Aron D. Mosnaim

Posttraumatic stress disorder in vietnam veterans clinical and EEG findings; possible therapeutic effects of carbamazepine

The adverse psychological effects of combat have been recognized since the Civil War, when they were generally viewed as transient anxiety reactions. After World War II intense attention focused on postwar syndromes, with special clinicai interest in reaction to stress related to battle. As a result of these studies, a diagnostic category “gross stress reaction” was included in DSM-I. Following the Vietnam War, it became evident that many veterans exhibited a complex mixture of psychiatric symptoms related to their combat experience, which often presented a diagnostic dilemma (Yager et al. 1984). The concept of posttraumatic stress disorder (PISD) was formalized with the establishment of explicit diagnostic criteria in the Diagnosis und ~r~fist~cul Manual of the American Psychiatric Association in 1980 (DSM-III). Critical comments on the validity of PTSD, however, have been raised by several investigators, who indicated that veterans with this condition could be classified into other existing diagnostic categories (Goodwin and Guze 1984). Psychophysiological (Blanchard et al. 1986) and psychological studies (Keane et al. 1984, 1985) have sought a more objective approach toward diagnostic assessment. Electroencephalographic (EEG) studies in patients with PTSD, however, are lacking. Many veterans with PTSD give a history of head trauma related to injuries sustained while in Vietnam, as well as to fights and accidents in civilian life. In this article, we describe the clinical EEG findings in our PTSD population, as well as preliminary data on the efficacy of carbamazepine in the treatment of this disorder. Carbamazepine was considered for the treatment of IO veterans with PTSD whose symptomatology included poor impulse control, violent behavior, and angry outbursts, as this drug has been reported to be effective in the treatment of agitation in mania and in episodic rage attacks (Petty 1986).

Isolation and characterization of phenylethylamine and phenylethanolamine from human brain

The Presence of endogenous 2‐phenylethylamine in mammalian tissues has long been suspected, in view of the fact that L‐phenylanine, a substrate for L‐aromatic amino acid decarboxylase (Lovenberg, Weissbach and Udenfriend, 1962), is found in substantial amounts in many neural and non‐neural tissues. It has been difficult to demonstrate the presence of phenylethylamine in tissues of untreated animals because this amine is an excellent substrate for monoamine oxidase (Mantegazza and Riva, 1963). Using paper chromatography and electrophoresis, Nakajima, Kakimoto and Sano (1964) tentatively identified phenylethylamine in many organs of animals pretreated with monoamine oxidase inhibitors. Phenylethylamine exerts, in animals pretreated with such inhibitors, behavioural stimulant effects similar to those induced by amphetamine (Mantegazza and Riva, 1963). These effects may in part be attributable to catecholamine release (Fuxe, Grobecker and Jonsson, 1967) and partly to a direct effect exerted by phenylethylamine itself (Fischer, Ludmer and Sabelli, 1967; Giardina, Pedemonte and Sabelli, 1972). The brain content of phenylethylamine in mice (Mosnaim and Sabelli, 1971), rabbits (Sabelli, Giardina, Mosnaim and Inwang, 1972) and rats (Fischer, Spatz, Heller and Reggiani, 1972) is increased by antidepressive treatments (imipramine, monoamine oxidase inhibitors, electroshock) and reduced by reserpine. The urinary excretion of phenylethylamine is decreased in depressed patients (Fischer, Heller and Miró, 1968; Boulton and Milward, 1971; Inwang, Sugerman, Mosnaim and Sabelli, 1972; Fischeret al., 1972).

Brain 2-phenylethylamine as a major mediator for the central actions of amphetamine and methylphenidate

Abstract 2-Phenylethylamine (PEA) was measured in rabbit brain by gas-liquid chromatography. D-Amphetamine sulfate (0.65 mg/Kg) initially reduced brain PEA levels to one-third of its usual content (30 min) and subsequently doubled brain PEA (4 hr). Brain PEA levels were reduced (30 min) and subsequently increased (ten-fold at 4 hr) by D-amphetamine sulfate (13 mg/Kg); tolerance to these two effects was observed in rabbits treated for three days with D-amphetamine. Methylphenidate HCl (30 mg/Kg) but not L-amphetamine sulfate (0.65 mg/Kg and 13 mg/Kg) induced a small, non-significant lowering of brain PEA (30 min) followed by a marked augmentation (4 hr) of brain PEA content. D-Amphetamine (30 min or 4 hr prior) increased the recovery of labeled PEA from the brain of rabbits injected intraventricularly with labeled phenylalanine, and reduced the recovery of labeled PEA after its intraventricular injection, suggesting that D-amphetamine accelerates both the synthesis and the disposition of brain PEA. Pretreatment with α-methyldopa (which depletes PEA and other brain amines) or with α-methyldopa hydrazine (which selectively reduces brain PEA content by inhibiting decarboxylase in peripheral tissues only) markedly reduced the CNS effects of D-amphetamine (behavioral stimulation in mice and rabbits, anti-convulsant effect in mice); these decarboxylase inhibitors enhanced the amphetamine-like effects induced by PEA in mice pretreated with a monoamine oxidase inhibitor. The ability of PEA depleters to selectively block the stimulant effects of D-amphetamine, together with the close structural and pharmacological similarities between amphetamine and PEA, and marked influence of amphetamine administration upon PEA brain levels, synthesis and metabolism, suggest to us that many of the central actions of amphetamine may be mediated by endogenous PEA.

Phenylethylamine in neuropsychiatric disorders

Phenylethylamine is an endogenous neuroamine conceptualized as the bodys natural amphetamine. PEA has been suggested to play a role in the etiology of several neuropsychiatric disorders. Increased PEA turnover in phenylketonuria contributes to the pathophysiology of this condition. Depressed and chronic paranoid schizophrenic patients show decreased and increased PEA urinary excretion, respectively. Parkinsonian patients show decreased urinary PEA excretion. In animals, drugs that relieve or produce depression and parkinson result in increased or decreased brain PEA levels, respectively. PEA has been postulated to play a role in the etiology of migraine headache and aggression.

A review of orthostatic blood pressure regulation and its association with mood and cognition.

AimsThis paper will review literature that examines the psychological and neuropsychological correlates of orthostatic blood pressure regulation.ResultsThe pattern of change in systolic blood pressure in response to the shift from supine to upright posture reflects the adequacy of orthostatic regulation. Orthostatic integrity involves the skeletal muscle pump, neurovascular compensation, neurohumoral effects and cerebral flow regulation. Various physiological states and disease conditions may disrupt these mechanisms. Clinical and subclinical orthostatic hypotension has been associated with impaired cognitive function, decreased effort, reduced motivation and increased hopelessness as well as dementia, diabetes mellitus, and Parkinson’s disease. Furthermore, inadequate blood pressure regulation in response to orthostasis has been linked to increased depression and anxiety as well as to intergenerational behavioral sequalae.Conclusions Identifying possible causes and consequences of subclinical and clinical OH are critical in improving quality of life for both children and older adults.

Cognitive functions in tardive dyskinesia

Cognitive functions of psychiatric patients with and without tardive dyskinesia were evaluated using the Wechsler Adult Intelligence Scale, Wechsler Memory Scale and Rey Auditory Verbal Learning Test. Schizophrenic patients with and without tardive dyskinesia did not differ in their performance on the administered psychological tests. However, affective disorder patients with tardive dyskinesia showed significantly more impairment on the Wechsler Memory Scale and Rey Auditory Verbal Learning Test than affective disorder patients without tardive dyskinesia. These findings suggest that affective disorder patients who develop tardive dyskinesia may have some predisposing brain damage or that tardive dyskinesia in these patients represents both a motor and a dementing disorder.

Pathways linkingl-phenylalanine and 2-phenylethylamine withp-tyramine in rabbit brain

Concentrations of labeled p-tyramine and 2-phenylethylamine were measured in rabbit brain 10 min after the intraventricular administration of either radioactive amine. In both cases the recoveries of the newly synthesized amine and of the unchanged precursor were significantly increased in animals pretreated with the monoamine oxidase inhibitor pargyline. Significant amounts of both amines were present in rabbit brain 10 min after the intraventricular injection of labeled L-phenylalanine. Pretreatment with pargyline increased their recoveries, whereas alpha-methyldopa (an L-aromatic amino acid decarboxylase enzyme inhibitor, L-AAADI) decreased them considerably, and no significant alteration was found in L-alpha-methyldopa hydrazine (a peripheral L-AAADI) pretreated animals. These results provide evidence for a new biochemical pathway in brain for p-tyramine biosynthesis, with L-phenylalanine (bypassing the formation of L-tyrosine) or 2-phenylethylamine as precursors. The significance and implications of these metabolic routes are discussed, especially considering that p-tyramine itself can be converted to catecholamines.

Biosynthesis of brain 2-phenylethylamine: Influence of decarboxylase inhibitors and d-amphetamine

Abstract 2-Phenylethylamine (PEA) is an endogenous brain amine which probably modulates affective behavior. Using a gas-liquid chromatographic method for the quantification of PEA (as its dinitrophenyl-sulfonic acid derivative), we found in rabbits 340.9 ± 45.8 ng of PEA/g of wet brain. Brain PEA levels were markedly decreased by the ip administration of 200 mg/Kg, 4 hrs before sacrifice, of the L-aromatic amino acid decarboxylase inhibitors α-methyldopa (28.2 ± 5.1 ng/g), L-α-methyldopa hydrazine (MK-486 [66.9 ± 13.0 ng/g]) or a combination of both (30.0 ± 3.3 ng/g). Since MK-486 inhibits only peripheral decarboxylase, brain PEA must be in part of peripheral origin. Another decarboxylase inhibitor, RO 4-4602 mg/Kg, 4 hrs before sacrifice) failed to affect brain PEA content. D-amphetamine (10 mg/Kg) induced a small depletion of PEA after 30 min in untreated animals; when given in combination with RO 4-4602, brain PEA content was markedly decreased. This supports the view that amphetamine releases PEA and stimulates its synthesis.

Enhancement of human natural killer cell activity by opioid peptides : similar response to methionine-enkephalin and β-endorphin

We studied the effect of methionine-enkephalin (MET) and beta-endorphin upon human peripheral blood lymphocyte natural killer cell (NKC) activity in a group of healthy volunteers (n = 27; 17 male and 10 female, age +/- SD and range of 32 +/- 6, 25-43 years and 36 +/- 11, 22-65 years, respectively). Aliquots from some individual samples were preincubated separately with different concentrations of either peptide (n = 12), while others were tested with only one of these substances (MET, n = 6; beta-endorphin, n = 9). Using each individual as its own control, MET (10(-8) and 10(-6) M) and beta-endorphin (10(-10) and 10(-8) M) significantly increased NKC activity (NKCA) (at least 20% over base value, effector-to-target cell ratio, 40:1) in 7 out of 15 and 7 out of 19 subjects, respectively. Results obtained from the rest of the samples were mixed, e.g., changes observed in NKCA were not significant or showed significance with only one of the peptide concentrations studied. Cells from individuals showing a significant increase in NKC lytic function following preincubation with either MET or beta-endorphin responded similarly to the other peptide (in both cases 5 out of 6 subjects), suggesting that enhancement of NKCA by MET and beta-endorphin may work through a similar mechanism.

Etiology and risk factors for developing orthostatic hypotension.

Orthostatic hypotension (OH) is regarded as a decrease primarily in systolic blood pressure on changing position from supine to erect. Based on clinical criteria, it is characterized by a decrease in systolic pressure of 20 mmHg and diastolic pressure of 10 mmHg within 1 to 3 minutes of standing after being supine. It is most prevalent in, although not limited to, the elderly population and is characterized by a variety of problems, including diminished cognition and disturbed emotion along with gate problems, falls, and brain and cardiovascular difficulties. Although often seen as an age-related condition, occurrence of OH is also associated with a number of autonomic nervous system neurodegenerative disorders. Medications may play a direct role in the risk of triggering OH; these drugs include, but are not limited to, agents used in the treatment of hypertension, myocardial ischemia, psychosis and schizophrenia, depression, Alzheimer and Parkinson disease as well as a vaccine approved for the prevention of cervical cancer. Most of these agents increase the risk for triggering OH through varying vasodilative mechanisms or through sympathetic nervous system interruption; for other drugs, no mechanism of action has been identified. These factors should be considered when diagnosing OH and when prescribing remedies for both patients with OH and those without OH; medications contributions to the severity and/or risk of developing OH could limit their use. However, their effects could be attenuated or even eliminated by modifying drug dosages.