Platelet monoamine oxidase activity in subjects tested for Huntington’s disease gene mutation

Summary. Monoamine oxidase activity (MAO) has been related to neuronal damage, since the oxidative deamination of biogenic amines produces free radicals that may enhance oxidative stress. Elevated enzyme activities in brain (MAO-A and MAO-B forms) and in platelets (MAO-B form) have been reported in several degenerative diseases, indicating that MAO activity may be involved in the disease progression. We estimated platelet MAO activity in a group of 59 patients (34 males) with HD, 20 subjects (7 males) at risk, and 29 (14 males) healthy subjects with positive family history for HD, categorized according to clinical features and the number of CAG repeat units (CAG-RN) at the Huntington gene. A group of 64 subjects (36 males) with negative family history for HD served as controls. In contrast to some previous studies, platelet MAO activities in both male and female patients (CAG-RN 40 to 62) with overt symptomatology, were not different compared to same sex control subjects. Subjects at risk (CAG-RN 39 to 52), though, showed significantly lower activities compared to same sex patients or controls. MAO activities seem to increase with disease progression, and tend to be higher in patients with dementia. The increases may be an epiphenomenon of disease pathology, but the possibility that an increase in the expression of the enzyme precedes the onset of the disease and contributes to enhanced oxidative stress should be considered in future longitudinal studies as a possible mechanism that accelerates disease progression.     

The interlocking finger test in patients with Parkinson’s disease and healthy subjects

The interlocking finger test (ILFT) is a bedside screening test in which the subject must imitate four bimanual finger gestures without symbolic meaning. We assessed the utility of the test in the cognitive evaluation of patients with Parkinson’s disease (PD). We evaluated 88 healthy subjects and 101 patients with PD using a simplified motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr and Schwab and England scales, Geriatric Depression Scale, Pfeffer Functional Activities Questionnaire, Clinical Dementia Rating, Mini-Mental State Examination, clock drawing test, digit span, word list battery of the Consortium to Establish a Registry for Alzheimer’s Disease assessment, Frontal Assessment Battery, semantic verbal fluency test, and the ILFT. Diagnoses of mild cognitive impairment and dementia were made using the Movement Disorder Society diagnostic criteria. ILFT scores in healthy subjects correlated significantly with age (p = 0.001) and only one healthy subject scored 2 in the test. ILFT scores were significantly lower in patients with PD and dementia (p = 0.001) and significantly correlated with cognitive and functional tests, but not with depressive symptoms (p = 0.607), Hoehn and Yahr scores (p = 0.907), or Schwab and England scores (p = 0.701). Twenty-five patients with dementia, three patients with mild cognitive impairment, and six patients with apparently normal cognition scored less than 3 in the ILFT. The area under the receiver operating characteristic curve for the ILFT to discriminate patients with dementia from those without it was 0.76 (cut-off score of 3/2: sensitivity of 61%, specificity of 0.85). In conclusion, the ILFT seems to be a useful bedside test to assess cognitive impairment in patients with PD.     

The monoamine oxidase B gene GT repeat polymorphism and Parkinson’s disease in a Chinese population

Monoamine oxidase B (MAOB) metabolises dopamine and activates neurotoxins known to induce parkinsonism in humans and primates. Therefore the MAOB gene (MAOB; Xp15.21-4) is a candidate gene for Parkinson's disease (PD). Longer length dinucleotide repeat sequences in a highly polymorphic GT repeat region of intron 2 of this gene showed an association with PD in an Australian cohort. We repeated this allele-association study in a population of 176 Chinese PD patients (90 men, 86 women) and 203 agematched controls (99 men, 104 women). Genomic DNA was extracted from venous blood and the polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis. There was no significant difference in allele frequencies of the (GT) repeat allelic variation between patients and controls (chi2 = 2.48; df = 5, P<0.75). Therefore the longer length GT repeat alleles are not associated with PD in this Chinese population. Possible reasons for the discrepancy between Chinese and Australian populations include a different interaction between this genetic factor and environmental factors in the two populations and the possibility that the long length GT repeat alleles may represent a marker mutation, genetically linked to another susceptibility allele in whites but not in Chinese. Methodological differences in the ascertainment of cases and controls in this cohort could also explain the observed differences. Further study is required to determine whether the longer length GT repeat alleles are true susceptibility alleles in PD.     

Small amygdala – high aggression? The role of the amygdala in modulating aggression in healthy subjects

Objective. Several lines of evidence suggest an association between the amygdala and the modulation of aggressive behaviour. Previous morphometric brain imaging studies have focused on the role of the amygdala in the context of pathologic neuropsychiatric conditions like depression, personality disorders, and dysphoric and aggressive behaviour in epilepsy. In order to better understand the physiological role of the amygdala in modulating aggressive behaviour we investigated the relationship between amygdala volumes and lifetime aggression in healthy subjects. Methods. Morphometric brain scans were obtained in 20 healthy volunteers. Amygdala volumes were measured by manually outlining the boundaries of the structure following a well established and validated protocol. Careful psychiatric and psychometric assessment was done to exclude any psychiatric disorder and to assess lifetime aggressiveness with an established and validated psychometric instrument (i.e. Life History of Aggression Assessment (LHA)). Results. All volunteers scored in the normal range of lifetime aggression. Volunteers with higher aggression scores displayed a 16–18% reduction of amygdala volumes. There was a highly significant negative correlation between amygdala volumes and trait aggression. Conclusion. The extent of volumetric differences in this study is remarkable and suggests that amygdala volumes might be a surrogate marker for the personality property of aggressiveness in healthy human beings.     

The active centers of monoamine oxidase types “A” and “B”: Binding with (14C)-clorgyline and (14C)-deprenyl

Summary The use of deprenyl, a monoamine oxidase (MAO) type B inhibitor, in potentiating the action of L-Dopa in the treatment of Parkinson's disease has attracted wide interest. Acetylenic amines as exemplified by pargyline, clorgyline, deprenyl and 3-dimethylamino-1-propylene have been called suicide inhibitors because an irreversible inhibition is produced by the action of the target enzyme on these compounds which act as substrates. MAO is a sulphydryl flavoprotein and nutritional iron is required for full enzyme activity. There is one mole of covalently bound flavin per mole enzyme. The isolated flavin is associated with the pentapeptide, Ser-Gly-Gly-Cys-Tyr. The mode of attachment is via the thio-ether of cysteine to the 8-position of the flavin, this being the case for the liver as well as the brain enzyme. The evidence that this enzyme exists in different functional forms which can be selectively inhibited by acetylenic inactivators prompted the study of the binding of inhibitors to the enzyme. It has been established that (¹⁴C)-clorgyline, (¹⁴C)-deprenyl and (¹⁴C)-2-phenylethylhydrazine (phenelzine) bind irreversibly and stoichiometrically (mole/mole) to the enzyme at its active centre. Substrates protect from inhibition. Isolation of (¹⁴C)-inhibitor adducts from fully inhibitor inactivated enzyme preparations after proteolytic digestion with Pronase/trypsin have shown that more than 90% of (¹⁴C)-inhibitor bound to the enzyme is associated with the MAO flavinpeptide adduct. Chemical and physical properties of the enzymatically derived (¹⁴C)-acetylenic-flavin-peptide adducts compared to model compounds suggest that the inhibitor binds with the 5-position N of the flavin.     

Ødegaard's selection hypothesis revisited: schizophrenia in Surinamese immigrants to The Netherlands

OBJECTIVE: The incidence of schizophrenia among Surinamese immigrants to the Netherlands is high. The authors tested ?degaard's hypothesis that this phenomenon is explained by selective migration. METHOD: The authors imagined that migration from Surinam to the Netherlands subsumed the entire population of Surinam and not solely individuals at risk for schizophrenia. They compared the risk of a first admission to a Dutch mental hospital for schizophrenia from 1983 to 1992 for Surinamese-born immigrants to the risk for Dutch-born individuals, using the Surinamese-born population in the Netherlands and the population of Surinam combined as the denominator for the immigrants. RESULTS: The age- and sex-adjusted relative risk of schizophrenia for the Surinamese-born immigrants was 1.46. CONCLUSIONS: Selective migration cannot solely explain the higher incidence of schizophrenia in Surinamese immigrants to the Netherlands.     

Variations in the monoamine oxidase-inhibitory activity (“tribulin?”) in pig's urine

Summary Sandler and his colleagues (see Sandler, 1982) have demonstrated the presence of an endogenous inhibitor of the enzyme monoamine oxidase (MAO) and of benzodiazepine receptor binding in the urine and blood plasma of man and rat. The concentrations of this material increased under stress conditions and it has been named tribulin. In the present experiments MAO-inhibitory activity was found in extracts of urine and plasma samples of domestic pigs. Evidence was obtained that the inhibitory activity was higher when pigs experienced slight discomfort. Thus it appears that pigs produce a substance similar to tribulin. It may become possible to use such MAO-inhibitory activity as an indicator in the assessment of interaction with the environment in pig husbandry.     

Physiological and biochemical principles underlying volume-targeted therapy—The “lund concept”

The optimal therapy of sustained increase in intracranial pressure (ICP) remains controversial. The volume-targeted therapy (“Lund concept”) discussed in this article focuses on the physiological volume regulation of the intracranial compartments. The balance between effective transcapillary hydrostatic and osmotic pressures constitutes the driving force for transcapillary fluid exchange. The low permeability for sodium and chloride combined with the high crystalloid osmotic pressure (approximately 5700 mmHg) on both sides of the blood-brain barrier (BBB) counteracts fluid exchange across the intact BBB. Additionally, variations in systemic blood pressure generally are not transmitted to these capillaries because cerebral intracapillary hydrostatic pressure (and blood flow) is physiologically tightly autoregulated. Under pathophysiological conditions, the BBB may be partially disrupted. Transcapillary water exchange is then determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Pressure autoregulation of cerebral blood flow is likely to be impaired in these conditions. A high cerebral perfusion pressure accordingly increases intracapillary hydrostatic pressure and leads to increased intracerebral water content and an increase in ICP. The volume-targeted “Lund concept” has been evaluated in experimental and clinical studies to examine the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.     

The clinical and biochemical investigation of L-deprenyl in Parkinson's disease with special reference to the “on-off” effect

Summary The effect of L-deprenyl in combination with L-Dopa was studied in 22 Parkinsonian patients, with various forms of on-off phenomena. L-deprenyl is a selective, irreversible inhibitor of monoamine oxidase type B, without tyramine potentiating property. The results were very encouraging with regard to amelioration of on-off effect. More than 80% of the patients with nocturnal akinesia, early morning akinesia, end-of-dose akinesia and non-dose-dependent akinesia, showed improvement. In 9 out of 22 patients, the off period disappeared. The platelet monoamine oxidase activity, which is of type B and similar to the brain enzyme, was fully inhibited by the daily dose of L-deprenyl. There was no significant change in serum prolactin level during the duration of 6 weeks' treatment with L-deprenyl.     

Semantic memory recognition is supported by intrinsic recollection-like processes: “The butcher on the bus” revisited

Dual-process models suggest that recognition memory is independently supported by recollection and familiarity. Current theories attribute recollection solely to hippocampally mediated episodic memory (EM), and familiarity to both episodic and semantic memory (SM) supported by medial temporal lobe cortex (MTLC) and prefrontal cortex. We tested whether, contrary to this view, recollection-like processes also intrinsically support SM recognition and whether MTL structures are involved in their execution. A semantic Process Dissociation Procedure (PDP) with famous and non-famous names was used in three experiments. Experiment 1 revealed that recollection-like processes in semantic memory were not associated with episodic memory for the public events, were predicted by performance on standard SM tasks and were independent of EM tasks, suggesting they are intrinsic to SM. Experiment 2 demonstrated the independence of the two process estimates by showing only familiarity was affected by shifting response criterion while only recollection estimates were significantly altered under divided-attention. Finally experiment 3 tested amnesic patients with varying degrees of hippocampal and MTLC damage. Despite normal overall fame recognition performance, recollection estimates were specifically affected by MTL damage. When damage was primarily hippocampal, only retrograde recollection estimates were reduced, while more extensive MTLC damage led to both retrograde and anterograde recollection deficits. We conclude that recognition of semantic information is supported by at least two independent processes akin to the ones that support EM recognition. Recollection-like processes are intrinsic to SM and likely do not reflect EM contribution to SM performance. Together with previous studies of recollection in remote memory, these data suggest that recollection is not a unitary phenomenon. In EM it involves autonoetic re-experiencing, and is supported by interaction of fronto-temporal networks; in EM and SM it supports retrieval of contextual/associative information regardless of consciousness type, and is dependent on intact MTL function. Familiarity processes and neural substrates may also differ between lifetime familiarity and within-session familiarity.     

The exercise redox paradigm in the Down’s syndrome: improvements in motor function and increases in blood oxidative status in young adults

Considerable evidence has indicated a pro-oxidant status in the brain of people with Down’s syndrome (DS), which may contribute to motor and cognitive impairments verified in this condition. On the other hand, previous studies addressing the role of physical exercise on oxidative stress and antioxidant status in DS have indicated conflicting results. Here, we investigated the effects of a supervised judo training of controlled intensity and monitored on the basis of lactate threshold on the blood oxidative stress status and motor coordination in 21 young adults with DS. The training extended over a period of 16 weeks and consisted of three sessions per week. The exercise improved the motor function and significantly decreased lactate production in the DS subjects. However, blood markers of oxidative damage to lipids (TBARS and lipid peroxides) and proteins (carbonyls) were increased by the judo training. Moreover, superoxide dismutase and catalase activity also increased, while glutathione peroxidase activity remained unaltered after exercise. These results reinforce the notion that physical exercise can improve motor disabilities in people with DS. More importantly, our findings demonstrate that the beneficial effects are accompanied by some degree of oxidative stress, suggesting that young adults with DS may be more susceptible to physical training-induced oxidative stress than adolescents with DS, which should be taken into account in physical training programs for this population.     

“Latent” infection with Toxoplasma gondii: Association with trait aggression and impulsivity in healthy adults

BackgroundLatent chronic infection with Toxoplasma gondii (T. gondii), a common neurotropic pathogen, has been previously linked with suicidal self-directed violence (SSDV). We sought to determine if latent infection with T. gondii is associated with trait aggression and impulsivity, intermediate phenotypes for suicidal behavior, in psychiatrically healthy adults.MethodsTraits of aggression and impulsivity were analyzed in relationship to IgG antibody seropositivity for T. gondii and two other latent neurotropic infections, herpes simplex virus 1 (HSV1) and cytomegalovirus (CMV). One thousand community-residing adults residing in the Munich metropolitan area with no Axis I or II conditions by SCID for DSM-IV (510 men, 490 women, mean age 53.6 ± 15.8, range 20–74). Plasma samples were tested for IgG antibodies to T. gondii, HSV-1 and CMV by ELISA. Self-reported ratings of trait aggression scores (Questionnaire for Measuring Factors of Aggression [FAF]) and trait impulsivity (Sensation-Seeking Scale-V [SSS-V]) were analyzed using linear multivariate methods.ResultsT. gondii IgG seropositivity was significantly associated with higher trait reactive aggression scores among women (p < .01), but not among men. T. gondii-positivity was also associated with higher impulsive sensation-seeking (SSS-V Disinhibition) among younger men (p < .01) aged 20–59 years old (median age = 60). All associations with HSV-1 and CMV were not significant.ConclusionsAggression and impulsivity, personality traits considered as endophenotypes for SSDV, are associated with latent T. gondii infection in a gender and age-specific manner, and could be further investigated as prognostic and treatment targets in T. gondii-positive individuals at risk for SSDV.     

The disposition of mentally disordered offenders in Australia: ‘Out of mind,out of sight’ revisited

The author surveys developments in the disposition of mentally disordered offenders since 1976. He focusses upon persons found mentally disordered or incompetent at or before trial, persons acquitted by reason of insanity and persons who become or are found mentally disordered after sentence. He concludes that the law in these areas remains in flux with different jurisdictions developing diverse initiatives resulting in major inconsistencies and in detainees seeking to avail themselves of international law.     

The right ear advantage revisited: Speech lateralisation in dichotic listening using consonant–vowel and vowel–consonant syllables

The dichotic listening task is typically administered by presenting a consonant–vowel (CV) syllable to each ear and asking the participant to report the syllable heard most clearly. The results tend to show more reports of the right ear syllable than of the left ear syllable, an effect called the right ear advantage (REA). The REA is assumed to be due to the crossing over of auditory fibres and the processing of language stimuli being lateralised to left temporal areas. However, the tendency for most dichotic listening experiments to use only CV syllable stimuli limits the extent to which the conclusions can be generalised to also apply to other speech phonemes. The current study re-examines the REA in dichotic listening by using both CV and vowel–consonant (VC) syllables and combinations thereof. Results showed a replication of the REA response pattern for both CV and VC syllables, thus indicating that the general assumption of left-side localisation of processing can be applied for both types of stimuli. Further, on trials where a CV is presented in one ear and a VC is presented in the other ear, the CV is selected more often than the VC, indicating that these phonemes have an acoustic or processing advantage.