The serotonin transporter in depressed patients: a qualitative study based on dissociation kinetics.
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Biomedical subjects
Publications and source records attributed to T G Bolwig.
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A quantitative autoradiographic study was made on the binding of the phosphatidylinositol system ligand [3H]inositol(1,4,5)-triphosphate (IP3) to forebrain sections from electroconvulsive shock (ECS)-treated rats. One group of rats was sacrificed 1 day and 1 month, respectively, after 12 ECSs administered three times weekly for 4 weeks. SHAM-stimulated rats served as controls. A single ECS did not change the [3H]IP3 binding in any of the brain regions examined. One day after the last of 12 ECSs, a decrease in [3H]IP3 binding (21%) was found within the CA1 region of the hippocampus and the piriform cortex (39%). In rats sacrificed 1 month after the last of 12 ECSs, the [3H]IP3 binding in piriform cortex had returned to control level. In the CA1 region of the hippocampus, the binding was still decreased (24%). It is possible that changes in the phosphatidylinositol system may play a part in the neurobiological events responsible for the therapeutic effect of electroconvulsive therapy.
The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients who had received surgical treatment, especially amygdalohippocampectomy (AHE), for the relief of medically intractable seizures. Forty-seven subjects, treated during the period 1987-1991 in the Danish epilepsy surgery programme (EPIKIR), entered a retrospective interview study. Of these, 37 had undergone AHE. Preoperative psychiatric morbidity was assessed through interview and available case notes, including a routine psychiatric interview. Postoperative psychiatric morbidity was assessed by the use of the Present State Examination. A total of six subjects (five AHE subjects) developed depressive disorders of various duration and severity after operation. In three subjects this occurred "de novo". No paranoid-hallucinatory psychoses developed within the follow-up period (a minimum of one year), and the presence of psychiatric disorders could not be associated with either lateralization of cerebral dominance of histopathological findings. Thus, depression appears to be the most frequent psychiatric problem following epilepsy surgery. Although the present study mainly deals with AHE, this finding is in accordance with the results of recent findings concerning anterior temporal lobe resection.
Positron emission tomography (PET) is a method for quantitative imaging of regional physiological and biochemical parameters. Positron emitting radioactive isotopes can be produced by a cyclotron, eg. the biologically important carbon (11C), oxygen (15O), and nitrogen (13N) elements. With the tomographic principle of the PET scanner the quantitative distribution of the administered isotopes can be determined and images can be provided as well as dynamic information on blood flow, metabolism and receptor function. In neurology PET has been used for investigations on numerous physiological processes in the brain: circulation, metabolism and receptor studies. In Parkinson's disease PET studies have been able to localize the pathology specifically, and in early stroke PET technique can outline focal areas with living but non-functioning cells, and this could make it possible to intervene in this early state. With positron emission tomography a quantitative evaluation of myocardial blood flow, glucose and fatty acid metabolism can be made as well as combined assessments of blood flow and metabolism. Combined studies of blood flow and metabolism can determine whether myocardial segments with abnormal motility consist of necrotic or viable tissue, thereby delineating effects of revascularisation. In the future it will probably be possible to characterize the myocardial receptor status in different cardiac diseases. The PET technique is used in oncology for clinical as well as more basic research on tumor perfusion and metabolism. Further, tumor uptake of positron labelled cytotoxic drugs might predict the clinical benefit of treatment.
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Obsessive-compulsive disorder (OCD) is a psychiatric illness, until recently considered a rare, mainly neurotic condition with poor prognosis. However, epidemiologic studies have shown that the condition has a 25-50 times higher frequency than previously assumed. A review of occurrence, phenomenology and comorbidity is given. Newer theories of etiology are discussed, underpinning neurobiological aspects of the illness. In its most severe forms OCD is a condition with a socially crippling course, but with the introduction of anti-depressants acting on serotonin reuptake the therapeutic possibilities have increased, especially when these drugs are given in combination with behaviour therapy.
Research in psychiatry with computed tomography, magnetic resonance, single photon emission computed tomography and positron emission tomography has until recently focused on schizophrenia. Results from the latest years suggest some of the same cerebral changes in affective disorder. Structural changes with enlargement of the lateral and third ventricles and broader sulci on the brain surface are frequently found in both patient groups compared to healthy volunteers. Areas with subcortical hyperintensity in the deep white matter and periventricular regions are frequently seen, especially in affective disorder bipolar patients, but seldom in schizophrenics. Functionally, the reduced activity in the prefrontal cortex in the depressive state is the most common finding together with hypoactivity in the left hemisphere. The aetiology and pathophysiological meaning of these brain changes remain unsolved.
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Increased levels of somatostatin (SS) and neuropeptide Y (NPY) have been demonstrated in the hippocampal formation after kindling. The increase might be specifically associated with kindling, or be an effect of repeated seizures per se. In order to separate these two components we studied the effects of repeated electroconvulsive shocks (ECS) on hippocampal SS-like and NPY-like immunoreactivity and SS mRNA and NPY mRNA in situ hybridization. ECS elicit seizures without having a demonstrable kindling effect. Rats were subjected to 10, 20, or 36 ECS (50 mA, 0.5 s), given as one shock per day, 5 days per week. One, 2 and 30 days after the last ECS, the rats were killed, together with sham-treated control rats, and processed for immunocytochemistry and non-radioactive in situ hybridization. There was a bilateral increase in SS-like and NPY-like immunoreactivity 1 and 2 days after the last ECS in the outer part of the dentate molecular layer. This is the terminal field of the hilar SS-containing and NPY-containing neurons, which displayed both increased immunoreactivity and hybridization signal of the cell bodies. There was also a bilateral de novo expression of NPY-like immunoreactivity in the mossy fiber system, but this was not accompanied by the appearance of a detectable NPY hybridization signal over the parent dentate granule cell bodies. The increase in SS-like immunoreactivity and hybridization signal was most pronounced in the rats that had received the largest number of ECS. This was not observed for the NPY-like immunoreactivity and hybridization signal, where the increase appeared similar after 10, 20 and 36 ECS.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced expression of the immediate early gene c-fos has been used as a marker of cellular activation in many different neuronal pathways. We wished to determine the neurochemical content and the connectivity of neurons, in which expression of c-fos is induced. For this purpose, a dual-immunocytochemical staining technique has been developed with avidin-biotin-peroxidase labelling using diaminobenzidine as the chromogen for c-fos protein located in the nucleus, and benzidine dihydrochloride (BDHC) in the presence of sodium nitroprusside to reveal cytoplasmic antigens (neuropeptide or retrograde tracer) in the same section. The blue granular BDHC reaction product in the cytoplasm combined with the homogeneous brown nuclear DAB staining for c-fos protein provides excellent resolution of dual-labelled cells even in tissue sections of 40 microns in thickness. The high sensitivity of the avidin-biotin-peroxidase immunocytochemistry and the stability of the reaction products provide an excellent tool for quantitative analysis of stimulated cells within a neurochemically defined cell group. The BDHC/DAB protocol was developed to identify activated cells in three experimental situations. Firstly, to investigate the phenotype of light-activated cells in the suprachiasmatic nucleus of the hypothalamus, c-fos protein DAB staining was carried out together with BDHC staining for peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP).(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of repeated electroconvulsive shock (ECS) on the activities of the three enolase isoenzymes present in rat brain: neuron specific enolase (NSE), non-neuronal enolase (NNE) and the hybrid enolase was investigated in piriform cortex. The activities were estimated on isoenzymes separated by agarose gel electrophoresis. Whereas the specific activities of NNE and hybrid enolase were unchanged in piriform cortex or ECS-treated rats the specific activity of NSE was increased by 16.3 percent (P < 0.02). The brain enolase isoenzymes are dimers of alpha- and gamma-enolase subunits. The calculated ratio between the gamma-subunit present in both NSE and hybrid enolase and the alpha-subunits present in both NNE and hybrid enolase was increased by 11.7 percent in piriform cortex of ECS-treated rats (P < 0.05). Previously, it has been shown that the gamma-subunit is only expressed in neurons whereas the alpha-subunit is expressed in both neurons and glial cells. The selectively increased expression of the enolase gamma-subunit in ECS-treated rats might either reflect an increased transcription of a whole group of neuronal genes or rather the trophic role of NSE in ECS-enhanced synaptic remodelling of the rat brain.
Repeated electroconvulsive stimulations represent one treatment modality for depressive disorders, but the mechanism leading to its effect is largely unknown. Studies of humans and rats have indicated that neuropeptide Y (NPY) is involved in major depression and anxiety. The purpose of the present investigation was to detect changes in the expression of preproNPY mRNA in the limbic cortex of rats exposed to electroconvulsive shocks (ECS) daily for 14 days. Twenty-four hours after the last ECS, the animals were sacrificed, brain sections were hybridized with a synthetic oligonucleotide probe complimentary to rat preproNPY mRNA. Semi-quantitative in situ hybridization histochemistry revealed an about ten-fold increase of preproNPY mRNA levels over the dentate gyrus and the piriform cortex in animals exposed to ECS compared to sham-treated controls. In the dentate gyrus dipped sections showed that the increase of gene expression took place in individual neurons in the polymorph layer. In the piriform cortex a moderate increase in the number of grains was observed over many individual cells in the pyramidal layer. These data show that the expression of preproNPY mRNA is markedly increased in specific brains regions after ECS, but whether this increase is a result of the ECS-induced seizures per se, or rather should be regarded as a protective adaptation to changes in neuronal activity pattern remains to be established.
Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT (computerized tomography) and rCBF (regional cerebral blood flow) as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.
OBJECTIVE: The purpose of this study was to evaluate whether ECT causes structural brain damage. METHOD: The literature review covered the following areas: cognitive side effects, structural brain imaging, autopsies of patients who had received ECT, post-mortem studies of epileptic subjects, animal studies of electroconvulsive shock (ECS) and epilepsy, and the neuropathological effects of the passage of electricity, heat generation, and blood-brain barrier disruption. RESULTS: ECT-induced cognitive deficits are transient, although spotty memory loss may persist for events immediately surrounding the ECT course. Prospective computerized tomography and magnetic resonance imaging studies show no evidence of ECT-induced structural changes. Some early human autopsy case reports from the unmodified ECT era reported cerebrovascular lesions that were due to agonal changes or undiagnosed disease. In animal ECS studies that used a stimulus intensity and frequency comparable to human ECT, no neuronal loss was seen when appropriate control animals, blind ratings, and perfusion fixation techniques were employed. Controlled studies using quantitative cell counts have failed to show neuronal loss even after prolonged courses of ECS. Several well-controlled studies have demonstrated that neuronal loss occurs only after 1.5 to 2 hours of continuous seizure activity in primates, and adequate muscle paralysis and oxygenation further delay these changes. These conditions are not approached during ECT. Other findings indicate that the passage of electricity, thermal effects, and the transient disruption of the blood-brain barrier during ECS do not result in structural brain damage. CONCLUSIONS: There is no credible evidence that ECT causes structural brain damage.
A 27-year-old man positive for human immunodeficiency virus (HIV) presented with severe depressive stupor, peripheral neuropathy, and myelopathy. The onset of psychiatric symptoms, closely followed by neurological symptoms, without other possible somatic etiology suggests that HIV itself might precipitate psychosis. The patient was treated successfully with electroconvulsive therapy. The advantages and risks are discussed.
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