QEEG alpha 1 changes after a single dose of high-potency neuroleptics as a predictor of short-term response to treatment in schizophrenic patients.

Baseline quantitative electroencephalographic (QEEG) characteristics and their changes after a single test dose of either haloperidol or clopenthixol were investigated in a group of 29 schizophrenics as possible predictors of short-term response to those drugs. On baseline QEEG assessment, responders (R) to subsequent treatment showed fewer slow and more fast activities than nonresponders (NR). A large overlap between R and NR with respect to these measures was observed, however, revealing their practical inadequacy to predict short-term response in individual patients. On the contrary, changes in alpha 1, observed 6 hr after the administration of a single test dose of either haloperidol or clopenthixol, discriminated to a very large extent between R and NR, correctly identifying 17 out of 18 R and 8 out of 10 NR. The QEEG test dose procedure might be used in the selection of the most appropriate antipsychotic drug for individual schizophrenic patients.

Pineal response to isoproterenol in rats chronically treated with electroconvulsive shock.

Chronic electroconvulsive shock (ECS) has been shown to induce a downregulation of beta 1-adrenergic receptors in the rat cerebral cortex. Because the secretion of melatonin in the pineal gland is regulated primarily by beta 1-adrenoceptors, in the present study we investigated the effect of chronic administration of ECS on pineal beta-adrenergic responsiveness to isoproterenol. To this purpose, young adult male rats received once daily for 8 days ECS (80 mA, 0.5 s) or sham ECS. On the day after the last ECS or sham treatment, they were injected with isoproterenol hydrochloride (1 mg/kg SC) or volume-matched saline at 1600 h. Two hours later they were killed by decapitation. Results showed that the isoproterenol-induced increase in the pineal melatonin content was blunted in rats treated with ECS as compared to sham-treated animals (shock x drug interaction = p < 0.01). These data indicate that chronic ECS treatment affects beta 1 receptor-mediated melatonin production in the pineal gland. Further studies need to elucidate whether the blunted melatonin response to isoproterenol in ECS-treated rats is due to a downregulation of pinealocyte beta-adrenergic receptors.

The human pineal gland responds to stress-induced sympathetic activation in the second half of the dark phase: preliminary evidence.

Previous reports by our group and by others showed that the human pineal gland is unresponsive to stress-induced systemic sympathetic activation either during the day or 3 hrs after the beginning of darkness. In the present study, we investigated whether a longer period of dark exposure is required to demonstrate a stimulatory effect of stress-induced sympathetic activation on the human pineal gland. For this purpose, plasma melatonin levels were measured in six healthy men (aged 25-34 yrs) both in resting condition and before and after a physical exercise performed between 02.40 and 03.00 h, 30 min after exposure to bright light (2000 lux). Light exposure lasted from 02.10 h up to 04.00 h. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. In the same subjects, plasma melatonin levels were measured also without exposure to light and with no exercise (control dark condition). The results showed that physical exercise, although inducing a rapid and short-term general sympathetic activation (as shown by significant changes in cardiovascular parameters) was able to increase light-depressed plasma melatonin levels only 5 hrs after the end of the stress (p < 0.0001, group X time interaction, two-way ANOVA with repeated measures). These findings suggest that the human pineal gland is responsive to systemic sympathetic activation induced by physical stress in the second half of the dark phase.

Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder.

Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.

Computerized EEG topography findings in schizophrenic patients before and after haloperidol treatment.

An increase of delta and fast beta activity in schizophrenic patients when compared with normal controls has been consistently reported. Topography of these abnormalities, in particular a possible frontal localization of delta, and their relationship to drug treatment and clinical status are still debated. In order to assess these issues, a multilead CEEG investigation was carried out in a group of 20 DSM-III-R schizophrenics, both before and after haloperidol treatment. All findings are described in terms of amplitude and relative power. Drug-free schizophrenics, when compared with a group of normal controls, showed a generalized increase of delta and fast beta, and a decrease of alpha 2 relative power. After acute treatment, patients showed a significant decrease of delta, and an increase of theta 2, beta 1, and beta 2. After 28 days of haloperidol treatment, similar changes were observed for delta, together with an increase of alpha 1, and a decrease of fast beta.

Physical stress in the middle of the dark phase does not affect light-depressed plasma melatonin levels in humans.

The human pineal gland has been shown to be unresponsive to stress-induced sympathetic activation during the day. However, the effects of stress on human melatonin production have received little investigation at night, when the pinealocytes should be physiologically responsive to noradrenergic stimulation. For this purpose, plasma melatonin and cortisol levels were measured in 7 healthy men (aged 25-34 years), both in resting condition and before and after a physical exercise performed between 23.40 and 24.00 h, 30 min after exposure to bright light (2,500 lx). The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. The results clearly showed that physical exercise does not affect light-depressed plasma melatonin levels, whereas it clearly increased plasma cortisol concentrations (p less than 0.002, two-way ANOVA with repeated measures), systolic blood pressure, pulse pressure and heart rate. These findings suggest that the human pineal gland is not responsive to systemic sympathetic activation induced by physical stress even in the middle of the dark phase.

Depressed nocturnal plasma melatonin levels in drug-free paranoid schizophrenics.

The 24-h profiles of plasma melatonin and cortisol were evaluated in 7 drug-free male paranoid schizophrenics and in 7 healthy subjects matched to the patients for age, sex, body weight, height and season of testing. Blood samples were obtained at 20.00, 22.00, 24.00, 01.00, 02.00, 06.00, 08.00 and 12.00 h. Light was turned off from 21.00 to 07.00 h. Compared with that of the normal controls, the circadian rhythm of plasma melatonin was absent in paranoid schizophrenics (F7.84 = 7.30, p less than 0.0001; two-way ANOVA with repeated measures) whereas the 24-h profile of plasma cortisol was preserved, although at a slightly higher level (F1.12 = 26.810, p less than 0.0002). The melatonin/cortisol ratio was significantly higher in healthy subjects than in the schizophrenic patients. A functional relationship between disturbances in the melatonin rhythm especially and schizophrenia may be proposed, although the significance of this relationship remains to be elucidated.

Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men.

The effect of chronic administration of phosphatidylserine derived from brain cortex on the neuroendocrine responses to physical stress has been examined in a placebo-controlled study in 9 healthy men. Phosphatidylserine 800 mg/d for 10 days significantly blunted the ACTH and cortisol responses to physical exercise (P = 0.003 and P = 0.03, respectively), without affecting the rise in plasma GH and PRL. Physical exercise significantly increased the plasma lactate concentration both after placebo and phosphatidylserine. The results suggest that chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man.

CEEG mapping in drug-free schizophrenics. Differences from healthy subjects and changes induced by haloperidol treatment.

A topographic CEEG investigation was carried out in 20 drug-free, DSM-IIIR diagnosed schizophrenics and in a group of matched healthy controls. The effects of acute and chronic haloperidol treatment were then assessed in the patient group. On the baseline recording, schizophrenics showed a widespread increase in delta, theta 1 and beta 3 amplitude. Acute haloperidol administration produced a decrease in delta and an increase in slow beta amplitude. After 28 days of treatment, delta and fast beta were reduced while theta 2 and alpha 1 were increased. CEEG abnormalities in schizophrenic subjects appear, therefore, to be reduced by chronic neuroleptic treatment.

Lateralization patterns of event-related potential and performance indices in schizophrenia: relationship to clinical state and neuroleptic treatment.

In a previous study we assessed lateralization patterns of verbal stimuli processing, by means of behavioural and neurophysiological measures, in a sample of drug-free schizophrenics and one of normal controls. The main findings obtained were the following: (1) a right visual field (RVF) advantage on reaction time (RT) and late positive complex (LPC) peak of the ERPs in normal subjects but not in schizophrenics; (2) a left visual field (LVF) significant advantage on P360 and slow wave (SW) amplitude in schizophrenics but not in controls; (3) a significantly longer RT and smaller P360 and SW for RVF stimuli in schizophrenics as compared to normals; (4) a significant contralateral effect of visual field on N180 at both the left and the right parietal site in normal controls and only at the right parietal site in schizophrenics. As a further step of this investigation we re-tested 9 schizophrenics after 28 days of haloperidol treatment. The post-treatment lateralization pattern of verbal stimuli processing was characterized by a RVF advantage on LPC peak amplitude and no visual field effect on P360 and SW, resembling the normal group pattern. Moreover, the N180 amplitude was found to be reduced. Relationships between lateralization pattern and clinical picture changes induced by haloperidol treatment are discussed.

C-EEG brain mapping in DSM-III schizophrenics after acute and chronic haloperidol treatment.

A multi-lead C-EEG investigation was carried out, in order to evaluate changes induced by acute and chronic treatment with haloperidol in DSM-III-R schizophrenics. After the acute treatment the main C-EEG changes were (1) a significant decrease of delta relative power (RP) over all the explored leads and of theta 1 over the occipital leads; (2) an increase in alpha 2 and beta 2 RP, as well as a decrease of beta 3 RP confined to the anterior temporal leads (T3, T4). During chronic treatment, C-EEG changes observed were (1) a significant decrease of delta RP and an increase of theta 1 RP; (2) an increase of alpha 1 and alpha 2 RP; (3) a significant decrease of beta 1, beta 2 and beta 3.

Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans.

The activity of brain cortex-derived phosphatidylserine (BC-PS) on the neuroendocrine and neurovegetative responses to physical stress was tested in 8 healthy men who underwent three experiments with a bicycle ergometer. According to a double-blind design, before starting the exercise, each subject received intravenously, within 10 min, 50 or 75 mg of BC-PS or a volume-matched placebo diluted in 100 ml of saline. Blood samples were collected before and after the exercise for plasma epinephrine (E), norepinephrine (NE), dopamine (DA), adrenocorticotropin (ACTH), cortisol, growth hormone (GH), prolactin (PRL) and glucose determinations. Blood pressure and heart rate were also recorded. Physical stress induced a clear-cut increase in plasma E, NE, ACTH, cortisol, GH and PRL, whereas no significant change was observed in plasma DA and glucose. Pretreatment with both 50 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.

Physical exercise at night blunts the nocturnal increase of plasma melatonin levels in healthy humans.

The effects of physical exercise on nighttime melatonin secretion have never been investigated in humans. For this purpose, plasma melatonin levels were measured at different times during the day and the night in seven healthy men (aged 26-33 yrs), both in resting condition and before and after a physical exercise performed between 10.40 and 11.00 p.m.. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximal work capacity (MWC) for 10 min, followed by other 10 min of bicycling at 80% of the MWC. The results clearly showed that physical stress at night significantly blunts the nocturnal increase in plasma melatonin levels (group X time interaction: p less than 0.00001; two-way ANOVA with repeated measures). These findings, taken together with the data of the literature, suggest that the response of the pineal gland to provocative stimuli may depend on its level of activity when the stimulus is applied.

Factors associated with increased noradrenaline levels in schizophrenic patients.

1. CSF NA levels were determined in a sample of DSM III-diagnosed schizophrenics and in a non-psychiatric control group. Schizophrenics with NA levels above and below the median were compared with respect to several clinical, historical, neuropsychological and biological variables. 2. Mean CSF NA levels were significantly higher in schizophrenics than in controls. 3. Schizophrenics with high CSF NA levels, as compared to those with low levels, had significantly higher scores on the CPRS subscale for positive symptoms. Moreover, in the former subgroup, C-EEG alpha relative activity was significantly lower and C-EEG beta relative activity was significantly higher in frontal and central leads. Two of the three patients who had been never treated with neuroleptics, and three of the six patients who had been neuroleptic-free for more than four weeks had high CSF NA levels. 4. These data support the relationship between increased CSF NA levels and the condition of overarousal of the schizophrenic patients, and suggest that prior neuroleptic treatment is not a major determinant of high CSF NA concentration in schizophrenics.

Dexamethasone suppression test in patients with primary obsessive-compulsive disorder and in healthy controls.

The dexamethasone suppression test (DST) was performed in 18 patients (11 women and 7 men) who met the DSM III-R criteria for obsessive-compulsive disorders (OCD), and in 20 healthy volunteers (12 women and 8 men). At 4.00 p.m., following dexamethasone administration, 5 patients (27.7%) and 1 healthy subject (5%) displayed plasma cortisol values well above the cut-off value of 50 ng/dl. A significantly different sex ratio was observed between suppressor and nonsuppressor patients with OCD (chi 2 = 4.40, p less than 0.03), because all nonsuppressor patients were male. Compared to the suppressors, nonsuppressor patients with OCD did not differ in any of the clinical and demographic variables investigated. Moreover, in our patient sample, the mean +/- SD total Hamilton Depression Rating Score (HDRS) was 14.8 +/- 2.5, and none of the nonsuppressors with OCD had a total HDRS greater than 17. These data suggest that a subgroup of OCD patients, particularly males, may escape the DST independently from the coexistence of depressive features.

Prevalence of psychiatric disorders among subjects exposed to a natural disaster.

A general practice study was carried out in 3 areas of the province of Naples, in southern Italy: Pozzuoli (PZ), a town exposed to significant seismic events in 1983, Monte Ruscello (MR), a village built to accommodate the victims of the earthquake, and Monte di Procida (MP), a town selected as a control since it is situated near PZ and was not significantly affected by the earthquake. The sociodemographic characteristics of the subjects examined were comparable in the 3 areas. The estimate of the real prevalence of psychiatric disorders according to Diamond & Lilienfeld was found to be higher in PZ and MR than in MP. Neurotic depression was the most frequent psychiatric diagnosis. The relative risk of mental disorders in subjects who reported none one or more social problems compared with those who reported none was more than 4 times greater in PZ and MR than in MP. Social problems also differed qualitatively, being more frequently related to living conditions in PZ and MR and to the primary social network in MP.