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Diagnostic stability in adolescent onset psychotic disorders.

The purpose was to examine the long-term stability of a diagnosis of psychotic disorder in adolescence and to focus on diagnostic change over time. A total of 88 patients with a first episode of early onset psychosis (before 19 years) were followed up an average of 10.5 years (range 5.1-18.2) after admission. This report includes the 68 patients who could be traced and interviewed with the Positive and Negative Symptom Scale and lifetime Structured Clinical Interview for DSM-IV diagnosis. An initial diagnostic split between schizophrenia spectrum and affective disorder had a good (> 80 %) Positive Predictive Validity and Sensitivity. The main diagnostic shift was an influx to schizophrenia spectrum disorder (n = 6). These patients resembled the stable affective group (n = 27) in premorbid and prodromal aspects but changed over time to resemble the poor outcome of the stable schizophrenia spectrum group (n = 28) albeit with fewer negative symptoms and a better social function. Family history of nonaffective psychosis in first or second degree relatives was often found in the "change to schizophrenia group". A diagnosis in adolescence of schizophrenia spectrum or affective psychotic disorder is usually stable over time. A subgroup of non-schizophrenia patients go on to develop a schizophrenia spectrum disorder.

Adolescent↗

Voluntary motor performance in psychotic disorders: a replication study.

Voluntary motor performance was used to investigate the hypothesis of a continuum of psychosis from depression through schizophrenia. 43 schizophrenic, 36 schizoaffective, 50 major depressive, 20 manic, and 25 nonpsychotic patient controls were tested for tapping speed, finger dexterity, hand grip strength, and neuropsychological motor performance. Sex was included as an independent variable, and the effects of psychotropic drugs were evaluated. A continuum of motor dysfunction from depression through schizophrenia was not obtained. A measure of current psychotic symptoms was not associated with motor or neuropsychological performance. Motor performance was significantly worse in schizophrenic, schizoaffective, and psychotic affective disorders, when compared to nonpsychotic affective disorders. In this final analysis, psychoticism was defined by history. The results are discussed in terms of the hypothesis that psychoticism is a trait that is independent of diagnosis.

Humans↗

Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders.

The dopamine D2 receptor gene is a candidate gene for schizophrenia because the potency of certain neuroleptics correlates with their affinity for this receptor. Case-control studies in 291 schizophrenics, 78 patients with affective disorders, and 579 controls on an association of a molecular variant of S311C of the dopamine D2 receptor with psychiatric disorders were conducted. The frequency of individuals with S311C was significantly higher in schizophrenics with the absence of negative symptoms (17.1%, P < 0.00001), but similar in schizophrenics with the presence of negative symptoms (5.7%, P = 0.46) when compared with the controls (4.1%). The frequency of S311C was significantly higher in familial schizophrenics from one local area but not in those from other areas. It was significant that S311C was frequently present in patients with mood-incongruent psychotic affective disorders (33.3%, P < 0.0001), but not in those with other affective disorders. These data suggest that S311C might be one of the genetic factors for symptomatic dimensions of delusions and hallucinations and might be involved in underlying clinical heterogeneity in schizophrenia and affective disorders.

Adult↗

Childhood precursors of affective vs. social deficits in adolescents at risk for schizophrenia.

Childhood attentional and neuromotor precursors of social competence and affective deficits in adolescents at risk for schizophrenia, adolescents at risk for affective disorder, and matched comparison adolescents were examined. The subjects were offspring of parents with schizophrenia or affective disorder and of normal parents matched on age, sex, and socioeconomic status from the New York High-Risk Project (Sample B). On the basis of interviews conducted when the subjects were children and adolescents, social competence was rated from child reports and parent reports, affective deficits were assessed by affective flattening ratings, and smiling was assessed by counting broad smiles. Adolescents at risk for schizophrenia had significantly greater social and affective deficits than adolescents at risk for affective disorder and comparison adolescents. In subjects at risk for schizophrenia, childhood neuromotor dysfunction predicted adolescent affective flattening, and childhood attentional dysfunction predicted adolescent social deficits. The results suggest that affective and social deficits in schizophrenia have different childhood precursors.

Adolescent↗

Saccadic disinhibition in patients with acute and remitted schizophrenia and their first-degree biological relatives.

OBJECTIVE: Performance on measures of saccadic inhibition and control was investigated in a large family study of schizophrenia to evaluate the utility of using antisaccade task performance as an endophenotypic marker of genetic liability for schizophrenia. METHOD: Ninety-five patients with acute schizophrenia and 116 of their first-degree biological relatives, 13 schizophrenia patients whose illness was in full remission, 35 patients with acute psychotic affective disorder, and 109 nonpsychiatric comparison subjects were administered antisaccade and prosaccade tasks. RESULTS: Both schizophrenia patient groups had a greater number of errors on the antisaccade task than did the first-degree relatives and the affective disorder group, which both had more errors than the comparison subjects. Among the first-degree relatives of the probands with acute schizophrenia, relatives of poor-performing patients performed worse on the antisaccade task than relatives of patients with good performance. Reflexive errors were not likely the result of interfering psychotic symptoms, medication, or medication side effects. Although the schizophrenia patients demonstrated other signs of saccadic abnormalities, these problems, which were not observed in their relatives even though they had high antisaccade error rates, seem unlikely to account for the higher antisaccade error rate of the schizophrenia patients. CONCLUSIONS: These findings suggest that saccadic disinhibition is strongly associated with the genetic liability for schizophrenia.

Acute Disease↗

Antipsychotic drugs for non-affective psychosis during pregnancy and postpartum.

BACKGROUND: Antipsychotics are commonly prescribed for women suffering psychotic illnesses during pregnancy and the postpartum period. The potential adverse consequences of these different options are multiple and complex, impacting on the foetus, neonate, infant and early development of the child as well as the woman herself. OBJECTIVES: To establish whether the benefits of taking antipsychotic drugs outweigh the risks for pregnant or post partum women. SEARCH STRATEGY: The Cochrane Schizophrenia Group's Register (January 2003) was searched in order to identify all published trials of women during pregnancy or the postpartum period. We inspected all references of all identified studies. If any studies had been found, the first authors of each included study would have been contacted. SELECTION CRITERIA: Randomised controlled clinical trials investigating the effects of any type of antipsychotic drug compared with any other treatment option (including standard psychosocial care, any other antipsychotic drug, or an alternative therapy such as electro-convulsive therapy or cognitive behavioural therapy) and involving pregnant women and/or women during the postpartum period diagnosed with a non-affective psychotic disorder. DATA COLLECTION AND ANALYSIS: Citations, and where possible, abstracts were independently inspected by reviewers and the papers ordered were scrutinised and quality assessed. Data would have been extracted independently by at least two reviewers. Binary outcomes were to have been analysed using Relative Risks (RR) and their 95% Confidence Intervals (CI). MAIN RESULTS: We found no trials that met the broad inclusion criteria. REVIEWERS' CONCLUSIONS: Current guidelines and clinical practice for the use of antipsychotic drugs in women with non-affective disorders during pregnancy and postpartum are not based on evidence from randomised controlled trials. Although ethical concerns have to date precluded the use of randomised controlled trials to address this research topic, the continued use of antipsychotic drugs in this group of women in itself poses significant clinical and ethical problems. Evidence is required from large pragmatic trials that reflect routine clinical practice, examine a broad range of outcomes and accurately quantify risks and benefits to both mothers and their offspring, so that comparison between different treatment options can be made.

Antipsychotic Agents↗

Depression subtyping: treatment implications.

The complexity of subtyping depression and the implications that such subtyping has on treatment choices are discussed in this article. The most recent edition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) directs clinicians to classify the mood disorders in depressed patients as unipolar, bipolar, due to a general medical condition, or due to substance abuse. The focus of this article is unipolar (major depression and dysthymia) and bipolar I and II disorders with and without feature specifiers for atypical depression, seasonal affective disorder, psychotic depression, and postpartum depression. Anxious depression, which is not a DSM-IV classification, is also reviewed.

Antidepressive Agents↗

Psychotic symptoms and age of onset in affective disorders.

Prevalence of hallucinations and delusions was studied in 1,763 patients with unipolar major depression, bipolar affective disorder, and schizoaffective disorder. The authors found that the presence of psychotic features was negatively associated with age of onset for the group as a whole, and bipolar affective disorder (manic or mixed type) specifically. The clinical implications of the findings are discussed.

Adult↗

Uses of clozapine in nonschizophrenic patients.

Clozapine is a novel antipsychotic agent used in the treatment of schizophrenic patients who have not responded to or have been unable to tolerate conventional neuroleptic therapy. In this paper, the literature surveying the uses of clozapine in the treatment of patients with nonschizophrenic illnesses, in particular psychotic affective disorders (bipolar disorder and schizoaffective disorder), will be reviewed. (A Medline search was done for all papers concerning clozapine; those that represented major contributions to the literature were used.) Results from a prospective study at McLean Hospital assessing the effects of diagnosis on response will be presented. Several other uses in nonschizophrenic patients will also be discussed. Because of its relative freedom from extrapyramidal side effects, it is an important agent in the treatment of patients with Parkinson's disease who also have psychotic symptoms. It may be effective in the treatment of tardive dyskinesia in nearly 50% of patients with that symptom. In addition, the drug may be useful in treating violent patients and those with certain movement disorders, atypical borderline personality disorder, or chronic psychotic symptoms. Due to the risk of agranulocytosis, clozapine cannot yet be considered a first-choice treatment for psychotic symptoms, but many studies indicate it to be helpful with a wide variety of treatment-resistant ones.

Adult↗

Measuring quality of life in first-episode psychosis.

Quality of life (QoL) measures are increasingly recognized as necessary parts of outcome assessments in psychosis. The present paper is a comprehensive study of patients with first-episode psychosis where QoL is measured by the commonly used Lehman Quality of Life Interview (L-QoLI). The aim is to examine if the L-QoLI maintain its original structure when used in a group of patients with first-episode psychosis, and to investigate what determines global subjective QoL with a specific emphasis on premorbid adjustment, duration of untreated psychosis (DUP) and clinical symptoms. The study indicates that the psychometric properties of the L-QoLI do not change significantly when used in first-episode samples. The patients report subjective and objective QoL in the fair to good range, with only a moderate association between the objective and subjective measures. Poor global satisfaction is predicted by being single, abusing drugs, being depressed, having a diagnosis of psychotic affective disorder, having poor premorbid social adjustment and DUP over 10 weeks. The study supports the notion that patients with first-episode psychosis construct QoL in the same way as other groups, and that longer durations of compromised function at this stage produces poor satisfaction with life rather than a downward readjustment of expectations.

Activities of Daily Living↗

The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review.

A modified dexamethasone suppression test (DST) has had unprecedented evaluation among biologic tests proposed for clinical use in psychiatry. It has not proved to reflect pathophysiologic changes at the level of the central nervous system or pituitary, and tissue availability of dexamethasone itself may contribute to test outcome. The sensitivity of the DST in major depression is limited (about 44% in over 5,000 cases) but is higher in psychotic affective disorders and mixed manic-depressive states (67% to 78%). The high specificity of the DST vs control subjects (over 90%) is not maintained vs other psychiatric disorders (77% specificity overall), and acute "distress" may contribute to nonsuppression of cortisol. The test may have power in differentiating severe melancholic depression, mania, or acute psychosis from chronic psychosis (87% specificity) or dysthymia (77% specificity). The DST status adds about 11% to the prediction of short-term antidepressant response. Suggestions that failure to maintain normal suppression of cortisol predicts poor outcome are not secure. Uncritical enthusiasm or excessive skepticism regarding the DST are unwarranted.

Adolescent↗

Linkage evidence of schizophrenia to loci near neuregulin 1 gene on chromosome 8p21 in Taiwanese families.

Positive linkage of schizophrenia to chromosome 8p22-21 loci had been reported in the Caucasian samples. This study was designed to replicate this finding by using eleven microsatellite markers on chromosome 8p22-21 in 52 Taiwanese schizophrenic families with at least two affected siblings. Two phenotype models (narrow: DSM-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other non-affective psychotic disorders) were used to define the disease phenotype. Maximum non-parametric linkage scores (NPL score) of 2.45 (P = 0.008) and 1.89 (P = 0.02) were obtained for the marker D8S1222 under the broad and narrow models, respectively. Positive linkage was found across about a 4-cM region. The marker D8S1222 was about 400 kbp distal to the exon 1 of glial growth factor 2 (GGF2), an isoform of Neuregulin 1 gene (NRG1), which has been highly suggested to be a candidate gene for schizophrenia. The results provide suggestive linkage evidence of schizophrenia to loci near NRG1 on chromosome 8p21 in an ethnically distinct Taiwanese sample. Further exploration of the candidate gene and nearby chromosome regions is warranted.

Alleles↗

Older people with schizophrenia: a community study in a rural catchment area.

BACKGROUND: An increasing number of older people with schizophrenia are living in the community but we still have little data on their clinical presentation, service use and functioning. METHODS: All patients over the age of 60 years with a primary diagnosis of a non-affective psychotic disorder who were known to health services were identified in a rural area of East England. Subjects were interviewed with the Present State Examination and other standardised interview instruments. RESULTS: Seventy-two subjects fulfilled study inclusion criteria. Forty-six of these had first become ill before the age of 60 years and 26 after (the very late onset group (VLO)). Eighty per cent were women and 26% had never married. Eighty-seven per cent lived in their own homes and 51% alone. In the preceding month, 41% of the sample had experienced psychotic symptoms and 15% depressive symptoms. Twenty-seven per cent of the sample were cognitively impaired. The earlier onset group had significantly higher rates of tardive dyskinesia and negative symptoms of schizophrenia and were treated with higher doses of neuroleptics. The VLO group had higher rates of hearing impairment (54% vs 15% p = 0.001) and of partial or no insight (93% vs 55% p = 0.004). CONCLUSIONS: Despite significant differences in presentation, elderly patients with schizophrenia and very late onset schizophrenia-like psychosis have much in common. Both groups are vulnerable with high levels of psychopathology, poor insight, sensory impairment and social isolation. The needs of older people with schizophrenia must be taken into account when services for older adults are planned.

Activities of Daily Living↗

Premorbid abnormalities in mania, schizomania, acute schizophrenia and chronic schizophrenia.

The aim of this study was to examine the hypothesis that differences in outcome among affective and non-affective psychoses are associated with differences in the degree of developmental deviance. We conducted a retrospective survey of first contact cases treated over a 20-year period in a psychiatric hospital serving a catchment area in South London. All patients with non-depressive functional psychosis residing in the catchment area who received their first psychiatric treatment between 1965 and 1984 were included in the study. Cases were classified according to the relative chronicity of their illness into four non-overlapping groups: mania, schizomania, acute schizophrenia and chronic schizophrenia. There was a linear trend in the association between illness chronicity and proxy measures of development deviance, such as premorbid unemployment, single status and poor academic achievement. Compared to individuals with mania, schizophrenic patients had a 3-6 times increased risk of premorbid abnormality. For patients with schizomania and acute schizophrenia, the risk was 1.5-3 times greater than for manic subjects. We conclude that the prevalence of premorbid abnormalities is highest among chronic schizophrenia, but similar disturbances also occur, to a lesser degree, in less disabling affective and non-affective psychotic disorders.

Acute Disease↗

Saccadic disinhibition in schizophrenia patients and their first-degree biological relatives. A parametric study of the effects of increasing inhibitory load.

Several studies have reported that patients with schizophrenia and their relatives perform poorly on antisaccade tasks and have suggested that this deficit represents saccadic disinhibition. If this proposition is correct, then varying task parameters that specifically increase the difficulty with which unwanted saccades can be inhibited should exacerbate deficits. Forty-two schizophrenia patients, 42 of their first-degree biological relatives, 21 psychotic affective disorder patients, and 38 nonpsychiatric comparison subjects were given fixation and antisaccade tasks. The introduction of distracters and the presence of visible fixation stimuli were parameters used to vary the difficulty in suppressing unwanted saccades (inhibitory load). It is known that the presence of a fixation stimulus at the time when a saccade must be inhibited results in fewer reflexive errors on antisaccade tasks. Performance on fixation tasks without (low load) vs with distracters (high load) and antisaccade tasks that had fixation stimuli still visible (low load) vs already extinguished (high load) at the time when the reflexive saccade must be inhibited was compared. The schizophrenia patients and their first-degree biological relatives showed evidence of increased saccadic disinhibition that was most pronounced during high inhibitory load conditions. These data indicate that dysfunctional inhibitory processes, at least in the oculomotor domain, are associated with the liability to schizophrenia. Results also suggest that this genetic liability may be related to dysfunctional prefrontal cortical areas that provide top-down inhibitory control over reflexive saccade generation.

Adult↗

PH-dependent behavior of erythrocyte membrane elevations. II Occurrence in moderate acidemic and alkalemic conditions.

Changes of the number of red cell membrane elevations revealed by freeze-etch electron microscopy are pH-dependent in vitro and in vivo. In healthy volunteers a decrease of the number of red cell surfaces with elevations was observed under moderate acidemic and alkalemic conditions. These changes were different in patients with Huntington's chorea and affective psychotic disorders. Elevations of the red cell membrane with the same diameter can be demonstrated in ultrathin sections, if sodium azide is added during the fixation procedure.

Erythrocyte Membrane↗

The concept of cycloid psychosis: sensitivity and specificity of syndromes derived by multivariate clustering techniques.

A total of 154 patients admitted for the first time to hospital for a psychotic or affective disorder in 1925 were rediagnosed in accordance with DSM-III and Leonhard's diagnostic system. Symptoms were rated in accordance with a rating protocol containing 33 items based on Leonhard's descriptions of cycloid psychoses. The patients were followed up through parish registers and hospital records. Of 42 cases considered to be cycloid psychosis at index admission, 34 were prognostically verified. The symptom ratings of the 154 patients were analysed by K-means cluster analysis to test whether the patients with cycloid psychoses would separate from the rest of the material. With a 2-cluster solution, 30 of 34 cases (88%) were contained in the same cluster. The sensitivity of the ratings was therefore judged to be acceptable. Specificity was low, however, since 19 cases in the cluster were differently diagnosed. A subcohort of 64 patients, satisfying at least 5 items of the rating protocol, was then analysed by Q-factor analysis to test whether nuclear cases of cycloid psychosis differ from symptomatically related syndromes. No such differences could be statistically verified; no symptom profile specifically indicating cycloid psychosis could be found. Prominent confusion symptoms appear, however, to be prognostically favourable, whereas motility symptoms without confusion seem to indicate an unfavourable course.

Affective Disorders, Psychotic↗

The bipolar unipolar dichotomy and the need for a consistent terminology.

A division of the major psychotic affective disorders into a bipolar (true manic-depressive) and unipolar (recurrent depressive or recurrent manic) group represents a clear advance in the classificatory work of affective illness which had been suffering from stagnation. Several investigations have already contributed provocative findings which support the heuristic value of this distinction. However, to be reliable a separation of bipolar from unipolar affective disorders must rely upon clear-cut definitions of the labels to be used in order to avoid inconsistency in terminology hampering the reliability of our findings.

Bipolar Disorder↗