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PubMed1995

Minor physical anomalies in psychoses: associations with clinical and putative aetiological variables.

This study of patients with functional psychoses set out to examine associations between minor physical anomalies (MPAs) and demographic, clinical, CT scan measures, and putative aetiological variables. 157 psychotic patients had minor physical anomalies assessed using a modified Waldrop scale. RDC diagnoses for these patients were: schizophrenia (n = 79), schizoaffective disorder (n = 31), mania (n = 24), major depression (n = 13), unspecified functional psychosis (n = 8), other organic psychosis (n = 2). 63 healthy white controls were also assessed with the modified Waldrop scale. Minor physical anomalies were not associated with any particular diagnosis. For white subjects, patients had significantly more MPAs than well controls. Anomalies of the palate were the most frequent item reported in patients and controls. For males, there was a weak association between the presence of MPAs and positive family history of a major psychiatric disorder. Those with MPAs required more frequent and longer psychiatric admissions, and showed impaired ability on a test sensitive to left parietal system function. Within the patient group, there were no associations between MPAs and gender, age at onset, negative symptoms, premorbid level of functioning, estimated premorbid intelligence, pregnancy and birth complications, and selected CT variables. Minor physical anomalies are found in a range of functional psychoses. There may be overlap between the various genes that predispose to psychiatric illness (especially in males) and those genes that predispose to developmental instability.

Adult↗

PubMed1996

Are reduced head circumference at birth and increased obstetric complications associated only with schizophrenic psychosis? A comparison with schizo-affective and unspecified functional psychoses.

Patients with schizophrenia have previously been found to have decreased head circumference (HC) at birth and increased rates of obstetric complications (OCs). To determine whether this is restricted to schizophrenia or also characterizes other rather similar psychoses, 30 patients with schizo-affective disorder or unspecified functional psychosis defined by Research Diagnostic Criteria were compared with 30 demographically matched control cases from the same delivery series on HC and OCs, blindly studied through hospital birth records. As compared with controls, the 30 nonschizophrenic patients had significantly decreased HC but not lower birthweight, shoulder circumference or shorter body length. HC was significantly decreased among female but not male patients. Rates of OCs were not significantly increased in the 30 nonschizophrenic patients versus controls. Neither HC nor OC rates were systematically associated with family history of psychosis or season of birth among patients. The findings indicate that these nonschizophrenic psychoses are similar to schizophrenia in having reduced HC at birth but dissimilar from schizophrenia in not having increased rates of OCs. The findings suggest that the gender focus in schizophrenia's etiology should be broadened to include other rather similar diagnostic categories.

Adult↗

PubMed2004

Neurotrophic factors and the pathophysiology of schizophrenic psychoses.

The aim of this review is to summarize the present state of findings on altered neurotrophic factor levels in schizophrenic psychoses, on variations in genes coding for neurotrophic factors, and on the effect of antipsychotic drugs on the expression level of neurotrophic factors. This is a conceptual paper that aims to establish the link between the neuromaldevelopment theory of schizophrenia and neurotrophic factors. An extensive literature review has been done using the Pub Med database, a service of the National Library of Medicine, which includes over 14 million citations for biomedical articles back to the 1950s. The majority of studies discussed in this review support the notion of alterations of neurotrophic factors at the protein and gene level, respectively, and support the hypothesis that these alterations could, at least partially, explain some of the morphological, cytoarchitectural and neurobiochemical abnormalities found in the brain of schizophrenic patients. However, the results are not always conclusive and the clinical significance of these alterations is not fully understood. It is, thus, important to further neurotrophic factor research in order to better understand the etiopathogenesis of schizophrenic psychoses and, thus, potentially develop new treatment strategies urgently needed for patients suffering from these devastating disorders.

Animals↗

PubMed2003

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Recent evidence suggests that genetic and biochemical factors associated with psychoses may also provide an increased propensity to think creatively. The evolutionary theories linking brain growth and diet to the appearance of creative endeavors have been made recently, but they lack a direct link to research on the biological correlates of divergent and creative thought. Expanding upon Horrobin's theory that changes in brain size and in neural microconnectivity came about as a result of changes in dietary fat and phospholipid incorporation of highly unsaturated fatty acids, we propose a theory relating phospholipase A2 (PLA2) activity to the neuromodulatory effects of the noradrenergic system. This theory offers probable links between attention, divergent thinking, and arousal through a mechanism that emphasizes optimal individual functioning of the PLA2 and NE systems as they interact with structural and biochemical states of the brain. We hope that this theory will stimulate new research in the neural basis of creativity and its connection to psychoses.

Brain↗

PubMed2005

Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses.

In the recent years, elevated homocysteine plasma levels have been reported to represent a risk factor not only for atherosclerosis, but also to be associated with dementia, depression and-in a gender-specific manner-schizophrenia. Here, we explored a possible association between homocysteinemia and psychiatric disorders. Fasting homocysteine, vitamin B12 and folate were determined in an ethnically homogeneous female population with different psychiatric disorders. Homocysteine was not elevated in females suffering from schizophrenia (mean, 11.6+/-5.8 micromol/l). As shown previously, increased homocysteine concentrations were associated not only with dementia of different aetiology (mean, 17.2+/-6.7 micromol/l; chi2=23.39, p<0.001, compared to the schizophrenia group), but also with depressive disorders (mean, 12.9+/-3.8 micromol/l; chi2=6.88, p=0.009). B12 and folate levels did not differ between different diagnostic groups. To further explore the connection between homocysteinemia and affective psychoses, a case-control study examining the C677T and the A1298C variants of methylenetetrahydrofolate reductase was conducted. The latter polymorphism not only was associated with affective psychoses in general, but also when divided in unipolar depression and bipolar affective disorder. In conclusion, we suggest that in females homocysteinemia is an unspecific risk factor for organic brain disorders like dementia, and possibly depression, but not for schizophrenia.

Adolescent↗

PubMed2006

Motoric neurological soft signs and psychopathological symptoms in schizophrenic psychoses.

Motoric neurological soft signs (NSS) were investigated by means of the Brief Motor Scale (BMS) in 82 inpatients with DSM-III-R schizophrenic psychoses. To address potential fluctuations of psychopathological symptoms and extrapyramidal side effects, patients were examined in the subacute state, twice at an interval of 14 days on the average. NSS were significantly correlated with severity of illness, lower social functioning, and negative symptoms. Modest, but significant correlations were found between NSS and extrapyramidal side effects as assessed on the Simpson-Angus Scale. Neither the neuroleptic dose prescribed to the patient, nor scores for tardive dyskinesia and akathisia were significantly correlated with NSS. Moreover, NSS scores did not significantly differ between patients receiving clozapine and conventional neuroleptics. Patients in whom psychopathological symptoms remained stable or improved over the clinical course showed a significant reduction of NSS scores. This finding did not apply to those patients in whom psychopathological symptoms deteriorated. Our findings demonstrate that NSS in schizophrenic psychoses are relatively independent of neuroleptic side effects, but they are associated with the severity and persistence of psychopathological symptoms and with poor social functioning.

Adolescent↗

PubMed2004

Health and development in the first 4 years of life in offspring of women with schizophrenia and affective psychoses: Well-Baby Clinic information.

The investigation of genetic high-risk (HR) groups provides the opportunity to study diathesis characteristics associated with schizophrenia (Sc) and affective psychoses. High-risk offspring of women with a history of schizophrenia, affective and other psychoses (n = 84), as well as normal-risk control (NC) offspring (n = 100), were studied from 0 to 4 years of age, using prospectively recorded information from Well-Baby Clinic (WBC) records. Blind assessment of an average of 25 contacts per subject yielded data concerning early life developmental, physical and behavioral characteristics associated with psychosis risk. As compared with controls, offspring of women with schizophrenia showed significantly increased rates of delayed walking, visual dysfunction, language skill disorders, enuresis, disturbed behavior (especially poor social competence), and multiple accumulated risk characteristics. Significant Sc-risk characteristics did not include impaired hearing, minor malformations, biological dysfunctions, or physical illness leading to treatment. Offspring of mothers with affective psychosis (Aff) showed only a significantly increased rate of delayed walking, with no significantly increased total aggregation of risk characteristics, compared with controls. The results suggest a limited overlap in the diathesis characteristics associated with risk for Sc vs. Aff psychosis. The importance of these early risk characteristics for the later development of psychopathology is being investigated in this sample.

Child Behavior Disorders↗

PubMed2006

Prader-Willi syndrome: atypical psychoses and motor dysfunctions.

Prader-Willi syndrome (PWS) is the result of a lack of expression of genes on the paternally derived chromosome 15q11-q13 and can be considered as a hypothalamic disorder. Its behavioral phenotype is characterized by ritualistic, stereotyped, and compulsive behaviors as well as motor abnormalities. After adolescence, recurrent affective psychoses are relatively frequent, especially in patients with uniparental disomy. These psychotic states have a subacute onset with complete recovery and comprise an increase of psychomotor symptoms that show resemblance with catatonia. Some evidence has emerged that gamma-aminobutyric acid (GABA) dysfunctionality is involved in both PWS and catatonia. Treatment of these atypical psychoses should preferably include GABA mimetic compounds like lorazepam, valproic acid, and possibly topiramate.

Adolescent↗

PubMed1985

Characteristics of the psychoses of late onset in children and adolescents (a comparative study of hallucinating children).

In a retrospective design, 20 children and adolescents with psychoses of late onset and hallucinations were compared with 20 children with conduct or emotional disorders who also had hallucinations. Marked differences emerged between the two groups. Psychotic subjects showed significantly more delusions, abnormalities in language production, inappropriate affect, bizarre behaviour, hypoactivity, and social withdrawal. Some subjects had symptoms which indicated a specially profound breakdown in personality functioning, but schneiderian and other schizophrenic symptoms were relatively rare. This questions their diagnostic value in the psychoses of late onset of children and adolescents.

Adolescent↗

PubMed1999

Atrophic and static (neurodevelopmental) schizophrenic psychoses: premorbid functioning, symptoms and neuroleptic response.

The question of whether schizophrenic-like disorders are neurodevelopmental or degenerative in origin has been argued since the time of Kraepelin. The authors provide evidence for the existence of two etiologically distinct endophenotypes of the psychoses contained within the rubric of familial non-affective psychosis (schizophrenia), one atrophic and the other neurodevelopmental. The atrophic psychosis, identified by progressive ventricular enlargement throughout adult illness, evidences progressive impairment of interests, relationships, and withdrawal from latency through adolescence, with emergence of trait-like negative symptoms which are only marginally responsive to conventional neuroleptics. This psychosis also exhibits delayed response of positive symptoms during neuroleptic treatment, and may also proceed to a praecox dementia in later life. In contrast, a putative neurodevelopmental psychosis, associated with static ventricles during the course of adult illness, also demonstrates preadolescent impairments, but impairments which do not progress to marked negative symptoms. Conventional neuroleptics appear to have little effect (except sedation) on positive symptoms, but appear to induce negative symptomatology and partial disengagement from the burden of persistent psychotic thought processes in such static ventricle psychoses. Thus, separate patterns of illnesses with different prodromal features, different treatment response patterns, and different patterns of residual (negative) symptoms appear to characterize patients with psychosis who have expanding as opposed to stable cerebral-ventricles at doses of neuroleptic at 10 mg haloperidol equivalents/day.

Adult↗

PubMed2002

A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses.

Evidence for neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia, patients with chronic psychotic bipolar disorder and normal controls. Groups were comparable on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also relatively similar on age at onset and number of hospitalizations. Using multivariate analyses of variance with sex and parental SES as covariates (our primary analyses), patients with schizophrenia were significantly more impaired than controls on seven of eight neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on declarative verbal memory, and showed moderate-to-large effect size decrements on abstraction, perceptual-motor speed and vigilance. Results were not attenuated when IQ was controlled, which was significantly lower in patients with schizophrenia. Analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.

Adult↗

PubMed1997

Therapeutic targets in late-life psychoses: review of concepts and critical issues.

Psychoses in late life are a diagnostic challenge because of disagreement over how these entities should be classified. The main diagnostic categories of late-life psychoses include dementia with psychotic symptoms, late-onset schizophrenia, delusional disorder, early-onset psychotic disorders extending through late life, late-onset mood disorders, psychotic disorders caused by medical conditions or medications, and delirium. First onset of psychotic symptoms in late life is commonly associated with identifiable structural brain abnormalities and reflects underlying brain pathology. We reviewed the available literature on late-life psychotic manifestations, focusing on diagnostic classification and treatment approaches. Antipsychotics are the mainstay of treatment for these conditions, but should be used cautiously in elderly patients because of their increased sensitivity to side effects. Overall, appropriate research data on the effectiveness of various antipsychotic agents for late-life psychotic conditions are lacking. Non-antipsychotic psychotropic medications may be of value in managing some of these conditions.

Affective Disorders, Psychotic↗

PubMed1997

Altered consciousness states and endogenous psychoses: a common molecular pathway?

Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

Consciousness↗

PubMed2002

Risperidone in the treatment of psychoses in the elderly: a case report series.

Risperidone is one of the newer atypical antipsychotic agents, which combines potent serotonin and dopamine receptor antagonism. It shows efficacy against the positive and negative symptoms of schizophrenic psychoses and other psychotic conditions, and has a low propensity to cause extrapyramidal side effects. The aim of these case reports in elderly patients is to provide the benefit of personal experience with risperidone to the body of published literature and to demonstrate the types of patients that may benefit from treatment. These cases were compiled retrospectively from data collected on referral and during routine hospital appointments. This series covers four main areas of concern when treating the elderly: low-maintenance dosing minimising the likelihood of adverse events; successful treatment of patients previously uncontrolled and experiencing side effects with other antipsychotics; the possibility of intermittent rather than continuous treatment; and the benefits to patients, carers and the health services. At low doses, risperidone is an effective and well-tolerated treatment for psychoses in elderly patients that improves the quality of life for both patients and their caregivers.

Aged↗

PubMed1992

Eye-tracking dysfunction in the affective psychoses and schizophrenia.

Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia.

Adolescent↗

PubMed2000

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses.

The D2 receptor (DRD2) is a binding site of many psychoactive drugs and it has been proposed as a genetic risk factor for psychiatric disorders. The aim of this investigation was to study the DRD2 S311C variant in major psychoses. We studied 1182 inpatients with diagnoses of bipolar disorder (n = 480), major depressive disorder (n = 269), schizophrenia (n = 366), delusional disorder (n = 44), psychotic disorder not otherwise specified (n = 23) and 267 healthy controls. Eight hundred and eighty-seven subjects were also scored for their lifetime symptomatology using the the Operational Criteria checklist for psychotic illness (OPCRIT). DRD2 variants were not associated with affected subjects even when possible confounders like gender and onset were considered. When we considered the 887 subjects with the symptomatologic analysis, we observed a significant association of the DRD2 S311C variant with both delusion and disorganization features. The association was present independently from diagnoses. Our results do not show that coding variants of the DRD2 S311C play a major role in conferring susceptibility to major psychoses, but they may be connected with disorganized and delusional symptomatology independently from diagnoses.

Adult↗

PubMed2002

Pro re nata medication for psychoses: the knowledge and beliefs of doctors and nurses.

OBJECTIVE: To examine the knowledge and beliefs of doctors and nurses in inpatient psychiatric units about pro re nata (PRN) (as needed) medications for psychotic disorders. METHODS: Medical (n = 44) and nursing (n = 80) staff in two metropolitan public hospital units completed a structured questionnaire about their use of PRN psychotropic medications on one occasion during the four months from March-June 1999. RESULTS: Nurses selected more indications for PRN antipsychotics than doctors (3.49 vs 2.72, p < 0.05), whereas doctors selected more indications for PRN benzodiazepines (3.77 vs 3.19, p < 0.05). The groups did not differ in the number of selected indications for using anticholinergics. For agitation, the majority of nurses viewed both benzodiazepines (56%) and antipsychotics (86%) as effective, with 60% preferring an antipsychotic. For the acute control of psychotic symptoms, 99% of nurses believed antipsychotics were effective and 58% benzodiazepines, with 87% preferring an antipsychotic. A large majority of doctors viewed both PRN benzodiazepines, 94%,and antipsychotics, 81%, as effective for agitation, and 55% preferred to use a benzodiazepine. For psychotic symptoms, 80% believed PRN antipsychotics were effective, but only 32% viewed benzodiazepines as effective, and 64% preferred to use an antipsychotic. Nursing staff identified more non-pharmacological techniques for managing both agitation and psychotic symptoms and reported using these more often than doctors. Junior staff, both nursing and medical, had less knowledge of non-pharmacological alternatives to PRN medication than senior staff. CONCLUSIONS: Disparities existed between doctors and nurses views on the indications for PRN medication in the acute management of psychoses, thus it is important for doctors to specify indications when writing PRN prescriptions. Despite evidence for the safety and effectiveness of benzodiazepines, there was widespread reluctance to use them as PRN medication in acute psychoses. Beliefs of some staff about PRN medications were at odds with the known properties of these medicines. Educational interventions for both nurses and doctors are required to achieve best practice in PRN medication.

Antipsychotic Agents↗

PubMed1991

[Effectiveness of zotepine in therapy-refractory psychoses. An open, multicenter study in eight psychiatric clinics].

Zotepine was administered to 45 patients suffering from therapy-resistant psychoses hospitalized in eight psychiatric institutes (University Hospital Okayama and affiliated institutions). The psychoses of these patients were characterised by positive symptoms--predominantly hallucinations and delusions--and could not be influenced by a large variety of conventional antipsychotics, such as haloperidol. Previous medications were discontinued or administered together with zotepine. To assess changes in the pattern of symptoms, the Brief Psychiatric Rating Scale (BPRS) was employed over a period of up to 12 weeks at 2-week intervals. Ten patients dropped out of the study because of undesirable effects or for other reasons. 35 patients completed the 12-week study according to schedule. There was a relation between general improvement and certain patient characteristics. Zotepine proved to be effective especially in the catatonic type of schizophrenia, in chronic schizophrenias with acute exacerbation (DSM-III) and in relatively young patients in whom the disease had existed for a short time only. In the 26 patients who were markedly, moderately or slightly improved, BPRS score had dropped significantly after only two weeks of treatment. This points to a rapid onset of the therapeutic action of zotepine.

Adolescent↗