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Biomedical subjects

F M Corrigan

Publications and source records attributed to F M Corrigan.

At least 19 recordsLinked to original sources

Psychotherapy as assisted homeostasis: activation of emotional processing mediated by the anterior cingulate cortex.

Although psychotherapy is successful in altering emotional distress, the biological mechanism by which it achieves this has not been the subject of intensive neurobiological investigation. Mindful processing of emotion has been proposed [Mindfulness-Based Cognitive Therapy for Depression, The Guilford Press, New York, 2002] to be a key factor in prevention of relapse in depressive illness and here that hypothesis is developed and extended to include other conditions in which emotion processing may be obstructed or dysregulated. Cognitive therapy, interpersonal psychotherapy, psycho-dynamic psychotherapy and dialectical behaviour therapy, each in a different way and with a distinct emphasis, encourage awareness of emotions and their associated cognitions and biographies, and their varying success may depend on the degree to which they achieve activation of internal healing processes. In eye movement desensitisation and reprocessing (EMDR), the selected target is formatted for endogenous processing which is facilitated and accelerated by eye movements or alternating bilateral auditory or tactile stimulation. The ability to sustain focussed attention on the affect and its visceral, cognitive and biographical components is postulated to activate a homeostatic process of distress resolution, seen most clearly in treatment of post-traumatic stress disorder (PTSD) with EMDR, in which resolution of distress can be intense and rapid while therapist input is non-directive, although supportive, empathic, and non-judgemental. Once the therapist has helped to frame the questions, the patient's brain will find the answers needed for the resolution of the distress and all the components of the traumatic event, whether visceral, cognitive, affective or interpersonal. The anterior cingulate cortex, especially the dorsal and rostral components, is suggested to be the key neurobiological substrate for the efficacious psychotherapeutic relief of distress, and relevant functional neuroimaging studies are summarised. One limitation of some previous imaging studies of emotion is that they have tended to use mild stimuli to discrete emotions. An alternative approach would be to image the brain during reprocessing of an unpleasant event which has profoundly affected the person so that the associated intense emotions could be clearly labelled and correlated with changes in regional brain functioning.

Affective Symptoms↗

Organochlorine insecticides in substantia nigra in Parkinson's disease.

The concentrations of organochlorine (OC) compounds in the substantia nigra (SN) were compared in Parkinson's disease (PD) with concentrations in brain from cortical Lewy body dementia (CLBD), Alzheimer's disease (AD), and nondemented nonparkinsonian controls (CON). The levels of the gamma isomer of hexachlorocyclohexane (gammaHCH, lindane) were significantly higher in PD tissues (mean +/- SD: 0.56 +/- 0.434 microg/g lipid) than in the other three groups (CLBD 0.052 +/- 0.101 microg/g lipid; AD none detected; CON 0.125 +/- 0.195; all differences from PD significant at p < .05, Mann-Whitney U-test). Dieldrin (HEOD) was higher in PD brain than in AD or control brain, while 1,1'-(2,2-dichloroethenyl diene)-bis(4-chlorobenzene) (p,p-DDE) and total Aroclor-matched polychlorinated biphenyls (matched PCBs) were only higher in PD substantia nigra when these concentrations were compared with those of CLBD. These findings are not inconsistent with the hypothesis derived from epidemiological work and animal studies that organochlorine insecticides produce a direct toxic action on the dopaminergic tracts of the substantia nigra and may contribute to the development of PD in those rendered susceptible by virtue of cytochrome P-450 polymorphism, excessive exposure, or other factors.

Alzheimer Disease↗

The role of dysregulated amygdalic emotion in borderline personality disorder.

Borderline personality disorder (BPD), is a condition that has a high mortality and is associated with much distress for the sufferers as well as with difficult management problems for health professionals. Taking emotional dysregulation as the core feature of BPD, the authors propose that the disorder arises from impaired modulation of subcortical inputs to consciousness. We hypothesize that the amygdaloid complex, and its connections with thalamus, cingulate cortex and insular cortex are critical in the development and maintenance of the disorder. If this is the case, peptides such as galanin, somatostatin and cholecystokinin will be the most important neurotransmitters, thus explaining the relative lack of efficacy of standard antipsychotic and antidepressant drugs.

Affective Symptoms↗

Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's disease.

As it had previously been demonstrated that there were reduced brain dopamine concentrations in monkeys who had been given polychlorinated biphenyls (PCBs) chronically, we hypothesized that organochlorine compounds in general, and PCBs in particular, might be important in the pathogenesis of Parkinson's disease (PD). In a study of caudate nucleus obtained post mortem from patients with Parkinson's disease and from controls, there were significantly higher concentrations of the organochlorine insecticide dieldrin and the PCB congener 153 in the PD tissue. DDE, PCB congener 180, and total PCBs (matched with a commercial preparation) also tended to be higher in Parkinson's disease tissue. We think that this is important preliminary evidence that diorthosubstituted PCBs may contribute to the pathogenesis of Parkinson's disease, and a greater presence of organochlorine insecticides in the PD tissue suggests that this may be in part the explanation for the association between PD and rural living.

Animals↗

Depression: immunological resignation of the will to live?

Evolution is assumed to promote the survival of the fittest by the greater success of the reproductive potential of those with the characteristics most suited to their environment. Little thought is given to how those least adapted fail to survive to reproduce. If the species, rather than the individual, has a drive to adaptation and survival, there should be a specific mechanism for those least adapted to withdraw from life. The immunological changes accompanying depression may facilitate heart disease, infection, parasitic infestation or other ill health, so that depression is a mechanism for those least resilient, or faced with most adversity, to succumb to illness. If depression is a state facilitating withdrawal from competition for reproductive success, major depressive illness may be the inappropriate and spontaneous occurrence of a mental state which has advantages for the species in allowing those 'least fit' to fail to survive. This hypothesis gives an empirically testable challenge to the view that the species has no evolutionary drive to survival and increased adaptedness to the environment, as well as explaining the more and more frequent occurrence of a specific mental state and its associated changes in the immune system.

Attitude to Health↗

High density lipoprotein fatty acids in dementia.

High density lipoproteins (HDL) are small plasma particles which may be able to pass through the blood-brain barrier. We have therefore studied the fatty acids of HDL in patients with dementia to determine whether the changes are consistent with those previously reported in brain tissue. The HDL phospholipid and the HDL cholesteryl ester both showed reduced concentrations of arachidonic acid (20:4n6) as compared to normal controls. HDL may be a useful plasma fraction for study of lipids in neurodegenerative diseases.

Aged↗

Abnormal content of n-6 and n-3 long-chain unsaturated fatty acids in the phosphoglycerides and cholesterol esters of parahippocampal cortex from Alzheimer's disease patients and its relationship to acetyl CoA content.

The long-chain fatty acid composition of cholesterol esters, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI) from parahippocampal cortex of Alzheimer's disease (AD) patients and control subjects was examined. In general the PC fraction contained less polyunsaturated long-chain fatty acids than did PE, PS or PI. Of the n-6 polyunsaturated long-chain fatty acids, PI contained the greatest incorporation of these acids followed by PE. There were significant differences between controls and AD patients in total n-6 EFAs. Arachidonic acid (C20:4n-6) was the predominant fatty acid of this family found to be present. In AD, PE and PS showed a deficit of adrenic acid (C22:4n-6) content and PE also contained less arachidonic acid. In AD subjects, the cholesterol esters contained significantly less n-3 polyunsaturated fatty acids with, specifically, a reduction in alpha-linolenic acid. Acetyl CoA content of hippocampal cortex was greater in AD patients than in control subjects indicating either an increased extent of oxidative metabolism or a failure to utilise acetyl CoA for anabolic processes. Abnormal magnitude of oxidative processes could give rise to the biosynthesis of PE and PS species containing less n-6 polyunsaturated fatty acids than occurs in control subjects.

Acetyl Coenzyme A↗

Parapsychotic grief, theory of mind and the concept of the soul.

The ability to deceive is regarded as the best evidence of the cognitive ability separating humans from other primates. An alternative would be to look at the concept of the soul, which has an archetypal significance, emerging in various geographically remote cultures over the course of history. The soul will be an elusive but not an impossible concept to study with neuroimaging. In parapsychotic grief the decreased may appear to the bereaved person without these hallucinations being considered as indicative of mental illness. If this is the sort of normal human experience which has led to the emergence of the belief in the immortality of the soul it may be a useful starting point for defining the neuroanatomical basis of souls which do not necessarily seek to deceive. As the human prefrontal cortex expanded and developed and strove to understand mental activity derived from subcortical structures the human attained an awareness of his own mind which has been construed as a separable insubstantial but indestructible entity. This idea would be bizarre if it were not archetypal and therefore must be closely linked to the development of the human central nervous system.

Grief↗

Organotin compounds in trimethyltin-treated rats and in human brain in Alzheimer's disease.

As blood tin concentrations are elevated in Alzheimer's disease and as some low molecular weight organotin compounds are neurotoxic, we have attempted to detect organotins in brain in Alzheimer's Disease. First we measured the concentration of trimethyltin (TMT) in the brains of rats which had been exposed to memory-impairing concentrations of TMT and, as the method of linking hydride generation, cryogenic trapping, gas chromotographic separation and atomic absorption spectrophotometric detection permitted the measurements of organotin compounds when the total tin was greater than 0.2 nanograms, we applied these techniques to human brain tissue, some of which showed neuropathological evidence of Alzheimer's Disease. No low molecular weight organotin compounds were detected in the human brain tissue, but it is possible that tin may be complexed with large organic molecules, the hydrides of which would not be volatile, but which could be identified by liquid chromatography.

Aged↗

Organochlorine compounds in human brain.

Having observed polychlorinated biphenyls (PCBs) in brain tissue obtained post mortem from two men we have carried out a study of organochlorine compounds in frontal cortex from patients with Parkinson's disease (PD) and from controls. No PCBs were found in any of those samples. There was no difference in the concentration of the DDT metabolite pp'-DDE in the PD brain samples. Dieldrin (HEOD) was significantly decreased in PD brain when analysed by lipid weight. While these findings would not support the hypothesis that PCBs may contribute to the development of Parkinson's disease in humans it remains possible that they may cause damage to the basal ganglia before being displaced from brain tissue.

Aged↗

Neurasthenic fatigue, chemical sensitivity and GABAa receptor toxins.

Following observation of fatigue syndromes in people who have been occupationally exposed to pesticides and insecticides which exert their toxicity through the GABAa receptor, we have formulated the hypothesis that fatigue syndromes in general may be secondary to altered sensitivity of the GABAa receptor. We discuss the possible involvement of organochlorine compounds which are widespread in the environment. Organophosphate compounds may have similar toxic effects through damaged cholinergic input to the dentate gyrus of the hippocampus where cholinergic and GABAergic transmission are closely linked.

Adult↗

Hippocampal tin, aluminum and zinc in Alzheimer's disease.

The use of inductively coupled plasma source mass spectrometry (ICP-MS) for multi-element analysis has led to the observation, in two separate studies, of increased blood tin in Alzheimer's disease (AD). We have therefore applied the technique of ICP-MS to hippocampal tissues obtained post-mortem from patients with AD and from controls. There was no significant difference in tin concentrations in AD. There were increased concentrations of aluminum and silicon, and reduced concentrations of zinc and selenium. It is postulated that displacement of hippocampal zinc by heavy metals may be important in producing clinical memory disturbance. However, analysis of the CA1 region, rather than of the dentate gyrus, would have been preferable.

Aged↗

Cholesterol metabolism and violence: a study of individuals convicted of violent crimes.

To examine the relationship between plasma lipoproteins and apolipoproteins in men with convictions for violent offences, blood was obtained from 15 men with a history of violence who were serving prison sentences for violent offences, and 25 age-matched male controls from the staff of the Argyll and Bute Psychiatric Hospital, who had no criminal records. The two groups did not differ in plasma total cholesterol concentrations, HDL-C, LDL-C, VLDL-C or in HDL subfractions. The most significant differences in the offenders were higher apoprotein AIV (3.62 vs 0.85: p = < 0.000001) and higher apoprotein E (7.70 vs 5.19: p = < 0.0002).

Adult↗