Monthly Archives: June 2011

Review of Thomas Kuhn’s ‘The Structure of Scientific Revolutions’ – Chapter 8

In Chapter 8 of Thomas Kuhn’s ‘The Structure of Scientific Revolutions’ is titled ‘The Response to Crisis’. Whereas in Chapter 7, Kuhn focuses on how the crisis in science arises in this chapter he elaborates on how the scientific community responds to this crisis. He makes the interesting point that in criticising one theory the scientist must propose an alternative otherwise this is not the pursuit of science.  What is also interesting is that he suggests that when this competitive process ends, the branch of science becomes static and in the example he gives it becomes a ‘research tool’. Kuhn suggests that there are always discrepancies even in the most successful of paradigms. With a move towards crisis there are increasingly divergent explanations and there is a loss of identity within the field. Indeed Kuhn maintains that all crises involve a blurring of paradigms. The crises are closed in one of three ways. In the first case, the crisis is handled. In the second scenario there is a resistance to radical approaches. In the final scenario the crisis leads to the emergence of a new candidate for paradigm.

Kuhn then goes onto discuss commentators on the field who refer to Gestalt theory in which a visual perception is dependent on the whole rather than part of an object. So if the reader looks at the cube below, the lower square face can be interpreted either as sitting at the front of the cube or the back of the cube. In both cases the square takes on a different meaning within the whole object that is perceived. In the same manner Kuhn suggests that new paradigms lead to a different way of seeing a body of empirical facts. He is quick to point out however that this is a crude analogy and that scientists do not quickly switch back and forth between paradigms. Nevertheless it illustrates the essence of his arguments well.

 

Alan De Smet, ‘Multistability‘ (Public Domain)

 

Kuhn then goes on to say that the scientist having identifed the anamoly central to a crisis will go on to explore the anomaly and to better characterise it. In crisis, speculative theories multiply and increase the chance of a successful paradigm being reached. He also suggests that philosophical enquiry into assumptions can challenge some of the tenets of the current paradigm. Finally Kuhn finishes by commenting that many scientists leading to scientific revolutions are deeply immersed in crisis and they are either very young or new to the field in change which he interprets to mean that there thinking has not been shaped by the component rules of a paradigm. However Charles Darwin would be a notable exception having published ‘On the Origin of Species’ at a mature age and with a comprehensive knowledge of the related fields in biology. Nevertheless there are numerous counterexamples and the main result of this chapter is that Kuhn provides the reader with very effective tools for thinking about science in transition.

* One thought I had here was that in the very early stages of a science there must be a lot of theories that are initially developed but which are quickly shaped by the experimental facts. In this way many theories would exist before quickly falling to experimental findings in which case there would be a ‘survival of the fittest’ theories  which are tested against each other. This has a number of implications.

Firstly that a philosophical system might define this pre-science phase in which a large number of theories exist without being tested against the experimental facts. The brain’s analytical and other abilities are used as an alternative to hypothesis testing in the real world in order to generate ‘realistic’ solutions based on experience and intuition. As time proceeds and assuming the system has an efficient or effective ‘memory’ and scientific enquiry produces a growing body of empirical facts the competitive process in which proponents of different models challenge each other’s models and refine their own leads to ‘fitter’ models (using evolutionary terms). However these models are adapted to the empirical facts which in turn are a byproduct of the initial enquiries in this area.In this manner, mathematics might offer the best ‘starting conditions’ for this philosophical enquiry as these starting conditions give philosophical enquiry the least opportunity for diverging from reality using such an approach.

Secondly fitter theories might well diverge significantly from an explanation of reality depending on their starting conditions although there might be other phenomenon which curtail that line of enquiry as this divergence becomes more evident. What this would also mean is that the development of the most effective scientific theories is not only a measure of how effectively a theory fits with the empirical data but is also a marker of how effectively a theory keeps the focus on the empirical data in which the theory initially flourished as well as a measure of how effectively the theory recruits and retains proponents.

References

Thomas Kuhn. The Structure of Scientific Revolutions. Narrated by Dennis Holland. (Paperback originally published in 1962). Audible. 2009.

Appendix

For a review of the Introduction see here.

For a review of Chapter 1 see here.

For a review of Chapter 2 see here.

For a review of Chapter 3 see here.

For a review of Chapter 4 see here.

For a review of Chapter 5 see here.

For a review of Chapter 6 see here.

For a review of Chapter 7 see here.

An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Purpose in Life and Rheumatoid Arthritis

The paper reviewed here is a 2008 paper purpose in life in patients with rheumatoid arthritis by verduin and colleagues and freely available here. Purpose in life while intuitively obvious is slightly trickier to define explicitly relating to the much broader category of meaning in life. This is reflected in the introduction where the authors discuss the similar usage of purpose in life and meaning.  They also recognise that both terms relate to motivation, the moral self as well as the move towards achieving aims which transcend the self. In this cross sectional study, the researchers use two measures of purpose in life. These are the
1. The purpose in life test. This is based on the work of victor frankl the existential psychotherapist. This is a 20 item instrument using a 7 point likert scale. The questions focus for example on goals, aims, meaning and purpose. A high score on the test indicates a high sense of purpose.
2. The purpose in life susbscale of the psychological wellbeing scale.  There are 20 questions which look for instance at making plans for the future and consideration of whether daily activities are trivial.
The researchers wanted to investigate the role of purpose in life in rheumatoid arthritis. In the previous literature they have reviewed they argue that coping mechanisms have not been evaluated as an important confounder. The researchers have recruited 300 people with Rheumatoid arthritis randomly from the rheumatology outpatient department. This may suggest that the sample group had a more severe form of rheumatoid arthritis if they were not being managed solely in primary care. The rating scales had been translated into Dutch although it wasnt clear on whether the Dutch version had been validated.  The researchers used the Health Assessment Questionnaire, the RAND 36 questionnaire (a measure of quality of life) and visual analogue ratings of disease activity, pain and fatigue. They also used a measure of coping in life.

The researchers sent out questionnaires to all 300 participants and received 52 percent of them back. The average age of participants was 60 with an average disease duration of 10 years. Encouragingly there was a good correlation between the purpose in life questionnaire results (spearmanns r = 0.62 p less than 0.001). Table 3  in the paper shows the relationship between the two purpose in life scales amd a number of sociodemographic factors. Interestingly the purpose in life outcome measure is related to leisure or social activities suggesting a concrete example of behaviours that correlate with the scale construct. In table 4, rather disappointingly there is no significant relationship between the purpose in life scale results and the main physical outcome measures although there is a significant relationship with the RAND summary scale mental health outcome measures in the expected direction. This makes it difficult to interpret the findings of a relationship between purpose and reduced pain and fatigue as they might properly be considered part of the secondary analysis in which case a correction for muliple comparisons may be needed. This is also a cross-sectional study which precludes the establishment of causality.

In conclusion, in the primary analysis there isn’t a relationship between the Purpose in Life outcome measures and the main physical outcome measures although there is a relationship with the mental health outcome measures. The secondary analysis suggests that subjective pain anf functioning may be correlated with purpose in life measures but this occurs in the context of the negative result in the primary analysis. A large randomised longitudinal study would be helpful in investigating this further.

Appendix

Having a Purpose in Life and the Risk of Cognitive Decline

Having a Purpose in Life Reduces the Risk of Death

An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

An Investigation of D3 Receptors and Brodmann Area 1 in Schizophrenia

The paper reviewed here is ‘Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia’ by Claudia Schmauss and colleagues and freely available here. I’ve selected this paper as the the researchers have some interesting findings in  a part of the brain known as the Somatosensory Cortex and more specifically in Brodmann Area 1. The study focuses on the question of whether schizophrenia results from a variation in a chemical receptor in the brain known as the D3 receptor. Know this paper is from 1993 and the sceptical reader will suggest that it must be irrelevant to the current debate in this area. In some regards this is true but 17 years on and some of the very basic questions in this debate remain unanswered. The research was undertaken at a time when there were lots of studies coming out with conflicting results although many were finding no evidence of a relationship between the D3 receptor and Schizophrenia (e.g this study finding no homozygosity in the D3 gene in people with Schizophrenia). While seemingly esoteric the question is of great importance in the development of drugs targetting this receptor. For instance this study showing that D3 receptors are occupied by typical antipsychotic drugs in addition to D2 receptors. Indeed a lot of the research has focused on Amisulpride as this is a selective D2/D3 antagonist as in this study looking at the efficacy in terms of psychopathology. The partial agonist properties of Aripiprazole at the D3 receptor have been similarly investigated as in this 2008 paper. In a review in 2006, the authors note that there is evidence of an association between the D3 receptor and substance misuse, cognitive deficits and schizophrenia.

As research in this area has progressed the findings have become more complex. The D3 receptor seems to play a role in the development of Tardive Dyskinesia which is sometimes seen as a side-effect of antipsychotics or can occur even in those who are neuroleptically naieve. This study in 2003 for instance finds evidence of a relationship with the D3 receptor although due caution is advised in this meta-analysis from 2006. A Russian study complicates the discussion by showing a relationship between the D3 Ser9Gly allele and limb-truncal but not orofacial Tardive Dyskinesia. Studies looking at specific brain regions have been undertaken including this 2006 study showed an association between D3 binding in the frontal cortex and positive psychotic symptoms in 20 people with schizphrenia. A story develops as knowledge about alleles become available. For instance an excess of a specific allele -7685-C was found in a Basque study of people with schizophrenia or schizoaffective disorder in 2005. The investigations have been extended to Alzheimer’s Disease with a relationship between the D3 receptor and psychotic symptoms evident in this 2004 paper  and this 2009 paper showing a relationship between striatal D2/D3 receptor availability and delusions in Alzheimer’s Disease. Returning to the main question though negative studies of ser9Gly polymorphism in Schizophrenia still persist as in this 2008 study. This 2010 Japanese paper combines a study with a meta-analysis and fails to find supporting evidence of a relationship between the D3 receptor and Schizophrenia. The researchers note that the previous studies have a small sample size.

Turning to the present study the authors undertook a post-mortem on a group of people who when they were alive had been diagnosed with schizophrenia and compared them to a control group and a group with Alzheimer’s Disease.  A diagnosis had been made retrospectively using the casenotes and the DSM-III criteria with the main subtypes being paranoid schizophrenia (n=8) and disorganised schizophrenia (n=4). The researchers selected Brodmann Areas 1-5 to study. The brains were dissected. The researchers obtained the RNA from the cells in the sections. They used a reverse transcriptase from a murine leukemia virus to engineer the complementary DNA sequences (cDNA) and then used a polymerase chain reaction (PCR) to amplify the cDNA before separating out the products using Southern Blotting. The researchers had identified both the mRNA sequence for the D3 receptor and a slightly different sequence. They questioned if this second sequence even acted as a G-Coupled receptor as it differed significantly at the Carboxyl Terminus. The main findings were that people with schizophrenia did not have mRNA sequences for the D3 receptors in several areas of the brain corresponding to the motor and somatosensory cortex when compared with the control group. The researchers comment on another group with affective disorder. They too were lacking in the D3 mRNA in the somatosensory cortex (although I think the researchers were slightly cheeky to include these results as it sounds as though the data is from another study which hadn’t yet been published). The group with Alzheimer’s Disease and the control group did have mRNA for the D3 receptors in the somatosensory and motor cortex. Perhaps the findings in both affective disorders and schizophrenia suggests that the medication they were taking over the course of the illnesses may have impacted on the mRNA expression. Alternatively it could of course represent a shared feature of the pathology independent of treatment. The findings in the group with Alzheimer’s Disease are interesting in light of the other studies described above and I note that the there is no reference to psychotic symptoms which would help to contextualise the results. Nevertheless these are interesting findings and as we can see from the above papers including the 2010 meta-analysis the debate about D3 receptors and Schizophrenia is still ongoing although the tool used to answer the questions have moved on.

 

Appendix – Brodmann Areas

Area 6 (Agranular Frontal Area 6)

FDG-PET, Frontal Dysfunction and Mild Cognitive Impairment

Areas 13 and 14 (Insular Cortex)

What does the Insular Cortex Do Again?

Insular Cortex Infarction in Acute Middle Cerebral Artery Territory Stroke

The Insular Cortex and Neuropsychiatric Disorders

Developing a Model of the Insular Cortex and Emotional Regulation Part 1

Developing a Model of the Insular Cortex: A Recap

The Relationship of Blood Pressure to Subcortical Lesions

Pathobiology of Visceral Pain

Interoception and the Insular Cortex

A Case of Neurogenic T-Wave Inversion

Video Presentations on a Model of the Insular Cortex

MR Visualisations of the Insula

The Subjective Experience of Pain*

How Do You Feel? Interoception: The Sense of the Physiological Condition of the Body

How Do You Feel – Now? The Anterior Insula and Human Awareness

Role of the Insular Cortex in the Modulation of Pain

The Insular Cortex and Frontotemporal Dementia

A Case of Infarct Connecting the Insular Cortex and the Heart

The Insular Cortex: Part of the Brain that Connects Smell and Taste?

Stuttered Swallowing and the Insular Cortex

Area 15 (Anterior Temporal Lobe – Controversial Area in Humans)

Review: The Anterior Temporal Lobes and Semantic Memory

Area 27 (Piriform Cortex)

Anosmia in Lewy Body Dementia

Area 28  (Entorhinal Cortex)

MRI Measures of Temporoparietal Atrophy During Prodromal Alzheimer Disease*

Areas 45, 46, 47 (Inferior Frontal Gyrus)

Which Bit of the Brain Detects the Emotions in Speech?

Medial Temporal Lobe

The Medial Temporal Lobe and Recognition Memory

Hippocampus

Review: Differences in Hippocampal Metabolism Between Amnestic and Non-Amnestic MCI Subjects

Anatomy of the Hippocampus

Review: Involvement of BDNF in Age-Dependent Alterations in the Hippocampus

Miscellaneous Subcortical Structures

Book Review: Subcortical Vascular Dementia

Review: Subcortical Vascular Ischaemic Dementia

Review: Psychiatric Disturbances in CADASIL

Review: Cognitive Decline in CADASIL

Review: Relationship Between 24-hour Blood Pressure, Subcortical Ischemic Lesions and Cognitive Impairment

Hypocretin and Neurological Disorders

A Case of Pontine and Extrapontine Myelinolysis with Catatonia

Generic Articles Relating to Localisation

A History of Human Brain Mapping

Book Review: Brain Architecture

Brain Folding and the Size of the Human Cerebral Cortex

An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.