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PubMed1983

Differential interactions of phencyclidine with tetrabenazine and reserpine affecting intraneuronal dopamine.

This study has examined the effects on synaptosomal (P2) dopamine of interactions of phencyclidine and some other stimulants with tetrabenazine and reserpine. Tetrabenazine and reserpine both enhanced the spontaneous synaptosomal release of [14C]dopamine and inhibited its formation from [14C]phenylalanine. The [14C]dopamine formation increases induced by phencyclidine and amfonelic acid, however, were affected differentially by coadditions of tetrabenazine and reserpine. At the lower concentrations, tetrabenazine either did not affect or augmented the dopamine formation enhancements by the stimulants. Reserpine at all levels blocked the synthesis enhancements and revealed inhibitory effects of phencyclidine and amfonelic acid upon dopamine formation; only at the highest concentration did the action of tetrabenazine mimick that of reserpine. Amphetamine stimulation of dopamine formation was affected by tetrabenazine and reserpine alike; the stimulation was either maintained or enhanced. Ketamine did not affect dopamine formation either by itself, with tetrabenazine, or with reserpine. In summary, tetrabenazine and reserpine affected synaptosomal dopamine formation and release in a comparable manner, but intraneuronal dopaminergic actions of phencyclidine and also of amfonelic acid may be influenced differentially by these two releasing agents.

Animals↗
PubMed1987

Toxins that affect voltage-dependent calcium channels.

At this time, there are five potential candidates for calcium channel specific toxins. All five of these toxins appear to affect the function of voltage-dependent calcium channels. Atrotoxin, beta-leptinotarsin-h and maitotoxin activate channels, whereas both taicatoxin and omega-conotoxin are inhibitors. Neither maitotoxin nor omega-conotoxin alters the binding of dihydropyridines to membranes derived from the cells upon which the toxins exert their effects. In contrast, both atrotoxin and taicatoxin inhibit the binding of dihydropyridines to ventricular membranes. It is not currently known whether beta-leptinotarsin-h affects the binding. The effects of maitotoxin and atrotoxin are blocked by dihydropyridines and verapamil. Direct binding studies with radiolabeled toxins have been performed only with omega-conotoxin, and the binding site density for this toxin appears to be at least one order of magnitude greater than the density of dihydropyridine binding sites in synaptosomes. Studies to examine the third and fourth criteria which we have listed (i.e. that the effects are not via a second messenger, or an enzyme activity) have not been reported for either beta-leptinotarsin-h or omega-conotoxin. Atrotoxin and taicatoxin, added outside a patch pipette, have no effects on calcium channels within the patch and are, therefore, probably not affecting calcium channels via a second messenger. Maitotoxin, however, affects the formation of inositol phosphates and, hence, could be affecting the channel indirectly. The fractions containing the toxic components atrotoxin and taicatoxin have no phospholipase or protease activity, and this is presumably true also for omega-conotoxin since it has been purified to homogeneity. Although all of the toxins have the potential to be important tools with which to study calcium channel structure and function, a number of experiments remain to be done in order to establish conclusively that these five toxins bind specifically to the voltage-dependent calcium channel. In conclusion, we would like to briefly mention why so much effort is being devoted to the search for these calcium channel specific toxins. Such a toxin would provide a very valuable tool in the study of calcium channels for a number of reasons. First, the toxin would be another ligand for the channel and, as such, would provide an alternative to organic ligands such as the dihydropyridines which are lipophilic and, in many tissues, have more than one binding site.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding Sites↗
PubMed1990

The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders.

We determined the frequency of antithyroglobulin and antimicrosomal antibodies in 173 consecutively admitted psychiatric inpatients. (We found antithyroid antibodies in 8% (5/65) of patients with DSM-III major depression, 13% (4/31) with biploar disorder, and in 0% (0/4) of those with schizoaffective disorder.) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole. The overall frequency of positive antithyroid antibody titers in patients with DSM-III affective disorder, 9% (9/99), did not differ from that in patients with nonaffective disorders, 10% (7/68). However, patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients. Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.

Adolescent↗
PubMed1990

Evidence against close linkage of unipolar affective illness to human chromosome 11p markers HRAS1 and INS and chromosome Xq marker DXS52.

The genetic basis of various subtypes of the affective disorders has been investigated by family, twin, and adoption studies, as well as by segregation and linkage analysis. Linkage analyses of bipolar disorder with the chromosome 11p15 DNA markers HRAS1 and INS, and the chromosome Xq28 markers for color blindness and G6PD have been reported. We have used restriction fragment length polymorphisms as markers to examine linkage in three extended families with unipolar affective illness, ascertained through probands with either recurrent unipolar or bipolar II illness. Using an inclusive definition of the affected phenotype, linkage could be excluded up to 28cM around the HRAS1-INS linkage group on chromosome 11p15, and up to 5 cM around the DNA marker DXS52 on Xq28. Negative linkage results were also obtained for two more restrictive definitions of affective illness. Thus, we find no evidence for the involvement of the chromosomal regions 11p15 and Xq28 with unipolar affective disorder in these three families.

Bipolar Disorder↗
PubMed1994

CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI.

Recently several steroid compounds have been discovered to act as neuromodulators in diverse central nervous system (CNS) functions. We wondered if neuroactive steroids might be involved in affective illness or in the mode of action of mood-regulating medications such as carbamazepine. Levels of the neuroactive steroids pregnenolone and progesterone, as well as the neuropeptide diazepam binding inhibitor (DBI) (known to promote steroidogenesis), were analyzed from cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) from 27 medication-free subjects with affective illness and 10 healthy volunteers. Mood-disordered subjects who were clinically depressed at the time of the LP had lower CSF pregnenolone (n = 9, 0.16 ng/ml) compared with euthymic volunteers (n = 10, 0.35 ng/ml; p < 0.01). In addition, pregnenolone was lower in all affectively ill subjects (n = 26, 0.21 ng/ml), regardless of mood state on the LP day, than healthy volunteers (p < 0.05). No differences were found for progesterone or DBI levels by mood state or diagnosis. Progesterone, pregnenolone, and DBI did not change significantly or consistently in affectively ill subjects after treatment with carbamazepine. CSF pregnenolone is decreased in subjects with affective illness, particularly during episodes of active depression. Further research into the role of neuroactive steroids in mood regulation is warranted.

Adult↗
PubMedDate not supplied

Childbearing in women with and without a history of affective disorder. II. Electroencephalographic sleep.

Electroencephalographic (EEG) sleep was examined longitudinally in 34 obstetrically healthy volunteers recruited early in pregnancy. All women were free of current psychiatric disorder. Fourteen women had a personal history of affective disorder, and 20 had no history of any psychiatric disorder. EEG sleep was recorded in subjects' homes at specified points from 12 weeks' gestation through 8 months' postpartum to examine the impact of childbearing on sleep and psychiatric symptoms in women with a history of affective disorder. EEG sleep measurements, as well as clinical ratings of sleep, indicated that sleep disturbances were most pronounced over the first 2 to 3 months' postpartum and were characterized primarily by interrupted sleep. The obstetrical course of these women was uneventful, and the outcome with respect to affective disturbances was highly favorable. Nevertheless, childbearing was associated with greater changes in total sleep time and with rapid eye movement (REM) latency reduction in women with a history of affective disorder, even in the absence of clinically significant mood changes. Findings suggest that the sleep system of women with a history of affective disorder may be more sensitive to the psychobiological changes associated with childbearing, as evidenced by earlier onset of sleep disruption over the childbearing course and a reduction in REM latency in the final trimester that persisted throughout the eighth postpartum month.

Adult↗
PubMedDate not supplied

Are schizophrenia and affective disorder related?: the problem of schizoaffective disorder and the discrimination of the psychoses by signs and symptoms.

Schizophrenia and affective disorder are separately classified. Schizoaffective disorder has been considered a variant of these, or representing several diseases. Some hypothesize a psychosis continuum. One test of these contrasting views involves discriminating the psychoses by their classic symptoms. We used discriminant function analyses to assess the ability of systematically recorded psychopathology to distinguish 167 DSM-III schizophrenics from 74 affectives. We divided the schizophrenics into chronic and schizoaffective subgroups. We discriminated chronic schizophrenics from affectives, but schizoaffectives overlapped both groups. Schizoaffective/unipolars were like chronic schizophrenics, and schizoaffective/bipolars were like affectives. However, these discriminations also substantially overlapped, and among non-affective positive features formal thought disorder was best at discrimination. Our findings do not fully support the present classification system, and suggest that its emphasis on hallucinations and delusions is overvalued.

Adolescent↗
PubMed1992

Trace dosages of the neurotoxins MPTP and MPP+ may affect brain dopamine in vivo.

The present study has examined the effects of systemically administered MPTP and MPP+ upon striatal DA and Dopac of C57 mice, also treated concurrently with either saline or reserpine. MPTP followed by saline did not affect DA level but decreased that of Dopac only at 5.0 mg/kg and higher dosages. The potency of MPTP affecting DA increased greatly when the neurotoxicant was followed by either 5.0 or 10.0 mg/kg reserpine; MPTP at 0.10 mg/kg and higher dosages significantly reversed the DA depleting effects of reserpine. MPP+ (1.0 or 10.0 mg/kg) with saline did not affect either DA or Dopac. In contrast, MPP+ at 0.10 mg/kg and higher dosages, when followed by 10.0 mg/kg reserpine, dose-dependently enhanced the DA depleting effects of reserpine. In agreement with the earlier results obtained in vitro, the present study indicates that MPTP administration at trace level dosages may lead to an inhibition of MAO in vivo. The effect of systemically given MPP+ on DA, however, appears to be more complex in nature, conceivably comprised of actions at the striatal neurones including the intraneuronal vesicles and, possibly, at the substantia nigra which may affect striatum in turn. That MPP+ may have reached brain areas in these experiments is also indicated by the observation of a significant striatal level of 3H-MPP+ after its systemic administration. In conclusion, irrespective of MPTP and MPP+ action mechanisms, trace levels of these neurotoxicants appear to affect brain dopamine neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Mutations in conformation-dependent domains of herpes simplex virus 1 glycoprotein B affect the antigenic properties, dimerization, and transport of the molecule.

Glycoprotein B (gB) is a component of the herpes simplex virus 1 envelope that is required for penetration of virions into cells. We constructed 11 mutants in the gB gene by deleting the carboxy terminus of the molecule, inserting linkers into the ectodomain and intracellular region, and creating point mutations in cysteine residues. To identify regions of the molecule that affect the formation of epitopes on gB, we cloned the mutated genes into a eukaryotic expression vector, transfected them in COS-1 cells, and reacted the gene products in immunofluorescence and immunoprecipitation tests with a panel of monoclonal antibodies. Our findings are as follows. (i) The ectodomain of gB between residues 600 and 690 is highly antigenic and contains residues that specify 8 continuous epitopes and affect the conformation of 12 discontinuous epitopes. Residues that form a novel neutralizing domain and affect the assembly of gB dimers are contained in this region. Dimerization of gB does not require the transmembrane region or the intracellular carboxy terminus. (ii) Transport of the insertion mutants was aberrant and depended on the site mutagenized. Insertions of linkers at residues 391, 413, and 479 of the ectodomain precluded the binding of neutralizing antibodies that recognize residues in four discontinuous-epitope domains; the latter mutant in intact gB was not translocated to the cell surface. In contrast, insertions at residue 600 of the ectodomain and 810 of the intracellular domain did not affect the conformation-dependent epitopes or gB transport. (iii) Substitution of serines for cysteine residues in a discontinuous-epitope domain in the midregion of gB altered the conformation of both proximal and distal sites. Seven epitopes were lost by mutagenesis of cysteine 382 and 4 epitopes by mutagenesis of cysteine 334. Together with previous findings, these results indicate that the ectodomain of gB contains three topographically distinct neutralizing regions, one of continuous and two of discontinuous epitopes. The continuous-epitope domains that map at the amino terminus are not altered by distal mutations. In contrast, the domains of discontinuous epitopes, assembled by juxtaposing residues on the surface of gB, are affected by proximal and distal mutations that alter the antigenic structure, processing, and surface transport of gB.

Amino Acid Sequence↗
PubMed1981

Assortative mating in affective disorders.

Assortative mating was determined in 170 spouses of patients with major affective illness (bipolar and unipolar). An increase in affective disorders was found in both wives of affected men and husbands of affected women. The data suggest that assortative mating is present in the familial transmission of affective disorder.

Adult↗
PubMedDate not supplied

Personal and family history of affective illness in patients with multiple sclerosis.

There is a high prevalence of affective illness, both depression and bipolar disorder, in patients with multiple sclerosis. In this study, the family history method was used to assess the prevalence of affective illness in first-degree relatives of patients with multiple sclerosis. There was not an excess of affective illness in the relatives suggesting that affective disorder associated with multiple sclerosis does not have a familial pattern similar to primary affective disorder. Clinical and theoretical implications of these findings are discussed.

Adult↗
PubMedDate not supplied

Psychiatric disorder in adolescent offspring of parents with affective disorder in a non-referred sample.

The relationship between parental psychopathology and psychiatric disturbance in 153 offspring aged 6-19 was assessed in 81 families randomly selected from a prepaid health plan. Offspring of parents with a history of affective disorders and of parents with non-affective psychiatric disorders had higher rates of psychiatric diagnoses and poorer adaptive functioning than children of parents who had never experienced a psychiatric illness. Offspring whose parents had affective disorder had a rate of affective disorder of 30% compared to a rate of 2% in the rest of the sample. This relationship between parental affective disorder and poor child outcome was observed when the separated and divorced families were removed from the analyses.

Adolescent↗
PubMed1994

The relationship of premorbid personality to subtypes of an affective illness. A replication study by means of an operationalized procedure for the diagnosis of personality structures.

The hypothesis of a relationship between types of premorbid personality and subtypes of an affective illness was tested on the basis of a diagnostically 'blind' assignment of biographical case history data on patients' premorbid development to patterns of personality traits. Data sets of 261 cases with various psychiatric disorders were examined. The rater (R.T.) had to score each item in a list of traits relevant for the diagnosis of the types that had been conceived by D.v.Z. and J.P. The assignment of the ratings to the type concepts was then performed by means of a computer programme. The results regarding the distribution of types over the clinical diagnoses yielded a statistically significant association of the 'affective types' of premorbid personality ('melancholic type' and 'manic type') with affective disorders and the 'neurotoid types' ('anxious insecure type' and 'nervous tense type') with non-affective disorders. Previous findings on the basis of a global rating of types in a smaller sample (n = 42) regarding personality types and subtypes of an affective illness could be replicated by means of the new, operationalized procedure in an enlarged sample (n = 80): On the one hand, a marked preponderance of the 'manic type' of personality was found in bipolar I patients, particularly pronounced in those with a predominantly manic course of the disorder; on the other hand, the 'melancholic type' of personality prevailed in bipolar II and unipolar depressive patients.

Adult↗
PubMed1994

Dimensional analysis of human EEG during experimental affective experience.

The present investigation was designed to study whether dimensional complexity of EEG discriminates between internal and external attentional demands during affective experience. In the first task Ss were waiting for a slight electric shock (affective intake condition). In the second task Ss were engaged in the controlled imagery involving the emotional experience 'programmed' during intake task (affective rejection condition). Both affective tasks were compared to the controlled rest condition. The results of imagery trial replicated previous demonstration of the increased dimension of EEG during imagery in comparison to perceptual processing, with differences, confined to frontal and partly to central sites. Affective intake trial in comparison to rest condition was characterized by significantly higher dimensional estimates over the central and more posterior (parietal and occipital) areas.

Adolescent↗
PubMed1996

The relationship between symptoms of post-traumatic stress disorder and pain, affective disturbance and disability among patients with accident and non-accident related pain.

Recent studies have reported a high prevalence of symptoms of post-traumatic stress disorder (PTSD) among individuals with chronic pain. Studies suggest that persons with pain and PTSD also display higher levels of affective disturbance. In the present study we examined self-reports of pain, affective disturbance, and disability among pain patients with and without symptoms of PTSD. Patients without PTSD symptoms were further subdivided into persons whose pain was the result of an accident or insidious in onset. Thus, three groups were examined: (1) persons with accident related pain and high PTSD symptoms (Accident/High PTSD); (2) persons with no or few symptoms of PTSD whose pain was accident related (Accident/Low PTSD); and (3) patients whose pain was not accident related and did not have PTSD symptoms (No Accident). No Accident patients were older than persons with accident related injuries, and both accident related pain groups were more likely than No Accident patients to be involved in litigation or receiving compensation. Thus, these variables were controlled for in the statistical analyses. Self-report of pain was also included as a covariate in the analyses examining group differences in affective disturbance and disability. Accident/High PTSD patients displayed higher levels of self-reported pain compared to the other two groups. The Accident/High PTSD group also had the highest levels of affective disturbance. Both accident groups tended to report greater disability compared to patients whose pain was not accident related. These findings suggest that PTSD symptoms in chronic pain patients are associated with increased pain and affective distress. Accident related pain, even without the presence of PTSD symptoms, appears to be associated with greater disability. The results indicate that the identification and treatment of PTSD symptoms in refractory pain patients may be a critical albeit subtle factor in the effective management of suffering and disability in this population.

Accidents↗
PubMed1992

Developmental changes of 6-phosphofructo-1-kinase subunit levels in erythrocytes from normal dogs and dogs affected by glycogen storage disease type VII.

1. The subunit proportions (L:M:C) of the PFK isozymes from normal adult erythrocytes were 2:86:12. Affected adult erythrocyte 6-phosphofructo-1-kinase (PFK) isozymes contained normal L-type (31%) and C-type (61%) subunits as well as a small amount (8%) of truncated M-type subunit. 2. When measured within 24 hr of birth, both normal and affected dog erythrocytes contained high PFK activities due to elevated levels of the L-type subunit. As the dogs matured, PFK activity decreased due to a greater than 99% loss of the L-type subunit. 3. By 2 weeks of age, the M-type and C-type subunits in normal dog PFK isozymes increased several-fold and attained near adult levels. 4. During post-natal development, the L-type subunit from affected dog erythrocytes decreased more rapidly than from normal dog erythrocytes; but it was maintained at a higher level in the affected adult erythrocytes. Also, in the affected dog erythrocytes, truncated M-type subunits were detected; and the initially high levels of the C-type subunit decreased approximately 50% after 4 weeks.

Aging↗
PubMed1989

Subjective dimensions of heroin urges: influence of heroin-related and affectively negative stimuli.

Thirty-five male drug-free heroin addicts rated their affect, craving, and withdrawal in response to boring, anxiety-eliciting, and heroin stimuli. Results revealed that: (a) heroin cues were more effective than boring or anxiety-eliciting cues in prompting self-reports of craving or withdrawal; (b) heroin cues produced an affective state characterized by self-reported low-pleasure and high anxiety/tension; (c) craving was not correlated with any particular affective state, but rather was associated with a variety of negative affects--anxiety, depression, fatigue, anger; (d) the coherence (intercorrelations) of affective, craving, and withdrawal measures was greatest when addicts made their self-ratings immediately after exposure to drug stimuli; and (e) while addicts routinely reported craving without withdrawal sickness, they virtually never reported withdrawal sickness without reporting craving. These results suggested that the potential for negative reinforcement subserved stimulus elicited craving and that craving involved cognitive appraisal processes (attributions, expectations).

Adult↗
PubMedDate not supplied

Parent-child closeness affects the similarity of drinking levels between parents and their college-age children.

College males reported drinking more frequently and in higher amounts than females. Correlations between quantity-frequency (QF) indices of drinking by parents and by their college-age children showed the greatest similarity between fathers and sons. Log linear analyses compared each parent's drinking level against each of three other factors that might affect the QF levels of college-age children: the relationship between parent and child, the effect of the parent's drinking on the parent, and how the parent's drinking affected their treatment of the child. The results supported models in which the relationship of each parent's drinking to the QF levels of both sons and daughters was affected by the closeness of the parent-child relationship. However, there was no support for models involving how each parent's drinking affected that parent or how each parent's drinking affected their treatment of the child.

Adolescent↗