Mathematical aspects of peridic catatonic schizophrenia

The mathematical study of periodic catatonic schizophrenia initiated by Danziger and Elmergreen is generalized by considering the class of differential equations that could be used to describe the periodic behavioral symptoms and periodic variation of biochemical levels in periodic catatonic schizophrenia. The existence of asymptotically stable periodic solutions is studied mathematically and the physical significance of such periodic solutions is discussed. The occurrence of relaxation oscillations is briefly considered. The research in this paper was supported partly by the U.S. Army Research Office (Durham) (Grant No. DA-ARO-D-31-124-72-C69) and partly by a Rutgers Research Council Faculty Fellowship.     

Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency. METHODS: Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records. RESULTS: The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment. CONCLUSIONS: A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion.     

Further studies of some aspects of a neurobiophysical model of schizophrenia

The neurobiophysical model of schizophrenia discussed previously (Bull. Math. Biophysics,26, 167–185, 1964;27, 21–26, 1965) is generalized further, to include catatonic and stuporous states. It is concluded that the development of schizophrenia will proceed through different stages of catatonic and non-catatonic states, depending on parameters which characterize on one hand the general inhibition of the individual, on the other hand what may be called his “stability.” Suggestions for possible clinical verifications of the conclusions are made.     

Successful use of olanzapine in adolescent monozygotic twins with catatonic schizophrenia resistant to electroconvulsive therapy: case report

We describe a case of monozygotic (MZ) male twins (14.6 years old) who suffered from a severe form of catatonic schizophrenia. On admission, the principal symptoms of the brothers were stupor, mutism, catatonic posturing, rigidity, negativism, and refusal of food and liquids. They were treated with electroconvulsive therapy (ECT) with no effect (twin A) and almost no effect (twin B). Both twins improved with initiation of olanzapine therapy. Twin B showed a marked improvement by week 2 on a dose of 10 mg daily (qd). Improvement in twin A was seen by week 4 on a dose of 15 mg qd. Twin B was discharged after 8 weeks and twin A after 11 weeks of olanzapine treatment. This appears to be the first report on concordant positive responses to olanzapine in MZ twins with catatonic schizophrenia, as well as, the first report on concordant resistance to ECT.     

Intellectual performance of chronic schizophrenic patients

Intellectual characteristics of 116 male chronic schizophrenic patients were investigated by using the Quick's test of intelligence. Indirectly, by this test the thinking of examinees was analysed. The examinees were divided into age-groups and differentially diagnostic groups. According to age, they were divided into three groups: from 25 to 40, from 41 to 50, and from 51 to 60 years. There were four differentially diagnostic groups: paranoid, catatonic, and hebephrenic patients and patients with schizophrenia simplex. The study has shown that the intelligence of chronic schizophrenic patients, divided into age groups, was significantly different. The average IQ of patients from 25 to 40 years was 82.9, from 41 to 50 years 67.4, and from 51 to 60 years 52.0. The intelligence of examinees divided into differentially-diagnostic groups was also significantly different. The average IQ of paranoid patients was 74.3, of catatonic patients 64.8, of hebephrenic patients 59.2, and of those with schizophrenia simplex 57.4. Most cases with IQ = 0 related to the group with schizophrenia simplex. The willing-instinctive personality sphere and perceptual disturbances in chronic schizophrenic patients appear to exert a significant influence on their intellectual characteristics.     

The switch mechanism in periodic catatonia and manic-depressive disorder.

Both in periodic catatonia and in manic-depressive disorders sudden switches occur in behavior, in the autonomic nervous system and in the catecholamine metabolism during the transition from interval or depression into catatonia or mania. Both the manic and the catatonic attacks seem to be superimposed on the basic depressive or schizophrenic illnesses. The attacks can be counteracted or suppressed by psychotropic drugs such as alpha-methyldopa, disulfiram, reserpine, haloperidol or chloropromazine which interfere with the catecholamine metabolism or their receptor sites. The involvement of the catecholamines may however be secondary to primary defects in the thyroid, the hypothalamus or the limbic system. The strict periodicity in periodic catatonia points to an accumulation of some active metabolite which may be produced centrally during the interval. At a certain level it may trigger the switch-mechanism and then be reduced during the catatonic phase. In periodic catatonia both the basic schizophrenic disease as well as the periodic manifestations are compensated by thyroxine-thyroid treatment.     

Developmental Profiles of Hormonal and Metabolic Parameters in Male Rats Selected for Catatonic Type of Response

Catatonia is a psychopathological syndrome which manifests itself clinically mainly as motor disorders (dyskinesia). Currently, catatonia is believed to be associated with such human psychic conditions as schizophrenia, bipolar disorders and depression. Despite high incidence, catatonia remains poorly studied, especially with respect to hormonal and metabolic consequences. Modeling catatonic responses on laboratory animals and subsequent analysis of their relationship with expression of important physiological characters (including hormonal and metabolic ones) allow better insight into associative links between psychic and physiological functions of an organism. This work aimed to analyze the parameters of lipid metabolism and testicular steroidogenesis during the neonatal (days 1, 7, 10 and 14), pubertal (7 weeks) and definitive (12 weeks) periods of ontogeny in male rats selected for the catatonic type of response—GC strain recognized as a model of human schizophrenia and depression. During the perinatal developmental period, which is critical for the formation of neuroendocrine regulation, male rats exhibited an increased secretion of androgens (mainly testosterone) required for masculinization of brain structures and some peripheral organs including the reproductive and musculoskeletal systems. In GC male rats, the perinatal testosterone peak was found to shift towards later periods (compared to Wistar male rats) being paralleled by increased serum levels of triglycerides and total cholesterol. During the period of sexual maturation, adult male rats also exhibited differences in the testicular production of testosterone and in lipid levels between the GC and Wistar strains. Throughout the ontogenetic periods studied, GC male rats had a lower body and testicular weight than Wistar rats. The data obtained indicate that genetically determined neuropathological responses of an organism are coupled to the destabilization of the hormonal and metabolic systems.     

Elevation of EGR1/zif268, a Neural Activity Marker,in the Auditory Cortex of Patients with Schizophrenia and its Animal Model

Neurochemical Research - The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by...     

Dissolution of the wakefulness-sleep cycle in patients with catatonic form of schizophrenia

Polysomnograms of two patients with catatonic form of schizophrenia of different duration of the disease were recorded and analyzed. Pronounced disturbances of the wakefulness-sleep cycle (WSC) were revealed. Apart from differences connected with duration of the disease and treatment with corresponding medications, there were detected the general features indicating dissolution of the central nervous system and the very wakefulness-sleep cycle. A certain similarity of the found WSC disturbances with the earlier shown WSC disturbances in rats with predisposition to catalepsy was noted. The conclusion is made about domination of diencephalic influences over the telencephalic one in the studied patients.     

Splitting schizophrenia: periodic catatonia-susceptibility locus on chromosome 15q15

The nature of subtypes in schizophrenia and the meaning of heterogeneity in schizophrenia have been considered a principal controversy in psychiatric research. We addressed these issues in periodic catatonia, a clinical entity derived from Leonhard's classification of schizophrenias, in a genomewide linkage scan. Periodic catatonia is characterized by qualitative psychomotor disturbances during acute psychotic outbursts and by long-term outcome. On the basis of our previous findings of a lifetime morbidity risk of 26.9% of periodic catatonia in first-degree relatives, we conducted a genome scan in 12 multiplex pedigrees with 135 individuals, using 356 markers with an average spacing of 11 cM. In nonparametric multipoint linkage analyses (by GENEHUNTER-PLUS), significant evidence for linkage was obtained on chromosome 15q15 (P = 2.6 x 10(-5); nonparametric LOD score [LOD*] 3.57). A further locus on chromosome 22q13 with suggestive evidence for linkage (P = 1.8 x 10(-3); LOD* 1.85) was detected, which indicated genetic heterogeneity. Parametric linkage analysis under an autosomal dominant model (affecteds-only analysis) provided independent confirmation of nonparametric linkage results, with maximum LOD scores 2.75 (recombination fraction [theta].04; two-point analysis) and 2.89 (theta =.029; four-point analysis), at the chromosome 15q candidate region. Splitting the complex group of schizophrenias on the basis of clinical observation and genetic analysis, we identified periodic catatonia as a valid nosological entity. Our findings provide evidence that periodic catatonia is associated with a major disease locus, which maps to chromosome 15q15.     

Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an inherited neurologic disorder with macrocephaly before the age of one and slowly progressive deterioration of motor functions. Magnetic resonance imaging shows diffusely abnormal and swollen white matter of the cerebral hemispheres and the presence of subcortical cysts in the anterior-temporal region and often also in the frontoparietal region. Mutations in the MLC1 gene, encoding a putative membrane protein, have been recently identified as a cause for MLC. Here, we describe 14 new mutations in 18 patients. Two identified polymorphisms lead to alterations of amino acid residues. The role, suggested by others, of a mutation in the MLC1gene in catatonic schizophrenia and the possible function of the MLC1 protein as a cation channel are discussed.     

Catatonia or depression: the GC rat strain as an animal model of psychopathology

The utility of "incomplete" genetic animal models of human diseases, in particular, psychoses, is discussed. The GC rat strain selected for predisposition to cataleptic reactions is described. It is shown that in many of their characteristics, GC rats are similar to schizophrenic and depressive patients. A possibility that akinetic catatonic states and depressions, hyperkinetic catatonic states and mania share common mechanisms is discussed. It is hypothesized that the GC strain may be an incomplete model of the common genetic and pathogenetic core of schizophrenic substuporous states and depression, which suggests the importance of returning to the issue of a unitary psychosis (Einheitpsychosis).     

Criterion and construct validity of the CogState Schizophrenia Battery in Japanese patients with schizophrenia

Background

The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia.

Methodology/Principal Findings

Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors.

Conclusions/Significance

This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia.     

A disease transmission model in a nonconstant population

A general SIRS disease transmission model is formulated under assumptions that the size of the population varies, the incidence rate is nonlinear, and the recovered (removed) class may also be directly reinfected. For a class of incidence functions it is shown that the model has no periodic solutions. By contrast, for a particular incidence function, a combination of analytical and numerical techniques are used to show that (for some parameters) periodic solutions can arise through homoclinic loops or saddle connections and disappear through Hopf bifurcations.Supported in part by NSERC grant A-8965, the University of Victoria Committee on Faculty Research & Travel, and the Institute for Mathematics and its Applications, Minneapolis, MN, with funds provided by NSF     

Smooth Pursuit and Visual Occlusion: Active Inference and Oculomotor Control in Schizophrenia

This paper introduces a model of oculomotor control during the smooth pursuit of occluded visual targets. This model is based upon active inference, in which subjects try to minimise their (proprioceptive) prediction error based upon posterior beliefs about the hidden causes of their (exteroceptive) sensory input. Our model appeals to a single principle – the minimisation of variational free energy – to provide Bayes optimal solutions to the smooth pursuit problem. However, it tries to accommodate the cardinal features of smooth pursuit of partially occluded targets that have been observed empirically in normal subjects and schizophrenia. Specifically, we account for the ability of normal subjects to anticipate periodic target trajectories and emit pre-emptive smooth pursuit eye movements – prior to the emergence of a target from behind an occluder. Furthermore, we show that a single deficit in the postsynaptic gain of prediction error units (encoding the precision of posterior beliefs) can account for several features of smooth pursuit in schizophrenia: namely, a reduction in motor gain and anticipatory eye movements during visual occlusion, a paradoxical improvement in tracking unpredicted deviations from target trajectories and a failure to recognise and exploit regularities in the periodic motion of visual targets. This model will form the basis of subsequent (dynamic causal) models of empirical eye tracking measurements, which we hope to validate, using psychopharmacology and studies of schizophrenia.     

Contingencies in the behaviour of the crab Heterozius rotundifrons

We recorded the responses of individual intertidal crabs, Heterozius rotundifrons, to stimuli presented singly and in combinations in the laboratory. Undisturbed crabs did not respond to the introduction of odour from a crushed conspecific but did respond strongly to food odour. Undisturbed crabs responded equally to food odour alone and a combination of food and odour from a crushed conspecific. When tactile stimulation was applied, as when the crab is grasped by a predator, individual H. rotunidfrons assumed a rigid, appendage-extended posture for several minutes. Tests with predatory fish showed that this catatonic posture is a very effective predator-defence mechanism. The duration of the catatonic state was decreased by the addition of food odour but increased by the addition of alarm odour (crushed conspecific) or the combination of alarm and food odours. Thus, which chemical stimulus was dominant was reversed by tactile input (i.e. dominance was contingent upon context). The effect of alarm odour on food odour responses lasted 4 h. Visual input in the form of a shadow passing over the crabs, either before or after tactile induction of the catatonic state, also increased the duration of that state. However, the duration of the catatonic state following exposure to both cues associated with danger (shadow+alarm odour) was similar to that of the control level. The crabs appeared to switch strategies when three cues associated with danger (tactile grasping, alarm odour and shadows) were detected, either simultaneously or over a 4-h period. The results illustrate the highly contingent nature of the behaviour of these crabs. Copyright 2000 The Association for the Study of Animal Behaviour.     

Symptoms of schizophrenia in Hispanic and Anglo veterans

This study explores cultural influences on symptoms and course of schizophrenic disorder. Hispanic veterans with schizophrenia are compared to a similar group of White non-Hispanic (Anglo) veterans. Symptoms were elicited with a structured diagnostic interview and a battery of rating instruments. Primary symptoms of schizophrenia (e.g., hallucinations, delusions, functional deterioration) were very similar for both groups. However, Hispanic patients reported a later age of onset, exhibited more somatization, and spent less time in the hospital than Anglo patients.This study was supported by a grant from the Veterans Administration Health Services Research and Development Service (Project 11R 81-633).     

The predisposition to catatonic reactions, monoamine oxidase and the delta-sleep peptide in rats]

MAO B/MAO A rations and the influence of delta-sleep inducing peptide (DSIP) on the two forms of MAO and on the predisposition to different types of catatonic reactions were compared in rats of GC strain selected from Wistar for predisposition to catalepsy, and in wild rats. In GC rats, the MAO B/MAO A ratio was increased, as compared to Wistar, in the brain stem and hemispheres, whereas in wild rats predisposed to catatonia it was increased, as compared to normal wild rats, only in the hemispheres. In GC rats, this increase of the MAO B/MAO A ratio was due to a decrease of MAO A and increase of MAO B activity, while in wild catatonic rats only due to heightened MAO B activity. Administration of DSIP abolished the susceptibility to catatonic reactions and normalized the MAO B/MAO A ratio both in GC and in wild catatonic rats. There seems to be a partial similarity of physiological mechanisms of catatonic reactions in laboratory albino and in wild rats.     

Transient oscillations induced by delayed growth response in the chemostat

In this paper, in order to try to account for the transient oscillations observed in chemostat experiments, we consider a model of single species growth in a chemostat that involves delayed growth response. The time delay models the lag involved in the nutrient conversion process. Both monotone response functions and nonmonotone response functions are considered. The nonmonotone response function models the inhibitory effects of growth response of certain nutrients when concentrations are too high. By applying local and global Hopf bifurcation theorems, we prove that the model has unstable periodic solutions that bifurcate from unstable nonnegative equilibria as the parameter measuring the delay passes through certain critical values and that these local periodic solutions can persist, even if the delay parameter moves far from the critical (local) bifurcation values.When there are two positive equilibria, then positive periodic solutions can exist. When there is a unique positive equilibrium, the model does not have positive periodic oscillations and the unique positive equilibrium is globally asymptotically stable. However, the model can have periodic solutions that change sign. Although these solutions are not biologically meaningful, provided the initial data starts close enough to the unstable manifold of one of these periodic solutions they may still help to account for the transient oscillations that have been frequently observed in chemostat experiments. Numerical simulations are provided to illustrate that the model has varying degrees of transient oscillatory behaviour that can be controlled by the choice of the initial data.Mathematics Subject Classification: 34D20, 34K20, 92D25Research was partially supported by NSERC of Canada.This work was partly done while this author was a postdoc at McMaster.     

Global asymptotic stability of a periodic solution to an epidemic model

In this paper a periodic delay differential equation with spatial spread is investigated. This equation can be used to model the growth of malaria which is transmitted by a mosquito. Using monotone techniques, it is shown that the following bifurcation holds: either the disease dies out or the density of infectious people tends to a spatially homogeneous, time periodic and positive solution.Research partially supported by NSF Grant MCS 810-4837