The association of diabetes mellitus with dementia in Parkinson's disease.
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Aged↗
Biomedical subjects
R Sandyk
Publications and source records attributed to R Sandyk.
Pineal calcification and its relationship to hallucinations in schizophrenia.
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Adult↗
Does melatonin mediate the therapeutic effects of 5-HT reuptake inhibitors in obsessive compulsive disorder?
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Humans↗
Magnetic fields mimic the behavioral effects of REM sleep deprivation in humans.
The discovery of rapid eye movement (REM) sleep by Aserinsky and Kleitman in 1953 initiated the impetus for sleep research and specifically the investigations of the effects of REM sleep deprivation (RSD) on animal and human behavior. The behavioral effects of RSD include the enhancement of motivational and "drive"-related behaviors. In laboratory animals, RSD has been reported to increase appetite, sexual behavior, aggressiveness, and locomotor activity. Moreover, RSD reportedly improves mood in patients with endogenous depression and heightens appetite and sexual interest in normal subjects. Since "drive"-related behaviors are thought to involve activation of limbic dopaminergic reward sites, RSD may enhance motivational behaviors through an action on limbic dopaminergic functions. In the present communication, we present two patients (one with multiple sclerosis and the other with Parkinson's disease) in whom treatment with magnetic fields produced behavioral effects which paralleled those observed in REM-sleep-deprived animals and humans. We propose, therefore, that the behavioral and mental effects of treatment with magnetic fields may be mediated via RSD and, by inference, involve activation of limbic dopaminergic reward sites.
Adult↗
Melatonin and petit-mal epilepsy: an hypothesis.
Intraventricular administration of the opioid peptide leucine-enkephalin has been reported to induce petit-mal-like seizures in rats. These seizures have been found to be an age-dependent phenomenon. In rats, the full manifestation of these seizures develops after 4 weeks of age during which time ethosuximide was effective in aborting these seizures, while phenytoin and phenobarbital were ineffective. The period associated with the development of enkephalin-induced seizures in rats coincides with an important milestone in pineal chronobiology. In rats, melatonin plasma levels peak at 3 weeks of age, a period which also corresponds with the emergence of melatonin circadian rhythms. It is proposed that melatonin mediates the anticonvulsant action of drugs effective for petit-mal (absence) epilepsy and that the pineal gland is implicated in the pathogenesis of this form of childhood epilepsy.
Animals↗
Calcification of the pineal gland: relationship to laterality of the epileptic foci in patients with complex partial seizures.
The right and left temporal lobes differ from each other with respect to the rate of intrauterine growth, the timing of maturation, rate of aging, anatomical organization, neurochemistry, metabolic rate, electroencephalographic measures, and function. These functional differences between the temporal lobes underlies the different patterns of psychopathology and endocrine reproductive disturbances noted in patients with temporolimbic epilepsy. The right hemisphere has greater limbic and reticular connections than the left. Since the pineal gland receives direct innervation from the limbic system and the secretion of melatonin is influenced by an input from the reticular system, I propose that lesions in the right temporal lobe have a greater impact on pineal melatonin functions as opposed to those in the left dominant temporal lobe. Consequently, since calcification of the pineal gland is thought to reflect past secretory activity of the gland, I predicted a higher prevalence of pineal calcification (PC) in epileptic patients with right temporal lobe as opposed to those with left temporal lobe foci. To investigate this hypothesis, the prevalence of PC on CT scan was studied in a sample of 70 patients (43 men, 27 women, mean age: 29.2 years, range 9-58; SD = 10.1) with complex partial seizures, of whom 49 (70.0%) had a right temporal lobe focus. PC was present in 51 patients (72.8%) and was unrelated to any of the historical and demographic data surveyed. In the patients with a focus in the right temporal lobe, PC was present in 46 cases (93.8%) as compared to 5 of 21 patients (23.8%) with left temporal lobe foci.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Dysmenorrhea and the pineal gland.
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Adolescent↗
Amelioration of experimental parkinsonism by intrahypothalamic administration of haloperidol.
Accumulation of amines in the degenerating axons of ascending catecholamine-containing neurons in the hypothalamus has been proposed as a site of function neurotransmitter release and may thereby participate in the development of motor impairment seen after central dopamine-depleting lesions. To test this hypothesis further the dopamine receptor antagonist haloperidol (1 microL of a 14 nmol solution) was injected directly into the lateral hypothalamus (LH) in 6 different injection regimes to determine whether amphetamine-induced turning could be attenuated with this treatment. The injection of haloperidol at 1 and 24 h (group 1), 24 h (group 2) or 6+ 7 d (group 3) after 6-hydroxydopamine (6-OHDA) did not modify amphetamine-induced turning. However, the injection of haloperidol at 1 h, 24 h, 7 d, and 8 d (group 4), days 1-7 (group 5), or gradual infusion (14 nmol/microliters/h) for 7 days (group 6) all reduced the 6-OHDA-induced turning to a level similar to that of controls. These results add further support to the contention that amines are released from the axons of degenerating neurones in the hypothalamus and that this phenomenon participates in the elicitation of behavioral impairment attributed solely to the loss of functional neurotransmitters from terminal fields. Furthermore, the data emphasize the importance of hypothalamic pathology in the development of Parkinsonism and suggest that intrahypothalamic administration of dopamine blocking agents might be useful in the treatment of Parkinsonism.
Amphetamine↗
Sensitivity of dopamine receptors in the lateral hypothalamus is altered in 6-hydroxydopamine treated rats.
Amine accumulation is observed in the lateral hypothalamus (LH) after nigrostriatal neurons degenerate. It has been proposed that this accumulation is a source of amines which are released into the hypothalamus thereby affecting the function of adjacent aminergic receptors. To approximate this condition of continuous exposure of LH receptors to endogenous amines, dopamine (DA) was injected into the LH of rats once daily for 5 consecutive days. A control group received 4 daily injections of tartaric acid vehicle and then DA on day 5. Rats pretreated with DA showed severe impairment of open field performance and motor reflex control on day 5 when they were compared to control animals which received vehicle pretreatment. In a second study, the DA receptor antagonist haloperidol was injected into the area of amine accumulation in the LH to determine whether this might block amine release from areas of accumulation thereby to attenuate lesion-induced rotation. Haloperidol administered once daily for 4 out of 7 days, once daily for 7 days or via a continuous infusion for 7 days, all reduced d,l-amphetamine-induced turning to control levels. These results suggest that prolonged exposure of hypothalamic DA receptors alters their sensitivity to subsequent doses of DA and that amine released from areas of accumulation may be blocked by haloperidol to enhance behavioral recovery from DA depleting lesions. Moreover, these findings indicate that the hypothalamus participates in the behavioral effects induced by DA depleting lesions and highlight the importance of hypothalamic pathology in Parkinson's disease.
Animals↗
Psychotic behavior associated with cerebellar pathology.
This report concerns a 27-year-old man in whom psychotic behavior emerged in association with a cerebellar tumor. This presentation supports previous clinical observations which postulate an intimate relationship between cerebellar pathology and the development of schizophrenia.
Adult↗
Late-onset schizophrenia: relationship to awareness of abnormal involuntary movements and tobacco addiction.
Although schizophrenia usually emerges at mid to late-adolescence, it has been estimated that almost 20% of schizophrenic patients develop their first symptoms in mid to late life (late-onset schizophrenia). The biological characteristics that distinguish patients with early onset from those with late-onset schizophrenia have not been well delineated. A subgroup of neuroleptic-treated schizophrenic patients develops tardive dyskinesia (TD) and the majority of these patients are unaware of their movements. To investigate whether early and late-onset schizophrenic patients with TD could be differentiated on the basis of awareness of involuntary movements, we compared the prevalence of awareness of these abnormal movements in patients with early (N = 40) and late-onset (N = 15) schizophrenia. We found a significantly higher prevalence of awareness of involuntary movements in patients with late-onset schizophrenia as compared to those with an earlier age of onset (86.6% vs. 25.0%, p < .0001). In a second study, we investigated whether early and late-onset schizophrenia could be differentiated on the basis of dopamine functions in the mesolimbic system. Since tobacco addiction is mediated via limbic dopaminergic functions, we investigated the prevalence of tobacco addiction in patients with early (N = 51) and late-onset (N = 13) schizophrenia. We found a significantly lower prevalence of tobacco addiction in patients with late-onset schizophrenia as compared to those with an earlier age of onset (15.4% vs. 54.9%; X2 = 6.49; p < .01). Our findings support the notion that distinct pathophysiological mechanisms underlie the development of early and late-onset schizophrenia.
Adult↗
Choroid plexus calcification as a possible marker of hallucinations in schizophrenia.
Several studies suggest that disturbances of serotonin (5-HT) functions may be involved in the pathophysiology of hallucinations in schizophrenia. It is now well established that the choroid plexus (CP) is innervated by serotonin (5-HT) neurons, which may regulate its activity, and it is possible that decreased 5-HT functions may facilitate the process of its calcification. It is thus conceivable that calcification of the CP may be associated with hallucinations in schizophrenia. I studied in 18 chronic schizophrenic patients the association of CP calcification (CPC) size as ascertained from CT scan, to severity of hallucinations and, for comparison, to four other positive symptoms as well as global psychopathology score. Analysis of variance indicated that CPC size was specifically associated with hallucinations (p < .001) and none of the other psychopathology measures. These findings reveal a relationship between CPC and hallucinations in schizophrenia and suggest that the former may be a neuroradiological marker of hallucinations in the disease.
Adult↗
Vitamin B12 and its relationship to age of onset of multiple sclerosis.
Attention has been focused recently on the association between vitamin B12 metabolism and the pathogenesis of multiple sclerosis (MS). Several recent reports have documented vitamin B12 deficiency in patients with MS. The etiology of this deficiency in MS is unknown. The majority of these patients do not have pernicious anemia and serum levels of the vitamin are unrelated to the course or chronicity of the disease. Moreover, vitamin B12 does not reverse the associated macrocytic anemia nor are the neurological deficits of MS improved following supplementation with vitamin B12. It has been suggested that vitamin B12 deficiency may render the patient more vulnerable to the putative viral and/or immunologic mechanisms widely suspected in MS. In the present communication, we report that serum vitamin B12 levels in MS patients are related to the age of onset of the disease. Specifically, we found in 45 MS patients that vitamin B12 levels were significantly lower in those who experienced the onset of first neurological symptoms prior to age 18 years (N = 10) compared to patients in whom the disease first manifested after age 18 (N = 35). In contrast, serum folate levels were unrelated to age of onset of the disease. As vitamin B12 levels were statistically unrelated to chronicity of illness, these findings suggest a specific association between the timing of onset of first neurological symptoms of MS and vitamin B12 metabolism. In addition, since vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of critical pathogenetic significance.
Adolescent↗
Amphetamine-induced rotational behavior in rats: relationship to hypothalamic and striatal degeneration.
When lesions are placed unilaterally in the nigrostriatal system of experimental animals, rotational behavior occurs in response to peripheral administration of dopamine (DA) agonists. In spite of considerable evidence to the contrary, it is assumed that in order for this rotation to occur, an almost complete depletion of striatal DA must be achieved. To test this hypothesis further, 20 male Sprague-Dawley rats were injected unilaterally with 2 microL of 8 micrograms/microL of 6-hydroxydopamine (6-OHDA) via acute injection needles or chronically indwelling cannulae. Acute injection of 6-OHDA resulted in a rotation rate of 7.2 to 18.9 revolutions per minute in response to peripheral amphetamine injection (5 mg/Kg) while injection of 6-OHDA through chronically indwelling cannulae produced rotation ranging from 1.4 to 9.9 rotations per minute. Under the conditions of either method of injection, the animals displaying the most severe rotation still showed partial denervation of striatal DA as revealed by catecholamine fluorescence histochemistry. Conversely, numerous animals demonstrating very low rates of amphetamine-induced rotation often displayed a complete loss of striatal, accumbens, and olfactory tubercle catecholamine fluorescence. Moreover, large quantities of lateral hypothalamic amine accumulation were observed in rotating rats indicating that this neurochemical change may be of functional significance for rotational responses. The present results, when taken into consideration with previous work, indicate that the routine selection of rotating animals for pharmacological testing for potential antiParkinsonian medication or intracerebral grafting purely on the basis of their rotational behavior does not necessarily imply that complete striatal denervation has occurred. Moreover, these findings demonstrate that amine accumulation in the lateral hypothalamus of rotating animals with DA depleting lesions is an important phenomenon implicated in the expression of rotational behavior in animals and possibly in the pathophysiology of Parkinson's disease.
Amphetamine↗
Multiple sclerosis: relationship between seasonal variations of relapse and age of onset.
The incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. The manifestation of MS, therefore, appears to be dependent upon having passed through the pubertal period suggesting an endocrine influence on the timing of onset of the disease. Since pineal melatonin secretion progressively declines from childhood to puberty and as melatonin exerts an immunomodulating influence, we have proposed that the dramatic decline in melatonin secretion just prior to the onset of the clinical manifestations of puberty may lead to disruption of immune responses resulting in either reactivation of the infective agent or in an increased susceptibility to pubertal or post-pubertal infection. Melatonin secretion undergoes annual rhythms with a zenith in winter and declines to a nadir in the spring. Thus, the fall in melatonin secretion in the spring may account for epidemiological findings revealing a high incidence of relapse of MS in the spring. If the manifestations of MS are related to the fall in melatonin secretion in the post-pubertal period, then one would expect patients with a pubertal onset of the disease to have a higher incidence of relapses in spring than in winter. To test this hypothesis, we investigated in 51 patients the relationship between the seasonal occurrence of the last MS relapse with the age of onset of first manifestation of MS. While 9 of 22 patients (40.9%) who relapsed in spring (March-May) had the onset of MS prior to age 18, only 2 of 29 patients (6.9%) who relapsed in winter (November-February) experienced the onset of first symptoms prior to the age of 18 years (p < .005). These findings thus support the hypothesis implicating the pineal gland and melatonin secretion in the timing of onset of MS. Moreover, the findings may have clinical implications with respect to the prophylaxis of MS relapse in patients who experience seasonally-dependent exacerbation of symptoms.
Adolescent↗
Nocturnal melatonin secretion in suicidal patients with multiple sclerosis.
Multiple sclerosis (MS) is characterised by the occurrence of patchy CNS demyelinating lesions, leading to various degrees of motor, sensory, affective, and cognitive deficits. MS is associated also with an increased risk of suicide accounting for a substantial rate of death among these patients. Post-mortem studies in suicide victims with various psychiatric disorders demonstrate a decreased concentration of serotonin (5-HT) and its metabolites in the brain. Since 5-HT is a precursor in the synthesis of melatonin and as pineal melatonin content was found to be low in suicide victims, we predicted lower melatonin secretion in suicidal versus non-suicidal MS patients during an acute exacerbation of symptoms. To test this hypothesis, we investigated nocturnal plasma melatonin levels in a cohort of 28 relapsing patients who were admitted consecutively to an inpatient Neurology service, 6 of whom had a history of suicide attempts and were having suicidal ideation at the time of admission. While both cohorts of patients were not distinguishable on any of the demographic data including use of psychotrophic drugs on the day of admission to hospital, the mean melatonin level in the suicidal group was significantly lower than in the control group (19.0 pg/ml +/- 11.9 versus 45.5 pg/ml +/- 27.1; p < .05). These findings support the prediction of the study implicating the pineal gland in the pathogenesis of suicidality in MS and reinforce the concept that a biological rather than a reactive etiology underlies the development of psychiatric symptoms in MS.
Adult↗
Subjective awareness of abnormal involuntary movements in schizophrenia.
A wide majority of schizophrenic patients with Tardive dyskinesia, a neurological disorder produced by chronic neuroleptic therapy, lack awareness of their involuntary movements. This by contrast to patients with Parkinsonism who usually are aware of their abnormal movements. In the following communication we present a series of studies which are aimed at providing further insight into the issue of awareness of involuntary movements in schizophrenic patients with tardive dyskinesia. In addition, we investigated whether edentulosness, which may be a risk factor for orofacial dyskinesias in the elderly, is also a risk factor for neuroleptic-induced orofacial dyskinesias. We found that: (a) one's awareness of involuntary movements is related to some but not all muscle groups, (b) tardive dyskinesia may be associated with a significant distress, (c) lack of awareness may be a feature of frontal lobe dysfunction in schizophrenia, (d) patients who lack awareness of their involuntary movements have a higher prevalence of pineal calcification, and (e) edentulosness, which is related to deficits in the orofacial sensorimotor system, increases the risk for neuroleptic-induced orofacial dyskinesias.
Adult↗
Biological determinants and risk factors for tardive dyskinesia in schizophrenia.
Tardive dyskinesia (TD), a neurological side effect of chronic neuroleptic treatment, develops in 20%-30% of psychiatric patients. The biological characteristics that distinguish schizophrenic patients who develop TD from those who fail to develop TD during neuroleptic treatment are currently the subject of intense research. The aim of the present report is to present biological characteristics and risk factors of schizophrenic patients with TD. The findings of the study demonstrate that: (1) the timing of onset of schizophrenia is a biological determinant for the development of severe TD. (2) the mode of onset of schizophrenia and specifically, an insidious onset is a biological risk factor of TD. (3) belligerent behavior may be a risk factor for TD. (4) postmenopausal schizophrenic patients are at increased risk for TD.
Adult↗