T. G. Bolwig

QUANTITATIVE RATING OF DEPRESSIVE STATES

A step‐by‐step analysis of Becks and Hamiltons rating scales showed that both, scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Becks scale and six items of Hamiltons scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.

The caudate nucleus in obsessive—compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study

Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.

Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats†

Repeated maternal separation of rat pups during the early postnatal period may affect brain‐derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced‐swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age‐dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

How does electroconvulsive therapy work? Theories on its mechanism.

This article reviews 3 current theories of electroconvulsive therapy (ECT). One theory points to generalized seizures as essential for the therapeutic efficacy of ECT. Another theory highlights the normalization of neuroendocrine dysfunction in melancholic depression as a result of ECT. A third theory is based on recent findings of increased hippocampal neurogenesis and synaptogenesis in experimental animals given electroconvulsive seizures. Presently, the endocrine theory has the strongest foundation to explain the working mechanism of ECT.

Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome

Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmissions in frontal-subcortical circuits are involved in Tourettes syndrome. To test the hypothesis that the brains 5-HT2A receptor binding is increased in patients with Tourettes syndrome, PET imaging was performed. Twenty adults with Tourettes syndrome and 20 healthy control subjects were investigated with PET-[18F]altanserin using a bolus-infusion protocol. Regions of interest were delineated automatically on co-registered MRI images, and partial volume-corrected binding parameters were extracted from the PET images. Comparison between control subjects and Tourettes syndrome patients showed increased specific [18F]altanserin binding, not only in the a-priori selected brain regions hypothesized to be involved in Tourettes syndrome, but also post-hoc analysis showed a global up-regulation when testing for a overall difference with a randomization test (p<0.03). Increased 5-HT2A receptor binding was found not only in regions closely related to subcortical regions in patients with Tourettes syndrome, but also in most other brain regions. Our data suggest that the serotonergic transmitter system is pathophysiologically involved in Tourettes syndrome and that a clinical trial with 5-HT2A receptor antagonists may be justified.

Cognitive deficits in obsessive/compulsive disorder on tests of frontal lobe functions

Individuals with obsessive–compulsive disorder (OCD) display frontal lobe deficits, but there are inconsistencies between various tests of frontal lobe functions and between the results from different studies. The objective of this work was to characterize frontal lobe dysfunctions in OCD patients. Fifteen patients and 17 control subjects matched for age, sex and intelligence were tested on classic tests of frontal lobe functions [Wisconsin Card Sorting Test (WCST) and tests of fluency], a smell identification test and one computerized test: the Intra/Extra Dimension test. The Intra/Extra Dimension test showed a significant difference between the two groups in reversal of response. The test of Figural fluency showed a significant difference between the two groups in numbers of produced figures. There were no differences on the WCST, verbal fluency and the smell identification test.

Electroconvulsive therapy in melancholia: the role of hippocampal neurogenesis

Objective:u2002 To elucidate the relationship between the effects of electroconvulsive therapy (ECT) on hippocampal anatomy and function in the therapy of melancholic depression and preclinical observations of increased neurogenesis in the hippocampus of experimental animals receiving electroconvulsive seizures (ECS). We emphasize the role of hypercortisolaemia in melancholic depression and in experimental hippocampal neurogenesis.

Deep venous thrombosis and pulmonary embolism following physical restraint

Objective:u2002 We describe a case of deep venous thrombosis (DVT) and pulmonary embolism (PE) following the use of physical restraint in a patient with a diagnosis of acute delusional psychotic disorder.

Systemic oxidatively generated DNA/RNA damage in clinical depression: associations to symptom severity and response to electroconvulsive therapy.

BACKGROUNDnDepression has been associated with increased oxidative stress and hypothesized to accelerate aging. Nucleic acid damage from oxidation is a critical part of the aging process, and a suggested early event in age-related somatic morbidities that are also prevalent in depression, such as dementia and type 2 diabetes. We hypothesized that increased severity of depression is associated with increased systemic oxidatively generated DNA and RNA damage, and that this increase is attenuated by an effective antidepressant treatment.nnnMETHODSnThe urinary excretion of markers of systemic oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N=28), moderately depressed, non-medicated patients (N=26) and severely depressed patients eligible for electroconvulsive therapy (ECT) (N=29). In the severely depressed patient group, samples were also obtained 1 week after the completion of ECT.nnnRESULTSnSystemic RNA damage from oxidation, as measured by 8-oxoGuo excretion, was higher with increasing severity of depression (controls<moderately depressed<severely depressed) (P for trend=0.004). The 8-oxoGuo excretion was further increased after clinically effective ECT compared with pre-ECT values (P=0.006). There were no differences in 8-oxodG excretion between the groups or pre- vs. post-ECT.nnnLIMITATIONSnSmall sample size and the inclusion of both unipolar and bipolar patients in the severely depressed group.nnnCONCLUSIONSnSevere depression is associated with increased systemic oxidatively generated RNA damage, which may be an additional factor underlying the somatic morbidity and neurodegenerative features associated with depression. Due to the lack of normalization by clinically effective ECT, the phenomenon does not appear to be causally linked to the depressive state per se.

Electrophysiological subtypes of psychotic states

Objective:u2002 This research sought neurobiological features common to psychotic states displayed by patients with different clinical diagnoses.