Negative cognition, depressed mood, and paranoia: a longitudinal pathway analysis using structural equation modeling

The role of negative cognition and effect in maintaining psychotic symptoms is increasingly recognized but has yet to be substantiated though longitudinal analysis. Based on an a priori theoretical model, we hypothesized that negative cognition and depressed mood play a direct causal role in maintaining paranoia in people with psychosis and that the effect of mood is mediated by negative cognition. We used data from the 301 patients in the Prevention of Relapse in Psychosis Trial of cognitive behavior therapy. They were recruited from consecutive Community Mental Health Team clients presenting with a recent relapse of psychosis. The teams were located in inner and outer London and the rural county of Norfolk, England. The study followed a longitudinal cohort design, with initial measures repeated at 3 and 12 months. Structural equation modeling was used to investigate the direction of effect between negative cognition, depressed mood, and paranoia. Overall fit was ambiguous in some analyses and confounding by unidentified variables cannot be ruled out. Nevertheless, the most plausible models were those incorporating pathways from negative cognition and depressed mood to paranoid symptoms: There was no evidence whatsoever for pathways in the reverse direction. The link between depressed mood and paranoia appeared to be mediated by negative cognition. Our hypotheses were thus corroborated. This study provides evidence for the role of negative cognition in the maintenance of paranoia, a role of central relevance, both to the design of psychological interventions and to the conceptualizations of psychosis.     

Time-Lagged Moment-to-Moment Interplay Between Negative Affect and Paranoia: New Insights in the Affective Pathway to Psychosis

Evidence suggests that affect plays a role in the development of psychosis but the underlying mechanism requires further investigation. This study examines the moment-to-moment dynamics between negative affect (NA) and paranoia prospectively in daily life. A female general population sample (n = 515) participated in an experience sampling study. Time-lagged analyses between increases in momentary NA and subsequent momentary paranoia were examined. The impact of childhood adversity, stress sensitivity (impact of momentary stress on momentary NA), and depressive symptoms on these time-lagged associations, as well as associations with follow-up self-reported psychotic symptoms (Community Assessment of Psychic Experiences and the Symptom Checklist-90-Revised) were investigated. Moments of NA increase resulted in a significant increase in paranoia over 180 subsequent minutes. Both stress sensitivity and depressive symptoms impacted on the transfer of NA to paranoia. Stress sensitivity moderated the level of increase in paranoia during the initial NA increase, while depressive symptoms increased persistence of paranoid feelings from moment to moment. Momentary paranoia responses to NA increases were associated with follow-up psychotic symptoms. Examination of microlevel momentary experience may thus yield new insights into the mechanism underlying co-occurrence of altered mood states and psychosis. Knowledge of the underlying mechanism is required in order to determine source and place where remediation should occur.Key words: momentary assessment methodology, stress, childhood adversity, psychotic symptoms, depressive symptoms     

Management of non-motor symptoms in advanced Parkinson disease

Progress in pharmacology has markedly improved the treatment of early Parkinson's disease. The management of advanced Parkinson's symptoms, however, remains a challenge. These symptoms are divided into motor and non-motor symptoms. Non-motor symptoms may appear early or late in the disease and sometimes even before the onset of the first motor symptoms confirming the diagnosis. The spectrum of non-motor symptoms encompasses autonomic dysfunctions, sleep disorders, mood disorders, impulse control disorders, cognitive dysfunction, dementia, paranoia and hallucinations. They are often less appreciated than motor symptoms but are important sources of disability for many PD patients. This review describes these non-motor symptoms and their managements.     

A comparison of neuropsychological dysfunction in first-episode psychosis patients with unipolar depression, bipolar disorder, and schizophrenia

The severity and profile of cognitive dysfunction in first episode schizophrenia and psychotic affective disorders were compared before and after antipsychotic treatment. Parallel recruitment of consecutively admitted study-eligible first-episode psychotic patients (30 schizophrenia, 22 bipolar with psychosis, and 21 psychotic depression) reduced confounds of acute and chronic disease/medication effects as well as differential treatment and course. Patient groups completed a neuropsychological battery and were demographically similar to healthy controls (n = 41) studied in parallel. Prior to treatment, schizophrenia patients displayed significant deficits in all cognitive domains. The two psychotic affective groups were also impaired overall, generally performing intermediate between the schizophrenia and healthy comparison groups. No profile differences in neuropsychological deficits were observed across patient groups. Following 6 weeks of treatment, no patient group improved more than practice effects seen in healthy individuals, and level of performance improvement was similar for affective psychosis and schizophrenia groups. Although less severe in psychotic affective disorders, similar profiles of generalized neuropsychological deficits were observed across patient groups. Recovery of cognitive function after clinical stabilization was similar in mood disorders and schizophrenia. To the extent that these findings are generalizable, neuropsychological deficits in psychotic affective disorders, like schizophrenia, may be trait-like deficits with persistent functional implications.     

Long-term follow-up and phenomenologic differences distinguish among late-onset schizophrenia, late-life depression, and progressive dementia.

OBJECTIVE: The diagnosis of patients with late-life onset of hallucinations and delusions but an absence of mood or cognitive disorder remains controversial. The authors used long-term follow-up and phenomenology to assess whether outcome varied by diagnosis. METHODS: Twenty-eight individuals with late-life psychosis but no mood or cognitive disorder were compared with 48 individuals with late-life major depression and 47 individuals with psychotic symptoms and late-life dementia. All subjects were followed for a minimum of 1 year. Data from the last time examined were used to determine likelihood of death at 84 months by Kaplan-Meier analysis in all groups and the likelihood of developing dementia in the depression and late-life onset psychosis groups at 120 months. RESULTS: Patients with dementia-plus-psychosis were more likely to die at 84 months than those with major depression or late-onset hallucinations and delusions. Subjects with depression or late-onset hallucinations and delusions did not differ in likelihood of developing dementia at 120 months. CONCLUSIONS: These results support the hypothesis that a condition characterized by psychiatric symptoms and no mood symptoms can begin in later life and that this disorder is not a precursor to dementia.     

Cognitive deficits and ethnicity: a cohort study of early psychosis patients in The Netherlands

Purpose

Incidence rates of psychotic disorders are higher in immigrant groups compared to native populations. This increased risk may partly be explained by misdiagnosis. Neurocognitive deficits are a core feature of psychotic disorders, but little is known about the relationship between migration and cognition in psychotic disorders. We examined whether immigrant patients have cognitive deficits similar to non-immigrant patients, in order to investigate the plausibility of misdiagnosis as explanation for increased incidence rates.

Methods

Patients who made first contact for non-affective psychotic disorder were assessed in the cognitive domains sustained attention, immediate recall and delayed recall. Immigrant patients were compared to Dutch patients on cognitive performance.

Results

407 Patients diagnosed with a non-affective psychotic disorder completed cognitive assessment (157 Dutch, 250 immigrants). Both Dutch and immigrant patients showed large cognitive deficits. Between-subgroup comparisons revealed large cognitive deficits for immigrants compared to Dutch, especially for immigrants from Morocco, Turkey and other non-Western countries.

Conclusions

These results indicate that immigrant status is associated with poorer cognitive functioning in early psychosis. The findings argue against diagnostic bias as an explanation for the increased incidence of psychotic disorders in immigrants.     

Correlates of psychotic symptoms among elderly outpatients.

Psychotic symptoms presenting in late life can offer a diagnostic challenge to the clinician. In this study, 140 geriatric outpatients were prospectively examined for psychotic symptoms and assessed on a number of demographic and clinical variables. Cognition was assessed using the Mini-Mental State Exam. Psychiatric diagnoses were made by DSM-III-R criteria. Twenty-seven per cent (N = 38) had psychotic symptoms, delusions being the most common type. Patients with psychosis were significantly more likely to have a previous history of psychosis, to have a lower MMSE and to live in a nursing home. Four diagnoses accounted for 79.5% of all psychotic patients. In order of frequency, these were dementia, major depression, delirium and organic psychosis (organic hallucinosis, organic delusional disorder). Psychotic patients were significantly more likely to have a diagnosis of dementia, delirium or organic psychosis than non-psychotics, but depression was significantly more likely to occur in patients without psychosis. Although psychotic symptoms occur in a variety of illnesses, elderly patients with psychosis should be carefully evaluated for these disorders.     

Investigating the association between neurocognition and psychosis in bipolar disorder: further evidence for the overlap with schizophrenia

Objectives: In schizophrenia, a distinction is made between psychosis with developmental and cognitive impairment on the one hand and psychosis without developmental impairment and positive symptoms on the other. In this study, we investigated whether this model can be extended to bipolar disorder by testing the hypothesis that neurocognitive functioning is inversely related to positive psychotic symptoms in bipolar disorder. Methods: Neurocognitive functioning and psychopathology were assessed in (i) 76 patients with bipolar disorder, (ii) 39 of their healthy first‐degree relatives, and (iii) 61 healthy controls. Cognitive performance of bipolar patients and their first‐degree relatives was investigated, taking into account the possible moderating effect of the level of expression of psychosis in patients and relatives. Results: Bipolar patients showed impaired cognitive performance on multiple cognitive domains, whereas performance of their relatives was comparable to that of controls. A history of psychotic symptoms in patients was suggestive of less likelihood of cognitive alterations in relatives, and the presence of subclinical psychotic symptoms within the group of relatives predicted better cognitive performance. Conclusions: The finding of similar psychosis‐cognition associations in bipolar disorder as implied by the two pathways leading to nonaffective psychotic disorders suggests that this model might be extended to the continuum spanning affective and nonaffective psychosis. This is in line with the idea of a partially overlapping vulnerability to bipolar disorder and schizophrenia and provides an explanation for the apparent differences in cognitive alterations in those at risk for the two disorders.     

Neuropsychology of subjects with ultra-high risk (UHR) of psychosis: A critical analysis of the literature

Cognitive disorders are currently considered as central components of disorders found in schizophrenia and are a major handicap for patients day to day. These disorders appear before the first psychotic episode, in the prodromal phase, during which time the symptoms are below the threshold for psychosis. People with these symptoms are considered as presenting an at-risk mental state (or at ultra-high risk, UHR of psychosis) and their risk for psychotic transition is between 20% and 40% within one year. Despite a number of studies, the chronology in which cognitive disorders appear in relation to the psychotic symptoms has not clearly been established and the study of the links between cognition and symptoms could improve our understanding of psychotic disorders. The detection of certain cognitive disorders before the onset of psychotic disorders could help improve early detection. We carried out a systematic analysis of the literature exploring cognitive disorders found in subjects with UHR for psychosis. The objective of most studies was to establish the predictive value for psychotic transition. Nevertheless study results have shown little consensus. Faced with this heterogeneity of results from past studies, we carried out a critical analysis of the literature and suggest areas of reflection for future research.     

Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis

Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically "at-risk" groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset.     

Treating Psychotic Symptoms in Elderly Patients

Research has shown that elderly patients are especially at risk for the development of psychotic symptoms. A combination of factors contributes to the increased risk for psychosis in this patient population. Various DSM-IV diagnostic categories including delirium, schizophrenia, delusional disorder, mood disorders, dementia, substance abuse, and medical-neurologic conditions can be associated with psychotic symptoms. In general, medications are prescribed for specific target symptoms, started at low doses, and titrated gradually. Although buspirone, trazodone, valproic acid, and carbamazepine have been used with some success, antipsychotic medications have been the primary treatment of psychosis in the elderly. Because the atypical antipsychotics offer effective management of psychotic symptoms combined with low liability of extrapyramidal symptoms, these agents may be the current treatment of choice for psychotic symptoms in the elderly when used cautiously.     

Bipolar disorder: anomalous brain asymmetry associated with psychosis.

OBJECTIVE: Anomalous cerebral asymmetry in schizophreniform disorders has been described, but its presence in psychotic mood disorders has not been established. Measures of cerebral asymmetry may distinguish patients with psychotic mood disorders from those with nonpsychotic mood disorders and from comparison subjects. To test this hypothesis, the authors examined functional cerebral asymmetry by using a metric based on magnetic source imaging. METHOD: A total of 33 subjects participated. Nine were patients with bipolar I disorder and a negative history of psychotic symptoms during mood disorder episodes, 12 were patients with bipolar I disorder and a positive history of psychotic symptoms during mood disorder episodes, and 12 were nonpsychiatric comparison subjects. Equivalent current dipole generators in both hemispheres were estimated for the 20-msec-latency somatosensory evoked field (M20) component produced by stimulation of the contralateral median nerve. RESULTS: The comparison subjects demonstrated asymmetry in anterior-posterior equivalent current dipole locations of the M20 (right anterior to left), and the bipolar subjects with no history of psychosis were similarly asymmetric. The bipolar subjects with a history of psychosis during mood episodes, however, demonstrated a reversal of cerebral asymmetry of the M20 (left anterior to right). CONCLUSIONS: Cerebral lateralization of the M20 distinguished bipolar subjects with psychosis from those without psychosis and comparison subjects. The M20 is generated in area 3b of the postcentral gyrus. These findings suggest anatomical displacement of the postcentral gyrus in psychotic disorders and support the hypothesis that anomalous cerebral asymmetry is a feature of psychotic disorders generally, including psychotic mood disorders.     

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.     

Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a psychotic mood disorder; a review

Delusional paranoia has been associated with severe mental illness for over a century. Kraepelin introduced a disorder called "paranoid depression," but "paranoid" became linked to schizophrenia, not to mood disorders. Paranoid remains the most common subtype of schizophrenia, but some of these cases, as Kraepelin initially implied, may be unrecognized psychotic mood disorders, so the relationship of paranoid schizophrenia to psychotic bipolar disorder warrants reevaluation. To address whether paranoia associates more with schizophrenia or mood disorders, a selected literature is reviewed and 11 cases are summarized. Comparative clinical and recent molecular genetic data find phenotypic and genotypic commonalities between patients diagnosed with schizophrenia and psychotic bipolar disorder lending support to the idea that paranoid schizophrenia could be the same disorder as psychotic bipolar disorder. A selected clinical literature finds no symptom, course, or characteristic traditionally considered diagnostic of schizophrenia that cannot be accounted for by psychotic bipolar disorder patients. For example, it is hypothesized here that 2 common mood-based symptoms, grandiosity and guilt, may underlie functional paranoia. Mania explains paranoia when there are grandiose delusions that one's possessions are so valuable that others will kill for them. Similarly, depression explains paranoia when delusional guilt convinces patients that they deserve punishment. In both cases, fear becomes the overwhelming emotion but patient and physician focus on the paranoia rather than on underlying mood symptoms can cause misdiagnoses. This study uses a clinical, case-based, hypothesis generation approach that warrants follow-up with a larger representative sample of psychotic patients followed prospectively to determine the degree to which the clinical course observed herein is typical of all such patients. Differential diagnoses, nomenclature, and treatment implications are discussed because bipolar patients misdiagnosed with schizophrenia are severely misserved.     

Neurocognition in schizophrenia: a 20-year multi-follow-up of the course of processing speed and stored knowledge

Individuals with schizophrenia have relative deficits in cognition, although little is known regarding the course of such deficits across the life span and at various stages of the illness. Furthermore, the relationship between psychosis and cognition has not been adequately explored to this point. Prospective, longitudinal, multi-assessment studies of the same patients across time are rare in the field and provide a unique opportunity to examine long-term changes in cognition among individuals with schizophrenia. As part of The Chicago Follow-up Study, we prospectively assessed 244 psychiatric inpatients, including individuals with schizophrenia, other psychotic disorders, and nonpsychotic depression. Assessments were conducted 7 times (once at index hospitalization and then 6 times subsequently for the next 20 years) to provide longitudinal data about cognition and symptoms, with a focus on 2 aspects of cognition: processing speed and the ability to access general knowledge. The Digit Symbol-Coding and Information subtests from the Wechsler Adult Intelligence scale were used to measure the 2 cognitive domains at each assessment. At all 7 assessments, individuals with schizophrenia performed more poorly than the other diagnostic groups on the 2 cognitive measures. However, after the acute phase (index hospitalization), individuals with schizophrenia demonstrated significant improvements in cognition and did not show evidence of cognitive decline over the remaining 6 assessments spanning 20 years. Our data support the presence of relative cognitive impairment in schizophrenia, as well as a pattern of stability in some cognitive areas after the acute phase. In addition, we find evidence for an association between relative cognitive impairment and psychosis.     

Do cognitive schema mediate the association between childhood trauma and being at ultra-high risk for psychosis?

Exposure to childhood trauma has been associated with psychotic symptoms, being at ultra-high risk for psychosis (UHR), and psychotic disorders such as schizophrenia. Negative self-beliefs have been shown to partially mediate the relationship between childhood trauma and paranoia and have been shown to be characteristic of patients with psychosis. However, whether the association between childhood trauma and being at high risk of developing psychosis (e.g., UHR) and paranoia symptoms is mediated by altered cognitive schema is unknown and warrants investigation to inform preventive interventions. Data was collected on 30 UHR patients from Outreach and Support in South London about exposure to childhood trauma, cognitive schema, paranoia and cannabis use. Relative to healthy controls (n = 38), UHR patients were significantly more likely to report exposure to various types of childhood trauma (emotional and sexual abuse, and emotional and physical neglect), had more negative schema and less positive schema about themselves and others, and were more likely to use cannabis more than once a month. Emotional neglect was found to be significantly associated with UHR status even after controlling for the effects of previous exposure to cannabis use (b = 0.262, 95% CI: 0.115–0.408), and this association was partially mediated by negative self-schema (b = 0.045, 95% CI: 0.004–0.159). Similarly, emotional neglect was significantly associated with paranoia (b = 1.354, 95% CI: 0.246-2.462), and this association was partially mediated by negative self-schema (b = 0.988, 95% CI: 0.323-1.895). These findings provide preliminary evidence about the cognitive mechanisms that may underlie the association between childhood trauma and later risk for psychosis.     

Cognitive and behavioural impairment in Parkinson's disease

Although Parkinson's disease (PD) has been considered to primarily affect motor abilities, increasing emphasis is being placed on cognitive and behavioural impairment in this disorder. Depression, dementia, psychosis and impulse control disorders have a major impact on quality of life for both patients and families. This article reviews cognitive and behavioural disturbances in PD and their relation to affective and motor symptoms, treatment of dementia associated with PD, and treatment approaches to psychosis in PD. We also discuss similarities between the dementia of PD and dementia with Lewy bodies.     

Brave New Worlds—Review and Update on Virtual Reality Assessment and Treatment in Psychosis

In recent years, virtual reality (VR) research on psychotic disorders has been initiated. Several studies showed that VR can elicit paranoid thoughts about virtual characters (avatars), both in patients with psychotic disorders and healthy individuals. Real life symptoms and VR experiences were correlated, lending further support to its validity. Neurocognitive deficits and difficulties in social behavior were found in schizophrenia patients, not only in abstract tasks but also using naturalistic virtual environments that are more relevant to daily life, such as a city or encounters with avatars. VR treatments are conceivable for most dimensions of psychotic disorders. There is a small but expanding literature on interventions for delusions, hallucinations, neurocognition, social cognition, and social skills; preliminary results are promising. VR applications for assessment and treatment of psychotic disorders are in their infancy, but appear to have a great potential for increasing our understanding of psychosis and expanding the therapeutic toolbox.Key words: psychosis, schizophrenia, virtual reality