Tuesday, June 07, 2011


I know that this blog wasn't intended for these types of updates, but I don't think I will see most of you any time soon, and an exchange of this type of information is long overdue. You may find what I say below to be extremely dry in parts, and for that I apologise. However, I hope that some of it sparks your interest at least a little.

A couple of years ago I decided to move into psychiatric research. This was partly precipitated by acknowledging that I didn't have a future in academic philosophy, firstly because I am rubbish at it and secondly because the career didn't really appeal to me. The latter reason isn't intended to disparage people who are academic philosophers, it just isn't for me. The former meanwhile means that if anyone has any philosophically orientated responses or questions about anything that follows, I probably won't be able to give a satisfying answer. I shall however try.

I am now focused specifically on schizophrenia, which has been of interest to me for some time, and which provided the original motivation to pursue my career. I work as a research assistant at the Institute of Psychiatry, which is a department of King's College. My current job involves conducting a clinical trial of a technique to optimise the way Olanzapine, which is a type of antipsychotic medication, is prescribed to patients. The technique works by taking blood samples from the patient and using the blood plasma concentration of antipsychotic medication to determine the best dose for that patient. In effect, it takes into account the particular metabolic and other biological differences that exist between patients that determine the percentage of medication actually having a therapeutic effect, rather being discarded by as waste, primarily in urine and faeces. I work as part of a research team and we liaise with clinical staff on inpatient psychiatric wards where patients with acute psychotic symptoms are brought to be treated. We then try to recruit eligible patients into our study, and collect blood samples and conduct a 90 minute psychiatric interview. The interview consists primarily of assessments of their schizophrenic symptoms, of the side effects they experience from their antipsychotic medication, and of their history of alcohol/substance use. The study will run for around 4 years, and for that time I will also be a part-time PhD student. My PhD will use the same patient cohort as the clinical trial, and will focus on the neurobiology of poor cognitive function in schizophrenia. I am currently thinking of investigating the questions: 'Does Olanzapine improve neurocognitive function?' and secondly, 'To what degree are neurocognitive deficits associated with schizophrenia the result of glutamatergic dysregulation?' The patient cohort I will be using is unique insofar as they are being treated with Olanzapine about as well as any group of patients ever realistically will be. How Olanzapine impacts the full range of schizophrenic symptoms is something that has been explored quite a bit in the past, but never with a group that is so effectively treated with the medication. As such, this is an ideal opportunity to investigate the potential of the medication to work in other domains rather than just psychosis. Indirectly then, the PhD will ask 'to what degree are cognitive symptoms the result of the dopaminergic dysregulation?', as this is the problem antipsychotic medication is intended to improve, and 'to what degree are cognitive symptoms the product of psychotic or negative symptoms'. I shall explain a little more of what all this really means in a moment. The second question in my PhD about glutamatergic dysregulation will be answered using either Positron Emission Tomography or Magnetic Resonance Spectroscopy to correlate levels of glutamate or glutamate transporters in the brain across different cerebral regions with cognitive symptoms. In addition to these two jobs, I also work as a nursing assistant in a number of psychiatric wards. These include open and secure wards, acute and long stay. This has allowed me to gain a fair amount of clinical experience of psychiatrically ill patients, with diagnoses from autism, eating disorders, alcohol abuse, or depression, to schizophrenia, bipolar disorder, etc.

Contrary to widespread belief, schizophrenia does not mean a fracturing of personality or psyche. 'Schizo-' does refer to fracturing, but the term was coined to refer to mental faculties. It is described as a complex psychiatric illness, and by Kurt Schneider as being characterised positive, negative, and general psychopathological symptoms. This view is still the norm in the medical categorisation and definition of the illness. The definitions of psychiatric illnesses used most commonly are presented in either the DSM or the ICD. Both these texts function as diagnostic manuals for psychiatrists, and contain the current definitions of each recognised psychiatric illness. Definitions vary slightly between the DSM and the ICD, and for that reason researchers and psychiatrists sometimes stipulate which text has been or should be used for making a diagnosis. To clarify, researchers don't make diagnoses, but they do sometimes screen control subjects for possible undiagnosed illnesses, or state in articles which text was used to diagnose the psychiatric participants they use. Schizophrenia typically becomes manifest for the first time in people in late adolescence, however may present at almost any time in a person's life. Studies indicate that smoking cannabis is a risk factor in developing schizophrenia. Meanwhile, psychosis can be induced by frequent and long term use of amphetamines and other stimulants. One type of psychotic illness is 'substance induced psychosis', which generally requires substantial and sustained use of amphetamine or cocaine over a period of weeks or months, and generally fades once the patient detoxes. Ketamine and PCP are sometimes used by researchers to create short term psychotic symptoms (such as thought disorder), which last for a few hours, in otherwise healthy participants.

Positive symptoms are conceptually understood as present in the participant as 'additions' to what is normal. This category includes hallucinations, delusions, anxiety, suspiciousness, grandiosity, and unusual thought content. Negative symptoms are viewed as 'subtractions' from what is normal, such as an impoverished or inappropriate emotional range or reactions during the conversation. People with schizophrenia sometimes present with little or no emotional responsiveness to the content of what they are saying. For example, if they are describing something sad, their facial expression and vocal tone will be almost indistinguishable from when they are talking about something happy. They may appear severely withdrawn, and their speech may demonstrate little or no tonal fluctuation during the conversation, or they may appear to be more or less incapable of laughing or of overtly demonstrating any other feeling. Other negative symptoms may involve a poor understanding of other people's emotions, motivations, or feelings. In psychological terminology they have a poor theory of mind. Additionally, they may appear to have a poor memory, poor executive function (reasoning, planning, strategising etc.), slow mental processing speed, poor abstract thinking, or difficultly maintaining attention on a task. General psychopathological symptoms involve just about everything else, including depression, disorientation, guilt, and poor insight.

The negative symptoms overlap to a degree with autistic symptoms. In fact the term 'autism' was originally coined to describe a category of schizophrenic symptoms, and was later appropriated to name the psychiatric disorder it is now associated with. The positive symptoms of schizophrenia, meanwhile, comprise psychosis, more or less. Psychosis is a state that can occur in numerous psychiatric illnesses, such as bipolar disorder (manic depression) or extremely severe depression. It is by far the most investigated aspect of schizophrenia, and it is also the most widely treated. Antipsychotic medications were initially developed as sedative drugs until a French physician during WW2 noticed that they also had an excellent therapeutic effect on psychotic patients. That led to a surge in the research into new pharmaceutical treatments of psychosis. Up until then physicians had used insulin shock therapy, ECT, and lobectomies to treat the illness, most of which is not particularly effective with the possible exception of ECT, which can provide some relief and is still offered to some patients on a voluntary basis. Antipsychotics work by reducing dopamine levels in the brain. While this helps to combat psychosis, it also results in a wide range of unpleasant side effects in most cases. Most of these look like Parkinson's disease as Parkinson's involves a depletion of dopamine in the basal ganglia in the base of the brain. So the patient's limbs may visibly shake, have joint rigidity, or they may move their tongue in and out of their mouth, gurn, chew, roll their eyes, or 'pill roll' with their fingers. Additionally, other side effects include feeling restless, moving their weight from one leg to the other, pacing, inability to sit still, inability to stop moving their legs or arms, etc. These side effects are one of the reasons why some patients stop taking their medication. But on a side note, if they stop taking their meds and their psychotic symptoms relapse, then they can be brought into hospital and sectioned under the mental health act and forced to take their medication again.

There are various sections of the mental health act. Some intended to detain people in hospital while they are being observed to allow clinicians to make the appropriate diagnosis, some intended to allow clinicians to force patients to take their medication, either while they are in the community or in hospital, and some as a substitute to a prison sentence, so they can serve their sentence in hospital rather than prison. Someone should only be detained in hospital and forced to take medication if they would otherwise represent a danger to themselves or others, and this is left to the interpretation of the patient's clinical team. However, their decisions are subject to scrutiny by the courts if the patient challenges it by going to a tribunal. Most patients who are sectioned and forced to take meds have solicitors and challenge their detention through tribunals.

Patients are sectioned for either being a danger to themselves or other people, but this is something that is very broadly interpreted. Evidence that psychotic patients represent a danger to other people is mixed. A recent large scale (involving 100s of cases) found that psychotic patients were not significantly more likely to commit serious violent crime, such as assault or murder, than the general population. However, they did also acknowledge that when they do, it is often in relation to their delusions or hallucinations, suggesting that treating such symptoms may help to lower crime rates in relation to people with psychosis. Meanwhile, the rate of suicide is much higher in psychotic patients than the general population, but so is the rate of depression, and suicidal ideation is much or likely to correlate with depressive symptoms rather than delusions, hallucinations, etc. suggesting that treating the depressive symptoms is more important than treating the psychotic symptoms when it comes to preventing self-harm. It is sometimes argued that the widespread belief that psychotic patients are more dangerous or unpredictable than healthy people is essentially unfounded and is largely or wholly a matter of societal/culture stigma. Stigma towards the mentally ill, society's treatment of them, and society's apparent inclination to purify itself of irrationality and difference are some of the subjects of Foucault's A History of Madness. In a similar vein, Thomas Szasz argues that mental illness isn't really illness, since it has no physical pathology (which is a very questionable assertion), and instead refers to behaviours most of us find difficult to deal with and so society detains these individuals in secure wards and forces them into treatment, ideally to make them behave like the rest of us. This is not a widely held view, and it is one that I think is very simplistic.

To return to the nature of schizophrenic illness, perhaps the most interesting symptoms are hallucinations, delusions, formal thought disorder, and lack of insight. While hallucinations have a clear definition - the presence of perceptual phenomena that have no external cause (although I suspect philosophers will want to discuss that definition), notable facts about hallucinations include that they occur in all 5 senses - visual, auditory, somatic, olfactory, and gustatory, and that they rarely co-occur such that a heard voice has a corresponding and concurrent visual hallucination. So most filmic representations of psychosis are normally inaccurate insofar as the individual normally sees hallucinatory figures who talk to them, rather than just hearing or seeing them in any given moment. Furthermore, visual hallucinations are quite rare. Roughly speaking most common are auditory hallucinations and then somatic, olfactory, and then visual or gustatory. Delusions are more difficult to define. They used to be thought of as unusual or bizarre beliefs that do not belong to the individuals cultural or societal belief system. But this is a poor definition. They are now widely regarded as unusual or bizarre beliefs that have a poor evidential or rational basis. The terms unusual and bizarre roughly speaking refer to highly unlikely/improbable and impossible respectively. An unusual belief may be that they are being targeted by MI5 on the basis that strangers give them funny looks in the street, or because they have noticed that cctv cameras follow them when they walk down the street; or that they are on the way to becoming a saint because God sent them a sign in the newspaper that morning. A bizarre belief may be that they have the ability to heal through touch or that their internal organs have been replaced with mechanical versions. It is questionable when a delusion is bizarre or not, and it isn't critical. The examples I gave would be variously described as non-bizarre or bizarre by different clinicians. More importantly the point at which a belief becomes a delusion is a much debated issue. Particularly since it relies when something is rational or irrational. This issue has been addressed to a degree in terms of cognitive psychology, which I will come on to.

Lack of insight refers to the patient's failure to identify themselves as being psychiatrically ill. Many or most schizophrenic patients do not believe they are ill. Instead, they provide delusional explanations of their symptoms, such as that they are being persecuted by demons, or that they have hypersensitive hearing and so their auditory hallucinations are actually speech being uttered by other people, but too quietly or far away for anyone else in their locale to hear. Almost every patient I have met had a different explanation of their symptoms, with only one person attributing them to being psychiatrically ill. Normally patients attributed hallucinations either to being persecuted by a supernatural being or a shadowy organisation, or that they had a superhuman ability such as the ability to read other people's minds, or a special contact with God. Another symptom, termed disorientation, involves the individual being 'lost' to a degree in time and place. They may remember the year, but fail to remember the date, day, or current time. Moreover, they may forget or be confused about other aspects of their life, such as where they currently are, or the identities of their family members. This is commonly tested by asking the patient the date and time, where they currently are, and about who the current prime minister is, current local mayor, or the current president of America. Patients who are very disorientated may severely confabulate events, or confuse people or places with their past. For example, one patient I met was convinced that she was in a hotel rather than hospital, and that I was someone from her past named Peter, who was the brother of her ex-partner. She believed that I had personally contrived for her to be in hospital, and that I planned to drug, rape, and kill her. Another person had merged all her hospital admissions with the present one, such that she believed she was in Lambeth hospital, which she wasn't, and that she was in the wrong room, and that someone had stolen her stuff, when in reality she had been admitted on this occasion with only the clothes she was wearing.

Formal thought disorder broadly speaking refers to incoherent or illogical thinking. What the person says may often become tangential, and in extreme situations almost entirely random given the topic of conversation. When asked to make semantic associations between things, such as 'what do you associate with a car?', the person may say fairly random words like sun, elephant, or start to talk at length again about God or whatever issue is preoccupying them. They may start to talk about how the individuals persecuting them drive cars, and then talk about the ways in which they are being persecuted, and the identity of the persecutors. This is often termed a flight of ideas. Meanwhile, formal thought disorder can also refer to other problems with thinking or conversation, such as stereotyped thinking, so the person focuses on one idea and will keep talking about it despite the clinician's attempts to change topic. They may only talk about their relationship with God, for example, and not respond to attempts to move on to other topics. Alternatively they may repeat single words, such as 'Jesus was the son of God, God, God'. Or they may show poor abstract thinking. This is typically tested by asking the individual to interpret proverbs, and to describe similarities between things, for example circle and triangle, or red and yellow.

Aspects of formal thought disorder almost certainly underlie delusions because delusions are normally irrational interpretations of internal, such as hallucinations, or external phenomena. On top of this, delusions often contain persecutory ideas, so they may believe the police or some group of people are 'out to get them'; or they may say that they are being attacked by ghosts or demons, which is an explanation sometimes given by patients for their somatic, auditory, and visual hallucinations. Additionally, schizophrenic patients may also be grandiose, so the person may think they are special, or unlike 'normal' people. One patient I remember stated that they had the special ability to heal through thought, and that this was because they had been chosen by God to be special. Another meanwhile said that they were a special human being, and so the staff had no right to keep them in hospital. They also said that they were the Virgin Mary and that their father was Elvis, and that they had brought good into the world, and that they were extraordinarily gifted musically and could not understand why no one seemed to appreciate how special they were. However, each of these symptoms are rarely all present in a patient. Normally, a patient will present with some combination of them, and this has meant that patients with a schizophrenia spectrum disorder are further labelled as either schizoaffective, in which the patient experiences severe changes in mood similar to those in bipolar alongside continuously present psychotic symptoms; schizophreniform, which refers to a brief or limited period of schizophrenic symptoms of more than 1 month, but less than 6, with no apparent relapse; paranoid schizophrenia, which is characterised by the strong presence of positive symptoms such as hallucinations, delusions, and persecutory ideas; disorganised schizophrenia, which is characterised by the relatively strong presence of negative symptoms; and finally undifferentiated schizophrenia, which covers those that don't fit any other category.

The cognitive deficits associated with schizophrenia include memory problems, both short term and long term memory, attention problems, processing speed, and executive functions. They tend to have reduced IQs compared with their IQ level prior to developing the illness. It is also unclear to what degree these deficits are the result of patients' preoccupation with their internal, hallucinatory, and delusional worlds. However, it is likely that irrational or illogical thinking correlates strongly with drops in IQ and executive function. It is less clear to what degree it correlates with attention and processing speed.

My PhD will examine some of these issues, alongside the question of how well antipsychotics treat these symptoms. Previous studies indicate that antipsychotics have little or no impact on cognitive deficits. If this is the case then they must involve neurotransmitters in the brain other than dopamine, and must exist outside of the psychotic symptoms of schizophrenia, as discrete symptoms. However these studies are unable to draw conclusions with much confidence because of the haphazard way medication is often prescribed. So this will be the starting point of my PhD.

There are three main neurotransmitters in the brain - dopamine, serotonin, and glutamate. All three are believed to be involved in schizophrenic symptoms. Dopamine hyperactivity is present in the mesolimbic region and is treated using antipsychotics. However, despite this treatment psychotic symptoms are still present in most patients. Moreover, they do not treat the other symptoms of schizophrenia at all. They are used to try and control hallucinations etc. and patients report that medication decreases the 'volume' of these hallucinations. As such it is believed that there is an underlying neurobiological condition which dopamine exaggerates, but in addressing the dopaminergic dysregulation in the brain with medication, current medication is not really addressing the fundamental biological problems involved in schizophrenia.

One possibility is that glutamate is responsible. There is a substantial body of research being conducted at the moment investigating this. So far new glutamatergic medication hasn't helped patients, but this is probably due to the right medication having not yet been found. More needs to be understood about which aspects of the glutamatergic system are dysfunctional to be able to design new and effective pharmaceuticals. During my PhD I will investigate this possibility using neuroimaging, and secondly to what degree glutamate is responsible for the cognitive symptoms.

I am going to bring this post to a very abrupt end. I am sorry for the degree to which the above at times felt like a statement of intent for my PhD. I had intended it to be a rapid discussion of some important points in schizophrenic research, but at times it may have drifted from that. If anyone has any questions, or would like any elucidation, please don't hesitate to ask. Perhaps the philosophically interesting questions haven't really been brought up. For me, there are various questions that are interesting, and for which I have no definite answer. Firstly, what is an illness and does psychiatric illness qualify? Secondly, what makes a delusion irrational? Thirdly, what medicine has to say about the nature of irrationality, or of supposedly abnormal perceptual experiences, and why are these problematic? Fourthly, what does schizophrenia and its related illnesses tell us about the way the mind works?

I have no doubt that psychiatric medicine stigmatises certain behaviours to a degree, but I think that all medicine is stigmatising to a degree. Foucault discusses how the leper houses became used to house the mentally ill during the middle ages, as they were normally positioned outside of the city walls. It seems to me that this is a good example of how all forms of disease or illness are shunned. AIDS patients do not get sent out of cities, but I would have thought that many people feel slightly uncomfortable around someone knowing that they have the illness. It is because mental health problems have always been considered forms of illness that they are stigmatised. The resulting, interesting question here, I think, is 'what is health'?


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