Neuroscience | Finding Neuron

Depression and why some of us are SAD

Posted on June 3, 2016 by Iasmina Hornoiu

I am warning you, this is going to be a long one! But it’s interesting, I promise.

There is a lot of confusion and mixed opinions when it comes to depression. Some people use the term inappropriately, to describe what is in fact grief (the feeling of sadness that humans, and presumably other animals, experience after a loved one has died, for instance), others tend to label depressed individuals as “weak”, “selfish”, “useless”, “cowards” etc.

At the same time, for the past 30 years, there have been extremely important discoveries in the field of affective disorders, which have helped eliminate many misconceptions and laid the foundation for a better understanding of what this set of disorders (affective disorders) are and what is actually happening in the brain of the ones “affected”. Moreover, according to some new theories, depression is in fact an evolutionary advantage in situations such as physical illness and dominance. When the body is sick it needs time and energy in order to recover, so the organism experiences depression in order to avoid activity and focus on recovery; in nature, many animals with a dominant status are forced (by a variety of factors) to occupy a lower hierarchical level, in which case “depressive” behaviours such as avoiding eye contact or sexual contact helps reduce the risk of attack by other dominant, more powerful individuals. There are many theories, as you can see, and this article is meant to present and analyse some of them.

We should start by clarifying a very important aspect: depression is different from grief. While the latter is a normal reaction to some external factor(s) with a negative emotional impact on our day-to-day lives, and dissipates by itself after a certain period of time, depression is a pathological, abnormal condition (either in its own right or as a symptom of other metabolic or neurodegenerative diseases). However, it should be noted, and this is one of the key concepts in understanding depression, that the way individuals interpret and react to various external events, which affect their mood, differs, which means that some individuals have a stringer predisposition to depression than others. Now, why is that? A variety of factors, both genetic and epigenetic (developmental, such as child abuse, neglect) play a role and often act synergistically, but we will deal with them (especially, the genetic factors) a bit later in the article.

Different types of depression

Major depressive disorder, also known as “the classical depression”, which is characterised by insomnia, anorexia and lack of joy and interest in things. At the opposite side of the spectrum, there is atypical depression, which manifests itself through increased sleepiness, weight gain and anxiety. Dysthymia is another form of depression, more difficult to diagnose, due to the fact that it presents itself with mild depressive symptoms. All these types discussed so far have been categorised as monopolar.

Bipolar depression refers to a kind of depression accompanied by periods of mania – manic episodes are characterised by elevated, euphoric mood, impulsiveness, hyperactivity and even psychotic symptoms (hallucinations, delusions). A case described by Dick Swaab in his book “We are our brains – from the womb to Alzheimer’s” portrays a woman, who developed mania following the death of her husband. She would talk and laugh hysterically, call the police in the middle of the night for no reason and eventually began to make up stories about people whom she had never met before, but who she believed were longtime friends of hers. After her manic episodes disappeared as a result of treatment, she developed severe depression. Luckily, her story has a happy ending, as she made a full recovery.

Bipolar depression is also associated with Seasonal Affective Disorder (SAD), characterised by extreme mood seasonal swings. In this article, I have dedicated an entire section to SAD, so I am not going to delve into it for now. Given all these particularities of BD, it is often regarded as a separate disorder (bipolar disorder or manic disorder), rather than another type of depression. As there are so many things to mention about depression, I will leave BD for future article.

Diagnosing depression

In order to be diagnosed with depression, one must have at least one of the two main symptoms: persistent sadness and marked loss of interest, as well as at least five secondary symptoms: disturbed sleep (either increased or decreased), disturbed appetite (increased or decreased), fatigue, poor concentration, feeling of worthlessness and excessive guilt, suicidal thoughts.

Depending on the number of these symptoms, as well as the degree to which they manifest, monopolar depression can be sub-divided into: sub-threshold depression (fewer than five secondary symptoms; no treatment needed), mild depression (fewer than five, but in excess secondary symptoms), moderate depression (more than five, plus functional impairment between mild and severe depression) and severe depression (most of the secondary symptoms and also true psychotic symptoms – yes! they can occur in severe monopolar depression as well, not just BD).

Biochemical pathways and brain systems involved in depression

In Ancient Greece, there was a biochemical theory of depression. It was believed that depression was caused by the failure of liver to eliminate toxic substances from the digested food, resulting in the accumulation of “black bile” (melan means “black” and chole means “bile”, which give the words melancholy). Biochemical theories nowadays have at their core three monoamines, which I am sure you are all familiar with: noradrenaline (a neuromodulator very similar to adrenaline) and serotonin and dopamine.

These two substances have long and diffuse projections throughout the nervous system and in levels lower than otherwise normal, they are said to be involved in affective disorders. For example, drugs such as Reserpine, used to treat the positive symptoms of schizophrenia by depleting dopamine (and also serotonin and noradrenaline) elicited depressive symptoms in schizophrenic patients.

Therapies involving monoamines

The idea is, you want to higher levels of monoamines in order to treat depression. Enzymes involved in the monoamine re-uptake mechanism from the synaptic cleft back into the presynaptic level and enzymes involved in the monoamine metabolism, such as monoamine oxidases (MAO) are the most common targets for the majority of anti-depressants.

Selective serotonin re-uptake inhibitors (SSRI) and selective noradrenaline re-uptake inhibitors (SNRI) – Prozac (Fluoxetine), Zoloft (Sertraline), Celexa (Citalopram), Paxil (Paroxetine) block serotonin reuptake and Effexor/Viepax/Trevilor/Lanvexin (Venlafaxine), Cymbalta (Duloxetine) inhibit the noradrenaline reuptake enzymes. For those of you who are currently under this treatment, be careful! Side-effects such as sexual dysfunction, insomnia, increased aggression and self-harm/suicide can occur. Moreover, SSRI are not so effective. They have a very long induction, which means that it takes a long time (2-3 weeks) for the therapeutic effects to start working, during which time there is a high risk of suicide (due to depression). They also have a placebo effect of 50%, which is not necessarily a bad thing as long as it works, but raises the question whether the monoamine hypotheses is really that valid in the case of depression.
Tricyclic antidepressants – also block the reuptake mechanism, resulting in more monoamines in the synaptic cleft. Amitril (Amitriptyline), Aventyl/Norpress/Noritren (Nortriptyline) and Tofranil (Imipramine) are a few examples. They are derived from Phenothiazines (such as Chlorpromazine), which are antipsychotic drugs (used to treat schizophrenia). Some of the side-effects are: chronic pain and suicide overdose.
MAO inhibitors – Nardil/Nardelzin (Phenelzine), USAN (Thanylcypromine), Marplan/Enerzer (Izocarboxazid) and Amira/Aurorix/Clobemix (Moclobemide) are very effective and widely prescribed for in major depressive disorder, bipolar disorder and anxiety disorder, although the first three pose the high risk of hypertensive crisis and death if the patient is consuming cheese or wine.

The big problem with these drug therapies is dependence – if antidepressants, especially Paroxetine and Venlafaxine are administered for a long period of time and then stopped, the patient is likely to experience Antidepressant discontinuation syndrome, characterised by flu-like symptoms, motor and cognitive disturbances.

Non-drug therapies

An alternative to pharmaceutical treatments is represented by transcranial magnetic stimulation (TSM) of the cortex, electroshock therapy – this is, apparently, very effective, BUT might result in impaired memory – and gene therapies. The latter refers to the insertion, via a vector or a plasmid, of genes that encode neurotransmitter molecules, receptor proteins or neurotrophic and neuroprotective substances. Given that many variations in genes for chemical messengers in the brain are responsible for the predisposition of certain individuals to depression, gene therapies, although still at a developing stage, provide powerful approaches to the treatment of affective disorders.

Over-activation of the stress axis

Another theory for the development of depression, which goes hand-in-hand with the “monoamine hypothesis” is that in depressed individuals there is an exaggerate amount of cortisol (a steroid) in the blood, which can affect the brain. Basically, our brains react to stressful situations by producing some hormones in the hypothalamus and pituitary gland (hypophysis), which eventually result in the production of cortisol. In turn, cortisol acts on these structures to inhibits their activity and, thus, preventing further increases in its level – this is an example of a negative feedback mechanism.

In normal people, a stressful situation will result in increased levels of cortisol, but this steroid will then revert to its normal levels. In depressed individuals, the stress axis (hypothalamus-pituitary-adrenal axis) becomes hyperactive and, as a result, a stressful event will result in the overproduction of cortisol.

In excess, cortisol affects brain structures involved in the control of emotions and fear, such as the cingulate cortex and amygdala (which explains the anxiety symptoms experienced by people suffering from atypical depression) and memory, such as the hippocampus, which explains the cognitive dysfunctions. Moreover, the activity in the prefrontal cortex, which normally inhibits the hypothalamus (overactive in depression) is decreased by cortisol. So, really, it is like a vicious circle.

Why is the stress axis hyperactive in the first place? Possibly due to decreased sensitivity of the cortisol receptors to cortisol, which might be the result of genetic as well as developmental factors (previously mentioned).

Monoamines play a role here, as increased levels of monoamines (by the administration of antidepressants) can determine neurogenesis in the prefrontal cortex and hippocampus, so these areas can function properly again and can, thus, inhibit the hypothalamus, so no longer hyperactivity of the stress axis!

Seasonal affective disorder (SAD)

Although I am planning to write about bipolar disorders in another article, I thought it is worth discussing SAD in this article as well, given that so many people, especially those living in the Northern hemisphere, suffer from it.

In the References section there is a document called “The recent history of seasonal affective disorder (SAD)”, which is a transcript of the 2013 Witness Seminar in London. I highly recommend this reading for two reasons: it is full of remarkable, extremely important information regarding SAD and the participants at this seminar included personalities such as Prof. Josephine Arendt, Prof, Norman Rosenthal, Prof. Alfred Lewy, Prof. Rob Lucas, who are pioneers of the SAD diagnostic criteria and underlying causes (for instance, Rosenthal is the first psychiatrist who diagnosed SAD).

As many of you probably know, and sadly from personal experience, SAD is a seasonal mood change disorder, a type of bipolar disorder, which determines depression during the autumn/winter seasons and hypomania during summer. In order to understand SAD, we must remember a few things about the circadian rhythm, which I have previously discussed in two articles: Why “sleep” and Even flies sleep and learn. In short, we have an internal, genetic “clock” inside our brains (in the Suprachiasmatic nucleus – SCN), which determines the body to function in an approximately 24-hour cycle and which is also entrained by the light-dark cycle. This is not only a circadian (day-night) clock, but also a seasonal clock, which means that changes in the environment (especially light and temperature) across the year entrain this clock and determine physiological and psychological changes in our bodies.

In SAD, there is an abnormal secretion of melatonin (the hormone that triggers sleep, when it is dark outside). Light inhibits this hormone: cells in our retina, which are not coding for visual information, send projections via a distinct pathway than the rods and cones. These cells, containing the peptide melanOPSIN, project via the retinohypothalamic tract to the SCN, “telling” the brain that it is dark outside, so the brain (SCN) determines the synthesis and release of melatonin from the pineal gland. When there is light outside, the production of melatonin is inhibited. The duration of melatonin secretion is also affected by the circannual changes – long secretion in short days and short in long days. The scientists who took part in the Witness Seminar discovered that melatonine production was increased during the depressive/winter phase and that sunlight decreased its production, thus, alleviating the symptoms of depression in SAD. A note here, sunlight is an effective treatment for SAD, not ordinary room light. This explains why, during winter, when people tend to spend more time indoors, their levels of melatonin increase. The reasons why room light does not inhibit melatonin production are the intensity of light (sunlight is five times more intense than room light) and spectral differences. More about SAD and bipolar disorder in a future article!

I hope this article made sense and that you enjoyed reading it!

References
SAD – Pdf of The Witness Seminar transcript

Beatty, 2000. The Human Brain – Essentials of Behavioural Neuroscience. Sage Publications. Inc., pg.464-471

Dick Swaab, 2014. We are our brains – From the womb to Alzheimer’s. Penguin Books, pp. 112-122

Image by Damaris Pop

Decoding autism

Posted on April 10, 2016 by Iasmina Hornoiu

About a year ago, I posted an article entitled Autism, which was meant to be more of an introduction into autistic spectrum disorders. Since then, I’ve been meaning to come back to this topic and provide more details about the mechanisms leading to autism, but I knew I need to do some proper research, which my student schedule didn’t really allow at that point.

The reason why I didn’t post any articles in the past three months is mainly my uni dissertation, which took up a lot of time. My chosen topic was Cellular mechanisms of autistic spectrum disorders. This assignment offered me the chance to read a lot of scientific papers and have a far better understanding of autism than I had before. As you probably guessed, this article draws quite a lot on my dissertation.

Some clarifications

When we refer to autism, we must be well aware that this is just an extreme end of the spectrum and that different neurodevelopmental disorders, sharing particular symptoms, are grouped under the term autistic spectrum disorders (ASD). The symptoms that characterise ASD are: impairments in social interaction, communication deficits and repetitive behaviours. Several factors have been linked to ASD, including gene dysregulations, alterations of the immune system and even environmental risk factors.

Discussing all the possible causes of ASD, could probably fit in a book, rather than a blog article, so I will only focus on gene dysregulations. However, if you have any kind of questions, feel free to post them in the comment section and I will try my best to answer them.

About glutamate and one its receptors

In biochemistry there are 20 different amino acids (the building blocks of proteins) and one of them is glutamate. This particular amino acid is very important because, apart from its role in the formation of proteins, it is also the main excitatory neurotransmitter in the brain. This means that glutamate is used to help the neurons communicate with each other and give rise to all sorts of brain activities we know about, including learning and memory.

When two neurons interact at the synapse (the space between the terminals of two interacting neurons), the neurotransmitter is released from the first neuron’s terminal and comes in contact with the second neuron’s terminal. But here’s the trick: in order for the neurotransmitter to have an effect on the second neuron, it has to activate certain structures on its terminal, called receptors. In the case of glutamate, there are three types of receptors, involved in different functions and with different mechanisms. The one we will be focusing on is the type I metabotropic glutamate receptor (mGluR). When this receptor interacts with glutamate, it leads to the translation of specific proteins involved in a process known as long-term depression (LTD), which influences learning and memory. Increased LTD is thought to play a key role in the development of ASD.

The FMRP protein

A few genes have been found to regulate the activity of mGluR and, through it, several cognitive processes. The Fragile X Mental Retardation 1 (FMR1) gene, which codes for the FMRP protein, is one of these genes. It interacts with mGluR-dependent proteins and is thought to regulate synaptic plasticity. During embryonic development, FMRP plays an important role in neural differentiation. Therefore, a mutation in the FMR1 gene leading to the absence of FMRP (a loss-of-function mutation) results in restricted brain development, impaired cognitive functions and autistic symptoms (previously mentioned). This mutation has been found in patients suffering from autism and especially from another brain disease, Fragile X Sydrome, which is the most common monogenic (determined by a mutation in a single gene) cause of autism. The activity of FMRP suppresses mGluR-dependent LTD, by inhibiting the synthesis of proteins involved in this process. Therefore, the absence of FMRP results in LTD, which primarily leads to mental disability.

Neuroligins and Neurexins

These represent transgenic protein families, which mediate synapse maturation in neurons using glutamate. Mutations affecting members of neuroligin and neurexin families have been found to be associated with autistic-like behaviours. The effects of these mutations on the brain are very specific, affecting cells in brain regions involved in learning and memory (CA1 pyramidal cells of the hippocampus, the Purkinje cells of the cerebellum), language (brainstem) and social interaction (somatosensory cortex). In normal situations, neuroligins and neurexins trigger mGluR-induced LTD, but their translation is inhibited by FMRP. The absence of FMRP leads to the loss of this inhibition, which results in mGluR-induced LTD.

Possible therapeutic strategies

Research on the links between mGluR transmission and genes involved in neural development resulted in a variety of therapeutic strategies for ASD. Genetic mGluR reduction and mGluR antagonists (drugs that act on this receptor by preventing glutamate to activate it) are the most common examples of treatments. Potential therapeutic candidates are Fenobam and Lithium, which act as antagonists at mGluR. Administered on animal models and on humans suffering from Fragile X Syndrome, these drugs have resulted in cognitive and behavioural improvements. Although there is hope in treating ASD, there is still a lot of research that needs to be done, especially since even diagnosing different autistic spectrum disorders is still a challenging task.

I hope this article gave you a little more insight into the mechanisms underlying autism and that you enjoyed reading it. As I mentioned above, any questions about this topic are welcomed.

References:

Baudouin, S. J. (2014). Heterogeneity and convergence: the synaptic pathophysiology of autism. European Journal of Neuroscience, 39(7), 1107-1113.

Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., Hutchison, J., Snape, M., Tranfaglia, M., Nguyen, D. V. & Hagerman, R. (2009). A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. Journal of Medical Genetics, 46(4), 266-271.

Espinosa, F., Xuan, Z., Liu, S. & Powell, C. M. (2015). Neuroligin 1 modulates striatal glutamatergic neurotransmission in a pathway and NMDAR subunit-specific manner. Frontiers in synaptic neuroscience, 7, 11-11.

Etherton, M., Foeldy, C., Sharma, M., Tabuchi, K., Liu, X., Shamloo, M., Malenka, R. C. & Suedhof, T. C. (2011). Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proceedings of the National Academy of Sciences of the United States of America, 108(33), 13764-13769.

Gao, R. & Penzes, P. (2015). Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders. Current Molecular Medicine, 15(2), 146-167.

Nosyreva, E. D. & Huber, K. M. (2006). Metabotropic receptor-dependent long-term depression persists in the absence of protein synthesis in the mouse model of fragile X syndrome. Journal of Neurophysiology, 95(5), 3291-3295.

Rojas, D. C. (2014). The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment. Journal of Neural Transmission, 121(8), 891-905.

Zalfa, F. & Bagni, C. (2004). Molecular insights into mental retardation: Multiple functions for the Fragile X mental retardation protein? Current Issues in Molecular Biology, 6, 73-88.

Image by Isuru Priyaranga

Even flies sleep and learn

Posted on December 24, 2015 by Iasmina Hornoiu

Sleep is a fascinating process that allows most of the creatures on Earth to function at their normal capacity and survive the environmental challenges. Recent theories support the idea that one of the main functions of sleep is not energy conservation or tissue restoration, as previously thought, but actually, enhancement of brain function. Sleep appears to be involved in consolidation of memories and improvement of learning. As you probably remember from the previous article, there are essentially to phases of sleep: REM and non-REM. The latter has been shown to be involved in consolidation of both declarative and non-declarative memories, whereas REM sleep is believed to enhance the formation of procedural and emotional (non-declarative) memories.

If you’ve ever wondered whether insects can sleep or not, the answer is yes. Several studies in Drosophila melanogaster , the fruit fly famous for Morgan’s discoveries of chromosomal inheritance, proved these flies have periods of ‘rest’. During rest , Drosophila stops moving and becomes more difficult to be aroused, which resembles what we understand by ‘sleep’. Moreover, it appears that these flies can form short-term and long-term memories, especially revealed by studies of olfactory associative conditioning. Surprising, isn’t it? Even though it is known that insects have brains, they seem too primitive, at a first glance, for complex cognitive functions such as memory and learning. Well, it’s obvious that insects are much smarter than we thought.

What’s more stunning is that, in Drosophila, just as in humans, sleep has evident effects on long term memory formation and sleep deprivation can dramatically affect this function. According to several studies, sleep homeostasis positively influences learning. During non-REM sleep, the brain shows slow oscillatory activity, which is characterised by waves of action potentials with low frequency and high amplitude. These slow waves are controlled by homeostatic processes and increase after learning tasks. Hence, sleep, which induces slow wave activity, plays a very important role in enhancing learning performances.

The homeostatic control of sleep has been somewhat elucidated by studies in our old friend, Drosophila. Organisms need not only a circadian clock (which sets a day-night rhythm, synchronising the body with the environment), but also a homeostatic system, which regulates sleep according to prior wakefulness. Just like in the circadian system, the homeostatic system seems to be genetically regulated and, eventually, resulting from neuronal activity.

Specialised sleep-promoter neurones in Drosophila, called the dorsal fan-shaped body (FB) neurones, become excited when the organism is sleep-deprived and fire action potentials (which can be surprising, given that non-REM sleep triggers reduced brain activity). It is not exactly known how the nervous system can sense lack of sleep, but it is believed that substances such as adenosine and unfolded proteins, released after prolonged wakefulness, are potential signals. Thus, after detecting too much wakefulness, dorsal FB neurones become excited and promote sleep. The gene that controls the function of the dorsal FB neurones is the crossveinless-c (cv-c) gene, which encodes for a protein that regulates different ion channels (especially potassium channels), leading to changes in electrical conductance and the excitability of the sleep-promoter neurones.

Just to give some more information and (possibly) complicate things a bit more, another link between sleep and long term memory is represented by the notch receptors, which have been found to be involved in the restoration of long term memory formation after sleep deprivation. Their main function is to influence the development of the nervous system in the embryo, but they also play a role in memory formation.

As you have probably figured out by now, it is quite hard to have a complete picture of what sleep is about and how it can influence memory and learning. However, scientists are doing their best to shed some light on these wonderful phenomena. And before you close this page, don’t forget an important point: even something small like the fruit fly is able to sleep and learn!

I’d like to thank my friends Parnian Doostdar and Lee Chi Yu for sending me most of the materials I used for this article.

For further information:

Article

Ackermann, S., Rasch, B., 2014. Differential effects of non-REM and REM on memory consolidation, Current neurology and neuroscience reports, vol. 14, p. 430

Donlea, J. M., Pimentel, D., Miesenbock, G., 2014. Neuronal machinery of sleep homeostasis in Drosophila. Neuron, vol. 81, pp. 860-872

Huber, R., Ghilardi, M. F., Massimini, M., Tononi, G., 2004. Local sleep and learning. Nature, vol. 430, pp. 78-81

Why “sleep”?

Posted on October 27, 2015 by Iasmina Hornoiu

In a previous article, we talked a bit about narcolepsy as one of the very intriguing sleep disorders. It was perhaps easy to understand why people suffering from narcolepsy could have a pretty hard time performing several normal tasks; however, most of us would probably relate less to narcolepsy. But something which almost everyone can agree to have experienced regularly, in one way or another, is sleep. In comparison with disorders associated with it or derived from its impairments, sleep itself might not seem so interesting. We all do it and we can’t deny how much we enjoy it and long for it after it stops. Yet, there is much more to sleep than we think.

Sleep is very important for the normal functioning of any being. For animals as well as for humans, sleep helps in energy conservation, body restoration, predator avoidance and learning aid. Different animals have different sleep-wake cycles, from nocturnal animals (like rodents), which sleep during the day and are active at night, and animals which sleep with only half of the brain (like dolphins), all the way to diurnal animals, like humans. Although humans are advised to sleep approximately 8 hours per night, some people sleep very little (around 2-3 hours/night) and still function perfectly fine. An example of such a situation is presented in the textbook of Rosenzweig et al. (pg. 389).

But what triggers sleep and how is it regulated?

Most of us are certainly able to recall a dream the next morning and the memory of that dream is usually accompanied by feelings and emotions we sometimes do not even experience in real life. We are often under the impression that our dream has lasted the whole night. In fact, there are two stages of sleep, one of which is associated with the formation of dreams. These stages, known as non-REM sleep and REM sleep, succeed each other in cycles lasting approximately 90 minutes. Just to define the terms, REM means rapid eye movement and represents the part of sleep with the most increased brain activity. Interestingly, during REM the brain seems to consume more oxygen than during arousal!

Normally, when we fall asleep we slip into the non-REM stage or the slow-wave sleep (SWL). This, in turn, is divided into four other stages: from light sleep to very deep sleep. During this phase, the brain is said to be truly resting and the body appears to repair its tissues. No dreams can be seen! The movement of the body is reduced, but not because the muscles are incapable of moving; it’s the brain which does not send signals to the body to move! One interesting feature of non-REM sleep is sleep-walking. This peculiar behaviour some people show while asleep usually takes place during the fourth (last) part of the non-REM sleep, when the person is the deepest sleep. This is the reason why it is very difficult to wake a sleepwalker up.

In turn, REM sleep (which starts after a 30-minute non-REM period) is the “active” part of our sleep. This time, the brain sends commands to the body, but the body seems to be in an almost complete state of atonia (immobility). The heart rate and breathing become irregular and the brain is not resting. In fact, our dreams happen during this time and more importantly, our long-lasting memories are thought to be integrated and consolidated.

When it comes to sleep regulation, many neuroendocrine systems and brain functions play a role. The circadian (or sleep-wake cycle), which is controlled primarily by the suprachiasmatic nuclei, in the hypothalamus, need special attention. For the purpose of this article, I won’t focus on the circadian clock now, but I will come back to this in a future article. The autonomic nervous system and parts of the brain such as the brainstem, the limbic system, especially the amygdala, and the forebrain modulate different aspects and stages of sleep. Amygdala, which I mentioned in a previous article about emotions and decision-making, is a brain region involved in the emotions such as fear. It also appears to be very active during REM-sleep and may account for the awful nightmares we often experience.

Many cognitive functions, such as intelligence, performance and emotions are associated with disrupted non-REM as well as REM sleep. To be more specific, REM-sleep loss appears to be associated with increased anxiety and stress and loss of emotional neutrality – this means that a person deprived of REM-sleep is more likely to react negatively to neutral emotional stimuli than in normal conditions. The explanations vary, but most of the studies agree that impaired REM sleep triggers increased release of noradrenaline, hyperactivity of amygdala and decreased function of prefrontal cortex (which tells “stop!” to the amygdala when it goes crazy). At the same time, people deprived of non-REM sleep could experience depression, due to deficiency in another neurotransmitter, this time an inhibitory one, called GABA (gamma-aminobutyric acid). Other problems linked to sleep deprivation are attention deficits, working memory impairments and usually affected divergent thinking (creative, innovative thinking).

Aging people seem to sleep less and this deprivation is also associated with conditions like Alzheimer’s. Moreover, sleep deprivation can kill you! Sustained sleep loss can cause low immune system and drop in body’s temperature, which can make bacterial infections fatal. Another consequence of sleep loss is increased metabolic rate, which leads to weight loss and eventually death. Don’t think this could be a good idea for a diet! More like for “die”!!! Having said that, most people should try their best to get enough hours of sleep.

I hope this article convinced you of the importance of sleep and as usual, any questions or comments are welcome 🙂

Further information:

Article 1 – about REM-sleep and emotional discrimination

Article 2 – about non-REM sleep and GABA

Article 3 – about how sleep loss affects behaviour and emotions

Article 4 – a review on many articles about the link between sleep deprivation and emotional reactivity and perception

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins

Rosenzweig et al., 2010. Biological Psychology – An Introduction to Behavioural, Cognitive and Clinical Neuroscience. 6th edition. Sinauer Associates Inc.,U.S., pg. 380-401

Both images by Gabriel Velichkova

Don’t be anxious about anxiety!

Posted on September 30, 2015 by Iasmina Hornoiu

I remember when I was a small child and my mum or my uncle would take me out to one of my hometown’s parks or to the shopping centre. For some reason, I so often experienced an unexplainable fear and even dizziness and the terror that I might faint. I also had the feeling I couldn’t walk in a straight line. But no one noticed. Whenever I went to an indoor show or a classical music concert where people were sat on their seats and all they had to do was watch something and not move, talk or most importantly, look at me, I was fine. Little did I know what the problem was as it never occurred to me it was a problem at all. I knew I was shy and self-conscious and in my head that was the reason for my fears of crowds.

After I hit puberty, those irrational fears and the following symptoms became amplified and I started to seek for some scientific explanations. By reading and talking to different people I finally found out about agoraphobia. As the name suggests, agoraphobia is basically the fear of open and/or crowded spaces. The most important steps, I think, in dealing with an anxiety is first of all realising you have one and identifying the type.

Anxiety disorders are very common worldwide (with about 2% of the population suffering from them) and they are characterised by the pathological expression of fear. The most common types of anxieties are: agoraphobia, panic disorder, obsessive-compulsive disorder, social phobia, specific phobia, generalised phobia, post-traumatic stress disorder.The manifestations as well as the characteristics and the severity of anxiety disorders differ from person to person. Moreover, some anxieties can derive from other anxieties, like panic disorders. No wonder it took me a while to figure out what was going on with me. Here’s the thing and I would like people who suffer or have suffered from anxiety disorders to think about it: we often do not realise we have an anxiety (because we believe the causes underling the symptoms are different, like lack of self-confidence, heart attacks, pure coincidence etc.) or we just refuse to admit the reality.

Although anxiety has been mentioned in scientific literature since the 16th century, it wasn’t until the 1800s when it started to be considered a mental illness. Before that, people attributed physiological and hormonal causes to anxieties.

Modern medical advances like fMRI and PET have made possible the discovery of the major role of the hypothalamic-pituitary-adrenal (HPA) axis in anxiety formation and development. Through a cascade of hormones released by this three-structure system, the brain responds to stress by activating the adrenal glands to produce cortisol. This, in turn, determines physiological changes which lead to exaggerated fight-or-flight reactions.

We shouldn’t pin all the blame on the hypothalamus though, as it only obeys two other structures: the amygdala and the hippocampus (which respond to the information processed in the neocortex). In this case, the amygdala and the hippocampus act as antagonists – the amygdala has a positive effect on the activation of the HPA axis, whereas the hippocampus suppressed this activation. This is how the normal fight-or-flight responses are regulated. Nevertheless, in patients suffering from anxiety disorders, hippocampal damage due to continuous exposure to cortisol (probably as a result of amygdala hyperactivity) leads to more cortisol being resealed from the adrenal medulla, thus the symptoms of anxiety becoming even more pronounced.

Several treatments, ranging from anxiolytic medications (benzodiazepines, alcohol, serotonin-selective reuptake inhibitors etc.) to psychotherapy have been developed in order to heal anxieties. Psychotherapy aims to get the patient accustomed to the stressor (the stimulus that produces anxiety) and, at the same time, to assure them of the extremely low risks potentially posed by that stimulus. In time, the fear of the stressor would disappear as the neuronal connections involving the stimulus processing would be altered.

I know I put between brackets alcohol as one of the many treatments against anxiety disorders. Indeed, due to its stimulating effects on the main inhibitory neurotransmitter, GABA. Essentially all drugs that can activate this neurotransmitter are considered anxiolytic, meaning they are able to treat anxieties. Keep in mind, though: This is should not be an excuse for people to become alcoholics 😛

In my case, the anxiety went away by itself, or maybe it was just me who kept on going to crowd places and telling to myself nothing bad was ever going to happen; which, to be honest, is a bit unrealistic – bad things can actually happen, but we should try to prevent them, instead of fearing them to the point when we would refuse to leave the house.

Hopefully, this article gave you a clearer idea about what triggers anxiety disorders and also made the anxious ones more confident that their fears don’t have to last forever.

Further information:

Article about anxiety

Short video on anxiety

Documentary about anxiety

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilkins pp. 665-670

Picture by Damaris Pop

Narcolepsy

Posted on September 21, 2015 by Iasmina Hornoiu

Can you think of any situation when, let’s say, you were talking to someone and suddenly that person would glance at you with boredom and their eyes seemed to slowly close as if they were on the verge of nodding off? This sort of situations can be very annoying and it would be a lie to say that you didn’t feel mad or at least slightly pissed off when they happened. You probably either ignored them or chose a more aggressive approach, in order to ‘wake’ them up.

But what if instead of just a very rude or uneducated person you would have to deal with someone who suffers from narcolepsy? Not only the person you would supposedly talk to is actually asleep, but waking them up is very likely to trigger unwanted behaviours.

As odd as it sounds, there are people in this world who can fall asleep instantaneously, without any previous warning, in the middle of doing anything ranging from reading and talking to cooking and driving. These people are called ‘narcoleptics’.

So what is narcolepsy?

Narcolepsy or the so-called syndrome of excessive sleepiness is a chronic neurological disorder that affects less than one percent of the population, therefore it is considered a relatively rare disease. Due to the multiple causes that lead to this disorder, narcolepsy has been considered either an autoimmune or a neurodegenerative disease. Often it is hard to be identified and wrong diagnosis is given, such as epilepsy (because cataplexy could resemble epileptic seizures) or schizophrenia (due to visual and sometimes auditory hallucinations).

Symptoms

The most common symptoms of narcolepsy are: sleep disturbance, cataplexy (muscle weakness), excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and abnormal rapid eye movement (REM) – in narcoleptics REM occurs extremely fast (within a few minutes), whereas normally it should manifest after one hour and a half. Nevertheless, patients who suffer from narcolepsy have also experienced increased appetite, automatic behaviour, sleep apnoea and memory problems (this is not due to cortical dysfunction, but to impaired attention).

Except for cataplexy, sleep paralysis and hypnogogic hallucinations, reduced attention and disorientation after waking from daytime naps are also common. Moreover, patients could suffer from aggressive behaviour, with temper outburst and irritability especially if woken up and they might also deny their condition.

Interestingly enough, despite the fact that narcoleptics have trouble with being awake during the day, they would often experience insomnia during the night. Their sleep deficiency can be accentuated by some forms of medical treatment.

Causes

It has been demonstrated that many factors are involved in the initiation and development of narcolepsy; these range from genetic factors, including the human leukocyte antigen DQ and DR (HLA-DQ and -DR) genes and polymorphism of certain type of genes (for instance tumour necrosis factor alpha or monoamine oxidase genes, both located on chromosome 6) to environmental factors (head trauma and various infections, such as the infection with Streptococcus pyogenes). HLA genes code for the HLA complex called antigens, proteins with an essential role in the immune functions and usually associated with autoimmune diseases.

In addition, latest discoveries have shown a decrease in levels of hypocretin-1 and -2 (also known as orexin-A and-B) in the cerebrospinal fluid and hypothalamus could account for the trigger of narcolepsy. Deficiencies of this neuropeptide might produce changes in monoamine oxidases, enzymes with an important role in the degradation of amine neurotransmitters, such as serotonin and dopamine. Low levels of dopamine dramatically influence the development of some psychiatric and neurodegenerative disorders (ADHD and Parkinson’s disease, respectively) including narcolepsy.

Treatment

Given the fact that the decrease of hypocretin tone plays an important role in the production of narcolepsy, an efficient solution would involve the increase in the concentration of these peptides. One way of achieving this is by intracerebroventricular administration of hypocretin-1 peptide, which appears to reduce the frequency of cataplexy and stimulate arousal in mice. Another even more efficient and less invasive method is represented by the intranasal administration, hence the neuropeptides being directly delivered to the central nervous system.

Serotonin was also discovered to have significant role in wakefulness and REM regulation, hence decrease levels of serotonin (5-HT) might induce narcolepsy. Therefore, medicines that could increase the levels of serotonin in narcoleptic humans might be a solution for this disease.

Most of the patients diagnosed with narcolepsy are recommended pharmaceutical treatments, which usually consist of the intake of certain doses of stimulants. Nevertheless, taking into consideration the side effects of these drugs and the limited adherence of the patients to the medications, alternative methods have been discovered. One of them is represented by behavioural and psychological approaches, for instance regularly scheduled naps during the day and daily exercises (but avoidance of activities that increase body temperature).

Since treatment involving cognitive stimulants is the most wide-spread, a lot of drugs are used in order to cure narcolepsy. A very common example is represented by amphetamines (such as Ritalin), which are known to increase levels of dopamine in the brain, reduce daytime sleepiness and inhibit the monoamine oxidases. Also Mazindol, Modafil and Selegiline are used as treatment for narcolepsy, as they reduce cataplexy and inhibit the monoamine oxidases. The amino acid L-tyrosine stimulates the production of noradrenaline and dopamine, therefore it also represents a solution (although more tests of its effects are required).

Some very important drawbacks that should be considered when using pharmaceutical stimulants in treating narcolepsy, and any disorder that affects the nervous system in general, are the possible adverse effects and the chances of dependence, abuse and tolerance. Although serious addiction problems haven’t been registered, high dosages increase the risk. According to some studies, 30-40% of narcoleptic patients using medicines have developed tolerance, therefore 1-2 days per week of no medication is recommended.

The most common adverse effects of the psychostimulants are headaches, insomnia, anorexia, irritability, heart palpitation. Patients must acknowledge that these drugs cannot be taken as brain enhancers and they must also be aware of the side effects and possible risk of addiction before deciding to undergo a medicine-based treatment.

I hope you enjoyed reading this article 🙂 It is actually highly based on an essay I had to write in my first year of university and therefore I am going to add the literature I used at the time in order to gather information.

Emotions and the brain

Posted on August 2, 2015 by Iasmina Hornoiu

Once upon a time, I promised I was going to write an article about how emotions affect our decision-making and why it is actually important not to ignore the feelings we have in certain situations…For several, unexplainable reasons I kept postponing this idea, and for that I am very sorry. Having said that, there is no better way of making up for this than to finally keep my promise. So, here we go!

I think I should start off with a small mention: emotions and feelings are distinct things, according to neuroscientist Joseph LeDoux. As he well puts it: “…feelings are what happen when we become consciously aware that our brain is reacting to some significant stimulus,” while it is possible that some brain structures, such as the amygdala “respond to emotional stimuli without the organism being aware of the stimulus.”

In order to achieve a better understanding of what the process of forming emotions involves, scientists talk about emotional experience and emotional expression. The latter refers to body manifestations and behaviours in response to certain stimuli, for example changes in facial expression, heart rate, sweating, skin conductance etc. It has been a subject of debate for several decades whether emotional experience or emotional response is the one responsible for formation of the other, or that they act independently. It is now believed that different emotions depend on specific parts of the brain and are determined by different neural circuits.

But why should we care about emotions in the first place? Some of you might find it strange, but emotions are intensely interconnected with reasoning and decision-making. And no, I don’t mean that they impair the process of making the right decision, it’s actually quite the opposite: most of the times we need emotions in order to be able to do what is best for us in a certain situation.

An interesting case: Phineas Gage

A man who has gone down in history for surviving a terrible accident at the work place, but maybe mostly because of his importance in understanding the role of emotions in decision-making, is a late 19th century foreman, Phineas Gage. He had been hired as a foreman on a railroad construction site in Vermont and one of his tasks was to sprinkle explosive powder into blasting holes. This sounds like a dangerous thing to do, but Gage was regarded as one of the best people in this field: he was said to be very efficient, energetic, balance-minded, tenacious, a smart and successful business man etc.

One moment of carelessness dramatically changed his life forever, and at the same time had a huge impact on the way scientists began to think of emotions. The powder exploded and a tamping iron entered Gage’s head under his left eye, passing through his left frontal lobe, and exited the skull, leaving a hole which measured more than 9 cm in diameter.

Gage survived, but he “was no longer Gage”, as his friends and acquaintances used to say. Apart from losing vision in his left eye, the man had no motor or sensory deficits, he could hear, touch, sense, walk and talk. It was his personality that was completely changed. He became capricious, irreverent, impatient, and behaved as if he did could not predict, nor care about any professional or personal failure. He was soon fired and found different jobs over time, most of which were related to the accident and the iron rod, which had turned him into some sort of freak.

Some explanations and brain functions

The limbic system is probably the first to come to mind if you refer to brain areas involved in emotions. It consists of structures around the thalamus or in the temporal lobe, such as the amygdala, the hypothalamus, the limbic cortex, the cingulate gyrus, the fornix, the corpus callosum etc. Each one of these structures is involved in specific types of emotion and in triggering certain behaviours or responses through the autonomic nervous system. For example, the amygdala is linked to fear and aggression. Different regions (nuclei) in the amygdala are associated certain functions, so that both emotional expression and experience require the amygdala in order to be formed. Projections from amygdala are sent to the hypothalamus, which determines the autonomic response, the brain stem for behavioural reaction and the cerebral cortex, which is involved in emotional experience. The amygdala is also thought to play a role in enhanced emotional memory.

Regulation of specific emotional behaviours depending on the limbic system is facilitated by one of the major neurotransmitters, serotonine. Neurones containing serotonin originate in the brain stem (in the Raphe nuclei) and send projections to the hypothalamus. Serotonine is associated with a decrease in aggressive behaviour, but at the same time is involved in dominance, as proven by studies in rhesus monkeys.

The Papez Circuit (named after the neurologist James Papez who came up with the idea of an “emotional system”) is composed of interconnected anatomical structures (many of which are part of the limbic system) that link emotional expression and emotional experience together. Papez proposed that the cingulate cortex determines emotional experience, while the major structure involved in emotional expression is the hypothalamus.

Below I have inserted a diagram showing the Papez Circuit, based on information from Bear et al. Note that the hippocampus is now thought to have less importance in the process of emotion formation.

The discussion above does not fully explain what happened in the case of Phineas Gage. There is much more to emotion than that! Given the fact that the iron rod severely affected Gage’s frontal lobe, we should definitely focus our attention on this structure, too. The frontal lobe and the prefrontal cortices are involved in planning, reasoning, social behaviour, motivation, defining our personalities etc. Damage to these regions, especially to the ventromedial prefrontal cortices, results in decision-making impairment. While the intelligence and the other body functions remain intact, the patient who has suffered the damage is no longer able to exhibit normal social behaviour. The patient becomes emotionless and this lack of emotions and self motivation makes them incapable of making the right decisions.

If instead of the ventromedial prefrontal cortices, another region of the prefrontal cortices is affected, there is a very strong possibility that the patient’s intellectual abilities are compromised, along with their ability to form emotions. This region is called the dorsolateral prefrontal cortices. The person with a damage in this brain area would encounter severe difficulties when it comes to operations on numbers, words, space etc.

Another brain structure involved in the process of emotion forming is located in the right hemisphere. If the somatosensory cortices of this area are injured, the result would be similar to what can be seen in the case of a damaged ventral prefrontal cortex, but there is something more…the processes of basic body singling are also disrupted. This can be observed in patients suffering from anosognosia, a disease in which the patient is unaware and denies their disability.

I have tried to comprise a lot of information and simplify things as much as possible. If you managed to get here with both eyes open, I couldn’t be happier. Hopefully, you can see now why we should also “think with our hearts” when we need to decide about a certain situation…because the “heart” is somewhere in the brain and it knows better than us what we need to do.

For further information:

Antonio Damasio,1995. Decartes’ Error. Vintage Books

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins pp. 564-581

Article about Phineas Gage

Image by Isuru Priyaranga

Yourself…and decision-making!

Posted on June 20, 2015 by Iasmina Hornoiu

I recently came across a very interesting post on Facebook, written in Romanian. This post especially caught my attention first of all because it had been made by a group very dear to me, Yourself; secondly, the topic was exactly the one I was thinking about for my next article. It’s about the role of emotions in decision-making. To be honest, this is something I’ve been studying for a while and I’ve been struggling to synthesise the main ideas for an article. But this post had it all: it is clear, concise, easy to read and definitely not boring.

I now have a very good starting point for my article. So in the meantime, I thought, why not translate it? 🙂

“When we were small it was easy to write letters to Santa, because we knew exactly what we wanted and we made choices with no difficulty. But as we grew older, things got a bit more complicated; the further we navigate the path to maturity and complexity of life, the more it becomes a challenge to make up our minds.

Why is it sometimes so hard to make choices?; Why do we get anxious and agitated whenever we have to face the impossibility of making a decision? Perhaps it comes down to the fact that the process of decision-making involves many options, and taking the variables into consideration involves both reason and emotions.

The logical process of decision-making is based on determining the value of each option. We often try to rule out as many emotional aspects as possible, to detach from them, and to evaluate each alternative in a logical, almost mathematical, way.

On the other hand, decisions we make in particular emotional states, such as when we are angry or extremely happy, are said to be “in the heat of the moment”. So, which one of these two alternatives represents the best way of making a decision?

Antonio Damasio, a Neuroscience specialist, performed studies on people with deficits in the prefrontal cortex (which is responsible for decision-making, among other cognitive functions) and the cortical structures involved in generating emotions. These people would hardly make even the simplest decisions, such as choosing between fish or chicken as a meal, going shopping, taking a walk etc. He also noted that these individuals were able to reasonably evaluate the consequences of their choices and objectively analyse the alternatives, but could not or it was extremely difficult to make any decision, no matter how simple they were.

Going back to the idea of multiple variables in decision-making, emotions are part of these variables and it is important to acknowledge their role in this process. Life is full of choices and decisions, and we have to face them all. Moreover, if our decisions are based on strong moral values, we will find the necessary means to deal with any potential challenge, regardless the final choice (which we could be quite uncertain about).”

I hope you enjoyed it! 🙂

Drawing by James Dowinton

Yourself Facebook page

Yourself website

Some mentions about the latest topic

Posted on June 16, 2015 by Iasmina Hornoiu

Some of you have emailed me asking about what things we should stay away from during pregnancy, in order to avoid changing the normal course of a baby’s development. If you remember from the article about gender identity and sexual preferences see here, one of the most important factors in an individual’s development is represented by sex hormones like androgens and oestrogen. They begin acting on our bodies in early pregnancy and even slight modifications in their functioning may dramatically affect our personality, preferences and behaviour as adults.

Given external factors can greatly influence these hormones, it is very important to know which ones fall into the category of risk factors and therefore possibly affect our development. As expected, these factors pose a threat during pregnancy, which is why pregnant women should be particularly cautious about their life style.

It has been suggested that taking aspirin while pregnant might increase the chance of the mother giving birth to a “more masculinised girl”. This is due to the actions of aspirin as a cyclooxygenase inhibitor; cyclooxygenase enzyme converts arachidonic acid into prostaglandins which apart from their well-known role in immune reactions, also seem to be involved in sexual behaviour. A decrease in the production of these compounds in female rats is thought to account for their man-like behaviour.

Other factors that present a risk of having a lesbian daughter are smoking and synthetic drugs. The exact mechanisms of their actions is still unclear and it might turn out that they are not in fact such a threat. But it’s always better to prevent something rather than be oblivious to it.

Also, stress during pregnancy can induce homosexuality in children, due to raised levels of cortisol which affects the production of sex hormones. So women caring a baby should try to stay as calm and relax as possible, even though that sounds like such a hard task especially when you’re pregnant!

If you have any other questions or you would like to add your thoughts to this post, do not hesitate to leave a comment.

Gender differences and sexual preferences

Posted on June 12, 2015 by Iasmina Hornoiu

When it comes to gender and sexual orientation, most of you would probably agree that it has always been a controversial topic. Not only are people’s opinions mixed about a variety of aspects related to gender and sex (the differences between males and females; the “gay problem”; the transgender and transsexual “trend” etc.), but it is also the complexity of these aspects that makes them difficult to be understood and accepted.

Do women’s brain differ to that of male’s? If so, what are the factors involved in the process of differentiation and when and how does all of this occur? Is homosexuality a choice or a genetic determination? Why do some people attempt to change their gender? These are some of the most common questions that have been raised throughout time and that I have come across. Nevertheless, one question that really got me thinking is: Are homosexuals, bisexuals, polysexuals, demisexuals, transgenders, transsexuals and so on NORMAL?

Hopefully, by the end of this article you will find some of these questions at least partially answered. Given the fact that the article is intended to cover such a diverse subject, I have decided to divide it into chapters. Having said that, let’s dig in!

Why do boys like blue and girls like pink?

It might come as a surprise that the behaviour of people according to their gender is not as much influenced by the society as one would expect. It is true that parents guide their children to behave in a certain way depending on whether they are boys or girls: the type of toys they are offered (action toys versus dolls); the kind of sports/activities they are encouraged to perform; the colours of their cloths and/or rooms etc. Moreover, it seems that this distinction between girls and boys is perpetuated in school by teachers: boys are expected to perform better tasks that involve mathematical and spatial reasoning, while girls are said to outperform boys in word comprehension and writing. Some have argued that all the previously mentioned are myths and that society should stop differentiating between genders when it comes to brain and intellect.

It turns out that these differences exit with or without the social stereotypes, or more precisely these stereotypes are based on real facts. Studies have shown that female monkeys prefer dolls, while male of the same species would rather play with toy cars and balls. This is not surprising if we consider the evolutionary roles of males and females inside the family and community: males have evolved specific abilities for more dynamic activities such as hunting and protecting their territory from enemies, thus their native spatial skills; females are structurally designed for more domestic activities, such as motherhood and housekeeping, therefore are more sociable and more inclined to have a better verbal memory than men.

So how are our brains programmed to develop certain male/female behavioural characteristics in us? It all comes down to genes. As we all know, at a chromosome level females differ from males in the heterosome pairs: XX for women and XY for men. Even though the X chromosome is larger and contains the majority of genes (including those coding for some masculinity traits), the Y chromosome has a crucial role in sex determination. The presence or absence of a specific gene called the sex-determining region of the Y chromosome (SRY) “decides” whether the foetus develops into a male or female. This gene codes for the protein testis-determining factor (TDF) which is responsible for the differentiation of the foetus’ genitals into testes.

The hormones produced by the testes (androgens), primarily the testosterone, have a very important role in the male development, as well as the oestrogen (like estradiol) influence the female features. During the first half of pregnancy, between the sixth and twelfth week, testosterone (produced at first by the Y chromosome) differentiates the sex organs into testes or ovaries. During the second half of pregnancy, the brain differences occur, due to a peak production of testosterone. The role of hormones in gender differentiation is important not only during the intrauterine period, but throughout the whole life of an individual. At puberty, the release of sex hormones induce the secondary female/male characteristics, such as facial hair, breasts, voice change etc.

It is important to note that the release of hormones is highly regulated by the nervous system and the endocrine system. Having said that, the pituitary gland secretes luteinising hormone (LH) and follicle-stimulating hormone (FSH) also known as gonadotropins which stimulate the gonads (testes and ovaries) to produce hormones. In turn, the pituitary gland’s hormone production is controlled by the hypothalamus through another hormone – gonadotropin-releasing hormone, which is influenced by the circadian cycle (more on this in a future article or if you have any questions, please address them to me). The adrenal glands also secrete a small amount of androgens.

Brain sexual dimorphisms

Yes! There are structural differences between the female and male brains and they are called sexual dimorphisms. The hypothalamus is a key region of the brain to sexual behaviour. As expected, a striking dimorphism can be observed here, more specifically within the preoptic area of the anterior hypothalamus. Here, the sexually dimorphic nucleus of the mammalian hypothalamus is significantly larger in males than in females. In humans, the preoptic area contains four clusters of neurons out of which at least one – INAH-3 (interstitial nuclei of the anterior hypothalamus-3)- was shown to be bigger in men. Also, the corpus callosum (the major neural pathway that connects the two cerebral hemispheres) and the bed nucleus of the stria terminalis (BST) are larger in men.

The abnormal (?!)

We finally got to the point where we discuss the “anything else other than heterosexuality” which is often classified as abnormal. Heterosexuality is known to predominate and is thought to be the only form of sexual orientation in all the other species apart from humans. Nevertheless, this couldn’t be further from the truth. Fish, birds, reptiles and even some mammalian species shown homosexual behaviour. It appears to be more common in birds than in mammals, although the examples are quite sufficient to prove that mammals are inclined to develop homosexual behaviour too. However, homosexuality among mammals is often temporary and is due to certain situations, such as better protection of the offspring, defence mechanisms and seeking help from other animals against enemies.

Having read the chapter about gender differences, we are entitled to assume that some sort of chemical and structural modifications generate gender identity and sexual orientation. Many of these changes happen in the womb. As explained above, genes and hormones play a very important role in the development of a foetus into a male or a female. But if these two factors don’t “agree” with each other, the individual will experience sexual and/or gender changes. The genetic and hormonal influences can be easily observed in twins: monozygotic twins have an incidence of 50% of both being homosexuals, while the percentage in dizygotic twins in 25%. At the same time, in the case of opposite sex twins, the female twin is more likely to develop congenital adrenal hyperplasia due to being exposed to her brother’s testosterone.

Before we go deeper into the subject, I would like to point out a few interesting things. The principal female sex hormone estradiol is actually synthesised from testosterone by the action of an enzyme – aromatase. At the same time, the androgen receptor gene is located on the X, not on the Y chromosome, so males have only one copy of this gene.

The fact that males have a single copy of the androgen receptor gene makes them prone to androgen-insensitivity, if the gene is not functional. The androgen-insensitive genetic males develop normal testes and produce testosterone, but they look and behave like genetic females. They are also attracted to men instead of women. The female version of this is represented by congenital adrenal hyperplasia. Women with this condition have been exposed to an abnormally large amount of testosterone and they develop a man-like behaviour, being more inclined to choose women as their sexual partners.

Even though the up-bringing of children and the social environment might have some influence on their sexual preferences and gender identity, the hormonal and central nervous system structural and functional changes have been demonstrated to be the cause. In most cases, if too much or too little amount of a specific hormone is released (or the receptors for that hormone are inactive or hyperactive) during pregnancy, this leads to changes in brain development. Previous studies have indicated that some structures in the hypothalamus are larger in homosexual men than in the heterosexual ones. Other differences have been observed in the brains of transsexual people. The bed nucleus of the stria terminalis, for example, is smaller in male-to-female transsexuals than in males, being more similar to the women’s BST.

Also, brain circuits appear to function differently according to sexual orientation. Usually, the way some brain areas respond to specific pheromones (see previous article about olfactory memory) and other stimuli is similar in heterosexual men and homosexual women and consequently, in heterosexual women and homosexual men. These functional and structural differences appear early in development and cannot be changed after birth by any social and environmental means.

I believe we can all agree now that there are many forms of “normal” in the world and that nature is a lot more open-minded than humans. We should learn to think outside the box and accept those who are not abnormal, but only different from us just as we are different from our parents, family, friends in terms of eye colour, food preferences, fashion style etc. Nevertheless, there is something I would like to place emphasis on: it’s one thing to be in a certain way and a completely different thing to choose something just because it’s cool or a lot of people do it. If you are one of those people who think being gay for instance is cool, but do not identify with it at all, my advice is: Don’t jump on the bandwagon! Be who you are and accept the others for who they are!

For further information:

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins pp. 534-560

Swaab, 2014. We are our brains – From the womb to Alzheimer’s. Penguin Books, pp. 55-71

Kandel, 2005. Psychiatry, psychoanalisis and the new biology of mind. Trei, pp. 122-126

Photo taken by myself and edited by Isuru Priyaranga