A new animal model for schizophrenia: interactions with adrenergic mechanisms.

Amphetamine-induced stereotyped behavior in animals is proposed as a model for schizophrenia. Chronic amphetamine administration produces stereotyped behavior and a paranoid schizophreniform syndrome in man, whereas in animals a behavioral sensitization to stereotypy is evoked. We now show that phenylethylamine (PEA), an amphetamine-like stimulant concentrated in the limbic system of human brain, produces stereotypy in rats with a behavioral sensitization when chronically administered. In comparing amphetamine-induced stereotypy with PEA-induced stereotypy, we found that the alpha-adrenergic blocking agents phentolamine and phenoxybenzamine selectively antagonize PEA stereotypy, whereas the beta-adrenergic blocking agent propranolol fails to alter significantly stereotypies evoked by PEA or amphetamine administration. Catecholamine depletion by alpha-methyl-p-tyrosine administration blocks stereotypies induced by both PEA amphetamine, whereas selective norepinephrine depletion antagonizes only PEA stereotypy; the amino acid precursors of both norepinephrine and dopamine potentiate stereotypies. Therefore, PEA-elicited stereotypy, but not amphetamine-elicited stereotypy, is dependent upon norepinephrine; the significance of this for the PEA animal model of schizophrenia is discussed.     

A multivariate prediction model of schizophrenia

Univariate prediction models of schizophrenia may be adequate for hypothesis testing but are narrowly focused and limited in predictive efficacy. Therefore, we used a multivariate design to maximize the prediction of schizophrenia from premorbid measures and to evaluate the relative importance of various predictors. Two hundred twelve Danish subjects with at least one parent diagnosed in the schizophrenia spectrum (high risk) and 99 matched subjects with no such parent (low risk) were assessed on 25 premorbid variables in seven domains (genetic risk, birth factors, autonomic responsiveness, cognitive functioning, rearing environment, personality, and school behavior) when the subjects averaged 15 years of age. Twenty-five years later, 33 subjects had received lifetime diagnoses of schizophrenia. Discriminant function analyses were used to discriminate schizophrenia outcomes from no mental illness and nonschizophrenia outcomes on the basis of premorbid measures. Regardless of the comparison group used, schizophrenia was predicted by the interaction of genetic risk with rearing environment, and disruptive school behavior. Within the high-risk group, two-thirds of schizophrenia outcomes were correctly predicted by these premorbid measures; three-quarters of those with no mental illness were also correctly predicted. Prediction was enhanced among those with two schizophrenia spectrum parents, lending support to a multiplicative gene x environment model. Implications for early identification/primary prevention efforts are discussed.     

A glutamatergic deficiency model of schizophrenia

Although the presence of hyperdopaminergia has been demonstrated in the brains of people with schizophrenia, at least in some circumstances, other neurotransmitters are important in this disorder, and a glutamatergic deficiency model of schizophrenia is proposed. It is suggested that the amount of sensory input allowed to reach the cerebral cortex is restricted by an inhibitory effect of the striatal complexes on the thalamus, thereby protecting it from being overwhelmed. Several strands of evidence are presented to support the concept that a weakened glutamatergic tone increases the risk of sensory overload and of exaggerated responses in the monoaminergic systems that could result in psychosis.     

Chronic fatigue syndrome and personality: A case-control study using the alternative five factor model

Neuroticism is the personality dimension most frequently associated with chronic fatigue syndrome (CFS). Most studies have also shown that CFS patients are less extraverted than non-CFS patients, but results have been inconsistent, possibly because the facets of the extraversion dimension have not been separately analyzed. This study has the following aims: to assess the personality profile of adults with CFS using the Alternative Five-Factor Model (AFFM), which considers Activity and Sociability as two separate factors of Extraversion, and to test the discriminant validity of a measure of the AFFM, the Zuckerman–Kuhlman Personality Questionnaire, in differentiating CFS subjects from normal-range matched controls. The CFS sample consisted of 132 consecutive patients referred for persistent fatigue or pain to the Department of Medicine of a university hospital. These were compared with 132 matched normal population controls. Significantly lower levels of Activity and significantly higher levels of Neuroticism-Anxiety best discriminated CFS patients from controls. The results are consistent with existing data on the relationship between Neuroticism and CFS, and clarify the relationship between Extraversion and CFS by providing new data on the relationship of Activity to CFS.     

A new philosophy for schizophrenia care

INTRODUCTION: Patients with psychotic illness are frequently dissatisfied with psychiatric services although it is unclear whether this can be explained as being due to the mental disorder itself, or to the lower quality of care received by this group of patients. We explored this issue by comparing service satisfaction from different user perspectives: patients and key relatives. METHOD: The satisfaction and needs of 52 patients with schizophrenia and 66 of their relatives were assessed using the Verona Service Satisfaction Scale (VSSS). RESULTS: Patients were generally more satisfied with services than relatives, but there was a high degree of consistency between the groups regarding the aspects of the service which they were most, and least, satisfied with. CONCLUSION: Patient satisfaction surveys can be used as reliable indicators of service quality and can highlight specific strengths and shortcomings in mental health service provision. Such surveys can be very useful to help improve the quality of care for patients and their relatives.     

A cognitive regulatory control model of schizophrenia

The spontaneously epileptic rat (SER) begins to exhibit both tonic convulsions and absence seizures from 6 weeks of age and SERs have stable seizures after 10 weeks of age. Low-dose administrations of levetiracetam (LEV) for 4- to 5-weeks-old SERs which did not show spontaneous seizures reduced both seizures 5 weeks after termination of administration. The hippocampus of SER exhibited decreased CA3 neurons, sprouting of mossy fibers, and hyperexpression of the brain-derived neurotrophic factor (BDNF). We attempted prophylactic LEV administrations in preseizure-manifesting SERs to evaluate if such a treatment regimen would protect the hippocampal sclerosis-like changes observed in SERs. The osmotic mini-pump administered LEV dissolved in saline to 4-weeks-old SERs for 4 weeks at 2.5 μl/h. LEV was administered at 420 mg/ml for 4 weeks in Group A. In Group B, LEV was given at 420 mg/ml for the first 2 weeks followed by doubling the dosage (840 mg/ml) in the following 2 weeks. LEV administrations in preseizure-manifesting SERs reduced the decrease of CA3 neurons and mossy fibers sprouting at 10-11 weeks of age in both group A and B. LEV attenuated BDNF expression in inner molecular layers of the dentate gyrus, striatum radiatum, and CA3 in 10- to 11- and 14- to 15-weeks-old SERs. In group B, LEV decreased BDNF expression in hilus and CA1 of 10- to 11- weeks-old SER. The present results suggest that prophylactic treatment with LEV in preseizure-manifesting SERs inhibits hippocampal sclerosis-like neuronal degeneration and/or regeneration.     

A comparison of five diagnostic systems for childhood schizophrenia and infantile autism

Five diagnostic systems designed to differentiate infantile autism and early childhood schizophrenia were compared by deriving scores on 44 children referred consecutively to the same clinical center. While the autistic scales devised by Rimland, Polan and Spencer, Lotter, and the British Working Party correlated significantly, the degree of correspondence (35%) indicated that several children obtained high autistic scores in one system but low scores in another. The BWP's term schizophrenia has more correspondence with the term autism used by others than with Rimland's schizophrenia. In the DeMyer-Churchill categorical system (early schizophrenia, primary autism, secondary autism, and non-psychotic subnormal), primary autism most resembles Rimland's concept of infantile autism as measured by his E-1 version. All other systems differentiate psychotic from non-psychotic children but do not distinguish any of the psychotic subgroups.This study was supported in part by Public Health Service Grant No. MH05154 and also by LaRue D. Carter Memorial Hospital, State of Indiana, Indianapolis, Ind.The authors wish to thank Dr. Bernard Rimland for providing his scoring key.     

A factor analytic study of symptoms in acute schizophrenia

The three-syndrome model of schizophrenic phenomenology has been well established in chronic illness. We report an attempt to replicate this concept in a sample of acutely unwell schizophrenic patients. Factor analysis was performed using PSE data collected within a week of admission from 114 patients who met DSMIII(R) diagnostic criteria for schizophrenia. Four main factors accounted for 58% of the variance. The first two factors closely resembled Liddle's disorganisation and psychomotor poverty syndromes. Hallucinations and delusions loaded separately under the third and fourth factors. To examine the validity of these four syndromes, the relationships between factor scores and other clinical data were examined. The disorganisation syndrome was associated with a history of multiple past admissions and a longer lifetime duration of in-patient treatment.     

A new questionnaire assessing coping strategies in relatives of patients with schizophrenia: development and factor analysis

This paper describes the development and validation of a questionnaire assessing the coping strategies adopted by relatives of patients with schizophrenia. The final version of the questionnaire includes 27 items, grouped into seven subscales (information, positive communication, social interests, coercion, avoidance, resignation and patient's social involvement), the intra-rater reliability of which ranges from 0.46 to 0.76. Cronbach's alpha coefficient, which tests the content validity of the subscales, ranges from 0.68 to 0.83. Factor analysis identifies three factors (problem-oriented coping strategies, emotionally focused strategies, and maintenance of social interests in association with patient's avoidance), accounting for 70.9% of the total variance. This questionnaire may be particularly useful for targeting and monitoring psychoeducational interventions in the families of patients with schizophrenia.     

A process model for the development of schizophrenia

Less than two decades ago scientists interested in the etiology of schizophrenia were still vigorously debating the nature-nurture controversy, with many adhering to the view that the illness grew either out of a constitutional deficit or a pathological family environment. Today, virtually all researchers adopt interactional models that include both constitutional and environmental factors. Interactional models are most often expressed in diathesis-stress terms: Development of schizophrenia requires both a biological vulnerability (diathesis) and stressful life circumstances that facilitate expression of the illness. Modern debate within the field now primarily focuses on understanding the characteristics of the biological diathesis, the stressful environment, and their interaction. Scientists using diathesis-stress theories have employed several research strategies (Rosenthal 1970): (1) consanguinity studies exploring the distribution of illness among the relatives of schizophrenics, (2) twin studies comparing the concordance of schizophrenic illness in monozygotic and dizygotic twin pairs reared together or apart, (3) retrospective studies examining the premorbid behavior and development of schizophrenic parents, and (4) prospective studies of children at high risk for schizophrenia. The population most frequently followed in prospective high-risk studies has been offspring of schizophrenics. Biological offspring of schizophrenics who are reared by their parents are at extremely high risk for becoming schizophrenic themselves, approximately ten times greater risk than the general population. The present paper will make use of the Israeli High-Risk Study to test a diathesis-stress model for the transmission of schizophrenia. The goodness of fit of this model to the data will be explored using a simple decision tree data analytic approach.     

A factor analytic comparison of five models of PTSD symptoms

This study examined the factor structure of PTSD symptoms in a sample of college students (n=344) reporting exposure to a range of traumatic events. The sample was randomly split and an exploratory factor analysis was conducted with half of the sample. The factor structure obtained in the exploratory analysis was evaluated against three other models using confirmatory factor analysis utilizing the second half of the sample. This series of factor analyses identified and confirmed a three-factor symptom structure consisting of intrusion/avoidance, dysphoria, and hyperarousal clusters. These results add to the body of literature which has found that PTSD includes a cluster of symptoms shared with other diagnoses (dysphoria) and a more specific factor related directly to the effects of encountering traumatic experiences.     

The five symptom dimensions and depression in schizophrenia

The aim of this study was to investigate the relationship between the five-factor model of psychopathology and depression in schizophrenia. Symptoms were rated using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS) in 105 chronic patients with schizophrenia. Principal-component analysis (PCA) produced a five-factor solution for the PANSS (psychomotor poverty, disorganisation, reality distortion, excitement, and depression), and a two-factor solution for the MADRS (psychological and behavioural depression). The PANSS depression factor was highly associated with the MADRS psychological depression factor but not with MADRS behavioural depression. By contrast, the PANSS excitement factor showed a strong positive correlation with the behavioural depression factor but not with psychological depression. These MADRS factors were not associated significantly with the core PANSS factors, including psychomotor poverty. It is suggested that depression exists as an independent domain, differentiated from negative symptoms, in the structure of schizophrenia symptomatology.     

Psychometric investigation of the specific phobia of vomiting inventory: A new factor model

Well‐validated, standardized measures are lacking for the assessment of emetophobia, the specific phobia of vomiting. The Specific Phobia of Vomiting Inventory (SPOVI) was recently developed and shows promise as a useful measure of emetophobia. The goal of the present study was to further examine and investigate the psychometric properties of the SPOVI in a large student sample (n = 1626), specifically focusing on its factor structure, measurement invariance across gender, and convergent/divergent validity. Confirmatory factor analysis results provide support for a one‐factor model of the SPOVI, in contrast to the previously proposed two‐factor model. Internal consistency of the SPOVI was good (α = 0.89) and measurement invariance across gender invariance was supported. The SPOVI also demonstrated good psychometric properties with respect to convergent and divergent validity. The present study's demonstration of the reliability and validity of the SPOVI suggests that the instrument may be a valuable tool for assessing emetophobia symptoms based on its one‐factor structure.     

A new look at reaction time in schizophrenia

Schizophrenia patients demonstrate impaired manual reaction time (RT), but not saccadic RT, when given traditional tasks. To determine whether the manual RT time impairment could be eliminated by providing imperative stimuli to the finger (thus providing stimulus-response compatibility), we tested 28 chronic schizophrenic patients on finger-lift RT to visual (VIS), tactile plus visual (TAC+VIS), and auditory plus tactile plus visual (AUD+TAC+VIS) stimuli. The patients (a) were significantly slower than controls (n=28) in all three tasks, (b) showed bimodality, with 43% of patients having means and variances nearly identical to control values, and (c) had RTs significantly closer to control values in the TAC+VIS and AUD+TAC+VIS tasks than in the VIS task. The inability to normalize finger-lift RT in schizophrenia represents a genuine slowing of this response system regardless of stimulus-response compatibility. We consider other possible explanations for the differences between manual and saccadic RT, including the notion that excess processing capacity for saccadic RT may be masking possible deficits in that system.