If you accidentally placed your hand on a very hot plate you would probably draw it away immediately. This is because your nervous system allows you to respond extremely rapidly to changes in your external environment. Your nervous system also monitors conditions within your body, keeping things under control.
The nervous system - the most complicated of all living systems - has developed to increase an individual's chances of survival. What in some lower animals is simply a site for coordinating responses to simple stimuli has, in humans, evolved into the most complicated structure ever known.

The human brain fulfils all of the coordinating functions of a basic nervous system but also helps to predict future events, to create symbols such as words and pictures, and to generate emotions: all of which offer an experience of life that extends beyond simple survival.

The basic components of the nervous system are the nerve cells, or neurons, which carry nerve (electrical) impulses through the brain and body.

Each neuron consists of:

Cell body; contains the nucleus and other structures needed to keep the cell alive
Dendrites; branching processes that carry the impulse towards the cell body
An axon; a long branching process that carries the impulse away from the cell body.

How are impulses transmitted?
Sensory cells receive information from external and internal stimuli, such as the hot plate. This information is converted into an electrical impulse that is transmitted from the sensory cells to the central nervous system CNS (the spinal cord and brain), along nerve cells.

The CNS processes the information and transmits it to the muscles or glands - known collectively as effectors - via motor neurons. The effectors act upon the information they receive.

In the hot plate example the effectors would be the muscle tissue which contracts to move your hand away from the source of the heat.

What is the nature of the impulse?
The generation of an electrical impulse involves the movement of charged particles (ions) across the membrane of a neuron. A resting neuron has a voltage across its outer membrane not unlike that in a battery; like a battery, the neuron will use the voltage to send out a current, when 'connected' in a circuit.

Transmission from neuron to neuron
When nerve impulses have travelled the length of the axon, they are faced with the difficulty of spanning a gap - the synapse -over which electricity is unable to flow. These synapses ensure that the impulses are not sent in an uncontrolled way around the nervous system.

How do synapses transmit impulses?

Impulses cross synapses chemically rather than electrically. When an impulse arrives at the end of an axon, it triggers a chemical chain of events which end with the release of packets of a chemical, the neurotransmitter, into the synapse.

The neurotransmitter flows across the gap to dock with specialized proteins called receptors embedded in the membrane of the next neuron. The interaction of neurotransmitter and receptor has the effect of converting the chemical message back into an electrical one. There are over 50 neurotransmitters in the nervous system, and many more different types of receptor.

Diagram of synaptic transmission

Structure and Function of the Brain
As part of their exploration of the brain, neuroscientists are attempting to understand the degree to which degenerative diseases of the nervous system and behavioural disorders can be traced to structural changes of the neurons and the variation in the concentration of neurotransmitters released in specific areas/regions of the brain. Their research examines the role of genes, the environment and individual experience in moulding the human mind.

Diagram of the Brain
The anatomy of the brain has been described in great detail over the last 200 years. However, our understanding of the function of each region remains sketchy. Neuroscientists continue to learn much about the division of labour in the nervous system by studying the effects of damage to restricted regions of the brain. Their findings suggest that the brain works as a hierarchy in which specific groups of neurons are delegated a limited set of tasks.

It might seem strange that all of our thoughts, creativity and behaviour can be reduced to small electrical currents, but complexity often emerges from simple components - just as Shakespeare's plays are rather more than letters arranged on a page.

The discussion surrounding the causes of mental illness incorporates the relative roles of genes, brain structure and the influences of the physical environment and experience on brain development.

Biologists are continuing to identify structural and chemical differences in key parts of the brain of people suffering with the distress caused by mental illness.
Where there are differences, researchers face the problem of exploring whether these changes are symptoms or cause. Sometimes, the exploration may point in the direction of the inheritance of a variant gene.

On other occasions, the outcome sheds little light on the origins of the disorder, but may offer suggestions for the development of drug therapies to alleviate or slow the progress of the symptoms.

The following articles offer some insight into current understanding of the contribution made by our biology to a range of mental illnesses.

Schizophrenia
The commonly held belief that schizophrenia leads to the development of multiple personalities stems from a misinterpretation of the word itself.
The term schizophrenia or 'split mind' was coined by the Swiss psychiatrist Paul Eugen Bleuler early in the twentieth century to describe a condition in some of his patients whose mental processes - such as perception, emotion and attention - appeared to be separate from one other.

Since no two people share the same experience of schizophrenia, diagnosis is made if an individual displays the following broad range of symptoms:

Delusions - False and unusual beliefs, which are often paranoid and very frightening
Hallucinations - Usually hearing voices, but can involve other such incoherent thoughts - Associations between unconnected ideas.
Odd behaviour - for example talking in rhymes, long periods with no movement
Failure to respond to positive or negative event
Emotional bluntness.

Many of the symptoms listed only appear during an acute attack. However,people with schizophrenia also display tiredness, poor concentration and lack of motivation long after the symptoms of an acute attack have disappeared, although many of these symptoms are the side-effects of antipsychotic drugs

Genes for schizophrenia?
The incidence of this mental illness in all populations is about 1 per cent, though the chance of an individual being schizophrenic rises to 10 per cent if a parent or sibling has the illness. An identical twin has a 45 per cent chance of developing schizophrenia if his or her co-twin has been diagnosed with it; suggesting that despite a significant genetic component, other factors appear to contribute to the development of schizophrenia in an individual.

The discovery of a possible cause of schizophrenia came about through chance followed by careful observation. In 1950, a French surgeon noticed that his patients were calmer when given an antihistamine called Chlorpromazine to reduce postoperative swelling before surgery.

Clinical trials suggested that Chlorpromazine had similar therapeutic effects to Reserpine, another drug that was also being investigated at the time. Reserpine is the active ingredient of snakeroot, a plant used for centuries in India to treat people suffering with mental illness. In addition to reducing the symptoms of acute schizophrenic episodes, both Chlorpromazine and Reserpine caused tremors and muscular rigidity, characteristic of Parkinson's disease. It is therefore not surprising that it was research into this disease which initially offered some insight into the causes of schizophrenia.

Neuroscientists investigating brain chemicals (neurotransmitters) found that people who had died of Parkinson's disease had lost almost all of the neurotransmitter dopamine in a specific region of the brain. The researchers speculated that if Reserpine and Chlorpromazine also caused a Parkinson-like state, they must be working by reducing brain levels of dopamine. If this was correct then the implication was that schizophrenia is caused by an abnormally high level of dopamine.

How neuroleptics work
We can think of the process of sending messages within the brain like the transport of freight. Lorries transport their contents from a depot to a port, cross the sea by ship, and continue their journey by road. Electrical nerve impulses travel down the nerve cell until they reach the end of the axon, where a synapse needs to be crossed. In the same way lorries need to be loaded onto ships, electrical impulses are converted to chemical neurotransmitters. If accessible, the lorries unload their goods and continue on their way. For the lorries to unload their goods and continue on their way the ports need to be open. If there is a blockade of the ports, however, less of the cargo can get through. In the same way, neurotransmitters can flow across the synapse but to take effect receptors must be 'free' on the next neuron.

Like ships blockading a port, neuroleptics such as Chlorpromazine 'blockade' the receptor docking sites of the adjacent neuron by attaching to the receptors themselves and preventing dopamine attachment. However, the more recent research by a different group of scientists suggests that there may be other receptors and transmitters involved. Clozapine is effective in the treatment of schizophrenia and is less likely to produce Parkinson's symptoms than Chlorpromazine.

The latest neuroleptics can relieve some of the non-acute symptoms of the illness and do not reduce the number of white blood cells, which was one of the more serious side-effects of Clozapine usage.

Other factors implicated as contributors to schizophrenia
It seems that genes have some influence over the onset of schizophrenia. Evidence for life stress events precipitating the illness is slightly less conclusive, but generally accepted. Other potential factors implicated include birth complications, maternal malnutrition and maternal influenza during the 25-30th weeks of pregnancy, each of which may slightly contribute to the likelihood of developing the illness.

Depression
Depression is a natural response to personal tragedy, loss or bereavement and is characterized by a change in mood or emotion and is thus termed as an affective (emotion) disorder.

Depression is only considered to be a serious problem if it lasts a long time or has developed independently of exposure to any extreme circumstances or grief, and is preventing the individual from living a satisfactory life. People may also experience depression after a long illness when daylight length decreases in winter (seasonal affective disorder) or during the first year after giving birth (postnatal depression).

Some people with depression also experience periods of mania during which they display an extremely elevated, expansive or irritable mood. Psychiatrists have thus identified two main types of mood disorder: unipolar affective disorder, depression without mania; and bipolar affective disorder (sometimes called 'manic depression'), depression with some episodes of mania.

Are genes involved?
The involvement of genetic factors in determining depressive illness (discussed by Michael 0' Donovan in the section Genes and Mental Disorders) is supported by studies in twins. If one of a pair of identical twins has an affective disorder, there is a 60% chance that the other twin will develop a similar condition, compared to only a 15 per cent chance in non-identical twins. These figures hold even if the twins have been separated early in their lives and brought up in different environments. O'Donovan's studies suggest that in the development of unipolar and bipolar affective disorders there are roles for both genes and environment.

A chance discovery!
An idea about the changes in the brain of a depressed person came about after the chance discovery of the effect of drugs administered for other unrelated conditions. Iproniazid, a treatment for tuberculosis, was found to lighten the mood of patients and in 1957 was marketed as the first anti depressant drug. It worked, but no-one quite knew why. Iproniazid was superseded by tricyclic antidepressants which act on the transmitters noradrenaline and serotonin. The tricyclics did not produce the side-effects encountered with Iproniazid, such as dangerous surges in blood pressure after eating certain foods.
Scientists suspect that depression may be caused by low levels of serotonin and have thus focused on developing of drugs acting upon this neurotransmitter only. These drugs called selective serotonin-reuptake inhibitors (SSRIs) include Prozac, the commercial name for fluoxetine.

How are these drugs thought to work?
Serotonin is released from the end of many nerve cells in the brain, passing across the very short gap of the synapse between one cell and the next, and then attaching to receptors on the second cell to trigger a nerve impulse. Under normal conditions, serotonin then leaves the receptor and drifts back across the synapse where it is taken back up by the first nerve cell.
The tricyclics and SSRIs block re-uptake which ensures that serotonin 'stays around' for longer in the synapse and can continue to trigger impulses in the second nerve cell. Blockade of serotonin reuptake by Prozac

Understanding the Brain Chemistry of Depression
Understanding how antidepressants work has led researchers to argue that depression is caused by too low a level of transmitters such as serotonin in certain areas of the brain.

There are, however, problems with this theory, not least the fact that the level of serotonin in the brain increases within hours of taking antidepressants, but it takes weeks to change the patient's mood.
Current research is investigating the effect of serotonin on another chemical in the brain called cortisol, the levels of which are higher in depressed patients than normal. Antidepressant therapy reduces these elevated levels of cortisol.

External factors
Other studies have suggested that exposure to severe stress may be a causal factor in the onset of depression. In one study, two-thirds of people suffering with depression revealed that almost all had faced an episode of severe stress in the preceding year, compared with a third of non-depressed participants.
Information of this type, together with other explanations of depression, raise the unanswered question: How do external factors which seem to cause depression influence the brain chemicals that underlie our moods?.
Health experts often recommend a combination of drug and talking treatments, such as psychotherapy, to help people cope with depression, since it is acknowledged that drug treatment does not address factors outside the brain.

Another chance discovery!
If the causes of unipolar depression are unclear, then those contributing to the symptoms of bipolar affective disorder are even less well understood. It is known that the metallic ion, lithium, seems to be effective at treating both depression and mania, suggesting a common origin for the two. It is also known that lithium shares chemical properties with sodium and potassium, the two elements responsible for setting up the small electrical impulses that are the basis of communication in the brain and nervous system.

Though it has been suggested that drinking and bathing in lithium-rich natural spa and spring waters could have pacified people for centuries, the modern discovery that lithium was able to reduce manic episodes is mainly attributed to an Australian physician John Cade. In 1949 Cade reported the calming effect of lithium, although at the high dosage administered it seems more likely that the patients were suffering from nausea. Serious medical interest had to wait until the 1960s when lithium compounds were routinely offered as treatment, alleviating the debilitating symptoms of this mental illness.

Alzheimer’s Disease
Alzheimer's disease, the most common cause of dementia, is a progressive degenerative and terminal condition thought to affect 3 per cent of the population over 65 and 10 per cent of those over 85. Typically, a person with Alzheimer's disease will progress from depression and decline in memory, to irritability, anxiety and speech deterioration and eventually death.
With a massive increase in the world's elderly population, research into the causes of this disease of old age is considered to be of great importance since it is estimated that the number of people with Alzheimer's disease could still be halved if onset could be slowed down by five years.

Plaques, tangles and genes
Unlike many other forms of mental illness, clear physical features are detectable in the brain of individuals suffering from Alzheimer's disease. At the beginning of the century, Alois Alzheimer observed plaques and tangles in microscopic sections of brain tissue taken after death from people who had suffered with the illness which now bears his name.

Tangles seem to occur when a particular protein, necessary for normal neuron function changes chemically and can no longer bind to the cell's internal 'skeleton'. Plaques form outside brain cells and are composed of a small protein called fiamyloid, which under normal conditions is a component of a larger protein embedded in the membrane of the cell.

Protein filaments in Alzheimer's disease. Transmission Electron Micrograph (TEM) of fl-protein filaments which occur in brain tissue in Alzheimer's disease.
Dr Huntington Potter, Science Photo Library.

The function of any protein is determined by its structure, which in turn is dependent on the sequence of DNA code in a gene. A change in the DNA sequence, a mutation, can lead to a change in the structure of the protein for which it carries the code.

Research has suggested that a mutation of a gene located on the 21st pair of our 23 pairs of chromosomes is responsible for the incidence of early-onset Alzheimer's disease in a very small group of patients. Evidence of the gene connection here is strengthened by the knowledge that people with Down's syndrome often have a high level of amyloid plaques present in the brain, a higher incidence of Alzheimer's disease symptoms in adulthood and an extra copy of the 21st chromosome.

However, since this gene mutation applies to only approximately 20 families worldwide, the vast majority of Alzheimer's cases cannot be attributed to it. More recent research has implicated other genes as possible contributors to Alzheimer's disease. The gene for a protein called apolipoprotein occurs in three different forms and it is thought that inheriting one of the three forms of the gene increases the risk of developing Alzheimer's disease by a factor of four. Not everyone with this gene type develops the disease and about half of the those with Alzheimer's disease do not have the gene, suggesting that the disease may be caused by an interaction of genes or genes and environment.

Chemical factors and possible treatments
Biochemists have known for some time that the neurotransmitter acetylcholine is found in lower concentrations in the brains of people with Alzheimer's disease.
This is thought to be a consequence of the destruction of the neurons in a region called the basal forebrain which, not unexpectedly, has been considered as an important structure in memory.

Drugs designed to increase acetylcholine levels, through inhibiting the naturally occurring breakdown of the neurotransmitter, offer improvement in memory in some cases. Limited success of this treatment and further research findings offer the possibility that there may be another form of dementia, distinct from Alzheimer's disease, which occurs as a consequence of the depletion of a number of neurotransmitters.

It is likely that the degenerative processes occurring in the brain are caused by a combination of genes and lifestyle. Those with a high genetic risk may be affected fairly early on even in the absence of high lifestyle risks, whereas life events may accelerate the degeneration in those considered to be at low genetic risk.