The Mystery Known as Depression, Part 6/12

6. THE NATURE OF THE IMPRINT

It seems that new research provides critical evidence on epigenetics, and how imprints through methylation can be passed down from one generation to another (Booij et al., 2013). A key could be repressed memory that endures and persists throughout our lives; it drives behavior, symptoms and aggravated depression. It turns out that imprints can be passed down from parents to baby and from grandparents to baby. Some genes which should be turned on are not, while those that should be off remain on. Critical in this process is methylation, which is a chemical reaction where a methyl group is transferred from a donor molecule (S-adenosylmethyonine) to the cytosine on DNA or a histone. The reaction is catalyzed by DNA methlytransferase (DNMT). A certain amount of methylation occurs naturally but trauma, such as maternal neglect in infancy, can cause excess methylation of key genes involved with the stress response. (Weaver et al, 2004) Methylation depends on the work of the chemical methyl group which is recruited when there is a traumatic event, and helps embed that memory. It seems that when there is a surge of methylation, part of it, the element 621-13, attaches or adheres to the gene. It is now part of the DNA and turns on or off certain hormones and other neuro-chemical processes. Once that happens and methyl is recruited, the genetic unfolding is thereafter altered.
In short, methylation can be an agent of (transcription) repression, or more exactly, a marker for it. In this context, repression is a systemic event that involves the whole body. If you reverse the methylation chemically (perhaps with new drugs they are developing), one can still have repression. But remove the repression through therapy and you may see demethylation. Until the studies are done, it's unclear how closely the two are linked, and in what tissues. A study at Duke University showed that when female mice were fed a diet rich in methyl it completed altered the fur pigment of the offspring. (Dolinoy, 2008) In other words, it acted like a genetic inheritance when it was not. It was the result of experience which is the linchpin of our theory--epigenetics.

In this context, traumatic events in very early childhood, (and I assume, including the period of gestation), leave a mark or tag on a gene that affects us possibly for life. They found that even grandparents affected the imprints of the grandchildren, which we will get to in a moment. But suffice to say that the experiences of our forebearers can endure and be passed down the genetic chain, the inheritance of acquired characteristics. This is something science thought impossible decades ago.

It is what we all know; that early love makes us stronger and less anxious. But it turns out that if the rat mothers were licked and groomed early on in their lives, that experience could be passed on to their offspring. The genes could be modified by the methyl group (and also other chemicals) in a beneficent way. In humans, that implies a good history in the mother means a good childhood for the children. And more loving by the mother, the less methylation in the child. And with less chronic stress hormone production there may be less chance of serious diseases later on, such as Alzheimer Disease.

To make sure that these changes in the rat pups resulted from experience and not hereditary, they let normally stable rat pups be raised by neurotic negligent mothers. And the result was still the same, unstressed babies. These babies had mothers who had normal amounts of methyl in their systems. Thus rats raised by loving mothers could pass it onto offspring even when the adopted mother was not loving. The genes for stress hormone output had minimal methylation. In other words love was passed down the genetic chain. So normal babies raised by negligent and inattentive mothers still had low methyl levels in their hippocampus. The babies started life one leg up, a good start in life despite a bad childhood. I believe that changes in the genes, methylation and acetylation, must occur very early as the whole neuronal system is evolving. So before we can state what causes depression or anxiety, we need to observe the early epigenetics at work. Again, pups born to unloving mothers were handed over to loving mothers, and those born to bad mothers reared by loving mothers still seemed to be normal and relatively unmethylated. Let us remember that methyl exists throughout the system but it is not the general amount of it but rather how much is found in specific genes (Weaver et al, 2004).

Another reason this research is important: they found that unloving mothers of rodents causes methylation of the estrogen receptors in female offspring. Then when they had offspring of their own the offspring were deficient in estrogen which made them less attentive and loving to their own babies. We as yet do not know how many key chemical processes can be affected by lack of early love. And more, we have no idea how many hormones are changed in neurotic mothers (heavily methylated) and how that affects myriad adult behaviors. Is depression inherited? There may be precursors for it which is never manifested if there were plenty of love later in childhood. Is some of the tendency to methylation inherited or epigenetically passed on? And does that form the basis for depression? It seems from the research just cited that that neurotic mothers (methylated), are ineluctably forced to be unloving, thus laying the groundwork for depression in the offspring later on (Weaver et al, 2004).

And what other hormones are depleted by this scenario? Are we born with a tendency to anxiety? Possibly, but then the imprint is not methyl so much as acetyl, in this case. With acetylation there are more faults in the repressive system. Acetylation (recruiting acetyl) pretty much produces the opposite of methylation, a tendency to open rather than close, toward expression rather than repression. The role of acetylation is inexact for now and requires further exploration.

Taken together these data suggest that trauma produced heavy methylation in those children who grew up in orphanages. And that process then affected much more in terms of brain and neuronal development. So when we find a mother who is not loving we need to know that she may being driven by her epigenes; she is a victim of those changes. Her cortisol/stress hormone level militates against maternal instincts. Methylation shuts down a number of “natural” behaviors. In neurosis we cannot be natural and appreciate nature because we are disconnected and alienated from our own nature, from our biography, history and feelings. We cannot rely on our feelings to guide us because they have effectively been shut down. Literally, the feelings are aliens. We have found in most patients but pronounced in depression, that patients on the verge of these feelings in sessions often run a fever. The body treats the feelings as a menace, a danger and something to be avoided; yet it is also what can liberate us.
Can we reverse or undo methylation? The research informs us that with rats who had been damaged, and raised by unloving mothers, when they were infused with trichostatin they did not show evident damage. As though the trauma never occurred. This drug removes methyl from the system. This is not exactly the same as demethylation. However, it did undo history (Weaver et al, 2004). This is what I think may be happening during the reliving and focusing on the imprint. There might be a change in methylation so as to reverse history; this is what we shall study in our future research projects. It seems to me the natural way provides far less possibility for collateral damage to the system. Since we already have found that chronically high cortisol levels have been reversed in our therapy, it would perhaps follow that methylation could also be reversed. In a way, the levels of methylation can be a marker for having been loved early on or not having been loved. We could tell more than the statements by the person who claims he was loved in his childhood if he were indeed not loved. How much denial is there?

Neurochemistry may be better relied on because biochemistry has no reason to lie and is not motivated by denial. It can be a marker for post traumatic stress. The more abuse as a child in these cases the more methylation produced. When we add this to our future research on telomeres and cortisol we will begin to have precise measures of the pain in us. And we will know when a drug is too dangerous for us, particularly the drugs like marijuana that tend to open us to ourselves; to our feelings and pain. Finally we will have a marker for the efficacy of certain psychotherapies. Does the therapy undo the past? Does it help relieve repression and therefore depression? Is there great first line pain in anxiety states? What seems to be the case is that love obviates methylation and produces normal beings.

K. J. S. Anand and associates state that in a number of suicides by violent means “the significant risk factors were those perinatal events that were likely to cause pain in the newborn.” (Anand & Scalzo, 2000) (More on the link between suicide and perinatal trauma below.) They also point out the carrying mothers who smoke heavily had babies more prone to criminality later on. And mothers who took drugs while pregnant had children far more prone to drug use, both serious opiates (morphine) and speed (amphetamine).

There are literally hundreds of studies now to bolster the hypothesis about early imprints, how they last and alter our systems. Some twenty years ago, most of this research had not been thought of. (Again, this is discussed in detail in Primal Healing. (Janov, 2006) In another revealing study carried out in Canada in 1998, David P. Laplante and Michael L. Meaney of Montreal’s McGill University looked at women who were pregnant during a severe ice-storm to assess the long-term effects of stress on their offspring. (Laplante, et al., 2004) The researchers write: “We suspect that high levels of prenatal stress exposure particularly in early in pregnancy, may negatively affect the brain development of the fetus... Imprinting at birth may predispose individuals to certain patterns of behavior that remain masked throughout most of adult life.”