How genes make up your mind
“You are nothing but a pack of neurons”, the late Francis Crick once wrote (1) in his discussion about the neural underpinnings of consciousness. Today we can add “You are nothing but a pack of genes”. Neurons are, after all, the result of the expression of genes. In this way we can argue that genes […]
“You are nothing but a pack of neurons”, the late Francis Crick once wrote (1) in his discussion about the neural underpinnings of consciousness. Today we can add “You are nothing but a pack of genes”. Neurons are, after all, the result of the expression of genes. In this way we can argue that genes are the building blocks of your brain. This is all quite basic neuroscience and indeed Crick would be one to know. But recent advances in the emerging field of imaging genetics demonstrate a much tighter link between your genetic makeup and how your brain – and mind – works.
Genes and neurons
Genes control the development of neurons to make up brains, but they also govern neuronal gene expression during our daily lives. The sleep-waking cycle is controlled by neurochemicals emerging from cells at the base of the brain. Genes control how neurons communicate with serotonin, dopamine or other neurotransmitters. Genes are responsible for every step of the neurotransmitter cycle, including the formation, transport, pre-synaptic expression and post-synaptic reception of the transmitter (see Figure 1). Genes work at every level of the neural process. They are the fundamental building blocks for both the structure and the functioning of the brain. They set the stage for how neurons and functional groups of neurons act in response to different inputs. Genes are therefore fundamental for the way we experience, think and behave.
Neurobiology of negative emotions
Let us take a step back from and look at a larger level of brain function: the neural substrates of emotions, specifically aversive emotions like fear, sadness and disgust. Emotions emerge from a network of brain regions that evaluate events and react to them. In one view, there are three aspects: evaluation, reaction and inhibition. Each is controlled by separate areas of the brain. Emotions can be evoked below the conscious threshold, and of course the brain basis of emotion is itself largely unconscious.
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Sensory inputs are constantly being judged by an evaluative systems located below the cortex. Two almond-sized structures embedded in the temporal lobe, the amygdalas, are central to such evaluations. The amygdalas can be activated both by conscious and unconscious signals of negative emotion – e.g. faces showing negative emotions, or speech with negative intonation. An example from our own lab is show in Figure 2, where we have asked a subject to report the gender of faces displayed one at a time on a screen. The faces express either neutral or unpleasant emotions, a fact subjects may not be aware of. Unpleasant facial expressions trigger activation of both amygdalas, right and left. This is a well-established effect (2).
Emotionally evaluated signals are forwarded to brain structures that prepare and execute behavioural responses. These include the hypothalamus, ventral striatum and insula. These structures are generally located in the core brain regions that we share with other mammals.
These structures make different contributions to emotional responses. For example, electrical stimulation of the hypothalamus in cats led to either fear or aggressive responses (3). Stimulation of the ventral striatum has been reported to induce stereotypical behavioural action patterns such as behavioural “freezing”.
The final step of this emotional network is dedicated to evoking or inhibiting emotional responses. Since the early studies of Harlow (4) the orbitofrontal/ventromedial (lower-middle) parts of the prefrontal cortex has been known to play a part in the control over emotional responses.
Things can go wrong in any part of this emotional network. The amygdala may be overly sensitive to specific input; the striatum, hypothalamus and insula may be hypersensitive to amygdalar activity; and the ventromedial PfC may be unable to inhibit emotional responses. In this simplified model of emotional processing we will just focus on the first step – the role of the amygdala in emotional evaluation.
Recent studies show that depending on your genetic makeup – or genotype – your amygdala may be more or less sensitive to a range of emotionally negative events.
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The genes of the mind
How do genes influence the emotional workings of brains? Recent studies now show that naturally occurring genetic variations – called polymorphisms – which code for serotonin affects our emotional reactions and thoughts. Humans have two common variations of a promoter region of the serotonin transporter gene (5-HTTLPR); a short (s) and a long (l) version. It has been shown that two allelic copies of the long variant leads to higher concentration of 5-HTT mRNA, which leads to a doubled reuptake of serotonin, compared to one or two short allelic variations. People who have two copies of the long genetic sequence in this region have less serotonin available in the synapse, due to the higher reuptake of the neurotransmitter.
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In a study using functional Magnetic Resonance Imaging (fMRI) Ahmad Hariri compared the activation of the amygdala in healthy volunteers. The volunteers were divided according to their 5-HTTLPR genotype – one group with one or two copies of the s allele, and the other group with two copies of the l allele. (Since two copies of the s allele are rare, the researchers had to combine one and two copies of the s allele into one group.) The groups were also matched for age, gender and IQ. Subjects switched between two tasks in the scanner: a simple sensimotor control task or an emotional response task: matching the facial emotions of a target face, expressing either anger or fear. This method is known to lead to activation of the amygdalas.
The researchers found that the actvation of the two amygdalas differed between the two groups (see Figure 4). The s group showed a significantly higher amygdala activation than the l group. In other words, the level of amygdala activation depended on what genetic makeup a person had. Having a short version of the 5-HTT genetic code leads to a higher level of synaptic serotonine, which again leads to a higher level of amygdalar response to aversive stimuli. This is consistent with the prediction described above.
While these results have provided us new information about how genes regulate brain function, one can ask: does this have any effect on thought and behaviour? Indeed it has! Studies demonstrate that carriers of the s allele, compared to l allele carriers, are more likely to show abnormal levels of anxiety (5) develop affective illness (6) and even acquire conditioned fear responses (7). Variations in the genetic makeup of the serotonin system has profound influence on our experience and behavior. Thoughts are shaped by genes.
Serotonin transporter genetic variation and the response of the human amygdala
Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, Egan MF, Weinberger DR
Science. 2002 Jul 19; 297(5580): 400-3
A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin (5- hydroxytryptamine, (5-HT)) function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
Links
References
- Francis Crick (1994) The Astonishing Hypothesis: The Scientific Search for the Soul. New York: Charles Scribner’s Sons
- Del-Ben CM et al. (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study. Neuropsychopharmacology. 30(9): 1724-34
- Brutus M et al (1986) Effects of experimental temporal lobe seizures upon hypothalamically elicited aggressive behavior in the cat. Brain Res 366 (1-2):53-63.
- Harlow JM (1848) Passage of an iron bar through the head. Boston Med.Surg.J. 34 (20):389-393.
- Lesch KP et al. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527
- Lesch KP & Mossner R (1998) Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol. Psychiatry 44, 179
- Garpenstrand H et al. (2001) Human fear conditioning is related to dopaminergic and serotonergic biological markers Behav. Neurosci. 115, 358
© Copyright 2006 T.Z.Ramsøy
Author information
Thomas Zoëga Ramsøy
Danish Research Centre for Magnetic Resonance
Copenhagen University Hospital Hvidovre
Denmark
“You are nothing but a back of neurons, the late F. Crick wrote according to Ramsoey who now adds “You are nothing but a pack of genes”. And I don’t know whether Ramsoey has left some room for me to give another addition:”You are nothing but a pack of light”(depending not only on Einstein’s equation E=MC sq. but on the implicit idea that derives from reading the starting part of this very bracketed sentence), however you usually forget this very scientific fact, and of course you are excused being all the time busy in physical object and even using light to enable you to see those objects. The excuse is indulgence in materialism or you may use any other term including “money”. Alas for this poor “unconscious” man being indulged in anything excluding the search for the TRUTH, neither looking at heaven/earth where marvels abounds nor within himself, the realm of miracles including that of genes.
Hypothesizing about the role of genes, Ramsoey claims that they
“set the stage for how neurons and functional groups of neurons act in response to different inputs.” This is fair enough, however to add, and of course still hypothesizing, he carries on to claim “Genes are therefore fundamental for the way we experience, think, and behave. I argue that is more than a hypothesis can bear :” experience” in addition: “think”, and furhermore: “behave”. I argue that such a claim(s) need much effort to scientifically prove any of these many notions which are “easy said than done”. S0, I suppose there remains the issue of proof of whatever claimed, and one more thing that the term “therefore” was a little far from logically-used a term.
I admire the way this article is presented to us, and could easily notice and appreciate the systematic and grdual building up the structure/ body of this scientifically strong analysis based on certain lab works (Hariri’s), nonetheless, one may find it plausibly unacceptable to take for granted a sort of unsustainable enough findings. In other words binding some outcomes with some philosophical theory is not less hard than “The Hard Problem”.
Finally, the genes set up the stage for the neurons, so marvelous a role they do, if this claim has got enough support. As for any claims of their being fundamental for the way we “experience”,”think”,”behave” : I believe that they are not. As dignified by beng human beings nothing is shaping us: We have been shaped since our creation.