergic system function that result from disturbed mother-infant relations represent a biological substrate or “risk factor” for a vulnerability to despair in later life…and a susceptibility to affective and anxiety disorders…. Rogeness and McClure (1996) reported lowered noradrenaline levels in children exposed to neglect, suggesting that this psychosocial stress modifies the genetic expression of the noradrenaline system. These authors concluded that early experience has long-lasting effects on neuromodulator functioning, and that genetic-environmental factors, especially during early critical periods of development, are important in psychopathogenesis. (Schore/ad/115)”
This morning I wake up thinking about this information and this book, or about these books, and I am thinking the problem happens when mothers can’t be mothers. Grandmother was probably not one that wanted to be a mother. Nor did her mother before her want to be a mother. Such is the legacy in our family of “liberated women.” We in America are busy liberating all women. We are liberating women around the world, including our sense of travesty about Islamic women. Yet what do we really know about the consequences?
Poor women. Women who were themselves raised in situations where their mothers were forced for whatever reasons to go out and go to work and to leave their infants under the care of somebody else. And with poor women the options are far less for finding adequate, competent, skilled day care providers. And if the early infant brain developmental needs are not met, the brain will not grow right.
I am trying hard to understand something that is far far far above my capacities at this point. Evidently the manifestation of full genetic potential is intricately involved with the brain’s ability to utilize oxygen to process its sugars so that the genes can manifest the growth of brain regions. It has something to do with anaerobic and aerobic access to and utilization of oxygen and the brain’s interaction with enzymes from the last trimester of pregnancy.