Posts Tagged ‘MAO’
A 51-year-old postmenopausal non-Hispanic white woman was treated for a hypertensive crisis at a regional medical center in eastern Arizona. She had complained of symptoms for one week prior to admission, including light-headedness, headaches, and high blood pressure by self-measurement. Ten days prior to admission, the patient had been enrolled in a university-sponsored research trial designed to investigate the extent to which vitamin C and soy isoflavones, as supplements to a habitual diet, could provide antioxidant effects by reducing in vivo oxidative damage to cells, either alone or synergistically. During trial screening the patient reported typically consuming soy or soy products twice a week; no regular alcohol consumption; no history of hypertension or cardiovascular disease (although there was a family history of mild hypertension); no current medical supervision or care for any chronic health problems; no current use of over-the-counter or prescription medications and a routine exercise pattern of three times a week for 30-60 minutes. The participant weighed 175 pounds (79.5 kg), stood 5’8″ (1.73 m), with a body mass index of 26.7 kg/m2.Early in the research trial, the patient was randomized to receive 500 mg vitamin C plus 5 mg/kg body weight soy isoflavones. On trial day 3, the patient reported to the investigators that she felt “odd” and “light-headed.” At the time, this was not attributed to the study-related supplements because the participant reported experiencing infrequent headaches for the past 20 years. On trial days 6 and 7 of the treatment period, the participant had her blood pressure checked by an automated machine; the readings were in the range of 140-150/92-98 mmHg vs. her usual BP of 120/82 mmHg. Due to this unexpected occurrence, the investigators requested that she stop consuming the supplements and drop out of the study. The incident was reported the university’s Institutional Review Board Research Compliance Office, and the research trial was allowed to continue. Unbeknownst to the investigators, the participant chose to ignore the request to discontinue the supplements and continued to take the supplements on trial days 8 and 9. On trial day 9 she found her BP to be 159/110 mmHg. That night, she experienced an intense headache, a feeling of anxiety, and difficulty sleeping. Around midday on trial day 10, she stopped by a regional medical center to have her BP checked by a medical professional before going hiking. At that time, her BP was 226/117 mmHg; she reported that “my head feels like it is going to explode” and she was admitted to the emergency room.
One plausible explanation for the hypertensive crisis experienced by this participant is the inhibition of monoamine oxidase by the isoflavones (e.g., daidzin, daidzein) or their metabolites (e.g., equol). Rooke et al. and Gao et al. both reported that daidzin, the plant precursor of the mammalian metabolite daidzein, and some of its structural analogs can inhibit mitochondrial monoamine oxidase in vitro. Additionally, Dewar et al. reported that equol, a mammalian metabolite of daidzein, was an effective inhibitor of rat liver monoamine oxidase in vitro. Since the soy isoflavone supplements used in the research trial consisted of 63% (178 mg aglycone units/g) genistein, 28% (79.1 mg aglycone units/g) daidzein and 9% (24.6 aglycone units/g) glycitein (percentages based on aglycone units), the daidzein in the supplement may have interacted with monoamine oxidase.
Monoamine oxidase is responsible for the deamination of monoamines, including serotonin, epinephrine, norepinephrine, dopamine and tyramine. Its inhibition will cause an increase in the blood levels of these compounds. Since tyramine acts as a vasoconstrictor, an increased tyramine level will cause an increase in blood pressure [5,6]. Review of the two-day food records recorded prior to the participant’s entering the study in addition to dietary information obtained after the hypertensive event indicated the participant’s normal diet typically contained multiple tyramine-containing foods. The participant confirmed that she had consumed several tyramine-containing foods during the study, including the day before and the day of her emergency room admission (Table 2). Thus, the high dose of supplemental isoflavones [397.5 mg isoflavones (aglycone units) containing approximately 111 mg daidzein (aglycone units)], in conjunction with her typical moderate to high tyramine diet, may have contributed to a monoamine oxidase inhibitor-type reaction. Although the studies by Rooke et al., Gao et al.  and Dewar et al. suggest such a reaction might be possible, we believe this is the first report published of a possible monoamine oxidase inhibitor reaction and subsequent blood pressure spike occurring in vivo due to intake of a soy isoflavone supplement. Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report
Why are women more prone to depression and mood disorders than men? And why do more women than men seem to suffer from food chemical related disorders, especially fibromyalgia?
Depressive disorders in women are commonly associated with reproductive events. This association may be due in part to the changing balance between estrogen, progesterone, and other hormones that affect neurotransmitter function throughout a woman’s lifecycle. […] Some data suggest that depression in women tends to respond differently to antidepressant treatment than depression in men, underscoring the need to examine the risk and treatment of depressive disorders in males and females separately. Women have benefited considerably from serotonin reuptake inhibitor anti-depressants that are currently available. These agents appear to be more effective than the older tricyclic antidepressants in treating various depressive disorders that occur commonly or exclusively in women. Additionally, serotonin reuptake inhibitors have increased tolerability in women, who generally experience more adverse effects from tricyclics and monoamine oxidase inhibitors than do men. Estrogen appears to enhance antidepressant response in postmenopausal women receiving estrogen replacement therapy. Special issues related to the treatment of depression in women.
Women have worse responses to monoamine oxidase inhibitors than men do? Why would that be? After all, it’s men who only have one copy of the MAO gene – which resides on the X chromosome.
Estrogen replacement treatment in menopausal women has been reported to have a positive effect on mood states. However, the addition of a progestin partially negates this positive effect in some women. The opposite effects of estrogen and progestin on mood may relate to their opposite effects on adrenergic and serotonergic neural function. In a double-blind, placebo-controlled, crossover study, 38 nondepressed menopausal women were cyclically treated with estrogen and estrogen plus progestin, or with placebo, for five 28-day cycles. This paper identifies the pretreatment attributes of women who do and do not have negative mood responses to progestin, and examines the relationship of these adverse side-effects to platelet monoamine oxidase (MAO), a marker of adrenergic and serotonergic functioning. Adverse mood responses to progestin occur in women with a long duration of menopause, low pretreatment serum estradiol and testosterone levels, high pretreatment serum FSH levels, low pretreatment platelet MAO activity, and pretreatment mood abnormalities. We conclude that adverse mood response to the addition of a progestin occurs in menopausal women who have low pretreatment gonadal hormone levels secondary to a long duration of menopause. Impaired central nervous system adrenergic and serotonergic functioning also may be a factor predisposing to a negative mood response to progestin. Individual differences in changes in mood and platelet monoamine oxidase (MAO) activity during hormonal replacement therapy in menopausal women.
In this case the above study finds that oestrogen decreases monoamine oxidase expression, and progesterone increases monoamine oxidase expression. Hence in these depressed women, decreasing monoamine oxidase activity with oestrogen (effectively giving them an MAOI), elevated their mood. More of the same:
the expression of several genes associated with embryo implantation (i.e. thrombomodulin, monoamine oxidase A, SPARC-like 1) can be induced by P[rogesterone] in vitro Progesterone regulation of implantation-related genes: new insights into the role of oestrogen.
It had previously been reported that estrogen treatment in menopausal women had a positive effect on mood, whereas the combination of estrogen plus a progestin had a negative effect on mood. We found that the women with a long duration of menopause and higher treatment serum estradiol levels had significantly more dysphoria when receiving a combination of estrogen plus progestin than did the women with a short duration of menopause and lower serum estradiol levels. However, both short and long duration menopausal groups showed improvement in mood when estrogen was administered alone. Platelet MAO levels, a marker of adrenergic and serotonergic function thought to relate to mood, were negatively correlated with serum estradiol levels during HRT. We suggest that these paradoxical findings may be secondary to a prolonged estrogen deficiency state in women with a long duration of menopause. Relationships of serum estradiol levels, menopausal duration, and mood during hormonal replacement therapy.
Of course if you have the kind of depressed monoamine oxidase activity that leads to food chemical intolerance, oestrogen is the last thing you need. When I first started to get more severe symptoms (during and shortly after coming off the pill), one of my theories was that I had ‘progesterone deficiency’ – a condition that exists only in alternative medicine. In mainstream medicine, you only have a deficiency or an excess of female hormones if your period has either stopped or your bleeding is abnormally heavy. So when I suggested progesterone deficiency to my (female) doctor at the time, she laughed at me and said hormonal problems were always caused by oestrogen deficiency, and the cure was the pill. Which fortunately I couldn’t take anymore as it had put me in hospital with deep vein thrombosis.
My cycle has always been as regular as clockwork. The pill did change my period – I never used to spot during the week before I was due. It’s only during the last few months that this after-effect of the pill has gone away and I stopped using the pill something like five years or more ago. Apparently some effects of the pill, including loss of sex drive and hormonal changes, can last up to ten years after the pill is discontinued. It’s no wonder so many women have problems getting pregnant these days!
Though I haven’t had my hormone levels tested, I’m fairly sure I have high oestrogen levels. I’m an hourglass shape and have a DD cup size, something that runs in my family. My grandmother had oestrogen-dependent breast cancer. At the time I started to get anxious about post-pill symptoms, progesterone deficiency fitted a lot of my symptoms. Of course I was on warfarin at the same time. Now it turns out that progesterone would have done me some good, by raising my MAO levels. I wonder how many other women with low MAO levels are out there thinking along the same lines as I did about progesterone deficiency?
But of course it’s always a bit more complicated than a simple inverse correlation between oestrogen and MAO:
The serotonin neural system plays a pivotal role in mood, affective regulation and integrative cognition, as well as numerous autonomic functions. We have shown that ovarian steroids alter the expression of several genes in the dorsal raphe of macaques, which may increase serotonin synthesis and decrease serotonin autoinhibition. Another control point in aminergic neurotransmission involves degradation by MAO. This enzyme occurs in two isoforms, A and B, which have different substrate preferences. […] MAO-A and -B mRNAs were detected in the dorsal raphe nucleus (DRN) and in the hypothalamic suprachiasmatic nucleus (SCN), preoptic area (POA), paraventricular nucleus (PVN), supraoptic nucleus (SON), lateral hypothalamus (LH) and ventromedial nucleus (VMN). MAO-A mRNA optical density was significantly decreased by E, P, and E+P in the DRN and in the hypothalamic PVN, LH and VMN. Ovarian hormones had no effect on MAO-B mRNA expression in the DRN. However, there was a significant decrease in MAO-B optical density in the hypothalamic POA, LH and VMN with E, P or E+P treatment. Pixel area generally reflected optical density. CONCLUSIONS: Ovarian steroids decreased MAO-A, but not B, in the raphe nucleus. However, both MAO-A and B were decreased in discrete hypothalamic nuclei by hormone replacement. These data suggest that the transcriptional regulation of MAO by ovarian steroids may play a role in serotonin or catecholamine neurotransmission and hence, mood, affect or cognition in humans. Ovarian steroid regulation of monoamine oxidase-A and -B mRNAs in the macaque dorsal raphe and hypothalamic nuclei.
Estrogen replacement therapy is widely used in postmenopausal women. The current study examines the effect of varying concentrations of estrogen on the levels of activity of monoamine oxidase A and -B in brain and in other tissues. […] High dose estrogen (5 mg/pellet) significantly decreased MAO-B activity and resulted in lesser or insignificant changes in MAO-A activity, respectively in liver (-30%, +1%), kidney (-22%, -11%), and uterus (-57%, -35%) (p Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat.
These are shockingly large percentage changes. It’s the decreased MAO-A activity in the hypothalamus and amygdala that’s particularly interesting, as they are primitive parts of the brain. Hypothalamus, amygdala, and limbic system keep cropping up in my research as sites where the processing of amines and glutamate is altered somehow in food chemical intolerance spectrum syndromes including autism and fibromyalgia. One researcher even thinks that the amygdala is damaged in fibromyalgia. The hypothalamus controls body temperature, hunger, thirst, fatigue, anger, and circadian cycles, and links the nervous system to the endocrine system via the pituary gland. The amygdala plays a role in the processing and memory of emotional reactions.
So the next question is, if oestrogen levels make women more vulnerable than men to amines, why are there something like six male aspergers for every female asperger?
Well we know that asperger’s/autism/schizophrenia/bipolar disorder/epilepsy and other overlapping disorders seem to be connected to changes in dopamine processing in the brain.
This discussion is followed by a more detailed description of estrogen’s actions upon the dopamine transporter, which is hypothesized to serve as one of the major mechanism involved with nigrostriatal dopaminergic neuroprotection. Overall, estrogen appears to inhibit dopamine transporter function by decreasing the affinity of the transporter. Such an effect could prevent neurotoxic agents from entering dopamine nerve terminals, thereby decreasing nigrostriatal neurodegeneration. Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system.
Women seem to be less vulnerable to some dopamine related disorders because dopamine is processed differently in the presence of oestrogen. They seem to be less likely to suffer the effects of high dopamine. In addition to this, men have a special region on the Y chromosome called the Sex-determining Region Y (SRY), and it is this one region on the Y chromosome that determines whether you develop as a male or a female.
SRY has been linked to the fact that men are more likely than women to develop dopamine-related diseases such as schizophrenia and Parkinson’s disease. SRY makes a protein that controls concentrations of dopamine, the neurotransmitter that carries signals from the brain that control movement and coordination. Sex-determining Region Y (SRY)
FACT 1: Use of monoamine oxidase inhibitors (MAOIs) are associated with significant weight gain:
Antidepressants such as tricyclic antidepressants and monoamine oxidase (MAO) inhibitors are most often associated with significant weight gain. Pharmacodynamics of drug-induced weight gain.
FACT 2: Common low activity monoamine oxidase single nucleotide polymorphisms are associated with increased weight and increased risk of obesity:
We investigated the association between the monoamine oxidase A (MAO-A) gene and obesity. […] The TDT analysis of the EcoRV polymorphism showed in obese subjects with a body mass index (BMI) >/=35 kg/m(2) a preferential transmission of the low activity-related allele (chi(2)(TDT) = 8.0, p = 0.005). Our findings may provide evidence of a candidate gene involved in obese subjects with a BMI >/=35 kg/m(2). Family-based association study between the monoamine oxidase A gene and obesity: implications for psychopharmacogenetic studies.
We found, however, that both MAOA and MAOB show an excess of the low-activity genotypes in obese individuals. Additionally, the MAOA genotype was significantly associated with both weight and BMI. Obesity is associated with genetic variants that alter dopamine availability.
FACT 3: Monoamine oxidase activity is disturbed in diabetes:
MAO activity in pancreatic tissue is significantly reduced in diabetes. This decrease in MAO activity is associated with an increase in pancreatic tissue levels of adrenaline (ADR) and noradrenaline (NA). Studies on the level of 5-hydroxyindoleacetic acid of pancreatic tissues suggest that serotonin level is also increased in diabetics. Many studies show that MAO inhibits insulin secretion. However, some of its substrates including, serotonin, adrenaline and noradrenaline have been shown to stimulate insulin secretion. In conclusion, the activity and subcellular localisation of MAO suggests that MAO may play an important role in pancreatic beta cell function and hence in the pathogenesis of diabetes mellitus. The effect of diabetes mellitus on the morphology and physiology of monoamine oxidase in the pancreas.
In other words, high MAO activity inhibits insulin secretion. A number of monoamines (serotonin, adrenaline, noradrenaline etc) themselves stimulate insulin secretion, therefore low monoamine oxidase activity automatically leads to higher insulin levels.
FACT 4: Glucose regulates monoamine oxidase activity:
Islet beta-cell monoamines are known to influence the insulin-releasing mechanisms. These amines are localized in the insulin-secretory granules and are inactivated by the enzyme monoamine oxidase (MAO), a hydrogen peroxide (H2O2)-generating enzyme. The activity of islet MAO may consequently be of importance for insulin secretion. In the present investigation, we studied the relation between islet MAO activity and plasma levels of insulin and glucose in obese (ob/ob) hyperglycemic mice and their lean littermates. In addition, the effect of glucose on the MAO activity of in vitro-cultured islets was studied. MAO activity was assayed with serotonin, dopamine (DA), and beta-phenylethylamine (PEA) as substrates. After an overnight fast in adult (age, 6 months) lean mice, islet MAO activity was increased by 35% to 70%. Plasma levels of glucose and insulin were markedly decreased as expected. However, fasting in adult obese mice either did not affect islet MAO activity (PEA and DA) or induced a slight decrease (serotonin) of approximately 25% (P < .05). Plasma glucose levels in adult obese mice were not significantly affected by the overnight fast. However, a correlation analysis based on individual adult obese mice (fed and fasted) showed a negative correlation between plasma glucose concentration and islet MAO activity with PEA (r = -.65, P < .02) and DA (r = -.66, P < .02), respectively. Further, a positive correlation (r = +.58, P < .05) was found between glucose level and islet MAO activity when using serotonin as substrate. There was no difference in islet MAO activity with PEA and DA as substrates in fed obese versus fed lean mice. Glucose modulation of islet monoamine oxidase activity in lean and obese hyperglycemic mice.
In other words, lowering blood glucose through fasting caused monoamine oxidase activity to increase dramatically. In obese mice, blood glucose remained high and monoamine oxidase activity did not increase.
My own blood glucose levels are consistently on the edge of high-normal, even on a low-carb diet, and if they got any higher I would actually be classified as a T2 diabetic.
This explains to me why low carbohydrate diets and intermittent fasting have helped myself and a number of people I know who are sensitive to food chemicals. Even regular low calorie diets seem to help some people. I’ve often noted that the consumption of amine containing foods has the ability to cause massive, sudden weight gain in myself. I’ve also noted that when I am on a ketogenic diet I have a higher tolerance of amines.
It also explains something else. I’ve met a lot of people who really, really believe that low carbohydrate diets are THE answer to everything, and these people have been overweight for years and nothing worked except low carbing. Often they describe symptoms that correlate with food chemical sensitivity. What these people do not know is that they are overweight because they have low monoamine oxidase activity.
I imagine that when you combine low monoamine oxidase activity with other polymorphisms that increase insulin or insulin-like growth factor output (like the vitamin D receptor polymorphism VDR Fok), you have a recipe for reactive hypoglycaemia, weight gain and diabetes. Another reason for me to suspect I have both of these polymorphisms.
So now it seems that ALL failsafe food chemicals raise insulin levels – glutamates, salicylates, and amines.
I’ll spell this out again for the sake of the low-carbers whose eyes glaze over: the reason obesity is an increasing problem these days is not just due to increased consumption of carbohydrate. It is also due to the grossly increased amounts of food flavour chemicals eaten in the modern Western diet.
WHETHER boys with autism suffer a severe form or just a mild version might depend on which version of a brain gene they inherit. And it is possible that the same gene variants influence the language and social skills of people generally.
Studies on twins and families have shown that heredity plays a big part in autism, but there seem to be many genes involved, and pinning down the ones responsible for autism is proving difficult. Instead, Ira Cohen, a psychologist at NYS Institute for Basic Research in New York, decided to look for gene variants that affect the severity of the condition.
Some people with autism have higher levels of the neurotransmitter serotonin in their blood, but no genes involved in serotonin synthesis have been directly linked to autism. So Cohen’s team looked at the gene coding for monoamine oxidase A (MAOA), an enzyme that inactivates serotonin.
A variation in the length of a control region at the start of the MAOA gene determines how much of the enzyme is produced. Men have only one copy of the gene, since it is found on the X chromosome, and approximately a third of them have the form that results in lower MAOA production.
The team tested 41 autistic boys to see which variant of the MAOA gene they had. They found a clear link with the children’s language and social skills. “Boys with less enzyme are not doing as well, not keeping up with their peers,” says Cohen. “Whereas boys with the high activity form show better progress in language and other skills.”
One previous study failed to find a link between autism and the MAOA gene, but that study looked only at whether one of the gene variants triggered autism. Cohen’s finding might make it possible to identify boys most likely to develop severe autism earlier on. But, Cohen says, a larger study is needed to check the result.
Although the team looked at only autistic children, it is possible the gene affects everyone’s language and social skills, says Tom Wassink, a psychiatrist at the University of Iowa. “Either way it’s interesting.” Brain chemical could be the key to autism severity
Well this explains why boys are more likely to develop autism and Asperger’s syndrome than girls. It also explains why I happen to have what I often describe as a “male” brain. LOL.
PEOPLE with a gene variant known to be linked to aggression may have been born with key brain differences that could make them more likely to snap under pressure.
The gene, called MAOA, produces the enzyme monoamine oxidase-A. Complete absence of this gene, though rare in humans, has been linked to aggressive behaviour in men, and mice engineered to lack MAOA are also unusually aggressive.
Many more people, however, carry a low-activity variant of the gene, known as MAOA-L. A study in 2002 found that men with MAOA-L who had been maltreated as children were more likely to exhibit antisocial behaviour than those with a similar background who had the normal MAOA gene.
Now psychiatrist Andreas Meyer-Lindenberg and colleagues from the US National Institute of Mental Health in Bethesda, Maryland, have discovered differences in brain structure and function that might underlie this link. They looked at the genes of 142 healthy men and women with no history of criminality, violence or abuse, and found that 57 had the MAOA-L variant. Brain scans of the same group revealed that the amygdala and cingulate cortex, which are involved in the perception and regulation of emotion, were on average significantly smaller in men and women with the L variant.
There were some differences in brain activity too. When the researchers showed the volunteers frightening images, the amygdala appeared to overreact in those people who had the L variant. And in the men with MAOA-L, regions that normally regulate the amygdala response, including the cingulate cortex and parts of the prefrontal cortex, were underactive (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0511311103). Thus while both sexes may have heightened emotional responses, men with MAOA-L “are less able to inhibit their responses”, says Meyer-Lindenberg.
To some extent, the differences between the sexes may arise because the MAOA gene lies on the X chromosome, so men have only one copy. Women have two copies of the gene, and so are likely to have higher levels of the enzyme monoamine oxidase-A.
The differences in brain structure may become established before birth. Low levels of the enzyme have been linked to high levels of brain signalling chemicals in the fetus, including serotonin, which might affect developing brain circuits.
However, Meyer-Lindenberg is careful to warn against using MAOA-L as a predictor of whether someone is likely to become violent. Many other genes may be involved, not to mention social and environmental factors. “There is certainly not enough evidence to feel that a person who has a combination of risks should be weighed differently in a legal sense,” he says.
Knowing whether someone is less likely to be able to control their emotional responses could, however, have enormous potential for tailoring drug or behavioural treatments for people who suffer trauma at an early age, says Essi Viding of University College London, a psychologist who studies psychopathic violence. A brain primed for violence?
One in 2.5 people have this gene. I suggest it has a developmental impact on the brain and is more inclined to produce specialisation/obsession traits. But, before all of us amine sensitive people panic that we are a slave to our emotions:
Good mothering can abolish the impact of a “bad” gene for aggression, suggests a new study, adding spice to the “nature-versus-nurture” controversy.
The findings come at a time when governments in Britain and Australia are seeking ways to crack down on antisocial behaviour, and refocus attention on the impacts of parenting.
The new work, on rhesus monkeys, backs an earlier study in people which gave the same result. “We think the findings are striking in parallel with the human studies,” says Stephen Suomi of the US National Institute of Child Health and Human Development in Bethesda, Maryland.
Speaking on Monday at a press conference in London to mark the opening of a conference on genes and aggression, Suomi said that his results strongly mirror those of a study in 2002 co-led by Terrie Moffitt of the Institute of Psychiatry at King’s College London (Science, vol 297, p851).
For 26 years, she and her colleagues followed the fate of 1037 children born in 1972 in Dunedin, New Zealand. They found that children were much more likely to grow up to be aggressive and antisocial if they had inherited a “short” version of a gene called MAOA. It makes monoamine oxidase A, an enzyme which helps to break down neurotransmitters such as serotonin, and was less efficient in the individuals with the “short” version.
But carriers only went off the rails if they had had an awful, abusive upbringing. Carriers with good mothering were usually completely normal, showed the New Zealand study. Now, Suomi has replicated the finding in the monkeys, showing that carriers of the “short” MAOA gene only turned bad when denied good mothering. “Good mothering has a buffering effect,” he says.
Suomi was reluctant to say what his findings might mean in humans. “Making cross-species analyses is always a dangerous thing,” he says. But an obvious implication is that a “bad” gene in humans could potentially be kept in check by good parenting.
“The general principle of parenting is important and can have impacts not only at the level of behaviour, but also in hormonal activities, brain chemistry, structure and function, and at the level of gene expression,” he says.
Failure to provide the correct mothering may reset the brain’s circuitry irreversibly to patterns of antisocial behaviour, aggression and self-destruction, possibly to enable sheer survival in the absence of motherly protection during infanthood.
Although the complex genetics and biochemistry have yet to be worked out, the research could ultimately lead to drugs which compensate for the “bad” genes, or prenatal screening tests which ensure that infants at risk receive optimal mothering in their first two years of life.
Suomi’s latest results have been accepted for publication in Biological Psychiatry. Good mothers stop monkeys going bad
Anyone who is sensitive to amines knows they still have control over their actions, even though they are manically happy, seething with anger or are deeply depressed, this doesn’t mean they have to carry out what their biology is telling them to do. And conversely:
BY ANY objective measure, comedian Billy Connolly is a towering success. Yet as a child he was sexually abused. Samantha Morton, Tom Cruise’s co-star in the film Minority Report, also suffered as a child, neglected after the messy break-up of her parents’ marriage and consigned to a series of children’s homes. But like Connolly she has turned out just fine.
What makes some maltreated kids triumph over their early problems while others turn antisocial or violent? A supportive school, caring friends, perhaps the right social worker or a loving relative – any or all of these may ride to the rescue in particular cases. But if you’re looking for a more reliable factor, try a brain enzyme called monoamine oxidase.
At least, that’s the message of a remarkable genetic study published last week in the journal Science(Vol 297, p 851). The research suggests that people endowed with an abundance of the enzyme are more likely to tough-out an unhappy or abusive childhood and lead a normal adult life than those born with lacklustre levels. And by no small margin: male victims of child abuse in the study were nine times as likely to turn thuggish and mean themselves if they were born with a sluggish version of the gene for the enzyme instead of a more active one.
So opens another chapter in the long-running and often rancorous debate about genes and criminality. Even before last week’s study was published, theologians and ethicists were press-releasing their concerns about its implications for our understanding of free will and moral responsibility, with one religious commentator, bizarrely, appearing to link the gene to original sin. Many critics will look at the study and think it proves only that science is still in thrall to its eugenics past, determined to put genetic makeup at the centre of complex social issues where it has no place. Others will think just the opposite – that science has at last proved there really is a gene for violence, and that a piece of wayward DNA is the real culprit for the psychological damage wrought by child abuse. Neither view makes any sense.
Until now, most research in this area simply looked at violent people or criminals and asked what was different about their biology, be it chromosomes, hormones or, in the 19th century, sloping foreheads. But of course our personalities are never going to be shaped entirely by genes when so much of who we are comes from mother nurture.
The new study is more sophisticated. It looks at nature and nurture together and asks whether the two might combine disastrously in some people and families to create cycles of violent behaviour – and claims the answer is an emphatic yes. While boys carrying the sluggish version of the gene were no more likely than others to go off the rails if their childhood was untroubled, a staggering 85 per cent turned into antisocial adults if their childhood was troubled.
This research is an improvement on old-style eugenics, but where does it take us? Nowhere, until a second team replicates the findings in a separate population. But let’s assume these researchers have hit on something. There can be no doubt that if it’s confirmed, this genetic link will help to explain why some children end up more damaged than others by childhood maltreatment. It might even throw light on why violence and antisocial behaviour are more common in men than women. The gene for the enzyme is on the X chromosome, so while boys must make do with a measly single copy, girls enjoy the luxury of always inheriting two.
Yet, being true doesn’t make a scientific explanation useful in practical terms. For example, the study seems to raise the prospect of the authorities one day genetically screening boys so they can offer extra support – perhaps a drug – to those with the sluggish gene. This is a non-starter. First you’d have to be sure that interfering with the enzyme didn’t affect other aspects of a child’s personality (it probably would). Even then this approach would be doomed. One in three males carries this sluggish gene. Even if you could medicate them all, you’d be fixing something that isn’t really broken. These boys are not victims of a toxic brain chemistry. They are victims of a toxic childhood. Take away the latter and you don’t have a problem.
In fact, any attempt to base social policy on this science would not just be impractical. It could be dangerous, fuelling complacency about those with the active gene. Monoamine oxidase is not like some sort of Star Trek force field, offering complete protection against all forms of wickedness. Plenty of boys with the active gene in the study became antisocial adults. And you don’t have to be a thug to be unhappy and unfulfilled. Were the kids who didn’t turn violent as content in life as they might have been? We can never know.
No doubt the finding will encourage lawyers to invoke the “genetic defence”. But judges should be cautious of this: there’s no evidence that the gene wipes out a person’s sense of right and wrong.
Child abuse and neglect are always wrong and always to be rooted out. It does not become any less wicked or deserving of vigilance because the victim has a gene that protects them from some of the consequences. There’s no pill for curing a hellish upbringing
These lucky people with an abundance of monoamine oxidase can probably eat chocolate and cheese until their heart’s content. They probably also bounce right back to their equilibrium from situations that make them angry, depressed, or happy.
The more research I do the more evidence I find that what we are dealing with is genetic. I suspect as they continue to study individuals with this gene variant they will find that as well as exhibiting more emotional responses, these individuals are more likely to be creatively or mathematically driven, more obsessive, and are more likely to be defined as geeks and nerds. Violence is the least of the issues involved!
The biology involved is far more complex than just this one version of the gene. There are many other genes involved and factors that can influence the expression of those genes. The result is the Gaussian curve we see in graphs of amine tolerance, and the massive natural variation in our society.
In 1911 a young chemist at the Lister Institute in London named Dr. Casimir Funk crystallized an amine substance from rice bran. He was sure this was the anti-beri-beri factor and dubbed it “vitamine” for “vital amine”. Thiamin
This is thiamin, also known as thiamine or vitamin B1. Thiamin injections can result in anaphylactic reactions. A number of websites tell me that thiamin is considered a natural anti-depressant and even that “high dose thiamine may increase levels of monoamines (serotonin, dopamine, norepinephrine) by inhibiting monoamine oxidase” with a reference to this PubMed study which has no abstract, so I can’t confirm it for myself. Other things that increase monoamines are antidepressants.
It is interesting to discover this, because when I trialled thiamin for my eczema, I realised very quickly that I had a violent negative reaction to it. My skin became very red, and I felt quite tired and stressed.
“In biochemistry, monoamines are a group of neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by an two-carbon chain (-CH2-CH2-). All monoamines are derived from the aromatic amino acids phenylalanine, tyrosine, histidine, and tryptophan.” Monoamines
Monoamines include “Thyronamines, a new group of compounds derived from thyroid hormones” One thyronamine can cause a rapid drop in body temperature.
Monoamine oxidase inhibitors (MAOIs) are a form of antidepressant that blocks the production of monoamine oxidase, the enzyme that breaks down monoamines. Monoamine oxidase is present in the liver, intestines, and MA releasing neurons throughout the CNS.
MAOI Side Effects include:
- CNS Stimulation
- disturbed thyroid hormones including flushing and chills, pallor or sweating
- anxiety, agitation, fear
- orthostatic hypotension and hypertensive crisis
- including dizziness and fainting caused by low blood pressure, and also high blood pressure
- stiff neck
- nausea and vomiting
- sluggishness and drowsiness
- sexual dysfunction
- weight gain
- lowered tolerance for alcohol
- and from increased tyramine consumption, excessive arteriole constriction, and stimulation of heart
- avoid red wine, cheese and chocolate whilst on MAOIs
- More on MAOIs
Sound familiar? It appears that tyramine may be the cause of my tachycardia.
A study found that “rat thyroid MAO activity is under the influence of TSH” TSH is thyroid stimulating hormone, one of the main thyroid regulators. Poor thyroid is connected to eczema, and salicylates depress the thyroid.
Theory: poor thyroid disrupts MAO production, which increases monoamines including thyroid related monoamines, which can further disrupt the thyroid. Vicious cycle. This is why a high fat, low carb diet helped me, it pulled me out of the downward spiral by kick-starting my thyroid again. Sunlight and vitamin D are also important for the thyroid, which ties into the seasonal connection.
Morphine and quinine are also amines.
In fact many reactive chemicals appear to be built around either amines, benzene rings, or other phenols. This includes many B vitamins!
Folic acid sounds like lovely stuff. It’s chemical name is:
Yey, we get an amine, benzene, and glutamic acid all for the price of one!
PABA is para-aminobenzoic acid. It contains amines and benzene. It is a B vitamin that is frequently used in sunscreens, a precursor to folate, and one to which food chemical sensitive individuals are known to react. This is interesting to me, because I was taking quite a bit of PABA in France to prevent sunburn when I came down with that disastrous bout of bronchitis.