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The social perceptual deficits of schizophrenia.

This article summarizes a series of studies conducted by our group that examined the social perceptual deficits of schizophrenia. Research suggested that social perceptual deficits are more pronounced in patients with nonparanoid schizophrenia than comparison groups comprising normal controls or individuals with paranoid schizophrenia. The social perceptual deficits of schizophrenia were affected by the level of abstraction of cue descriptors; the level of emotional arousal engendered by the situation; the presence of extraneous, emotionally arousing stimuli; and the familiarity of the situation. These deficits were not found in standardization and cross-validation samples of normal controls, suggesting that these differential deficits represent a characteristic of the disorder rather than a psychometric confound. Social perceptual deficits in schizophrenia were significantly associated with verbal recall memory and relatively unrelated to visual vigilance. These latter findings were used in a study on rehabilitation of cue perception which showed that memory rehabilitation significantly improved cue perception whereas attention focusing strategies had no appreciable effects.

Affect↗

Analysing the matrix of transference.

In this paper, the background experiential states forming the matrix of transference are discussed in terms of the interplay of three modes of generating experience: the autistic-contiguous, the paranoid-schizoid and the depressive. Portions of three analyses are discussed in an effort to illustrate clinically some of the ways in which analytic technique is shaped by an understanding of the predominant mode or modes of experience forming the context of the transference-countertransference at any given moment. There is a focus on the ways in which the analyst's interventions must often be directed to the contextual level, or matrix, of transference (for example, the significance of the way the patient is thinking, talking or behaving) before it becomes possible to address other interrelated aspects of transference (for example, the unconscious symbolic meanings of what the patient is thinking, saying or enacting).

Adult↗

Stimulant-induced psychosis, the dopamine theory of schizophrenia, and the habenula.

While one of the original underpinnings of the dopamine theory of schizophrenia was the paranoid psychosis which often develops during the binges or speed runs of chronic amphetamine addicts (and, more recently, in cocaine addicts), neurochemical studies of such drug abusers or from animals given continuous stimulants in an effort to model stimulant psychoses have not played a major role in the further evolution of this theory. One clear persisting alteration produced by continuous amphetamine is a neurotoxicity to dopaminergic innervations in caudate. Yet continuous cocaine administration apparently does not induce a similar neurotoxicity and this makes this effect a poor candidate for an underpinning of stimulant psychoses. However, it has recently been found that both continuous amphetamine and cocaine induce a strong pattern of degeneration which is highly confined to the lateral habenula and its principal output pathway, fasciculus retroflexus. This finding has led to a reconsideration of the role of these structures in psychoses. The habenula, as the chief relay nucleus of the descending dorsal diencephalic system (consisting of stria medullaris, habenula and fasciculus retroflexus), is an important link between limbic and striatal forebrain and lower diencephalic and mesencephalic centers. Studies of glucose utilization have consistently shown the habenula to be highly sensitive to dopamine agonists and antagonists. Lesions of habenula produce a wide variety of behavioral alterations. The dorsal diencephalic system has major and predominantly inhibitory connections onto dopamine-containing cells and it mediates part of the negative feedback from dopamine receptors onto dopamine cell bodies. It represents one of the major inputs in brain to the raphe nuclei and has anatomical and functional connections to modulate important functions such as sensory gating through thalamus, pain gating through central gray and raphe and motor stereotypies and reward mechanisms through substantia nigra and the ventral tegmental area. It is argued that alterations in these pathways are ideal candidates for producing the behaviors which occur during psychosis and that future considerations of the circuitry underlying psychoses need to include this highly important but relatively neglected system.

Animals↗

Lethal violence and psychosis: a clinical profile.

To investigate the relationship between lethal violence and psychosis, the authors examined symptomatology, neuropsychological functioning, and the nature of perpetrator-victim relationships of patients with psychotic disorders who were committed to a forensic psychiatric hospital following violent, primarily criminal behavior. A severely violent group, composed primarily of psychotic patients charged with murder, was compared with a less severely violent group that was composed primarily of psychotic patients involved with property crimes. As compared with the less violent group, the severely violent group was more likely to have delusional beliefs about specific personal targets and to have delusions about significant others being replaced by impostors. These beliefs were accompanied by higher scores on neuropsychological tests of intellectual and academic abilities. A high number of their blood relatives were victims of psychotic murder. These results indicated that a higher incidence of lethal or near lethal acts of violence may characterize intellectually intact but psychotic individuals with organize delusions involving personal, accessible targets.

Adult↗

[How dangerous are patients with mental disorders?].

The question of potential violence on the part of people with a mental disease has caused considerable controversy in recent decades. While in the eighties the prevailing opinion was that they have no increased risk of aggression, recent studies, especially from Scandinavia and Canada, show a moderate but reliable coherence between violent crime and paranoid and schizophrenic diseases. The danger of people with a mental disease is assessed essentially through the following five study-approaches: Studies to assess the criminal rate of hospitalised patients, the prevalence of mental disorder, studies on prisoners who are committed to a psychiatric facility, and long-term analyses of cohorts. Special emphasis is attached to investigations on homicides. Other investigative questions are concerned with the influence of psychopathological symptoms, the importance of comorbid disturbances and sociological aspects. The studies agree that the risk of violence is decisively increased in people who suffer from schizophrenia, through additional substance abuse, comorbidity with personality disorders, absence of treatment and social desintegration. An unprejudiced approach to this sensitive theme of aggression in people with schizophrenia with regard to further effective prevention and therapy is required.

Aggression↗

Neuroleptic malignant syndrome after neuroleptic discontinuation.

1. Neuroleptic withdrawal can cause autonomic and behavioral symptoms (nausea, vomiting, diarrhea, diaphoresis, myalgia, anxiety, restlessness) and movement disorders (withdrawal emergent parkinsonism, withdrawal dyskinesia, covert dyskinesia). 2. Neuroleptic malignant syndrome (NMS) is a rare but extremely severe adverse reaction to neuroleptic drugs characterized by extrapyramidal and autonomic symptoms, altered level of consciousness and abnormal laboratory findings. 3. Withdrawal neuroleptic malignant syndrome, though an even rarer condition (only 7 cases reported to date), should alert to consider the possibility that abrupt neuroleptic discontinuation can be complicated by NMS. 4. The pathophysiology of withdrawal medical symptoms may be related to a cholinergic rebound; withdrawal neuroleptic malignant syndrome may be attributed to an "imbalance" in the dopaminergic system. 5. The authors report two cases of NMS precipitated by the abrupt withdrawal of neuroleptic drugs.

Antipsychotic Agents↗

[The effect of the beta-adrenergic blocking agent propranolol in mania (author's transl)].

Six patients with the diagnosis of acute mania were treated with high doses of the beta-adrenergic blocking agent propranolol. One of these patients was treated during two manic phases. Psychopathologic change during treatment was rated daily by a psychiatrist not informed on the patients medication. The IMPS (Inpatient Multidimensional Psychiatric Scale) was used. Three cases were placebo-controlled under double blind conditions. Four times we had a second medication period, twice with propranolol and once with oxprenolol and dexpropranolol respectively. Propranolol was administered every 4 h (six times per day), starting with single doses of 20-40 mg. Doses were increased individually under control of pulse rate, blood pressure, and ECG. Augmentation of doses was continued until an effect on manic symptomatology was undoubtedly seen or until therapy had to be discontinued because of side-effects. In four patients definite improvement of manic symptomatology could be achieved during altogether five manic phases within usually two treatment periods of 5-15 days. Manic behavior disappeared completely in two of these patients. The effective dosage of propranolol varied between 280 and 2320 mg per day. All of the improved patients relapsed after discontinuation of the drug. In the only case on dexpropranolol (5 days up to 900 mg daily) the effect was questionable. No extrapyramidal side-effects were observed. In one patient treatment was discontinued because of lack of cooperation, in another because of extrasystoles. Gastrointestinal bleeding occurred in the patient who received dexpropranolol. This complication was possibly due to other medication. Other side-effects were insomnia, hypertension, precordial pain, abdominal pain as well as the expected hypotension and bradycardia. The significance of these results regarding the catecholamine hypothesis of manic-depressive illness is discussed.

Adolescent↗

Another view of schizophrenia subtypes. A report from the international pilot study of schizophrenia.

Schizophrenia subtypes are defined predominantly my manifest symptoms and behavior. This report, based on sign and symptom data from the International Pilot Study of Schizophrenia, addresses three questions: (1) Are traditional subtype diagnoses applied similarly across cultures? (2) Are the various traditional subtypes symptomatically distinguishable from one another? (3) Can cluster analytic techniques define a more distinctive set of schizophrenic subgroups? Present State Examination data were reduced to 27 psychopathologic signs and symptoms. Profile analysis of variance results indicate that each subtype appears similar, regardless of center of origin. However, this is based on a lack of distinguishing features between different subtypes. On the other hand, when a cluster analytic technique was used, it showed one large and three small subgroups, each readilty distinguishable from the others. These subgroups, labeled "usual," "flagrant," "insightful," and "hypochondriacal," are described clinically. If replicated or validated, such subgroups may prove meaningful in future considerations of subdivisions of the schizophrenia syndrome.

Culture↗

Cerebrospinal fluid corticotropin-releasing factor increases following haloperidol withdrawal in chronic schizophrenia.

Corticotropin-releasing factor (CRF), an endogenous neuropeptide, has been shown to coordinate endocrine, behavioral and autonomic responses to stress. However, while previous studies of cerebrospinal fluid (CSF) CRF in schizophrenia have not demonstrated significant differences compared to control groups, these studies have not examined the effects of symptom severity or antipsychotic medication. CSF CRF concentrations increased in 18 of 21 male schizophrenic (DSM-III-R) patients after maintenance haloperidol was replaced by placebo (P < 0.0001); there was also a trend for relatively greater increases in relapsers. CRF concentrations were not significantly related to severity of psychosis, depression, anxiety or negative symptoms. During haloperidol treatment, but not after medication withdrawal, worse childhood premorbid adjustment was associated with higher CSF CRF levels. Finally, in contrast to the positive correlation between CSF CRF and norepinephrine concentrations reported in depression, a negative trend was seen in this schizophrenic sample.

Adult↗

Autism and developmental receptive language disorder--a follow-up comparison in early adult life. II: Social, behavioural, and psychiatric outcomes.

This paper focuses on general social functioning in two groups of young men, one with autism and one with developmental receptive language disorders, who were first assessed at the ages of 7-8 years. At that time, although matched for nonverbal IQ (mean 92-93) and expressive language, the Language group showed significantly fewer social and behavioural problems. At follow-up, when aged on average, 23 to 24 years, the Autism group continued to show significantly more impairments in terms of stereotyped behaviour patterns, social relationships, jobs, and independence. However, problems in all these areas were also common in the Language group. Many still lived with their parents, few had close friends or permanent jobs, and ratings of social interaction indicated abnormalities in a number of different areas. On a composite measure of social competence only 10% of the Language group was assessed as having severe social difficulties compared to 74% of the Autism group. Nevertheless, 65% were rated as having moderate social problems and only 25% were rated as being of near/normal social functioning. Two individuals in the Language group, but none in the Autism group, had also developed a florid paranoid psychosis in late adolescence. As in the follow-up of cognitive and linguistic functioning (see Mawhood et al., 2000, this volume, pp. 547-559), discriminant function analysis, which had clearly distinguished between the groups as children, now showed much greater overlap between them. Regression analysis indicated that although early language ability appeared to be related to outcome in the Autism group, there was little association between any measures of childhood functioning and prognosis in the Language group. Theoretically, these findings have implications for our understanding of the nature of autism and other pervasive language disorders, and of the relationship between them. Practically, they demonstrate the very persistent problems experienced by individuals with developmental language disorders, and their need for much greater help and support than is presently available.

Activities of Daily Living↗

Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates.

Recent brain imaging studies suggest that schizophrenia may be related to abnormally high amphetamine-induced dopamine release. It is known that repeated use of amphetamine may cause paranoid psychosis and persisting stereotypies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [11C]raclopride were used to determine central D2-dopamine receptor density (Bmax) and apparent affinity (K(D)app) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K(D)app was increased, suggesting [11C]raclopride competition with elevated concentration of dopamine. At 7 and 14 days after withdrawal, there was a 19-26% decrease in Bmax but no change in K(D)app as compared to baseline. Although this study was performed on two monkeys only, there was thus no support for the view that chronic intermittent hyperactivity of the dopamine system may be related to an upregulation of striatal D2-dopamine receptors. Repeated administration of amphetamine may, rather, cause a long-lasting downregulation of the D2-receptor density, which may be a neurochemical correlate to the abnormal movements, anhedonia, anxiety, and depression seen in psychostimulant abusers.

Amphetamine-Related Disorders↗

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes.

Dopamine is a major neurotransmitter in the central nervous system, and its receptors are associated with a number of neuropathological disorders such as Parkinson's disease and schizophrenia. Although the precise pathophysiology of schizophrenia remains unknown, the dopaminergic hypothesis of the illness assumes that the illness results from excessive activity at dopamine synapses in the brain. Because, at present, the diagnosis of schizophrenia relies on descriptive behavioral and symptomatic information, a peripheral measurable marker may enable a simpler, more rapid, and more accurate diagnosis and monitoring. In recent years, human peripheral blood lymphocytes have been found to express several dopamine receptors (D(3), D(4), and D(5)) by using molecular biology techniques and binding assays. It has been suggested that these dopamine receptors found on lymphocytes may reflect receptors found in the brain. Here we demonstrate a correlation between the D(3) dopamine receptor on lymphocytes and schizophrenia and show a significant elevation of at least 2-fold in the mRNA level of the D(3), but not of the D(4), dopamine receptor in schizophrenic patients. This increase is not affected by different antipsychotic drug treatments (typical or atypical). Moreover, nonmedicated patients exhibit the same pattern, indicating that this change is not a result of medical treatment. We propose the D(3) receptor mRNA on blood lymphocytes as a marker for identification and followup of schizophrenia.

Adult↗

Behavioral and psychological symptoms of dementia in developing countries.

BACKGROUND: Little is known about the prevalence of, or associations with behavioral and psychological symptoms of dementia (BPSD) in developing countries. METHODS: Individuals diagnosed as having dementia according to DSM-IV criteria (mild and moderate cases as defined by the Clinical Dementia Rating scale only), together with their main caregiver, were recruited from 21 centers in 17 developing countries. People with dementia were directly assessed with the Community Screening Interview for Dementia and the Geriatric Mental State Schedule (GMS); GMS data were processed by the AGECAT computer program to yield diagnostic information on 8 psychiatric syndromes. Caregivers answered direct questions about behavioral symptoms of dementia (BSD) and completed the Zarit Burden Inventory. RESULTS: At least one BSD was reported in 70.9% of the 555 participants. At least one case-level AGECAT psychiatric syndrome (not including the organic syndrome) was exhibited by 49.5% of people with dementia. Depression syndromes (43.8%) were most common followed by anxiety neurosis (14.2%) and schizophreniform/paranoid psychosis (10.9%). Caregivers were more likely to report BSD in people with dementia who were married, younger and better educated. More advanced dementia, poorer functioning and the presence of depression or anxiety were each associated with BSD. BSD, and psychiatric syndromes (anxiety neurosis and schizophreniform/paranoid psychosis) predicted caregiver strain after controlling for cognitive impairment. BPSD are poorly understood, leading to shame and blame. CONCLUSIONS: BPSD are common among people with dementia in developing countries, though we found marked regional variations. Representative population studies are needed to clarify prevalence and impact, but our research suggests considerable unmet need, with much scope for intervention. Raising awareness of the problem should be the first step.

Aged↗

Continuous amphetamine intoxication: an animal model of the acute psychotic episode.

When amphetamines are administered to humans every few hours for several days, either during the 'speed runs' of addicts or in controlled laboratory settings, the psychosis which reliably results is similar to paranoid schizophrenia in a number of important aspects. This unique regimen of drug intake, which involves the continuous presence of stimulants over a prolonged period of time, can be simulated in animals using subcutaneously implanted slow-release silicone pellets containing d-amphetamine base. Monkeys and rats implanted with these pellets develop stages of behavioural alterations which are somewhat similar in sequence to those observed in humans who have received frequent doses of amphetamine. An initial period of hyperactivity and exploratory behaviour is followed by the gradual development of motor stereotypies which become virtually incessant. A period of relative inactivity then appears which is followed, at 4-5 days after pellet implantation, by a late stage. This final stage is characterized by 'wet-dog' shakes, parasitotic-like grooming episodes, and a variety of other forms of hallucinatory-like behaviour. At about the same time there are distinctive and partially irreversible alterations in dopaminergic innervations of the caudate nucleus, but not in mesolimbic dopamine innervation of the nucleus accumbens or in several other neurotransmitter systems. Continuous amphetamine administration may reproduce some aspects of the prolonged excitation which accompanies an acute psychotic episode and may be a fruitful model for the clarification of the dopamine theory of schizophrenia.

Animals↗

Behavioral inhibition system (BIS), behavioral activation system (BAS) and schizophrenia: relationship with psychopathology and physiology.

OBJECTIVE: The Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) have been conceptualized as two neural motivational systems that regulate sensitivity to punishment (BIS) and reward (BAS). Imbalance in BIS and BAS levels has been reported to be related to various forms of psychopathology. Since sensitivity to stress has been supposed to be a pathway for the development of psychotic symptoms, the aim of this study is to examine BIS and BAS scores in schizophrenia and their relationship with psychopathology and physiology. METHOD: Forty-two patients with schizophrenia (26 men, 16 women), stable on atypical antipsychotics, and 37 healthy controls (17 men, 20 women) were assessed with the use of the Behavioral Inhibition and Behavioral Activation scales. Since increased average heart rate (HR) and decreased heart rate variability (HRV) have been reported in patients with schizophrenia and have been shown to correlate with inhibited behaviour, these psychophysiological measures were also obtained. The BIS/BAS data and HR/HRV data were both analyzed by a (M)ANOVA. Correlation coefficients were computed for associations between BIS/BAS data, HR/HRV data, and patient variables. RESULTS: On the BIS, patients showed higher sensitivity to threat than control subjects. Higher BIS sensitivity correlated with longer duration of illness, and lower negative symptoms on the PANSS. The BAS scores did not reveal differences between patients and controls. In patients, low BAS sensitivity correlated with low dosage of medication. On the physiological measures patients showed a significantly higher HR and lower HRV compared to controls, which was limited to clozapine treated patients. No correlations were found between HR/HRV scores and BIS/BAS scores or patient variables. CONCLUSIONS: Male as well as female patients with schizophrenia are more sensitive to threat than healthy controls. This may reflect a trait-related characteristic, and is not reflected in state-related psychophysiological measures.

Adult↗

The psychoanalytic impasse.

In the study of impediments to the success of psychoanalysis as a treatment method, the character structure of the analysand has received the most attention. Psychoanalysis has come to be used for the treatment of an ever-widening range of psychopathological states, and the analysts have become confronted with a greater incidence and variety of clinical situations which can develop into therapeutic obstacles. Whether the psychoanalytic impasse will become a therapeutic stepping-stone or an obstacle to treatment often depends upon the emotional response of the therapist and his resultant behavior. Accordingly, there has been a heightened interest in the study of countertransference. Some therapists equate the psychoanalytic treatment of patients with severe character deformations with "wild" analysis and therefore feel needless guilt and anxiety when they attemtp to treat patients who suffer from them; thus they increase the likelihood of their becoming therapeutic obstacles. We have considered the psychoanalytic impasse as an inevitable aspect of the analytic sequence and discussed countertransference reactions in this context. Technical complications resulting from adverse countertransference reactions are examined both in terms of the patient's provocations and responses in the analyst. Among the analyst's responses, three were emphasized: (1) helpless fellings which represent the patient's helplessness and vulnerability; (2) rage reactions; and (3) profound anxiety reactions. The patient's need to construct and environment similar to the early traumatic environment within the analysis can become a very difficult situation for a therapist. The resolution or at least understanding of these interactions becomes equivalent to the lifting of infantile amnesia, a step which has been considered the essence of psychoanalytic resolution. Thus, adverse reactions can become keys to the gaining of fundamental insights, permitting the analytic process to continue its inevitable course.

Anxiety↗

Subclinical polydipsia and polyuria in young patients with schizophrenia or obsessive-compulsive disorder vs normal controls.

1. Increased water intake and output is more common among psychiatric patients, especially those with schizophrenia, than in the general population. Animal studies suggest that polydipsia and polyuria derive, in part, from dopamine dysregulation. Stimulated by these observations this study sought to elucidate relationships among water homeostasis, monoamine metabolism, and electrolyte excretion in schizophrenic patients with and without paranoid hallucinatory symptoms (PH vs. NP), thought to reflect hyper- and hypo-dopaminergic states respectively, and to compare these with those shown by patients with obsessive compulsive disorder (OCD). 2. 24 hr-urine samples for electrolyte, monoamine and metabolite measures were taken from 14 schizophrenic patients with PH symptoms, 13 with predominantly nonparanoid (NP) symptoms, 11 OCD patients and 27 healthy controls (matched for age, weight and creatinine production). Water intake and serum electrolytes was sampled during psychological testing. 3. PH patients drank 2-3 times more than the others in a 3-4 hr test, yet 24 hr-urinary volumes were 75% larger in both PH and NP patients than in the two comparison groups. 4. Daily potassium excretion was a bit higher in PH patients, but concentrations of sodium, potassium and phosphate tended to be lower in PH and NP patients than in the others. 5. Positive associations of electrolyte with homovanillic acid excretion were consistent across groups and not directly related to medication. But associations of electrolyte excretion with noradrenergic activity in controls were absent in psychotic patients and associations with serotonin in OCD patients were absent in the other groups. 6. Increased water intake and output in PH patients along with the disturbed association with noradrenergic metabolism are consistent with altered autonomic activity in these patients. 7. The independence of measures of water homeostasis from dopaminergic medication indicates that the associations in clinically responding PH patients of polydipsia with DA function (decreased DA levels) may be pertinent to this subgroup but not to schizophrenia in general.

Adolescent↗

Gender differences in borderline personality disorder: findings from the Collaborative Longitudinal Personality Disorders Study.

A majority of the literature on borderline personality disorder (BPD) focuses on its occurrence in women or does not specifically assess for gender differences in clinical presentations. Some studies report that men with BPD may be more likely to be diagnosed with substance use disorders, as well as paranoid, passive-aggressive, narcissistic, sadistic, and antisocial personality disorders (PDs). Additionally, women with BPD appear to be more likely to report histories of adult physical and sexual abuse and to meet diagnostic criteria for post-traumatic stress disorder (PTSD) and eating disorders. The purpose of the present study was to further examine gender differences in BPD. Using baseline data from the Collaborative Longitudinal Personality Disorders Study (CLPS), men and women who met criteria for BPD were compared on current axis I and II disorders, BPD diagnostic criteria, childhood trauma histories, psychosocial functioning, temperament, and personality traits. Men with BPD were more likely to present with substance use disorders, and with schizotypal, narcissistic, and antisocial PDs, while women with BPD were more likely to present with PTSD, eating disorders, and the BPD criterion of identity disturbance. Generally speaking, women and men with BPD displayed more similarities than differences in clinical presentations. The differences that did emerge are consistent with those found in epidemiological studies of psychopathology and therefore do not appear unique to BPD. Additionally, many gender differences traditionally found in epidemiological samples did not emerge in BPD subjects. For example, no difference was found in rates of major depressive disorder, a condition that is more prevalent in females. Thus, BPD pathology may be a prevailing characterization that can attenuate usual gender-based distinctions.

Adolescent↗