Polymorphism of the tryptophan hydroxylase 2 (TPH2) gene is associated with chimpanzee neuroticism.

In the brain, serotonin production is controlled by tryptophan hydroxylase 2 (TPH2), a genotype. Previous studies found that mutations on the TPH2 locus in humans were associated with depression and studies of mice and studies of rhesus macaques have shown that the TPH2 locus was involved with aggressive behavior. We previously reported a functional single nucleotide polymorphism (SNP) in the form of an amino acid substitution, Q468R, in the chimpanzee TPH2 gene coding region. In the present study we tested whether this SNP was associated with neuroticism in captive and wild-born chimpanzees living in Japan and Guinea, respectively. Even after correcting for multiple tests (Bonferroni p = 0.05/6 = 0.008), Q468R was significantly related to higher neuroticism (ß = 0.372, p = 0.005). This study is the first to identify a genotype linked to a personality trait in chimpanzees. In light of the prior studies on humans, mice, and rhesus macaques, these findings suggest that the relationship between neuroticism and TPH2 has deep phylogenetic roots.

[Experience in using the latent activity of leukocytic lactate dehydrogenase isoenzymes for the integral estimate of the level of free radical oxidation in patients with neurotic disorders].

The aggregatory properties of a leukocytic homogenate were studied by analyzing the activity of its lactate dehydrogenase (LDH) isoenzymes from patients with neurotic disorders on admission and during treatment. As a parameter reflecting the aggregatory properties of the leukocytic homogenate, the latent activity of LDH isoenzymes was studied. On admission, the patients were shown to have a lower latent activity, which restored during treatment to the control values, than in the control group. There was also a synchronous pattern of a change in the osmotic stability of red blood cells with the latent activity of leukocytic LDH isoenzymes in the treated patients. It is obvious that latent activity values reflect the level of free radical oxidation in the body. For detailed testing of the aggregatory properties of a cellular lysate, the trends in the latent activity of LDH isoenzymes were examined, which failed to reveal an unambiguous recovery of the observed parameters during therapy. Based on the findings, the author discusses whether this method can be used to analyze the time course of changes in a psychopathological process and to predict its outcome.

Association analysis of MAOA and COMT with neuroticism assessed by peers.

There are several reported associations between depressive disorders, panic disorder, and obsessive-compulsive disorder (OCD) and a variety of polymorphisms in the monoamine oxidase A (MAOA) gene. Associations have also been reported between the catechol-O-methyltransferase (COMT) gene and both OCD and bipolar depression. However, the role of these markers has not been explored for the personality trait of neuroticism (N), a normally distributed quantitative trait, which is highly genetically correlated with anxiety and depression and may be a vulnerability to either type of disorder. We explored the possible role of MAOA, COMT, and their interaction on N using a selected extremes design. From a sample of 2,085 individuals, each assessed for N by two independent peers rather than using self-report questionnaires, we selected 57 individuals from the top 10% of scores, and 62 individuals from the bottom 10%. Using selected extreme low subjects as the controls, rather than an unselected control group gives roughly twice the power of a standard case-control design. We typed a functional variable number tandem repeat (VNTR) in the MAOA gene promoter, and a functional polymorphism in the coding region of the COMT gene. Two novel alleles in the MAOA VNTR were identified on the basis of their size, and their structure examined by sequencing analysis. We found weak evidence for association with COMT genotype, when the females and males were considered separately, and for MAOA genotype in males only. There was no significant interaction between COMT and MAOA.

Structural abnormalities and changes in Na,K-ATPase activity in erythrocyte membranes in patients with neurotic disorders.

We studied structural and metabolic characteristics of erythrocyte membranes in 19 patients with neurotic disorders (neurasthenia and dysadaptation). Microviscosity of the lipid phase in erythrocyte membranes increased in 13 patients, and Na,K-ATPase activity decreased in 6 patients. Various changes in test parameters are probably associated with different adaptive capacities of the organism under stress conditions.

[Correction by succinic acid of behavioral and physiological parameters of neurosis-like condition in white rats]. / Korrektsiia povedencheskikh i fiziologicheskikh pokazatelei nevrozopodobnogo sostoianiia belykh krys vvedeniem iantarnoi kisloty.

The neurosis-like state of white rats is accompanied by development of cerebral hypoxia. Negative symptoms of the neurosis-like state (behavioral, anatomic and energy) were decreased by per os administration of succinate (30 mg/kg) during the second half of the neurotization process. Succinate provided chiefly the delayed action on the system arterial tension, on the succinate dehydrogenase and NADH dehydrogenase activity. The effects depended on the propensity of a rat to the catatonic "freezing". The "freezing" was detected by a specific breathing pattern: a short inhale and a long pause. In "freezing" rats succinate corrected the system tension to a greater extent, while in "non-freezing" animals it corrected to a greater extent the succinate and NADH dehydrogenase activities. The positive effect of succinate administration is probably associated with its antihypoxic properties.

Genetic covariation of neuroticism with monoamine oxidase activity and smoking.

Variation in the personality trait of neuroticism is known to be affected by genetic influences, but despite a number of association studies, the genes involved have not yet been characterized. In a recent study of platelet monoamine oxidase in 1,551 twin subjects, we found a significant association between monoamine oxidase activity and scores on the Eysenck Personality Questionnaire neuroticism scale. Further analyses presented here indicate that both neuroticism and monoamine oxidase activity are associated with variation in smoking habits, and that adjusting for the effect of smoking strengthens the association between MAO and neuroticism. Analysis of the genetic and environmental sources of covariation between neuroticism, smoking, and monoamine oxidase activity show that approximately 8% of the genetic variance in neuroticism is due to the same additive genetic effects that contribute to variation in monoamine oxidase activity, suggesting that variation in neuroticism is associated in part with aspects of serotonin metabolism.

Platelet monoamine oxidase activity, ego strength, and neuroticism in soldiers with combat-related current posttraumatic stress disorder.

AIM: To assess possible differences in platelet monoamino oxidase-B (MAO-B) activity, ego strength, and neuroticism in combat-experienced soldiers with or without current posttraumatic stress disorder (PTSD). METHOD: The soldiers with current PTSD (N=36) and a control group of 34 healthy soldiers were matched in combat experience, time passed between combat experience and the study, demographic variables (age, marital status, education), and smoking status. Platelet MAO-B was assayed fluorometrically, ego strength was measured by the Croatian version of the Ego Identity Scale, and neuroticism by the N-scale from Eysenck's EPQ-R questionnaire. RESULTS: Soldiers with combat-related current PTSD had lower platelet MAO-B activity than the control group (9.1+/-3.9 vs. 11.9+/-4.0; p<0.05), as well as lower ego-strength (86.3+/-8.3 vs. 108.6+/-13.4; p<0.05) and higher neuroticism (23.5+/-13.2 vs. 5. 9+/-4.7; p<0.05). There was no association of ego strength or neuroticism with platelet MAO-B activity. CONCLUSION: Ego identity strength and emotional stability are associated with successful coping with combat trauma. The involvement of platelet MAO-B activity in biological basis of ego strength and neuroticism could not be demonstrated.

[The microcirculation and the succinate and NADH dehydrogenase activities of the brain in neurotic disorders of the higher nervous activity in white rats]. / Mikrotsirkuliatsiia i aktivnost' degidrogenaz SDG i NADH-DG mozga pri nevroticheskikh narusheniiakh vysshei nervnoi deiatel'nosti u belykh krys.

A correlation was made between microcirculation and energy metabolism in the brain of 50 neurotized rats. Neurotic disorders were defined by characteristics of conditioning, arterial pressure, breathing rate and heart rate. In vivo biomicroscopy revealed modification of the state of blood vessels at rest and inverted reaction of brain pial vessels of neurotized rats to bilateral occlusion of common carotid arteries. Ratio of activities of respiratory cycle enzymes (succinate and NADH-dehydrogenases) was indicative of hypoxic state of the animals under study.

[The normalizing effect of air ions on neuroticized rats with different typological behavioral characteristics]. / Normalizuiushchee vliianie aéroionov na nevrotizirovannykh krys s raznymi tipologicheskimi osobennostiami povedeniia.

The work was carried out in 98 white male rats weighting 200-250 g. Typological properties of behaviour were estimated by locomotor activity in the open field. Neurosis was induced by electro-pain irritation (15 min daily during 3 weeks), accompanied by the white noise (4 h daily). The rats were influenced by air ions generated by Chizhevsky air ionizer ("Elion-132") for 2 h daily during the period of neurotization. It was shown that the degree of some pathological changes in neurosis depended on typological properties of rats. Air ions were established to prevent completely development of physiological changes typical for the model of experimental neuroses, i.e., increase of arterial pressure, Hildebrandt index and gastric ulcer formation. Air ions significantly decreased the number of gastric mucous membrane erosions. Air ions normalized activity of respiratory enzymes (succinate dehydrogenase and NADH-dehydrogenase) in rat brain cells and activated their exploratory behaviour.

Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer's disease resemble embryonic development--a study of molecular forms.

The pattern of molecular forms of acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) separated by density gradient centrifugation was investigated in the brain and cerebrospinal fluid in Alzheimer's disease (AD), in human embryonic brain and in rat brain after experimental cholinergic deafferentation of the cerebral cortex. While a selective loss of the AChE G4 form was a rather constant finding in AD, a small but significant increase of G1 for both AChE and BChE was found in the most severely affected cases. Both in normal human brain and in AD a significant relationship could be established between the AChE G4/G1 ratio in different brain regions and the activity of choline acetyltransferase (ChAT). A similar decrease of the AChE G4 form as observed in AD can be induced in rat by experimental cholinergic deafferentation of the cerebral cortex. The increase in G1 of both AChE and BChE in different brain regions in AD is quantitatively related to the local density of neuritic plaques which are histochemically reactive for both enzymes. In human embryonic brain, a high abundance of G1 and a low G4/G1 ratio for both AChE and BChE was found resembling the pattern observed in AD. Furthermore, both in embryonic brain and in AD AChE shows no substrate inhibition which is a constant feature of the enzyme in the adult human brain. It is, therefore, concluded that the degeneration of the cholinergic cortical afferentation in AD as reflected by a decrease of AChE G4 is accompanied by the process of a neuritic sprouting response involved in plaque formation which is probably associated with the expression of a developmental form of the enzyme.

[The Na+,K(+)-ATPase activity in the brain structures of neuroticized rats differing by the threshold of nervous system excitability]. / Aktivnost' Na+,K(+)-ATFazy v strukturakh golovnogo mozga nevrotizirovannykh krys, razlichaiushchikhsia po porogu vozbudimosti nervnoi sistemy.

A 2-week neurotization of two rat lines formed a long-term stress and increased neuronal Na+,K(+)-ATPase activity in hippocampus, locus coeruleus and n. raphe dorsalis, whereas the glial enzyme activity was decreased in hippocampus and N. raphe dorsalis. (Line H). In rats with low threshold of excitability (line L), the decrease of the Na+,K(+)-ATPase activity occurred in n. raphe dorsalis and hippocampus. After a 15-day rest, the activity decreased in all the structures of the line rats, whereas in the line L rats the activity was still increased in hippocampal neurons. Differences between the rat lines and dependence of the enzyme activity on the functional state of the nervous system, are discussed.

[Determination of fucokinase activity in the blood of schizophrenic patients]. / Bestimmung der Fukokinaseaktivität im Blut schizophrener Patienten.

An investigation was conducted into whether dopamine induces an alteration in the fucolysation of glycoproteins, starting from the dopamine hypothesis of schizophrenia and taking the fucokinase activity determined in erythrocytes of schizophrenic patients as parameter. As with patients with "schizoaffective psychosis" and those with manic-depressive disorders, who were likewise examined, it was found that the enzyme activity of schizophrenic patients was no different than that found in the blood of a control group.

Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity.

The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.

Plasma glutamate decarboxylase activity in neuropsychiatry.

Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses and neurologic diseases. Unmedicated schizophrenic patients showed no difference in plasma GAD levels compared to controls. Administration of neuroleptics together with anticholinergic agents increased plasma GAD activity in schizophrenic patients. Compared to controls, patients with major depression and bipolar illness showed significantly lower GAD activity. No effect of antidepressants and minor tranquilizers on plasma GAD activity was found. Relatively lower GAD activity was shown in neurotic patients. The enzyme activity in plasma of patients with Huntington's chorea (HC) was lower than control levels. The plasma GAD concentrations correlated with cerebrospinal fluid concentrations in five HC patients.

[Alteration of Ca2+, Mg2+-ATPase activity from rat hypothalamus and myocardium in development of the neurotic state]. / Izmeneniia aktivnosti Ca, Mg-zavisimoi ATf-azy v gipotalamuse i miokarde pri formirovanii nevroticheskogo sostoianiia u krys.

Simultaneous decrease of Ca2+, Mg2+-ATPase activity occurred in rat hypothalamus and myocardium during experimental neurosis. The decrease of the enzymatic activity was more distinct in hypothalamus than in myocardium. In hypothalamus the decreased enzymatic activity maintained within a week after completion of the excitation of the animals.

[Subcellular changes in the cortex of the motor analyzer and hippocampus of dogs with locally manifested neuroses]. / Subkletochnye izmeneniia v kore dvigatel'nogo analizatora i gippokampa sobak pri nevroze s lokal'nym proiavleniem.

In experiments on dogs with local neurosis-continuous flexion of the foreleg-changes were revealed in the beta-rhythm amplitude and the frequency of mean unit activity in the motor cortex, and the appearance and increased amplitude of the theta-rhythm in the hippocampus. Specific activity of Na+-K+-activated, and Mg2+-dependent ATPase decreases in subcortical fractions of the experimental animals' cerebral cortex by 55.0% in the synaptic membranes and 2 to 2.5 times in light and heavy synaptosomes, respectively. In similar fractions of the dorsal hippocampus, the activity of the enzyme decreases by 30.0% in the synaptic membranes and increases by 16.6% in the light synaptosomes and by 6.6% in the heavy ones.