Eureka: Psychiatry

Chapter 1

First principles

Introduction

Overview of psychiatry

Theoretical basis of psychiatry

Ethical and legal issues in psychiatry

Classification of psychiatric disease

Global mental health

Introduction

Psychiatry focuses on the prevention, diagnosis and treatment of mental health disorders.

Mental health disorders are common, often chronic conditions. To treat them to best effect, a thorough understanding of the patient’s psychological and social experiences is required, with additional attention to the patient’s physical condition. Despite mental health disorders being distinguished from physical conditions, they often appear as part of or in conjunction with them. Conditions that first appear to be psychiatric disorders are occasionally found to have a physical cause and vice versa.

Historically, mentally ill people were cared for by lay people and the clergy because their problems were considered to be spiritual rather than medical in origin. Psychiatry as a discipline increasingly established its medical identity from the early 1800s. Subsequent progress in neurosciences, genetics, social sciences and psychoanalytic theory in the 20th century established psychiatry as a medical specialty in its own right.

Over the centuries, there have been huge changes in the public perception of mentally ill individuals and in the treatment approaches used. However, negative views regarding the origins of mental illness persist in many societies. The stigma – sense of disgrace – attached to mental disorders further undermines a patient’s well-being and increases their social isolation.

Overview of psychiatry

Starter questions

Answers to the following questions are on page 40.

1.   Why is stigma more of a problem for psychiatric patients?

2.   Why is psychiatry often considered unscientific and subjective?

3.   Why do psychiatric patients have a shorter life expectancy?

Mental health

The World Health Organization (WHO) defines health as ‘A state of complete physical, mental and social well-being, and not merely the absence of disease.’ However, mental health is a state of mental well-being that is not defined simply by the absence of disease. It is a state in which each individual is able to work productively, achieve their own potential and cope effectively with the usual stresses of life. Mental health underpins the ability to experience emotions, engage effectively with others and enjoy life.

Each individual experiences a wide range of emotions in everyday life in response to ordinary events. In addition, many social, physical and psychological factors impact upon feelings and emotions:

Social factors include life events, poor education, stressful working environments, discrimination, domestic violence and poverty

Physical factors include physical ill-health, genetic factors, drugs and medications

Psychological factors include a person’s personality, cognitive style and response to traumatic events

The boundary between mental health and mental ill-health is hard to define as it is based on the observation of complex emotions and responses.

Prevention of mental health disorders

The prevention of mental health disorders and the promotion of mental well-being are the focus of a considerable number of research projects and public health campaigns. Mental health promotion focuses on improving living conditions and encouraging the adoption of healthy lifestyles. Strategies include:

Early childhood interventions, e.g. preschool psychosocial activities for disadvantaged populations, child and youth development programmes and mental health promotion in schools

Increasing access to education for women in disadvantaged circumstances

Social support for elderly people

Reducing poverty

Violence prevention programmes

Psychiatry as a specialty

Psychiatry as a medical specialty ‘feels’ different from other branches of medicine. Students often feel unskilled and unprepared for working with mental health patients. Despite the advances that have been made, public perceptions and the stigma relating to mental health disorders still impact upon the practice of this specialty.

Students and psychiatry

Psychiatry can seem daunting because of the specific vocabulary that is used, the very detailed approach to patient assessment and the apparently complicated decision-making processes involved. A fear of psychiatric patients and mental health settings is compounded by misleading media portrayals. Inexperienced students are fearful of upsetting patients by saying the wrong thing.

You can take a number of approaches to overcome barriers to learning:

Engage with the terminology used in psychiatry at an early stage (see Chapter 2).

Become familiar with the signs and symptoms elicited in the mental state examination. This is just the psychiatrist’s version of a physical examination. A careful observation and description of the patient’s presentation is the first step in making a diagnosis

Liaise closely with the nursing staff in mental health teams. They can help identify patients who will be able to work well with you. See as many patients as you can

Ask questions. Decisions made by psychiatrists and mental health teams depend not only on a sound knowledge of psychiatry, but also on a detailed knowledge of each individual patient and their circumstances. This can make decisions look subjective as they differ between patients, but the mental health teams will be able to explain the reasoning behind their decisions

Be curious and interested. Patients have stories to tell and many will appreciate the opportunity to discuss these with you

Stigma and psychiatry

Stigma is a significant problem for individuals with mental illness. The stigma and discrimination that affect those with mental health conditions are experienced in many ways (Table 1.1).

Isolation

Historically, the stigma associated with mental health disorders has been exacerbated by the confinement of patients behind closed walls in asylums. Patients were set aside from both ordinary life and other forms of health-care provision in general hospitals.

Internalising stigma

People with mental health problems internalise society’s views, leading to shame, low self-esteem, withdrawal from others and poor social functioning. Modern psychiatric practice aims, wherever possible, to deliver care to patients in their own environment. This diminishes the boundary between physical and mental health problems, at the same time as reducing the stigma associated with the service as a whole.

Psychiatrists and stigma

Psychiatrists and other mental health workers experience stigma as a consequence of their profession. Psychiatrists have always occupied a slightly different role from other doctors due to their presence in legal proceedings and their role in the compulsory confinement of the severely mentally ill. As a result, psychiatrists may be feared and mistrusted in a way that other doctors are not.

Culture and psychiatry

Most psychiatric disorders present in all cultures, but the features displayed within them vary in different cultural settings. To understand the presentation of any illness you must be sensitive to the culture of the patient in which it arises.

Cultural beliefs

Different beliefs influence the nature of patient’s symptoms, such as delusions, or their behaviour when distressed. What may appear to be a delusion in one culture may be a culturally accepted belief in another. This raises questions about the nature of psychiatry and psychiatric illness: one society may accept something as being within the bounds of normal behaviour, when in another culture it would be considered mental illness requiring treatment.

Ishaar is a 42-year-old Somali refugee. He fled his country during the civil war after his village was invaded by militia who raped and tortured his female relatives and killed his brother. He is visiting his general practitioner (GP) with persistent headaches.

Through the Somali interpreter, Ishaar describes terrible headaches, difficulty sleeping and poor appetite. He is preoccupied by guilty thoughts about the family members who are still in Somalia and blames himself for not having been able to prevent the violence that he witnessed. He believes the headaches are a punishment for this, caused by the curse of an evil spirit that is taking away his energy. He weeps while he is explaining this.

The Somali interpreter explains that many Somalis do not recognise mental illness and seeking help for a mental health disorder is often seen as shameful. In Somali society, it is common to interpret physical symptoms as a consequence of spiritual interference. He explains that Ishaar wants treatment for his headaches and is working with religious elders to help him cope with his distress.

The GP recognises that Ishaar is depressed and that his beliefs are part of his cultural background rather than delusions or psychotic symptoms. He works closely with the interpreter to explain how he is going to help Ishaar with his symptoms using medication and counselling.

Migrant populations

Specific groups, for example refugees and asylum seekers, often have a higher prevalence of disorders such as post-traumatic stress disorder as a consequence of experiencing or witnessing acts of war and violence. Their assessment requires a specific consideration of:

Language and communication, using skilled interpreters

Cultural differences, considering beliefs that affect the patient’s presentation, e.g. in some cultures it is normal to believe that spiritual forces can impact upon bodily function

How culture affects the patient’s understanding of mental illness and willingness to accept treatment and access care

The impact of the illness on the patient’s social environment, employment and integration into the community

History of psychiatry

Evidence of primitive attempts to treat mental disorders date back to at least 5000 BC. Attitudes have ranged from supportive approaches offering sanctuary and support in asylums to physically abusive treatments aimed at casting out demons (Figure 1.1).

In the Roman era, mentally ill people were treated with physical treatments such as cold baths and purges, and medications such as opiates to induce sleep. By Saxon times, beating to exorcise the devils responsible for the illness was the standard approach.

Early hospitals for the mentally ill appeared in medieval times. However, many of these hospitals were associated with the mistreatment of their mentally ill patients and appalling standards of care. Many mentally ill individuals were taken under the care of the clergy, who tried to rid them of their ‘religious madness’ – any extreme belief in the existence of supernatural intervention in human affairs.

The asylum era

By the 17th century, abnormal beliefs that had previously been considered to be evidence of possession by the devil became a matter of illness. Doctors began to replace the clergy in caring for the ‘insane’, giving rise to the medical model of mental illness.

Figure 1.1 The evolution of mental health care.

Asylums took over medical care, and many sufferers lived in them for many years. The asylums varied enormously from tiny, caring homely institutions to those where cruelty and corruption were rife. One notorious asylum was the Bethlam Hospital in London (known as Bedlam), where members of the public paid to view the mentally ill patients who were restrained in chains in their cells.

Little effective treatment was available, although numerous physical approaches to treatment arose in this era, many of which were dangerous (Table 1.2).

Moral therapy

A new movement of humane asylums, started by the Quaker religious movement, appeared in the UK in the late 18th century. These provided ‘moral therapy’ and rehabilitation of the patient into everyday life, avoiding all forms of punishment and restraint.

Madness became seen as a disorder of mind and body that required medical attention and treatment. Psychiatrists began to classify disorders, discriminating between different presentations, considering contributory factors and identifying disorders with different outcomes. This paved the way for the use of psychoanalysis and new psychoactive medications for specific disorders in the 1950s.

The rise of psychoanalysis

Psychoanalysis arose from the work of Sigmund Freud. A group of psychological theories and associated treatment techniques gained popularity in the early 20th century. Central to the original psychoanalytical approach were the following beliefs:

Behaviour, emotions and psychiatric disorder have their roots in underlying psychological processes

An individual’s development is determined by events in childhood that have often been forgotten but continue to influence their attitudes and behaviour

Defence mechanisms, which protect the mind from difficult thoughts and ideas, are employed in situations that arouse anxiety

Human behaviour is affected by irrational but unconscious ideas and drives

Conflicts between conscious thoughts and unconscious thoughts give rise to psychological disturbance and emotional disturbances such as anxiety or depression

Although some of Freud’s theories have been rejected, psychoanalytic thinking continues to have a significant impact on modern psychiatry. Most psychiatrists apply a biological approach to psychiatric disorder and a psychodynamic approach to understanding their patients’ difficulties.

The chemical revolution

Prior to the 1950s, there were no medications to target specific psychiatric conditions. Medications such as opiates and bromides, which were generally sedating, were used for everything. In the 1950s the introduction of lithium, followed by antidepressant and antipsychotic medications, brought about a major change in the treatment of inpatient populations. For some patients, successful treatment meant they were able to leave institutional care for the first time in many years and continue their treatment in the community (Figure 1.2).

The many medications now available to treat mental health conditions are known as psychotropic drugs. Their use has grown so much that they are now the leading class of medication sold in the USA, with antidepressants being the most frequently prescribed. There is a risk that the increased availability of these medications can result in overprescription and an overreliance on medication instead of counselling and psychotherapies for milder mental illness.

Neuroscience and psychiatry

Modern neuroscience began to develop more rapidly in the 1960s. Information about neurotransmitters and neurobiological changes has offered explanations for disorders such as Alzheimer’s disease and has lead to advances in treatments for depression and psychotic disorders. As a result, there is no longer a clear discrimination between neurological and psychiatric (‘functional’) disorders (see page 8).

Figure 1.2 The number of patients in longterm care before and after the introduction of psychoactive medication.

Community care

In the 1980s and 1990s, the delivery of psychiatric care changed from being based in large hospitals to being provided predominantly through community mental health services. Many psychiatric hospitals were closed, and most patients who had lived for years in long-stay hospitals were rehabilitated into the community.

Although some hospital beds remain for patients who are too unwell to be treated in the community, most services have been reconfigured to deliver care in the patient’s home. New services include:

Crisis intervention services, which provide rapid-response care for patients with acute illness

Early intervention services, providing psychiatric input for patients with newly diagnosed psychotic illness

Home treatment teams, to provide ongoing input for patients with mental disorders

Rehabilitation teams, which focus on reintegrating patients into their social setting after significant illness

Assertive outreach teams, providing care for patients who are limited in their engagement with mental health services

Collaboration with primary care

The physical health of patients with psychiatric disorder is often poor, with much higher rates of cardiovascular disease than in the general population. Smoking, a poor diet and a lack of exercise contribute to the latter. On average, patients with severe chronic mental health disorders die more than 15 years earlier than those without. In addition, more individuals with mental illness die by suicide.

Physical health must be regularly assessed in this population. A close collaboration between the mental health and primary care teams ensures that physical health conditions are monitored and treated.

Theoretical basis of psychiatry

Starter questions

Answers to the following questions are on page 40.

4.   Why has the distinction between mind and body become less clear?

5.   How do we know which neurotransmitters are implicated in different psychiatric disorders?

Modern psychiatry is founded on principles derived from the biological, psychological and social sciences.

Early classification systems which separated mental disorders into those caused by physical or anatomical changes in the nervous system and ‘functional’ disorders lacking a physical basis no longer hold. Twentieth century research demonstrated the genetic, biochemical and endocrinological dysfunctions underlying many ‘functional’ disorders. Accordingly the boundary between neurology and psychiatry is eroding. However, there are significant obstacles to elucidating the processes that underpin both healthy mental functioning and dysfunction:

The complexity of the human brain, which contains many different cell types (neurones) and relies on the healthy functioning of a vast array of chemicals responsible for the transmission of information between cells (neurotransmitters)

The disparities between humans and other species in brain functioning, which makes it difficult to develop animal models for research

The near impossibility of carrying out investigations in the live human brain

The lack of biochemical markers to confirm the diagnosis of particular conditions

The neuroplasticity of brain cells (see page 21). The connections between the cells are continually changing in response to environmental stimuli, developmental processes and experiences, medications, drugs and diseases

Neuroanatomy

The nervous system is made up of two main cell types: neurones and glial cells:

Neurones are the main functional cells in the brain. They process information and communicate with other cells via axons. These are projections from the cell body via which neurones communicate electrically and chemically (Figure 1.3)

Glial cells (glia) support the neurones by maintaining the cellular environment of the nervous system (Table 1.3). They make up about 80% of the cells in the nervous system

Anatomical divisions: the central and peripheral nervous systems

Anatomically, the nervous system has two main functional divisions (Figures 1.4 and 1.5):

The central nervous system (CNS), which comprises all the cells within the brain, brainstem and spinal cord

The peripheral nervous system, which comprises all the cells and nerves outside the brain, brainstem and spinal cord. It includes the spinal and cranial nerves, sympathetic and parasympathetic nerves and nerves that supply the gut (enteric nervous system)

Figure 1.3 The structure of a typical neurone.

Functional divisions: somatic and autonomic

Functionally, the nervous system is divided into two types: somatic and autonomic. These link all the central and peripheral neuronal activity to allow continual adaptive responses to internal and environmental changes:

The somatic system is involved in controlling conscious and unconscious sensation and voluntary movement. It conveys information to the brain (the afferent or sensory input) and from the brain to the muscles (the efferent or motor output)

The autonomic nervous system (Figure 1.5) is the part of the efferent system that is responsible for controlling the internal organs. It also regulates homeostasis – the maintenance of stable internal bodily conditions. The autonomic nervous system has two divisions:

The sympathetic nervous system, best known for the fight or flight response

The parasympathetic nervous system, which maintains internal bodily conditions in a steady state

Figure 1.4 The divisions of the nervous system. CNS, central nervous system.

Figure 1.5 The divisions and innervations of the autonomic nervous system. CN, cranial nerve.

The emotion of fear arises in response to a real or perceived threat. It is accompanied by physical sensations including rapid breathing, an increased heart rate, increased muscle tone, sweating, ‘butterflies in the stomach’ and increased alertness. This is the fight or flight response, mediated by the sympathetic nervous system. It prepares the body to run away or stay and fight.

The central nervous system

The CNS is made up of the brain, brainstem and spinal cord (Figures 1.6 and 1.7).

The brain

The brain is composed of two cerebral hemispheres, each of which is made up of four major lobes. The cerebral hemispheres are responsible for the reception, processing and integration of information so that decisions and responses can be made.

The four main lobes have different functions (Figure 1.8 and Table 1.4):

Figure 1.6 The divisions of the nervous system.

Figure 1.7 Gross anatomy of the central nervous system.

Occipital lobe – interpretation of visual information

Parietal lobe – sensory functioning

Temporal lobe – language, learning, memory, interpretation of emotion, hearing, smell and taste

Frontal lobe – motor function and thought processing

Figure 1.8 The lobes of the brain.

The frontal lobe controls many activities associated with personality. These include the ability to predict the consequences of current actions, the choice between good and bad actions and the suppression of socially unacceptable behaviours.

Pick’s disease is a type of dementia that predominantly affects the frontal and temporal lobes. Patients initially exhibit marked personality and behavioural changes. As a result, it is often misdiagnosed in the early stages as other psychiatric disorders, for example depression.

Structural organisation of the cerebral hemispheres

The cerebral hemispheres are made up of grey matter and white matter.

The cortex, or grey matter, is the outer layer of the cerebral hemispheres consisting mainly of the cell bodies of neurones. These interconnect to form pathways from the cerebral cortex to the brainstem, spinal cord and nuclei (compact clusters of neurones) that lie deeper in the cerebral cortex. The cortex is the thinking, processing part of the brain.

The subcortical layer, or white matter, lies beneath the cortex. It contains the neuronal axons which have protein coatings called myelin sheaths. These form subcortical pathways connecting different areas of cortex and linking the cortex to the rest of the CNS. The deep cortical nuclei lie within these subcortical pathways. These are three clusters of functionally related cells: the basal ganglia, the limbic system and the thalamus and hypothalamus.

Functional organisation of the cerebral hemispheres

The cortex is functionally organised into motor, sensory and association areas. It has key roles in memory, attention, cognition, perception, language and consciousness (Table 1.4).

The two hemispheres are connected via the corpus callosum, which is composed of neuronal axons.

In children who start to learn a musical instrument before the age of 6 years the corpus callosum is increased in volume. This reflects the increased connectivity between the two sides of the brain supporting the improved coordination of the two hands involved in playing an instrument. This in turn further improves their future musical ability.

Lateralisation of function

The right and left hemispheres have different functions. Some activities such as motor control are bilateral but others are localised. For example, the left hemisphere is involved in the analysis of information and in speech. The right side of the brain is related to information synthesis, creativity and musicality.

Normal brain functioning requires all areas of the brain to be working in balance with each other. Particular changes in behaviour and functioning have been mapped to different areas of the brain (Table 1.4).

Frontal leucotomy (commonly known as lobotomy) involves severing fibres in the corpus callosum between the frontal lobes. In the 1940s and 1950s, this was performed on severely disturbed patients with schizophrenia, anxiety and mania. Although it reduced the distressing symptoms, many patients experienced devastating changes including apathy, loss of initiative, decreased concentration and disinhibition.

The limbic system

The limbic system is a group of functionally linked areas that lie on the medial aspect of the temporal lobe (Figures 1.9 and 1.10). It has a number of roles of relevance to psychiatry including:

Spatial memory and the acquisition of information

Emotional reactions to external stimuli

The interpretation of emotional reactions in others

Figure1.9 The structure of the limbic system.

Figure1.10 The functional connections of the limbic system.

Complex motor control

Pain perception

Social interaction

The thalamus and hypothalamus

The thalamus and hypothalamus lie beneath the cortex. They integrate information from the cortex and maintain the body’s internal homeostasis. The thalamus plays a role in consciousness by moderating the overall activity level in the brain. The hypothalamus controls automatic, unconscious behaviours.

The thalamus

The thalamus is made up of 12 nuclei, nine of which are organised into three groups (Table 1.5). The thalamus connects the cerebral cortex with the brainstem. It integrates and transmits information relating to sensation and movement in the control of:

Memory formation

Arousal

Consciousness

The hypothalamus

The hypothalamus lies on either side of the third ventricle. It is made up of 13 nuclei and receives input from the limbic system. It is connected to the pituitary gland via the infundibulum (Figure 1.11).

The hypothalamus is responsible for maintaining homeostatic equilibrium, being involved in:

Pituitary endocrine function

Efferent output to the autonomic system. It controls the autonomic nervous system and coordinates the autonomic and endocrinological responses in the stress response.

Figure1.11 The hypothalamus.

Thermoregulation, feeding, thirst, control of the circadian rhythm and memory

Functionally, there are three main hypothalamic pathways that control endocrine function. These are referred to as hypothalamic axes (Table 1.6).

The hypothalamus can be damaged in thiamine deficiency. This can occur in Korsakoff’s syndrome as part of chronic alcoholism. In this disorder, patients have profound anterograde and retrograde amnesia and a tendency to confabulate (invent facts to fill memory gaps).

Hypothalamic control is important in the maintenance of homeostasis, variations in mood and the stress response. The hypothalamic–pituitary–adrenal axis is a complex set of interactions between the hypothalamus, pituitary and adrenal glands, that controls levels of endogenous steroids and reactions to stress. This may be disturbed in conjunction with significant changes in mood, for example in depression.

Certain endocrine disorders (Addison’s, Cushing’s, thyroid and parathyroid disease) precipitate mood disorders such as depression, highlighting the influence of hormones on mental state.

Physiology of stress

Stress has been implicated in the aetiology of many mental health disorders. Any event has the potential to cause an individual to feel stressed. A mild degree of stress is constructive as it prepares an individual to meet everyday challenges such as examinations. Greater degrees of stress are, however, experienced as unpleasant and become harmful. They diminish the individual’s ability to perform adequately and may ultimately lead to physical or psychological dysfunction.

The hypothalamic–pituitary–adrenal axis plays a major role in preparing the individual to cope with stressful circumstances. The physiological and psychological responses to stress have three main stages: alarm, resistance or adaptation, and exhaustion (Table 1.7 and Figure 1.12).

Figure 1.12 Short- and long-term stress responses.

The basal ganglia

The basal ganglia are a group of interconnected nuclei deep in the cerebral hemispheres made up of the:

Caudate nucleus

Putamen

Globus pallidus

They are responsible for the coordination and control of movement. The main neurotransmitter in the basal ganglia is dopamine.

The subthalamic nuclei (below the thalamus) and substantia nigra (in the brainstem) work closely with the basal ganglia to control movement (Figure 1.13).

Parkinson’s disease is a movement disorder caused by decreased dopaminergic transmission in the basal ganglia. Similar symptoms often appear in patients taking antipsychotic medications, which work by blocking dopaminergic transmission throughout the brain.

Neurophysiology

Neurones communicate via action potentials, which are transient waves of electrical current. These underlie all coordinated mental activity, including emotions, feelings and actions. They are also the basis of the changes that occur in mental health disorders.

The action potential

An action potential is a transient alteration in electrical charge across the cell membrane caused by changing concentrations of sodium (Na+) and potassium (K+) ions. It starts at one end of the neurone and is conducted along the membrane to reach the synapses, which are the junctions to the connecting neurones.

Phases of an action potential

The membrane potential (Figure 1.14) has five phases:

A resting potential of –70 mV: a negative charge inside the cell which is described at this point as hyperpolarised.

Depolarisation. A stimulus from another neurone causes a rapid movement of Na+ and K+ in opposite directions across the neuronal membrane. Voltage-sensitive Na+ channels open when depolarisation occurs. Na+ rapidly enters the cell as its concentration is much higher outside the cell than inside, and there is a negative charge inside. The movement of Na+ ions into the cells triggers the opening of further Na+ channels until the net influx of Na+ is greater than the net efflux of K+.

Firing of the action potential. Once a threshold voltage has been crossed, all the Na+ channels open. This increases further the inward surge of Na+. This forms the spike of the action potential. The size and duration of the spike depend on the number of channels present and how long they are open for. A brief period of inactivation then follows as movement of the ions across the channel is blocked.

Figure1.13 The structure of the basal ganglia.

Figure1.14 The action potential. Initial depolarisation (red) is slow until a threshold is reached that opens the fast Na+ channels. Repolarisation (orange) initially overshoots the resting membrane potential (blue).

Repolarisation. As the Na+ ion channels close, the cell begins to repolarise. Pumps in the membrane have to actively transport Na+ out of the cell against the concentration gradient and K+ re-enters the cell.

Refractory period. The Na+ channels are inactivated and the inward K+ current is at its strongest. No action potentials can be generated at this point. This phase prevents the neurone from rapid repeat firing and cell death due to cellular depletion.

The action potentials alter the ionic gradient in the next section of membrane, which triggers opening of the voltage-gated Na+ channels. This next section then depolarises so that the impulse travels along the neurone.

The synapse

The synapse is the microscopic space between two neurones that are the site of the cell-to-cell communication. The action potentials are transmitted across these gaps via the release of specific chemicals known as neurotransmitters into the synapses (Figure 1.15). The following steps take place:

Figure 1.15 Neurotransmitter release at the synapse.

The action potential arrives at the nerve terminal and depolarises the presynaptic nerve terminal

Depolarisation opens Ca²+ channels in the presynaptic terminal, causing an influx of Ca²+ ions. This stimulates phosphorylation of the calcium-binding proteins in the presynaptic terminal and allows the presynaptic vesicles that contain the neurotransmitter to bind with the presynaptic membrane

This results in the formation of a small channel through which the vesicles discharge their contents into the synaptic cleft

The neurotransmitter diffuses across the synaptic cleft and binds with a postsynaptic receptor. This causes a change in the postsynaptic membrane potential, which generates an action potential in the postsynaptic neurone

Psychiatric medications target different neurotransmitter systems. Blockade and activity at the various neuroreceptors is immediate. However, the therapeutic effect of each psychotropic medication usually takes some weeks to develop fully, i.e. there is a therapeutic delay. This suggests that processes following on from neuroreceptor blockade have to take place for therapeutic effect.

Neurotransmitters and receptors

There are more than 100 known neurotransmitters, which can be subdivided into two main types (Table 1.8):

Small molecule neurotransmitters that mediate fast synaptic signalling

Larger neuropeptides that mediate slower synaptic signalling. These are involved in ongoing background synaptic transmission, in which small amounts of transmitter are continually released without generating action potentials postsynaptically

The nervous system is able to communicate effectively and accurately as different neurotransmitters work specifically on their matching receptor sites to achieve different effects (Table 1.9). Changes in many different neurotransmitters have been implicated in psychiatric disorders.

Most neurones can release more than one neurotransmitter. The different neurotransmitters are contained in separate synaptic vesicles within the same nerve terminal. Lower frequency nerve stimulation causes the release of small vesicles alone. High-frequency stimulation causes the release of both small and large vesicles. The pattern of neurotransmitter release thus varies, leading to different effects.

Curare is an acetylcholine antagonist that binds to acetylcholine receptor sites at the neuromuscular junction. It prevents the transmission of impulses across the synapse and results in paralysis. It has been used for centuries by South American tribes as an arrow poison.

Neurotransmitter receptors

The receptors are proteins on the postsynaptic membranes that usually bind specifically to certain neurotransmitters (Figure 1.16). This binding results in activation of the post-synaptic neurones. The receptors can only return to an inactive resting state when the neurotransmitter is removed or inactivated. They are then ready to receive further neurotransmitters.