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.     

Visuospatial memory deficits in adolescent onset schizophrenia

Visuospatial memory encoding deficits have been reported in adults with schizophrenia, while adolescents with schizophrenia have not been specifically investigated with visuospatial memory encoding and retrieval paradigms. A cross sectional study of delayed matching-to-sample performance in 19 right handed, male, anti-psychotic medication na?ve adolescents with undifferentiated schizophrenia and 28 age, gender, IQ and handedness matched healthy participants was completed. The adolescent-onset schizophrenia group demonstrated significant impairment in visuospatial memory, independent of the degree of delay, consistent with an encoding impairment. The impaired encoding phase of visuospatial memory in the adolescent-onset schizophrenia group is consistent with findings in adult onset schizophrenia samples, suggesting a developmental stage-independent deficit.     

Adult quality of life and associated factors in adolescent onset schizophrenia and affective psychotic disorders

BACKGROUND: Subjects in treatment for affective disorders are usually less satisfied with life compared to subjects with schizophrenia. AIMS: The aims of this study were to compare subjective quality of life (QoL) at adult age of adolescent onset psychotic disorders and analyse associated factors. METHOD: Fifty-three patients with adolescent onset psychotic disorders were followed up at age 25, diagnostically re-evaluated according to the DSM-IV and assessed with the Positive and Negative Symptoms Scale, the Strauss-Carpenter Scale and the Lancashire Quality of Life Profile. RESULTS: Subjects diagnosed with schizophrenia or schizoaffective disorder (n = 27) experienced significantly lower overall QoL than subjects with psychotic mood disorders (n = 26). Overall QoL was strongly associated to depressed mood (R2 = 0.49) in the schizophrenia group and to degree of employment (R2 = 0.39) in the mood disordered group. CONCLUSION: Depression is a major concern in the evaluation and treatment of patients with schizophrenia, while vocational support seems particularly important after an episode of psychotic mood disorder.     

Visuospatial working memory deficits in adolescent onset schizophrenia

This study determines that visuospatial working memory (VSWM) deficits are evident in adolescent-onset schizophrenia, while the spatial strategy and spatial span components of VSWM are spared. These findings imply that frontal-striatal-parietal neural networks are dysfunctional in adolescent-onset schizophrenia, while mid-dorsolateral and ventrolateral PFC functions remain intact: the current conceptualisation of schizophrenia as a progressive neurodevelopmental disorder is consistent with these results.     

Culture and schizophrenia and other psychotic disorders.

The comparative study of schizophrenia and related disorders across cultures has come a long way since Kraepelin advocated its cause, following his trip to Java at the beginning of the last century. The principal development since then has been the burgeoning of interest in the field, culminating in innovative and ambitious international collaborative research by the WHO. Despite reservations about covert ideology or about the more overt methodologic difficulties, the balance of evidence from these and similar studies suggests that: It is feasible to conduct such research despite the numerous hazards. There is a certain uniformity to the way schizophrenia presents globally; there are equally significant cultural differences. The outcome of schizophrenia appears to be better in developing, than developed cultures; reasons for this are far from clear, nevertheless, it can be safely assumed that culturally-determined processes, whether social or environmental, are partly responsible. Overall, the study of schizophrenia in different cultures has proved useful in establishing the pancultural and the culture-specific properties of this and related disorders.     

Developing therapeutics for schizophrenia and other psychotic disorders

Although the second-generation or atypical antipsychotic drugs have been breakthrough medicines for the treatment of schizophrenia and other psychotic conditions, cognitive dysfunction and to some extent negative symptoms of the disease continue to be the main cause of poor vocational status of the patients. Thus, the majority of investigational drug development efforts today target these unmet medical needs. This review postulates that the field of schizophrenia research has advanced sufficiently to develop biochemical hypotheses of the etiopathology of the disease and target the same for revolutionary disease modifying therapy. This postulate is based on recent studies that have begun to provide a testable etiopathology model that integrates interactions between genetic vulnerability factors, neurodevelopmental anomalies, and neurotransmitter systems. This review begins with a brief overview of the nosology and etiopathology of schizophrenia and related psychotic disorders to establish a context for subsequent detailed discussions on drug discovery and development for psychotic disorders. Particular emphasis is placed on recent advances in genetic association studies of schizophrenia and how this can be integrated with evidence supporting neurodevelopmental abnormalities associated with the disease to generate a testable model of the disease etiopathology. An in-depth review of the plethora of new targets and approaches targeting the unmet medical need in the treatment of schizophrenia exemplify the challenges and opportunities in this area. We end the review by offering an approach based on emerging genetic, clinical, and neurobiological studies to discover and validate novel drug targets that could be classified as disease modifying approaches.     

Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic disorders

Early-onset psychotic illnesses in children and adolescents are not as rare as is commonly believed. These disorders, which include schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, and major depression with psychotic features, often have a chronic and severe course and poor long-term outcome. Many patients with early-onset schizophrenia have greater functional impairments than most patients with adult-onset schizophrenia. Magnetic resonance imaging studies show that patients with early-onset schizophrenia experience substantial gray matter loss during adolescence, which is not observed in studies of patients with adult-onset schizophrenia. The chronic course, severe functional impairments, and poor prognosis of early-onset psychosis create a great need to identify effective and safe treatments for youth with psychosis. Although atypical anti-psychotics have been considered superior to traditional antipsychotics, there has been little controlled information to inform clinical decisions until recently. Over the past 5 years, several studies have been initiated to address these questions. The results of the studies completed to date are reviewed.     

Risk for suicide in schizophrenia and other psychotic and nonpsychotic disorders

To determine the rate of suicide in young, early phase schizophrenics and other psychotic disorders, and to analyze risk factors for suicide, a large sample of patients was prospectively assessed at index hospitalization and then followed up systematically after discharge. Thirty-six patients committed suicide and these patients were compared with those who did not commit suicide for major diagnostic and prognostic factors. Results indicated the following: a) During early years, schizophrenics and other types of psychotic patients were more likely to commit suicide than nonpsychotic patients. b) Similarly, among depressives, psychotic depressed patients were more likely to commit suicide than nonpsychotic depressed patients. c) Schizophrenics and other psychotic patients were especially vulnerable to suicide within the first 6 years of their first hospitalization. d) Among the combined sample of psychotic patients (schizophrenic and other psychotic patients), those at greater risk for suicide were unmarried, white, high IQ, male patients with a more gradual onset of disorder and were of "chronic" Research Diagnostic Criteria subtypes.     

Suicidal behavior in patients with schizophrenia and other psychotic disorders.

OBJECTIVE: Patients with schizophrenia are known to be at high risk for suicide attempts and dying by suicide. However, little research has been conducted to determine whether the risk for suicidal behavior is elevated among patients with psychosis in general. METHOD: This study evaluated 1-month and lifetime rates of suicidal behavior among 1,048 consecutively admitted psychiatric inpatients (ages 18 to 55 years) with DSM-III-R psychotic disorders. Demographic, clinical, and diagnostic correlates of suicidal behavior were examined. RESULTS: A high rate of suicidal behavior was found in the group: 30.2% reported a lifetime history of suicide attempts, and 7.2% reported a suicide attempt in the month before admission. The highest 1-month and lifetime rates were found in patients with schizoaffective disorder and major depression with psychotic features. Ratings of the medical dangerousness of the most recent suicide attempt on the basis of the extent of physical injury were higher in patients with schizophrenia spectrum psychoses. Agreement was high between emergency room assessments and semistructured interview assessments of suicidal behavior. CONCLUSIONS: Rates of suicidal behavior were high across a broad spectrum of patients with psychotic disorders; patients with a history of a current or past major depressive episode (as a part of major depressive disorder or schizoaffective disorder) were at a greater risk for suicide attempts, but patients with schizophrenia, on average, made more medically dangerous attempts. Risk factors for suicidal behavior in patients with psychosis appear to vary compared to those for the general population.     

Does operational diagnosis of schizophrenia significantly impact intellectual deficits in psychotic disorders?

Background Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. Methods Using Wechsler Adult Intelligence Scale – Revised (WAIS‐R) data for 55 inpatients with schizophrenia and 28 inpatients with non‐schizophrenic psychotic disorders (NSPD) (schizophreniform disorder, brief psychotic disorder, delusional disorder, psychotic disorder due to a general medical condition, and psychotic disorders not otherwise specified), intelligence performance was compared between schizophrenia and NSPD and among different subtypes of schizophrenia. Results There were no significant differences in intelligence quotient (IQ), verbal IQ (VIQ) and performance IQ (PIQ) discrepancy, and subtest scores of WAIS‐R between the patients with schizophrenia and those with NSPD. These diagnostic groups were not discriminated well by any WAIS‐R variables. Schizophrenia patients with prominent negative symptoms, on the other hand, had a significantly larger IQ discrepancy (VIQ > PIQ) than those without prominent negative symptoms and NSPD patients. Intelligence performance in schizophrenia did not differ with respect to diagnostic subtypes and longitudinal courses. Conclusions The current study failed to show diagnostic usefulness of WAIS‐R in discriminating schizophrenia and other psychoses. A diagnosis of schizophrenia does not significantly impact intellectual deficits in psychotic disorders.     

Bipolar disorder,schizophrenia, and other psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum disorders

Summary. Individuals with attention-deficit/hyperactivity disorder (AD/HD) and autism spectrum disorders (ASD) often display symptoms from other diagnostic categories. Exclusion criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Statistical Classification of Diseases and Related Health Problems (ICD-10) impede the use of categorical diagnoses to describe the particular problem constellation in a patient. In this study, we describe the prevalence and patterns of comorbid bipolar and psychotic disorders in 241 consecutively referred adult patients with AD/HD and/or ASD. Thirty per cent of patients with AD/HD had comorbid ASD and 38% of patients with ASD had comorbid AD/HD. Of the subjects with ASD, 7% had bipolar disorder with psychotic features, and 7.8% had schizophrenia or another psychotic disorder. The corresponding figures for the patients with AD/HD were 5.0% and 5.0%, respectively. Current diagnostic criteria have to be revised to acknowledge the comorbidity of bipolar and/or psychotic disorders in AD/HD and ASD.     

Patterns of service use among persons with schizophrenia and other psychotic disorders

OBJECTIVE: This study assessed 12-month service use patterns among people with psychotic disorders and sought to identify determinants of service use. METHODS: As part of a large two-phase Australian study of psychotic disorders, structured interviews were conducted with a stratified random sample of adults who screened positive for psychosis. Demographic characteristics, social functioning, symptoms, mental health diagnoses, and use of psychiatric and nonpsychiatric services were assessed. Data were analyzed for 858 persons who had an ICD-10 diagnosis of a psychotic disorder and who had been hospitalized for less than six months during the previous year. RESULTS: People with psychotic disorders had high levels of use of health services, both in absolute terms and relative to people with nonpsychotic disorders. Those with psychotic disorders were estimated to have an average of one contact with health services per week. Use of psychiatric inpatient services was associated with parenthood, higher symptom levels, recent attempts at suicide or self-harm, personal disability, medication status, and frequency of alcohol consumption. Services provided by general practitioners (family physicians) were more likely to be obtained by older people, women, people with greater availability of friends, those with fewer negative symptoms, and those whose service needs were unmet by other sources. People who were high users of health services also reported having more contact with a range of non-health agencies. CONCLUSIONS: The predictors of service use accounted for small proportions of the variance in overall use of health services. The role of general practitioners in providing and monitoring treatment programs and other psychosocial interventions needs to be acknowledged and enhanced.     

Predictors of risk of nonadherence in outpatients with schizophrenia and other psychotic disorders

We investigated the course of adherence to medication recommendations in 162 patients with psychotic disorders in ambulatory treatment. Data were collected using the clinic's outcome assessment program, maximizing the generalizability of the study. Patients initially adherent to their medication regimens maintained their adherence for an average of 13.3 months. Patients initially nonadherent developed adherence after an average of 5.6 months of treatment. Demographic factors and illness history were unrelated to adherence. This study replicated previous findings of the concurrent association between adherence and global functioning level, substance use, and working alliance with therapist. Cox regression analyses revealed that working alliance, global functioning, and being prescribed clozapine predicted longer maintenance of adherence. Working alliance was the most significant and consistent predictor of adherence to medication recommendations.     

Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders.

BACKGROUND: The increase or emergence of obsessions was compared in young patients with recent-onset schizophrenia or other psychotic disorders taking clozapine and other antipsychotic drugs. METHOD: We conducted a retrospective cohort study. Subjects were 121 consecutively admitted patients diagnosed with DSM-III-R schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychotic disorder not otherwise specified. Obsessions were diagnosed according to DSM-IV criteria. RESULTS: More clozapine-treated subjects (20.6%) than subjects treated with other antipsychotic drugs (1.3%) experienced an emergence or increase of obsessions (p<.01). CONCLUSION: Use of clozapine is associated with the emergence or increase of obsessions in early-phase schizophrenia.     

Sex differences in outcome and recovery for schizophrenia and other psychotic and nonpsychotic disorders

OBJECTIVE: It is generally believed by the field of psychiatry that women with schizophrenia have better outcomes and higher rates of recovery than their male counterparts, because many studies on the topic support this finding. Fewer data are available to assess potential sex differences among individuals with other psychotic disorders. This study used longitudinal data on sex differences previously unavailable to the field to examine long-term global outcome, potential recovery, course of illness, and rehospitalization for schizophrenia, other psychotic disorders, and nonpsychotic disorders. METHODS: A total of 239 young psychiatric patients (mean age of 23.4 years) were assessed prospectively at the index hospitalization and then followed over 15 years at five follow-up points (at a mean of two, 4.5, 7.5, ten, and 15 years). The sample consisted of 69 patients with schizophrenia, 56 with other psychotic diagnoses, and 114 with nonpsychotic psychiatric disorders. RESULTS: Sex differences in outcome were found for both patients with schizophrenia and those with other psychotic disorders, with women consistently showing better functioning over time, more frequent periods of good functioning and periods of recovery, less likelihood of uniformly poor outcome, and fewer and shorter rehospitalizations. Unlike both groups of patients who were psychotic, the patients with nonpsychotic disorders showed no significant sex differences in outcome. CONCLUSIONS: Both longitudinally and at each individual follow-up point, the data suggest that women with schizophrenia and with other types of psychotic disorders generally show better outcome than men with similar diagnoses. The sex differences in outcome for patients with schizophrenia were consistent over time. However, these sex differences were only moderate in size compared with the much larger difference in outcome between the diagnostic groups. The longitudinal data add a new dimension to previous research and suggest that sex differences in outcome are not specific to patients with schizophrenia but rather occur among patients with psychotic disorders in general.     

Cognitive deficits and functional outcome in schizophrenia

Cognitive dysfunction is a core feature of schizophrenia. Deficits are moderate to severe across several domains, including attention, working memory, verbal learning and memory, and executive functions. These deficits pre-date the onset of frank psychosis and are stable throughout the course of the illness in most patients. Over the past decade, the focus on these deficits has increased dramatically with the recognition that they are consistently the best predictor of functional outcomes across outcome domains and patient samples. Recent treatment studies, both pharmacological and behavioral, suggest that cognitive deficits are malleable. Other research calls into question the meaningfulness of cognitive change in schizophrenia. In this article, we review cognitive deficits in schizophrenia and focus on their treatment and relationship to functional outcome.     

Bridging the gap between schizophrenia and psychotic mood disorders: Relating neurocognitive deficits to psychopathology

BackgroundThe neurobiological relationship between schizophrenia and psychotic mood disorders is not well understood. Neurocognitive deficits have been described in both types of disorders and have been proposed to reflect underlying neurobiological dysfunction. Examining the relationship between neurocognitive function and psychopathology could help illuminate the neurobiological relationship between schizophrenia and psychotic mood disorders.MethodsParticipants included 72 individuals with DSM-IV schizophrenia, 25 individuals with schizoaffective disorder or bipolar disorder with psychotic features, and 72 community controls. Standardized scores and correlations between four domains of neurocognition and psychopathology were examined.ResultsIndividuals with schizophrenia and psychotic mood disorders scored similarly on several dimensions of neurocognitive function and psychopathology. The relationships between neurocognitive function and psychopathology were similar in the two groups.ConclusionsIndividuals with schizophrenia and psychotic mood disorders were similar in terms of both the level of impairment in neurocognitive function and psychopathology, as well as in the relationship between the two dimensions of illness. These results suggest that schizophrenia and psychotic mood disorders such as schizoaffective disorder and bipolar disorder with psychotic features are on a neurobiological continuum.     

Cognitive deficits in recent-onset and chronic schizophrenia

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia.