[What is the age of onset in schizophrenia?].
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Biomedical subjects
Publications and source records attributed to J Moring.
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The ether lipid analogs (R)-PAF, (R)-ET-18-OMe and (R)-Lyso-PAF can form bilayers. Using differential scanning calorimetry (DSC) and small angle X-ray diffraction, we have investigated bilayers formed entirely of these molecules. Small angle X-ray diffraction experiments strongly indicated that these bilayers are interdigitated at 98% relative humidity in the gel phase. The slight differences in the structures of the ether lipids affect their thermal behavior and packing properties. Of the three, (R)-Lyso-PAF shows the highest phase transition temperature, broadest phase transition peak and smallest enthalpy change. These characteristics may be attributed to hydrogen bonding of the -OH group at sn-2 position of its glycerol backbone to water or to other (R)-Lyso-PAF molecules. The interdigitated structure shows that these bilayers are similar to lipid bilayers and suggests that these molecules could easily insert themselves into membranes to reach their respective active sites or to perturb the membranes. The packing and thermal characteristics of (R)-Lyso-PAF may help explain its biological inactivity.
BACKGROUND: The aim was to give estimates of the incidence of different mental disorders from a Finnish prospective epidemiological follow-up study, the UKKI Study. METHOD: The original probability sample consisted of 1000 persons, aged 15-64 years. The baseline survey took place in 1969-71, and follow-up surveys were conducted 5 and 16 years after the baseline survey. The research methods included a personal psychiatric interview and data collection from different registers. The diagnostic system was based on the ICD-8 classification. RESULTS: The estimated annual incidence of all mental disorders was close to 15 per 1000 both between baseline and the 5-year follow-up as well as between the 5-year and the 16-year follow-up. During the entire 16-year follow-up period the annual incidence of all disorders was 14 per 1000 in men and 17 per 1000 in women. The annual income of neurotic disorders was 10 per 1000 in men and 14 per 1000 in women, and that of psychotic disorders 2 per 1000. CONCLUSIONS: In the literature, there are huge differences in the results concerning incidence of mental disorders. The results of the present study were rather close to those of the Swedish Lundby Study, but nowhere near the results of the American ECA Study.
The single crystal structures of the two diastereomeric 4-heptadecyl derivatives of (1R,5S)-3,6,8-trioxabicyclo[3.2.1]octane have been determined by X-ray diffraction to be (1R,4R,5S)-heptadecyl-3,6,8-trioxabicyclo[3.2.1]octane (I) and (1R,4S,5S)-4-heptadecyl[3,6,8-trioxabicyclo[3.2.1]octane (II), respectively, which have an exo or axial 4-heptadecyl group, and an endo or equatorial 4-heptadecyl group, respectively. The structures of I and II had been suggested by their phase-sensitive 2D NOESY 1H-NMR spectra, but are now established unambiguously. These optically pure non-ionic lipid-like amphipathic molecules (I and II) represent the first 3,6,8-trioxabicyclo[3.2.1]octanes for which single crystal structures have been solved. Crystals of both isomer I and isomer II were orthorhombic with space group P2(1)2(1)2(1), and had unit cell dimensions of a = 9.586, b = 43.14, c = 5.289 A, and a = 7.34, b = 51.8, c = 5.636 A, respectively. The structures of I and II were both solved by using direct methods to R = 0.045 and R = 0.086, respectively. Both I and II pack in stacked bilayers with interdigitating and tilting hydrocarbon chains. The molecular and hydrocarbon cross sections are I: S = 50.70 A2, sigma = 19.00 A2; and II: S = 41.37 A2, sigma = 18.26 A2.
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MK-801, a noncompetitive antagonist of the NMDA (N-methyl-D-aspartate) receptor, has protective effects against excitotoxicity and ethanol withdrawal seizures. We have determined membrane/buffer partition coefficients (Kp[mem]) of MK-801 and its rates of association with and dissociation from membranes. Kp[mem] (+/- SD) = 1137 (+/- 320) in DOPC membranes and 485 (+/- 99) in synaptoneurosomal (SNM) lipid membranes from rat cerebral cortex (unilamellar vesicles). In multilamellar vesicles, Kp[mem] was higher: 3374 (+/- 253) in DOPC and 6879 (+/- 947) in SNM. In cholesterol/DOPC membranes, Kp[mem] decreased as the cholesterol content increased. MK-801 associated with and dissociated from membranes rapidly. Addition of ethanol to SNM did not affect Kp[mem]. MK-801 decreased the cooperative unit size of DMPC membranes. The decrease was smaller than that caused by 1,4-dihydropyridine drugs, indicating a weaker interaction with the hydrocarbon core. Small angle x-ray diffraction, with multilayer autocorrelation difference function modeling, indicated that MK-801 in a cholesterol/DOPC membrane (mole ratio = 0.6) causes a perturbation at approximately 16.0 A from the bilayer center. In bilayers of cholesterol/DOPC = 0.15 (mole ratio) or pure DOPC, the perturbation caused by MK-801 was more complex. The physical chemical interactions of MK-801 with membranes in vitro are consistent with a fast onset and short duration of action in vivo.
A nationwide Finnish sample of schizophrenics' offspring given up for adoption was compared blindly with matched controls, who were adopted offspring of non-schizophrenic biological parents. The adoptive families were investigated thoroughly using joint and individual interviews and psychological tests. The biological parents were also interviewed and tested. Among the 155 index offspring, the percentage of both psychoses and other severe diagnoses (borderline syndrome and severe personality disorders) was significantly higher than in the 186 matched control adoptees. This supports a genetic hypothesis. However, notable differences between these two groups only emerged in the families which were rated as disturbed. Thus the genetic effect (i.e. the differences between high and low genetic propensity) was only manifested as a psychiatric disorder in the presence of a disturbed family environment. The impact of disturbed family relations was strongest in the presence of the appropriate genotype.
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Admission to a close ward was analyzed at the Department of Psychiatry, University of Oulu using 888 patients and their 1861 assessment and treatment episodes. Of all referrals for involuntary assessment (n = 237, 12.7% of all episodes) a total of 44 (2.4%) used "questionable" juridical criteria: the final diagnosis was not psychosis. In the follow-up, the admission of the questionable patients was mainly considered a clinical necessity, and at least one third of them were diagnosed as being psychotic and 2 committed suicide. An elevated probability of belonging to the questionable group was seen among patients in their first treatment episode, with minimal professional education, female sex, short treatment time, or residence in a rural area. The result suggests that some inequality existed between women and men, less and more educated and residents of urban and rural areas. The results also reflect conflict between the ethics and clinical practice of involuntary commitment, and the phrasing of the law, especially its diagnostic limitation to psychotic states only.
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Small angle x-ray scattering has been used to investigate the structure of synaptoneurosomal (SNM) membranes from rat cerebral cortex. Electron micrographs of the preparation showed SNM with classical synaptic appositions intact, other vesicles, occasional mitochondria, and some myelin. An immunoassay for myelin basic protein placed the myelin content of normal rat SNM at less than 2% by weight of the total membrane present. X-Ray diffraction patterns showed five diffraction orders with a unit cell repeat for the membrane of 71 to 78 A at higher hydration states. At lower hydration, 11 orders appeared; the unit cell repeat was 130 A, indicating that the unit cell contained two membranes. Electron density profiles for the 130-A unit cell were determined; they clearly showed the two opposed asymmetrical membranes of the SNM vesicles. SNM membrane/buffer partition coefficients (Kp) of imidazobenzodiazepine and 1,4-dihydropyridine (DHP) calcium channel drugs were measured; Kp's for DHP drugs were approximately five times higher in rabbit light sarcoplasmic reticulum than in SNM. Ro 15-1788 and the DHP BAY K 8644 bind primarily to the outer monolayer of vesicles of intact SNM membranes. Nonspecific equilibrium binding of Ro 15-1788 occurs mainly in the upper acyl chain of the bilayer in lipid extracts of SNM membrane.
A recently-detoxified heroin addict was exposed to a battery of drug-related stimuli which he had previously assisted in identifying as personally relevant. Skin conductance was measured during exposure to both drug-related stimuli and neutral stimulus items. The amplitude of the first skin conductance response following stimulus presentation and the number of skin conductance responses during stimulus presentation were significantly different for the drug-related and neutral stimuli. Post-exposure subjective ranking of the drug-related items differed markedly from pre-exposure ranking; and the post-exposure subjective rankings were closer to the ranked order of the measured physiological responses than the pre-exposure subjective rankings. The use of cue exposure assessment in planning treatment for relapse prevention and the possible importance of idiosyncratic cues in the environment are discussed.
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Amiodarone is a drug used in the treatment of cardiac arrhythmias and is believed to have a persistent interaction with cellular membranes. This study sought to examine the structure and location of amiodarone in a membrane bilayer. Amiodarone has a high membrane partition coefficient on the order of 10(6). Small angle x-ray diffraction was used to determine the position of the iodine atoms of amiodarone in dipalmitoylphosphatidylcholine (DPPC) lipid bilayers under conditions of low temperature and hydration where the DPPC bilayer is in the gel state. The time-averaged position of the iodine atoms was determined to be approximately 6 A from the center (terminal methyl region) of the lipid bilayer. A dielectric constant of kappa = 2, which approximates that of the bilayer hydrocarbon core region, was used in calculating a minimum energy structure for membrane-bound amiodarone. This calculated structure when compared with the crystal structure of amiodarone demonstrated that amiodarone could assume a conformation in the bilayer significantly different from that in the crystal. The results reported here are an attempt to correlate the position of a membrane-active drug in a lipid bilayer with its time-averaged conformation. This type of analysis promises to be of great use in the design of drugs with greater potency and higher specificity.
A nationwide Finnish sample of index offspring given up for adoption by schizophrenic women has been compared blindly with matched controls, that is, adopted-away offspring of nonschizophrenic biologic parents. The adoptive families have been investigated directly by joint and individual interviews and psychological tests. Interviewing and testing of biologic parents is in progress. In the total sample, thus far examined, of 124 index offspring, 9 (7.3%) have become psychotic; of 147 control offspring, 2 (1.4%) have become psychotic.
A nationwide Finnish sample of schizophrenic mothers' offspring given up for adoption was compared blindly with matched controls (i.e., adopted-away offspring of nonschizophrenic biological parents). The offspring were born 1927-79. To date, a total of 247 adoptive families (112 index and 135 controls) have been investigated and rated. Of the 10 psychotic cases, 8 are offspring of schizophrenics and 2 are control offspring. However, no seriously disturbed offspring is found in a healthy or mildly disturbed adoptive family, and of those offspring who were psychotic or seriously disturbed, nearly all were reared in disturbed adoptive families. This supports the hypothesis that a possible genetic vulnerability has interacted with the adoptive rearing environment.