Unmedicated Chronic Schizophrenic Patients Research Articles

Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism

Spontaneously occurring abnormal behaviors in animals have recently received considerable attention, both in veterinary medicine and as a potential model for abnormal behavior in several human mental disorders. Stereotypies are abnormal repetitive, unvarying, and functionless behaviors that are often performed by captive and domesticated animals housed in barren environments. They closely resemble the stereotypies of autistic and mentally retarded patients, stereotypies of unmedicated chronic schizophrenic patients, certain classes of simple tic in Tourette’s syndrome, and several drug-induced behaviors. However, evidence for a common mechanism has been lacking. Stereotypies in human mental disorders are indicative of profound brain dysfunction involving the basal ganglia, and are associated with pervasive voluntary-motor impairments and psychological distress. Here we show that stereotypy in captive Orange-Wing Amazon Parrots ( Amazona amazonica) is correlated with poor performance on the same psychiatric task (the ‘gambling task’) as stereotypy in autistic and schizophrenic patients. The task measures recurrent perseveration—the tendency to inappropriately repeat responses. Thus, the more stereotypy a parrot performed, the more likely it was to inappropriately repeat itself from trial-to-trial on the task; and the more rapidly it made repeated, but not switched, responses. These results parallel the executive motor impairments seen in human patients, and therefore suggest that, like in human patients, stereotypy in caged parrots reflects a general disinhibition of the behavioral control mechanisms of the dorsal basal ganglia. If this result holds true in other laboratory species, stereotypic animals are likely to be of questionable utility in behavior, neuroscience, and neuropharmacological experiments. In humans, stereotypies and obsessive–compulsive behaviors are considered to be mutually exclusive categories of behavior, with different neural substrates, and different treatment strategies. These results, therefore, suggest that the pharmacological treatment of stereotypies in veterinary medicine based on the assumption that they are equivalent to human Obsessive–Compulsive Disorder may be inappropriate. As stereotypies in captive animals develop in response to the captive environment, these results also emphasize the role that the environment may play in eliciting or exacerbating stereotypy in human patients. Finally, by parallel to human patients, there is a potential psychological distress in animals showing these behaviors.

Plasma TBARS levels in unmedicated chronic schizophrenic patients

Although the fields of systems and integrative biology are in full expansion, few teams are involved worldwide into the study of reproductive function from the mathematical modeling viewpoint. This may be due to the fact that the reproductive function is not compulsory for individual organism survival, even if it is for species survival. Alternatively, the complexity of reproductive physiology may be discouraging. Indeed, the hypothalamo-pituitary-gonadal (HPG) axis involves not only several organs and tissues but also intricate time (from the neuronal millisecond timescale to circannual rhythmicity) and space (from molecules to organs) scales. Yet, mathematical modeling, and especially multiscale modeling, can renew our approaches of the molecular, cellular, and physiological processes underlying the control of reproductive functions. In turn, the remarkable dynamic features exhibited by the HPG axis raise intriguing and challenging questions to modelers and applied mathematicians. In this article, we draw a panoramic review of some mathematical models designed in the framework of the female HPG, with a special focus on the gonadal and central control of follicular development. On the gonadal side, the modeling of follicular development calls to the generic formalism of structured cell populations, that allows one to make mechanistic links between the control of cell fate (proliferation, differentiation, or apoptosis) and that of the follicle fate (ovulation or degeneration) or to investigate how the functional interactions between the oocyte and its surrounding cells shape the follicle morphogenesis. On the central, mainly hypothalamic side, models based on dynamical systems with multiple timescales allow one to represent within a single framework both the pulsatile and surge patterns of the neurohormone GnRH. Beyond their interest in basic research investigations, mathematical models can also be at the source of useful tools to study the encoding and decoding of the (neuro-) hormonal signals at play within the HPG axis and detect complex, possibly hidden rhythms, in experimental time series.

A review of training in neuropsychiatry

The boundary between neurology and psychiatry has never been sharply defined. It remains the case that a number of conditions (e.g. epilepsy, head-injury sequelae, dementia, and conversion hysteria) are seen by both neurologists and psychiatrists (Reynolds & Trimble, 1989). Few neurologists would dispute that there may be a marked psychiatric element to the presentation of multiple sclerosis, and it has long been noticed that even unmedicated chronic schizophrenic patients sometimes exhibit abnormalities of movement and so-called “soft” neurological signs such as dysgraphia and clumsiness (Lishman, 1988). These and other conditions may all on occasion present to the neuropsychiatrist.

Fluvoxamine improves negative symptoms in treated chronic schizophrenia: An add-on double-blind, placebo-controlled study

Although antipsychotic drugs are highly effective in alleviating positive symptoms of schizophrenia they have little impact on the negative symptoms of the illness. These symptoms, including apathy, social withdrawal, blunted affect, and motor retardation present serious obstacles to the successful rehabilitation of chronic schizophrenic patients and have been the focus of renewed interest (Crow 1980; Andreasen and Olsen 1982). The hypothesis of schizophrenia, based on a significant correlation between antipsychotic potency of neuroleptic drugs and their propensity to block dopamine receptors (Seeman et al 1976; Snyder 1976) is widely accepted, but other neurotransmitters may have a role in the pathogenesis, particularly of negative symptoms. Evidence pointing to serotonergic dysfunction in schizophrenia has accumulated. Increased plasma (Garelis et al 1975; DeLisi et ai 1981; Freedman et al 1981) and platelet (Jackman et al 1983) serotonin concentrations in chronic schizophrenics including a possible link to cortical atrophy (DeLisi et al 1981) have been reported and our group (Lerer et al 1988) found a blunted prolactin response to fenfluramine challenge in unmedicated chronic schizophrenic patients compared to normal controls. Furthermore, improvement in negative symptoms of schizophrenia has been reported as a result of treatment with serotonin active agents, fenfluramine (Stahl et al 1985), ritanserin (Gelders et al 1986) and ¢yproheptadine (Silver et al 1989). Clozapine, which appears to be effective in treatmentresistent positive and negative symptoms of chronic schizophrenia, has a high serotonergic:dopaminergic blocking ratio (Kant ct al 1988. Richelson 1984). There is little evidence that antidepressants can ameliorate negative symptoms of schizophrenia, although tricyclic and monoamine oxidase inhibiting (MAOI) antidepressants may be useful in schizophrenic patients demonstrating depressive symptoms (Siris et al 1978). However, the recently developed antidepressants such as fluvoxamine (Benfield and Ward 1986) acting specifically on the serotonergic system may be effective in treating primary negative symptoms of schizophrenia. We report the results of a doubleblind add-on study of fluvoxamine in chronic schizophrenic patients. To our knowledge this is the first such report.

EEG power variation in schizophrenic subgroups: Effects of emotionally salient stimuli

Eighteen unmedicated chronic schizophrenic patients and 13 normal controls were tested in a paradigm designed to examine functional changes in electroencephalographic (EEG) activity following presentation of emotionally salient auditory stimuli and control tones. Five standard bands of EEG spectral power were examined at bilateral frontal and temporal surface recording sites. The schizophrenic subjects were assigned to diagnostic subgroups on the basis of DSM-III-R criteria following independent clinical examination by two staff psychiatrists. Those subjects who met DSM-III-R criteria for paranoid schizophrenia were assigned to one subgroup (PS subgroup), while those who met DSM-III-R criteria for either residual or undifferentiated schizophrenia were assigned to a second subgroup (R/US subgroup). Analysis of Variance of EEG activity recorded at bilateral frontal (F1 and F2) and temporal (T3 and T4) scalp leads revealed significant diagnosis-related differences in alpha and beta-2 activity at temporal recording sites, and in beta-1 and beta-2 activity at frontal recording sites. Post-hoc tests revealed that significant differences in all four measures occurred in the R/US subgroup, which showed a decrease in temporal alpha and an increase in temporal beta-2 power as compared to controls. These variations in EEG activity appeared to demonstrate a degree of subgroup specificity, as the R/US subgroup also differed significantly from the PS subgroup on most of these measures. Significant subgroup-specific lateralization effects were also observed for temporal lobe delta activity and for frontal lobe beta-1 activity. These findings are interpreted in terms of subgroup-specific alterations in the processing of sensory information in schizophrenia, particularly when such information is emotionally salient. They suggest that subgroup differences in emotional and clinical state may be reflected in differential changes in EEG spectra within the schizophrenic population.

3H-imipramine binding in blood platelets of schizophrenic patients

3H-Imipramine binding was studied in the blood platelets of 51 unmedicated chronic schizophrenic patients. Univariate analyses of log-transformed data revealed that B max was significantly lower in shcizophrenic patients than normal volunteers; K d was nonsignificantly higher in the schizophrenics. A multivariate analysis of variance indicated the K d and B max both differ significantly between normal controls and shcizophrenic patients in the direction of increased K d and decreased B max in the schizophrenics. These results indicate that decreased platelet imipramine binding is not specific for major depression.

The dexamethasone suppression test in newly hospitalized schizophrenic patients.

Of 15 unmedicated chronic schizophrenic patients with acute exacerbations and 15 healthy controls given the dexamethasone suppression test (DST), 11 patients and two controls were nonsuppressors. The results add to the evidence that the DST has limited value in psychiatric diagnosis.

Platelet monoamine oxidase and clinical phenomenology of schizophrenia

Platelet monoamine oxidase activity (MAO) was determined in 39 unmedicated chronic schizophrenic patients and 88 normal control subjects. Platelet MAO activity did not distinguish paranoid from nonparanoid patients or patients who met Taylor and Abrams criteria for narrowly defined schizophrenia from other schizophrenics. Enzyme activity was not related to either prognostic scores or age at onset of illness. MAO activity was decreased in patients compared to controls, and was lower in males than in females. Our findings indicate that clinical phenomenology, as defined in the present study, is of limited use in identifying biological subtypes of schizophrenia with deviant platelet MAO activity.

Arousal related to excretion of noradrenaline metabolites and clinical aspects of unmedicated chronic schizophrenic patients

1. 1. The interrelationship between the following psychophysiological, biochemical and clinical measures have been investigated in a group of unmedicated chronic schizophrenics; skin conductance level and orienting responses to tones; heart rate; excretion of vanillylmandelic acid (VMA), sulphate and total methoxyhydroxyphenylglycol (MHPG); clinical ratings of symptom severity. 2. 2. More severely ill subjects showed evidence of overarousal and had higher skin conductance levels and heart rates, and less habituation of skin conductance orienting responses to tones than the less severely ill. These measures were not related to ratings of anxiety. 3. 3. Physiological measures of peripheral autonomic function (skin conductance level and heart rate) were unexpectedly inversely related to VMA excretion, a noradrenaline metabolite putatively of peripheral origin, and to MHPG excretion. 4. 4. The central processes of habituation and symptom severity were more closely related to excretion of MHPG than VMA. This offers support for the suggestion that this noradrenaline metabolite more closely reflects brain noradrenaline turnover than VMA. The inverse relationship between MHPG excretion and measures of arousal suggests that brain noradrenergic transmission is not directly related to arousal levels in schizophrenia. 5. 5. Studies of these variables in control subjects will determine whether these findings are specific to schizophrenia.

Suppression of prolactin by dopamine agonists in schizophrenics and controls.

Prolactin levels were determined in plasma samples obtained before and after administration of apomorphine or L-dopa to otherwise unmedicated chronic schizophrenic patients or control subjects. Basal prolactin levels did not differ in these two groups. Suppression of prolactin levels after each dopamine agonist was highly significant. Suppression in schizophrenics was slightly less than in controls following apomorphine and slightly greater following L-dopa. The authors discuss the implications of these findings as well as the limitations of the prolactin regulatory system as an index of dopamine agonist sensitivity.

Platelet serotonin concentration and monoamine oxidase activity in unmedicated chronic schizophrenic and in schizoaffective patients.

Elevated blood serotonin, perhaps secondary to reduced platelet MAO, has been reported in a group of chronic schizophrenic patients. We have failed to find elevated platelet serotonin, or any relationship between platelet serotonin and MAO either in a group of unmedicated chronic schizophrenic patients or in a group of schizoaffective patients. Possible reasons for these discrepancies are discussed.

Correction

Back to table of contents Previous article Next article ArticleNo AccessCorrectionPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.133.6.720-cAboutSectionsView articleAbstractPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleAbstractIn "Decreased Blood Platelet MAO Activity in Unmedicated Chronic Schizophrenic Patients" by Edward F. Domino, M.D., and Sumathy Sampath Khanna, Ph.D. (March 1976 issue), the units of MAO activity were incorrectly described as µmol/mg protein/hour; this should have read nmol/mg protein/hour. This error was pointed out to us and to Dr. Domino by Ross J. Baldessarini, M.D. Dr. Domino has informed us that the problem resulted from typographical errors on the original manuscript and wishes to apologize for any confusion this may have caused Journal readers. The staff wishes to thank Drs. Domino and Baldessarini for correcting this error. Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByNone Volume 133Issue 6 June 1976Pages 720-c-720 Metrics PDF download History Published online 1 April 2006 Published in print 1 June 1976

Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients

The authors found lower platelet monoamine oxidase (MAO) activity in 13 unmedicated chronic schizophrenic male patients in comparison to 13 mentally normal control male subjects--a finding that agrees with previous studies showing MAO activity to be low in the platelets of chronic schizophrenic patients. The authors urge that studies exploring endocrine factors and the role of hospitalization be undertaken to attempt to explain this finding.

Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine. Application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients.

On the basis of post-mortem studies it has been proposed that the central deficit in schizophrenia may be in noradrenergic transmission. It has also been proposed that there is a substantial central contribution to the excretion of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and more particularly of its sulphate conjugate in man. There is throught to be a lesser central contribution to the excretion of the other major noradrenaline metabolites, vanillylmandelic acid (VMA) and the glucuronide conjugate of MHPG. A strong negative correlation was found between severity of illness in a group of 18 unmedicated chronic schizophrenic patients and their 24-h excretion of MHPG-sulphate but not of MHPG-glucuronide or VMA. However there was no significant difference in the mean excretion of MHPG conjugates or of VMA between the schizophrenic group and an institutional control group. This supports the idea of a relation between MHPG-sulphate excretion and central noradrenergic activity, but suggests that reduced brain noradrenaline turnover is neither necessary nor sufficient for schizophrenia to occur. One possible explanation is that reduced turnover pre-disposes towards a more severe illness in schizophrenics.

Elevated blood serotonin concentrations in unmediated chronic schizophrenic patients: a preliminary study

The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.