Bob Kentridge 1995

S2 Psychopathology: Lecture 1.

Biological Models of Psychopathology.

Psychopathologies are, as their name suggests, expressed as abnormalities in people's psychological processes and consequently their behaviour. In the first half of this course you will have learned about explanations and treatments for pathological psychological conditions which are themselves based in psychology. This approach rests on explanations that these conditions are caused by factors like people's maladaptive psychological reactions to events in their lives or abnormalities in the way they perceive events or their inappropriate attributions of responsibility for events. Much of the treatment of psychopathology that takes place today rests on a quite different form of explanation and treatment - biological models of psychopathology. Here the kind of causes proposed are physical not mental and treatments are directed at the body, not the mind, using drugs, or, in extreme cases, surgery. In this lecture I want to address two questions. First, 'why did the biological approach arise and why is it so prevalent?' and second, 'what basis and evidence is there for biological explanations of psychopathology?' In the course of dealing with the second question we will cover a few basics of neuroscience.

What has motivated biological models of psychopathology?

It is strange, in a way, that we should try to explain mental phenomena physically. In these days of brain-imaging when we can see changes in brain activity which correspond to changes in people's thoughts and actions it is not so surprising, but these physical explanations of mental phenomena have been around much longer than that. (In fact, even now, unambiguous evidence for correlations between changes in brain activity and specific psychological phenomena is hard to find). Hippocrates in his Sacred Disease (from the fifth century B.C.), for example, asserted that
"Men ought to know that from the brain, and from the brain alone, arise our pleasures, joys, laughter and jests, as well as our sorrows, pain, grief, and tears, ... It is the brain which makes us mad or delirious ... These things that we suffer all come from the brain, including madness."
Hippocrates originated the humoral theory of the body - the theory that the body is composed of four fluids - blood, phlegm, yellow bile and black bile. Imbalances between these fluids cause both physical and mental disease. An excess of black bile, for example, caused melancholia and could be treated by appropriate medicines or changes in diet. Ancient Chinese explanations of madness also involved imbalances between classes of substances and forces - the yin and the yang which may be physically caused and treated. Hippocrates humoral theories remained popular into the middle ages although spiritual explanations in terms of witchcraft and demonic possession gained much ground (these explanations also sometimes allowed 'treatment' by physical interventions such as trepanning even though not physically caused - physical treatment of ailments with non-physical causes is still around today).

In our terms none of these 'biological' theories seem to have any evidential basis, yet they survived for long periods of time. One explanation might be that they were intimately bound up with explanations and treatments of physical ailments which had some success. If psychopathology is regarded as mental illness (now you can see why I have struggled to avoid using 'mental illness' in place of 'psychopathology') then it is natural to employ the same sort of people and procedures to deal with it that are used in treating physical diseases. In fact some people regard biological models of psychopathology as just being one extreme of the more general medical model of psychopathology, also including psychological approaches, with their sequences of identifying pathologies, the symptoms associated with them, diagnosis, therapy and cure. This 'anti-psychiatry' standpoint runs the risk, however, of glamourising psychopathology just as tuberculosis aroused romantic notions of illness in the 19th century - both, however, can be very unpleasant for their sufferers. One question we can ask then is whether our current biological models of mental illness are supported by direct evidence rather than being merely shadows of biological models and treatments of physical illness.

Before considering the types of explanations and treatments offered by biological models of psychopathology it is worth stressing one general point. The existence of a physical effect on a psychological condition does not imply a physical cause for that condition. For example, just because a drug can alter the mood of a depressive it does not follow that the person was depressed because of a chemical imbalance rectified by the drug. In these lectures I want to be careful to distinguish between treatment and causation. Sometimes biological treatments are given assuming biological causes and psychological treatments are excluded or become secondary. In other cases we may accept that a problem has a psychological cause but a biological treatment may be more practical or successful than psychological or social intervention.

Biological explanations, evidence and mechanisms.

Biological explanations of psychopathologies are usually couched in terms of some abnormality or damage to a part of the brain. Psychological functions are held to depend on the normal operation of specific brain systems. So, when one particular system cannot operate normally the consequence is a psychological dysfunction.

Biological treatments also carry the assumption that some part of the brain serves a particular psychological function. They do not, however, assume a physical cause for psychopathology. A brain system may, for example, become overactive as a result of psychological causes. Either psychological or biological intervention could return it to a more normal level of operation. In both cases we need to understand how the psychological processes may be divided up between parts of the brain and how these particular systems operate physically.

Now let us consider whether contemporary work in neuroscience really provides clearer evidence for localised physical bases of psychological function than Hippocrates had for his humoral theory.

Anatomy.

It has been assumed for a long time that different parts of the brain subserve different psychological functions. An early example is Gall's science of phrenology - discerning people's personalities by studying the shapes of their skull and, by inference, the shapes of their brains. Gall did not really have any good evidence for his maps of brain function, however, systematic experiments on the psychological effects of brain lesions in animals and on the effects of brain-damage in people caused by accidents or strokes has since given us quite a detailed picture of the specialised roles of at least some parts of the brain. Unfortunately the functions we can attribute to these brain regions are often far removed from the factors we may imagine to lie behind psychopathology. Brain mapping is telling us a great deal about the subdivision of the visual processes of perception but not much about personality. There are, however, notable exceptions - some parts of the brain have been linked to the production of normal emotional responses to events in animals and even to the recognition of status in social hierarchies (amygdala). Other brain regions have been implicated in modulating and switching between these affective responses (prefrontal cortex). Clearly damage or dysfunction in either of these areas (which are quite densely interconnected) might lead to psychopathology.

Neurotransmitters.

Many biological models of psychopathology are not, however, based on anatomical divisions of the brain, but on chemical ones. In order to understand this we need to know a little about the way in which the nerve cells (neurons) which make up the brain interact.
You'd see a diagram of a neuron image here if you were using a graphical web browser like Mosaic or Netscape.
The human brain is comprised of about 10 billion neurons, each of which can transmit signals along its fibres as a wave of electrochemical activity. It is, however, thought, that brain functions rely on collective interactions of activity in many neurons. The average neuron can interact with about 10 thousand other neurons. These interactions are almost all entirely chemical in nature. The end of the nerve fibres that carry outgoing signal from a neuron contact parts of other neurons in structures called synapses. There is a tiny gap between the two cells. When a signal (action potential) travels down the first neuron and reaches the end of the fibre tiny quantities of a special chemical called a neurotransmitter are released which flow across the gap (synaptic cleft) to the second (postsynaptic) neuron. There are sites on the second neuron which are specialised to receive this neurotransmitter. When the neurotransmitter locks onto one of these receptor sites a reversible chemical change takes place which alters the electrical properties of the second cell. If enough receptors are activated the second neuron may generate its own electrochemical action potential. Once it has released its neurotransmitter the first (presynaptic cell) cell will reabsorb it so it does not remain in the synaptic cleft and continue to stimulate the second cell. Transmitter which is not reabsorbed is eventually broken down by enzymes.
You'd see a diagram of a synapse image here if you were using a graphical web browser like Mosaic or Netscape.
Drugs effect the action of neurotransmitters by a number of methods - these are the main ones: The reason that different drugs may be used to treat specific conditions is that there are many different types of neurotransmitters used in the brain and different drugs act on them selectively. The neurons which use some of these neurotransmitters are also often anatomically localised - so one might even be able to modify the effects of localised physical damage using drugs. A great deal of work has gone into discovering whether particular neurotransmitters, or anatomically localised pathways of neurons using particular transmitters, have distinct psychological roles. Much of the work I will discuss later in the course concerns the neurotransmitter dopamine which has linked to the signalling of pleasure or reward, to the initiation of actions and to feeding control in studies of animals - cocaine and amphetamines are examples of some drugs which stimulate dopamine systems.

Lines of Evidence.

We now know a little about how the brain works and so have some idea about how it might fail. Neurons in particular brain areas may be damaged or die, or they may fail to produce the right amounts of particular neurotransmitters. How can we make a connection between defects like this and psychopathologies?

One source of evidence is to examine the brains of sufferers directly. Inevitably this must be done after they have dies. Post-mortem examination can reveal differences in both the structure of and amounts of neurotransmitters found in parts of normal people and sufferer's brains. These studies are very difficult, however, both because of the limited numbers of brains available for one reason or another and because drug-treatment during a patients lifetime can often mask any inherent abnormalities.

Some measurements are also possible when people are alive. The levels of neurotransmitters in people's brains can be assessed indirectly by measuring the amounts of the breakdown products of these transmitters in their urine. Brain scanners can detect gross structural brain damage (CAT, MRI) or changes in the activity of relatively large regions of the brain (PET fMRI). The interpretation of data obtained in these ways can be very difficult, however. In addition to the spatial and temporal limitation on the resolution of brain scanners there are problems in finding tasks which might clearly differentiate psychological processes in patients and control subjects. In metabolite studies there are the problems determining whether changes in breakdown product levels imply over- or under-effectiveness of the precursor transmitter in the brain.

If we have a theory about the causation of a psychopathology which rest on a behaviourally measurable factor like the ability to perceive reward correctly or the ability to suppress responses then we are able to investigate these factors in animals. It is then possible to discover whether particular brain areas or neurotransmitter systems mediate this behaviour by selectively damaging them.

If we believe a pathology has a physical cause which is not acquired but is inherited then we can also look for evidence using methods of behaviour genetics. Care must be taken, however, that genetic causes are not attributed to conditions which might be due to upbringing. For this reason studies simply looking for patterns of illness in family trees can be difficult to interpret. Studies in which the prevalence of disease is compared between ordinary and identical twins or between twins reared together and apart yield more conclusive evidence but the subjects are hard to find.

Finally, of course, we can simply assess the effectiveness of treatments in patients. If treatments vary in their effectiveness according to their potency in effecting a particular neurotransmitter system we take this as evidence for the involvement of that system in the pathology. It is not, however, evidence of a causative role.

Sources.

Every abnormal psychology textbook I've looked at has a chapter giving a historical introduction and a quick overview of neurons and synapses - Davison and Neale (the recommended text) is fine, although there was a little more history in Kendall and Hammen's 'Abnormal Psychology'. Silverston, T. and Turner, P. (1978) Drug treatment in psychiatry, second edition. London: RKP, goes into more detail about drug action than the abnormal texts but does not assume too much background knowledge (being written for medical students and doctors!). The introduction to Luria, A.R. (1973) The working brain. London: Penguin has more discussion of phrenology and its successors.