Inherited disease

Are a child’s genes the causes for their anxiety?

gettingwell4 0-1 star Wasted resources, Amygdala, Brain development, Brainstem, Cerebrum, Epigenetics, Limbic system, Lower brain, Stress , , ,

This 2015 Wisconsin macaque study was another attempt to justify the school’s continuing captivity of thousands of monkeys. The researchers performed a study that – if its experimental design was truly informative for helping humans – could have been done with humans.

A problem I saw in the news coverage was that the finding of:

“35 percent of variation in anxiety-like tendencies is explained by family history”

was attributed to genetics, with headlines such as “Anxious Brains Are Inherited, Study Finds.” The lead researcher encouraged this misinterpretation with statements such as:

“Over-activity of these three brain regions are inherited brain alterations that are directly linked to the later life risk to develop anxiety and depression.”

However, the researchers produced this finding by running numbers on family trees, not by studying genetic samples to assess the contributions of genetic and epigenetic factors!

The study’s “family history” correlation was different than finding an inherited genetic causation that wasn’t influenced by the subjects’ caged environments!

The study found:

“Metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression.

The brain circuit that was genetically correlated with individual differences in early-life anxiety involved three survival-related brain regions. These regions were located in the brain stem, the most primitive part of the brain; the amygdala, the limbic brain fear center; and the prefrontal cortex, which is responsible for higher-level reasoning and is fully developed only in humans and their primate cousins.”

The 592 subjects were the human-equivalent ages of 3 to 12 years old. Primate brainstems and limbic systems are fully-developed BEFORE these ages.

The researchers skipped over potential evidence for the important contributions of epigenetic factors to “the later life risk to develop anxiety and depression” that change the studied brain areas during womb-life, infancy, and early childhood. Studies such as:

show:

  1. A developing fetus adapts to being constantly stressed by an anxious mother.
  2. When these adaptations persist after birth, they may present as physiological and behavioral maladaptations of the infant and young child to a non-stressful environment.
  3. Later in life, these enduring changes may be among the causes of symptoms such as the anxious overreactions the current study found.

http://www.pnas.org/content/112/29/9118.full “Intergenerational neural mediators of early-life anxious temperament”

Epigenetic changes in the developing brain change behavior

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Hippocampus, Limbic system, Neurochemicals, Serotonin, Stress , , , , ,

This 2015 review cited 143 studies to tie together findings in epigenetic chemistry and behavioral neuroscience.

In addition to studies I’ve previously curated, other research included:

  • a 2012 study which completely abolished mouse maternal behavior by silencing a gene encoding an estrogen receptor;
  • a 2012 study which found that stress-induced changes in the rat hippocampus were heritable;
  • a 2014 study that distinguished between transgenerational and intergenerational epigenetic effects such as:

    “in utero exposure to nutritional status, stress, or toxic environmental factors that act on the developing embryo and its germ line”

  • a 2013 study that showed how genomic imprinting coordinated:

    “Genetic coadaptation where beneficially interacting alleles evolve to become coinherited.”

The current status of research incorporating both epigenetic chemistry and behavioral neuroscience was summed up as:

“A large number of behavioral epigenetic studies attempt to correlate epigenetic marker changes at global levels and in mixed populations of cells with phenotypic changes.

Specific changes at specific gene levels and at single cell levels correlating with behavioral changes remain largely unknown.”

http://www.pnas.org/content/112/22/6789.full “Epigenetic changes in the developing brain: Effects on behavior”

Stress in early life can alter physiology and behavior across the entire lifespan

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Brain development, Cerebrum, Cortisol, Epigenetics, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Stress, Testosterone , , , , , , , ,

I’ll quote a few sections of this 2014 summary of 111 studies concerning stress, including the authors’ research:

“The brain is the central organ of stress and adaptation to stressors because:

  • It not only perceives what is threatening or potentially threatening and initiates behavioral and physiological responses to those challenges,
  • But also is a target of the stressful experiences and the hormones and other mediators of the stress response.

The stress history of parents is a significant factor in the resilience of their offspring.

Environmental stress transduces its effects into lasting changes on physiology and behavior, which can vary even among genetically identical individuals.

Stress in early life can alter physiology and behavior across the entire lifespan.

Structural stress memory is even more apparent with regard to gene expression in stress-sensitive brain regions like the hippocampus.

Individual history is important and that there is a memory of stress history retained by neurons at the cellular level in regions like the hippocampus.

Stress has a number of known effects on epigenetic marks in the brain, producing alterations in DNA methylation and histone modifications in most of the stress-sensitive brain regions examined, including the hippocampus, amygdala, and prefrontal cortex.”

It seemed to be taboo to note that most of – and the largest of – detrimental effects of stress occurred during womb-life in the mother’s environment. The authors instead opted for a politically correct “the stress history of parents” phrase.

Referenced studies had findings relevant to the earliest periods of life, including Figure 1:

interactions

“Those organs that show the highest levels of retrotransposon [a repeat element (mobile DNA sequences often involved in mutations) type formed by copy-and-paste mechanisms] activity, such as the brain and placenta, also seem to be both steroidogenic and steroid-sensitive.”

However, Figure 1 was given a beneficial context, and other studies’ findings weren’t mentioned in their contexts of detrimental effects on fetuses of mothers who were stressed while pregnant.

http://www.pnas.org/content/112/22/6828.full “Stress and the dynamic genome: Steroids, epigenetics, and the transposome”

Non-PC alert: Treating the mother’s obesity symptoms positively affects the post-surgery offspring

gettingwell4 4-5 stars Advanced knowledge, Epigenetics , ,

This 2013 Quebec human epigenetic study found that DNA methylation – chemical modification that causes genes to express differently – as durably detectable between siblings born before and after their mother’s gastric bypass surgery.

The younger, post-maternal-surgery siblings were found to have DNA indicating reduced risks of developing diabetes and heart disease when compared with the DNA of their older, pre-maternal-surgery siblings. The mothers’ average weight loss was 103 lbs.

It was notable to see this famous research reference cited:

“Prenatal exposure to famine during the Dutch hunger winter of 1944 is associated with obesity with less DNA methylation (“undermethylation”) of the imprinted insulin-like growth factor 2 (IGF2) gene in exposed offspring relative to their unexposed siblings.”

It was also notable to see the reactions to this non-politically-correct finding. For one example, this news article was in full-fledged denial, stating:

“Nor do investigators know whether a father’s weight loss might have a similar impact. It’s also possible that epigenetic inheritance wasn’t at play.”

Other news coverage expressed the memes that:

  • Pregnant women can abuse anything and everything with impunity without any consequent damage to their fetus, and
  • There wasn’t the tiniest chance that the mother was involved in any of their child’s adverse outcomes. When the child’s diverted developmental and behavioral consequences manifested, political correctness would dictate that these arose out of some unknown factors.

http://www.pnas.org/content/110/28/11439.full “Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery”

Treating the father’s symptoms of an inherited disease can epigenetically treat the son

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics , , ,

This 2014 La Jolla rodent study showed that treating the symptoms of an inherited disease can, through epigenetic DNA methylation, positively treat the symptoms in the subjects’ offspring.

The disease studied was Huntington’s, which is the most common inherited neurodegenerative disease:

  • The treatment induced epigenetic changes in the expression of genes on the male Y chromosome.
  • The treated male subjects were bred, and their sperm carried both the Huntington’s disease and the epigenetic changes that reduced the symptoms.
  • The male offspring showed both delayed onsets of Huntington’s disease and reductions of specific symptoms when compared with both the treated subjects’ female offspring and the control group non-treated subjects’ male offspring.

Per the definitions in A review of epigenetic transgenerational inheritance of reproductive disease and Transgenerational effects of early environmental insults on aging and disease, for the term in the study’s title “transgenerational effects” to apply, the researchers needed to provide evidence in at least the next 2 male and/or 3 female generations of:

“Altered epigenetic information between generations in the absence of continued environmental exposure.”

The study instead provided evidence for intergenerational effects.

http://www.pnas.org/content/112/1/E56.full “HDAC inhibition imparts beneficial transgenerational effects in Huntington’s disease mice via altered DNA and histone methylation”