The relationship of excess cognitive impairment in MCI and early Alzheimer's disease to the subsequent emergence of psychosis

BACKGROUND: Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with greater cognitive impairment. Knowing when the cognitive course of AD + P subjects diverges from that of subjects without psychosis would enhance understanding of how genetic variation results in AD + P and its associated cognitive burden. This study seeks to determine whether the degree of cognitive impairment and cognitive decline in early AD predicts subsequent AD + P onset. METHODS: 361 subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis were evaluated every 6 months until psychosis onset. RESULTS: Severity of cognitive dysfunction was a strong predictor of AD + P up to two years prior to psychosis onset. Cognition did not decline more rapidly prior to onset of AD + P. CONCLUSIONS: Individuals who will develop AD + P already demonstrate excess cognitive impairment during the mild stages of disease. Genetic variation and brain pathophysiology may lead to a cognitive risk phenotype which is present prior to dementia onset.     

Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype.

OBJECTIVE: Psychotic symptoms occur in 30%-60% of individuals with Alzheimer disease (AD) with psychosis (AD+P). AD+P identifies a distinct AD phenotype, with increased severity of cognitive impairment and a more rapid cognitive decline. Using factor and cluster analysis, we previously proposed two subtypes of patients with AD+P, one characterized by misidentifications and hallucinations (Misidentification), the other by persecutory delusions (Paranoid). We hypothesized that these two groups differed in their patterns of cognitive impairment, compared with AD subjects without psychosis. METHODS: Subjects (N=119) with possible or probable AD were assessed with a comprehensive neuropsychological test battery at the time of initial presentation. Psychotic symptoms were ascertained with the CERAD Behavioral Rating Scale. Cognitive test scores were compared among groups by use of general linear-regression models, with age, education, and duration of illness entered as covariates. All results were corrected for multiple comparisons. RESULTS: The Misidentification group was significantly more impaired than the Non-Psychotic group on tests of verbal fluency and visuospatial function. The Paranoid group did not differ from the Non-Psychotic group on any test. CONCLUSIONS: These results support the identification of the Misidentification and Paranoid groups as distinct subgroups of AD+P. The ability to detect meaningful biologic associations of AD+P in future studies would be enhanced by separate analysis of the Misidentification and Paranoid phenotypes.     

Apolipoprotein E and alpha-1-antichymotrypsin genotypes do not predict time to psychosis in Alzheimer's disease

Psychotic symptoms occurring in Alzheimer's disease (AD + psychosis, AD + P) are a marker for a more rapidly deteriorating phenotype. We have developed a polygenic model of AD + P risk, conditioned on the presence of AD. Whether risk genes for AD itself contribute to AD + P risk is not established, although our model predicts they will not. The most important identified genetic determinant of sporadic, late-onset AD is the apolipoprotein E epsilon 4 allele (APOE4). The effect of APOE4 on AD phenotype is to reduce the age of onset of AD. Prior studies examining the association of APOE4 with AD + P have reported conflicting results. However, no prior studies have examined if APOE4 reduces time to onset of psychosis in AD. The objective of this study was to examine the effect of APOE4 and alpha1-antichymotrypsin/AA (ACT/AA) genotypes on time to psychosis onset in subjects with AD. A longitudinal study of psychosis incidence in 316 subjects with AD with no history of current or prior psychotic symptoms at entry was undertaken. APOE and ACT genotyping was conducted per established protocols. Data were analyzed by survival analysis and Cox proportional hazards models. There were no significant associations of APOE or ACT genotypes with time to psychosis onset and no significant interaction of these genotypes with time to psychosis onset. There remained no significant associations after covarying for age, age of AD onset, degree of cognitive impairment, gender, race, and education. This is the first study to examine the genetic prediction of psychosis onset in AD. The findings support the hypothesis that these two genetic determinants of AD risk do not contribute to the risk of development of psychotic symptoms in AD.     

Alzheimer disease subjects with psychosis have increased schizotypal symptoms before dementia onset.

BACKGROUND: Recent findings have demonstrated the familiality of psychotic symptoms occurring during Alzheimer disease (AD with psychosis, AD+P), particularly for subjects with multiple psychotic symptoms. We have proposed a model in which genes that confer a small risk for psychosis interact with neurodegenerative illness to yield manifest psychotic symptoms during AD. One prediction of this model would be that AD+P subjects would have evidence of increased degrees of subsyndromal psychosis before AD onset. METHODS: We used the psychosis (positive symptoms) and psychotic personality disorder sections (paranoid, schizoid, and schizotypal) of the Family Interview for Genetic Studies (FIGS) to interview the primary caregivers of AD subjects. Caregivers were specifically instructed to answer questions with regard to the subject's behavior before AD onset. Interviewers were blind to presence of psychosis during AD. Subjects were grouped by whether they had at least one or had multiple psychotic symptoms during AD. RESULTS: Scores on the FIGS subscales were generally low, reflecting a low frequency of endorsement of psychotic symptoms before AD. There was a trend for the schizotypal scores to be elevated in the AD+P group, which was highly significant in the AD+P group with multiple psychotic symptoms. There was no significant association of paranoid or schizoid scores with either group. CONCLUSIONS: Although limited by small sample size and retrospective design, these data are novel in that they indicate an association of subsyndromal psychotic symptoms before AD onset with psychosis in AD. Subsyndromal psychosis might be useful for classifying AD+P families for genetic mapping studies. Prospective confirmation is required.     

The interrelations between psychosis, behavioral disturbance, and depression in Alzheimer disease

Behavioral changes are common in Alzheimer disease (AD), and heterogeneous in their presentation. Subtle personality changes tend to occur early; these include apathy, irritability and inability to pay attention. Later agitation, aggression and disinhibited behaviors may appear. We have utilized the Columbia University Scale for Psychopathology in Alzheimer's Disease to monitor a number of behavioral symptoms in 235 patients with early probable AD. Markov analyses were used to predict the probability of developing or retaining a given symptom at 6-month follow-up. The results show that the symptoms of psychopathology in AD fluctuate with time. Agitation was both the most frequent and persistent symptom, while paranoid delusions and hallucinations were less persistent. Most behavioral disturbances, except paranoid delusions, were associated with greater cognitive impairment. There was no association between depressive features and either cognitive or functional impairment. These results have important implications for the optimal treatment of the psychopathological symptoms of AD.     

Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease

Psychotic symptoms in subjects with Alzheimer disease (AD with psychosis, AD+P) define a phenotype characterized by greater cognitive burden than in AD without psychosis. We have proposed that genes of small effect may contribute to the risk for expression of psychosis in multiple disorders, including AD. Recently, sex-differential association of a three-locus haplotype, including a G-->A transition at codon 108/158 of catechol-O-methyltransferase (COMT) resulting in a Val-->Met substitution, has been reported to confer an increased risk for schizophrenia. The main objective of the study was to determine if COMT genetic variation is associated with risk of psychosis in AD, and included a case-control study of 373 individuals diagnosed with AD with, or without, psychosis. All subjects were characterized for alleles at the three loci associated with schizophrenia, RS737865, COMT G-->A 108/158 (RS4680), and RS165599, and for a C/T transition adjacent to an estrogen response element (ERE6) in the COMT P2 promoter region. Both single locus and haplotype tests of association were conducted. Logit models were used to examine independent and interacting effects of alleles at the associated loci. All analyses were stratified by sex. In female subjects, RS4680 demonstrated a modest association with AD+P; RS737865 demonstrated a trend towards an association. There was a highly significant association of AD+P with the four-locus haplotype, which resulted from additive effects of alleles at RS4680 and ERE6 (or RS737865, as this locus was in almost absolute linkage disequilibrium (LD) with ERE6). In male subjects, no single locus test was significant, but there remained a strong association between AD+P and the four-locus haplotype. This association appeared to result from interaction of the ERE6/RS737865, RS4680, and RS165599 loci. Genetic variation in COMT is associated with AD+P, and thus appears to contribute to psychosis risk across disorders. Sex-differential associations of COMT with psychosis may result from variation at, or in LD with, ERE6. Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted.     

Psychotic symptoms in Alzheimer's disease are not associated with more severe neuropathologic features

Psychotic symptoms in Alzheimer's disease (AD) have been associated with increased rates of cognitive impairment and functional decline. Prior studies have been conflicting with regard to whether AD patients with psychosis (AD+P) have evidence of more severe neuropathologic findings at postmortem exam. We examined the severity of neuritic plaques and neurofibrillary tangles in six brain regions--middle frontal cortex, hippocampus, inferior parietal cortex, superior temporal cortex, occipital cortex, and transentorhinal cortex-in 24 AD+P subjects and 25 matched AD subjects without psychosis (AD-P). All analyses controlled for the presence of cortical Lewy bodies, and corrected for multiple comparisons. We found no significant associations between neuritic plaque and neurofibrillary tangle severity and AD+P, and no significant associations with any individual psychotic symptom. The association of AD+P with a more rapidly progressive course of AD appears to be mediated by a neuropathologic process other than increased severity of plaque and tangle formation.     

Psychosis in Parkinson's disease without dementia: Common and comorbid with other non‐motor symptoms

Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety‐one non‐demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater‐administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep‐wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non‐motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non‐motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep‐wakefulness, and incipient cognitive decline in PD. © 2012 Movement Disorder Society     

New-onset psychosis in HIV-infected patients

BACKGROUND: Psychiatric symptoms and disorders are becoming increasingly evident in human immunodeficiency virus (HIV)-infected patients. As psychotic symptoms may be severe and require immediate behavioral management, the authors sought to determine the frequency and clinical characteristics of new-onset psychosis not obviously attributable to substance abuse or delirium in these patients. METHOD: The authors reviewed the English-language literature since 1981 by means of the Index Medicus and MEDLINE for reports of new-onset psychosis in HIV-infected patients and also examined the charts of 124 HIV-infected patients who had been followed up at the San Diego Veterans Affairs Medical Center since 1984. Cases of substance-induced psychosis and delirium were excluded. RESULTS: Results reflect a combination of cases from the authors' study and cases of new-onset HIV-associated psychosis reported in the literature (N = 31). Results of the initial neurologic evaluation, including computed tomography (CT) scan and examination of the CSF, were normal in a majority of patients (CT = 12 of 23 patients; CSF = 10 of 14 patients). Psychotic symptoms improved with neuroleptic treatment although side effects were frequently seen. In some patients (N = 12) psychosis was the presenting manifestation of HIV infection or acquired immunodeficiency syndrome. A proportion of patients (N = 7 [23%]), especially those with an abnormal CT and EEG at the time of presentation with psychosis, tended to have a relatively rapid deterioration in cognitive and medical status. Differences between studies in population and method made it impossible to determine the frequency of new-onset psychosis in the general HIV-infected population. CONCLUSIONS: A common clinical feature noted in new-onset psychosis in HIV-infected patients was acute or subacute onset of symptoms, which included delusions, hallucinations, bizarre behavior, mood or affective disturbances, and mild memory or cognitive impairment. The etiological association of the HIV infection to the psychosis is yet to be established.     

Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003

OBJECTIVE: The authors reviewed studies published between 1990 and 2003 that reported the prevalence, incidence, and persistence of, as well as the risk factors associated with, psychosis of Alzheimer's disease. METHOD: PubMed and PsycINFO databases were searched by using the terms "psychosis and Alzheimer disease" and "psychosis and dementia." Empirical investigations presenting quantitative data on the epidemiology of and/or risk factors for psychotic symptoms in Alzheimer's disease were included in the review. A total of 55 studies, including a total of 9,749 subjects, met the inclusion criteria. RESULTS: Psychosis was reported in 41% of patients with Alzheimer's disease, including delusions in 36% and hallucinations in 18%. The incidence of psychosis increased progressively over the first 3 years of observation, after which the incidence seemed to plateau. Psychotic symptoms tended to last for several months but became less prominent after 1 year. African American or black ethnicity and more severe cognitive impairment were associated with a higher rate of psychosis. Psychosis was also associated with more rapid cognitive decline. Some studies found a significant association between psychosis and age, age at onset of Alzheimer's disease, and illness duration. Gender, education, and family history of dementia or psychiatric illness showed weak or inconsistent relationships with psychosis. CONCLUSIONS: Psychotic symptoms are common and persistent in patients with Alzheimer's disease. Improved methods have advanced the understanding of psychosis in Alzheimer's disease, although continued research, particularly longitudinal studies, may unveil biological and clinical associations that will inform treatments for these problematic psychological disturbances.     

Psychotic symptoms in Alzheimer disease: evidence for subtypes.

OBJECTIVE: Psychotic symptoms in Alzheimer disease (AD) identify a phenotype with distinct neurobiology and genetic architecture. The authors investigated whether AD with psychosis is homogeneous or is a composite of subtypes. METHODS: Authors performed factor and cluster analyses of the psychotic-symptom items of the CERAD Behavioral Rating Scale in 188 probable and possible AD subjects who have displayed at least one psychotic symptom. RESULTS: Exploratory factor analysis resulted in a one-factor solution that comprised misidentification delusions, auditory and visual hallucinations, and the misidentification of people. Persecutory delusions were also frequently present and were independent of the misidentification/hallucination factor. Cluster analysis yielded similar results. CONCLUSION: Misidentification/hallucinations and persecutory delusions may identify two subtypes of psychosis in AD. Longitudinal study is needed to determine whether these proposed subtypes remain stable and independent over time or merge into a single group over the course of illness.     

Evidence for a relationship between mentalising deficits and paranoia over the psychosis continuum

OBJECTIVE: Failing of mentalising has been suggested to underlie certain symptoms of psychosis. An as yet unresolved issue is whether mentalising deficits reflect a characteristic which can also be detected in people at risk for psychosis or people with evidence of subclinical expression of psychosis. This study wanted to assess an aspect of mentalising in four groups with different levels of psychosis vulnerability, and to examine associations between mentalising and symptoms of psychosis. METHOD: The study included i) 40 patients with psychosis, ii) 49 non-psychotic first-degree relatives (familial risk), iii) 41 subjects from the general population with a high level of positive psychotic experiences (psychometric risk) and iv) 54 healthy controls. All subjects performed the 'Hinting Task'. RESULTS: There was a significant association between psychosis risk and impairment on the Hinting Task (beta linear trend=0.37, p<0.001). Using the control group as the reference, the association with impairment on the Hinting Task was highest for the patient group (beta=0.46, p<0.001), whereas the familial risk group (beta=0.16, p=0.06) displayed an intermediate probability of failure. The psychometric risk group did not significantly differ from the control group (beta=0.04, p=0.653). In the patient group, impairment on the Hinting Task was associated with current hallucinations and paranoid symptoms. In the familial risk group, there was an association between the Hinting Task and paranoid symptoms. DISCUSSION: These results suggest that vulnerability to psychosis is expressed as an impairment in mentalising, which may have a mediating role in the formation of certain positive symptoms of psychosis.     

Increased familial risk of the psychotic phenotype of Alzheimer disease

BACKGROUND: Psychotic symptoms in patients with AD (AD with psychosis [AD+P]) define a phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. OBJECTIVE: To determine if AD+P aggregates within families. METHODS: Case-control study of AD+P frequency in 461 siblings of 371 probands diagnosed with AD. All siblings were ascertained as part of a genetic investigation and also were diagnosed with AD. Statistical analysis used Generalized Estimating Equations to adjust for clustering within families. RESULTS: AD+P in probands was associated with a significantly increased risk for AD+P in family members (OR, 2.41; 95% CI 1.46-4.0; p = 0.0006). The correlation among siblings for AD+P status was modest: 0.16. CONCLUSION: AD+P demonstrates familial aggregation. Further studies are required to investigate a possible genetic basis of AD+P.     

Phenomenology and clinical correlates of delusions in Alzheimer disease.

OBJECTIVES: The objectives of this study were to determine whether anosognosia, depression, and elevated mood are associated with delusions in Alzheimer disease (AD), and to examine the validity of standardized diagnostic criteria for psychosis of dementia. METHOD: The authors assessed a consecutive series of 771 patients with AD attending a dementia clinic with a comprehensive neuropsychologic and psychiatric evaluation that included specific measures of delusions, hallucinations, anosognosia, depression, and elevated mood. RESULTS: Delusions were found in one-third of the patients and hallucinations in 7%. Most patients with hallucinations also had delusions. A principal component analysis of the Psychosis Dementia Scale, which rates the presence and severity of delusions, produced the factors of paranoid misidentification and expansive delusions. Paranoid, but not expansive, delusions increased across the stages of the illness. Anosognosia and depression were significantly and independently associated with the presence of delusions, whereas elevated mood was significantly associated with expansive, but not paranoid, delusions. A multiple logistic regression analysis demonstrated that delusions in AD were significantly associated with depression, anosognosia, overt aggression, and agitation. CONCLUSIONS: Anosognosia, depression, global cognitive deficits, and elevated mood are the main psychiatric correlates of paranoid misidentification and expansive delusions in AD, whereas overt aggression and agitation are the most frequent behavioral concomitants of psychosis in AD.     

Apolipoprotein-E (APO-E) genotype and symptoms of psychosis in Alzheimer's disease.

The authors examined the association of Apolipoprotein-E (APO-E) genotype to symptoms of psychosis and depression in 501 patients diagnosed with probable (n=343) or possible (n=158) Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. They observed the following APO-E genotypes: epsilon2/epsilon3 (n=19); epsilon2/epsilon4 (n=14); epsilon3/epsilon3 (n=228); epsilon3/epsilon4 (n=203); epsilon4/epsilon4 (n=37). In contrast to previous reports, the results did not indicate a relationship between either the epsilon4 allele or the epsilon2 allele and symptoms of mood disturbance in AD. However, an elevated risk for psychosis was shown, specifically, at the severe stage of cognitive impairment, among AD patients carrying the epsilon4 allele, after effects of age, gender, education, and level of cognitive impairment were controlled.     

The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer disease

BACKGROUND: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis, AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. We recently found that AD subjects homozygous for long alleles (l) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior. OBJECTIVE: To examine whether the 5-HTTPR ll genotype confers an increased risk of AD+P, and of the combined AD+P/aggressive phenotype. METHODS: The 5-HTTPR genotype was determined in 332 subjects diagnosed with possible or probable AD. All subjects received structured psychiatric assessments and were categorized with regard to their history of aggressive behaviors and psychotic symptoms. RESULTS: Consistent with other reports, AD+P was associated with a significant increased risk for aggressive behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll genotype and with an increased l allele frequency. Subjects with the combined behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll genotype and highest l allele frequency. CONCLUSION: The 5-HTTPR l allele appears to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this association in a similar behaviorally well-characterized independent sample is needed.     

Apolipoprotein epsilon4 advances appearance of psychosis in patients with Parkinson's disease

BACKGROUND: Psychosis is one of the most serious complications of advanced parkinsonism, but many patients are spared. The genetic factors predisposing to psychosis are unclear. OBJECTIVES: To assess the association between apolipoprotein E (APOE) polymorphism and the development of psychosis in patients with Parkinson's disease (PD). METHODS: Eighty-seven patients with advanced PD were assessed. Psychosis was diagnosed in 50 patients who manifested paranoid delusions, hallucinations without insight, or disorders of perception. Time of onset of psychosis was retrieved from the medical records and caregivers' recall. APOE genotype was determined by restriction enzyme digests of amplified alleles. Cox models of logistic regression and Kaplan-Meier survival curves were used to assess factors determining early development of psychosis. RESULTS: APOE epsilon3/epsilon4 allele was carried by 20 patients (14 with psychosis), epsilon2/epsilon3 by 11 patients (10 with psychosis), epsilon3/epsilon3 by 55 patients (25 with psychosis) and epsilon2/epsilon4 by one patient who had psychosis. The mean age of onset of PD symptoms was 60.0 +/- 12.5 years. The mean duration of motor symptoms at the onset of psychosis was 7.3 +/- 4.3 years for the 15 patients harboring an APOE epsilon4 allele and 10.1 +/- 6.2 years among those who did not carry APOE epsilon4 (n = 35). The APOE epsilon4 allele was significantly associated with earlier onset of psychosis (P < 0.05) when the age of onset of motor symptoms and presence of dementia were included in the Cox regression model. Carrying the APOE epsilon4 allele was a significant risk factor for earlier appearance of psychosis with a hazard ratio of 3.24 (95% CI 1.62-6.46) while dementia by itself did not increase the risk. CONCLUSION: Parkinson's disease patients who carry the APOE epsilon4 allele develop psychosis earlier.     

Prevalence and clinical correlates of psychotic symptoms in Alzheimer's disease

Psychotic symptoms occur commonly in Alzheimer's disease (AD), predict a more rapid rate of cognitive decline and increase the risk of aggressive behaviour. Seventy patients with probable AD, recruited from an old age psychiatry service, were assessed to determine the prevalence and clinical correlates of delusions and hallucinations. Psychiatric symptoms were measured using the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Hamilton Rating Scale for Depression (HRSD) and the Depressive Signs Scale (DSS). Thirty-four per cent of the sample experienced delusions and 11% hallucinations in the previous month. Men were more likely than women to have experienced psychotic symptoms. Psychotic and non-psychotic groups did not differ in age, age at illness onset, dementia severity, HRSD or DSS scores. This study confirms the high prevalence of psychotic symptoms in AD patients encountered in clinical practice, and suggests that psychosis and depression represent independent behavioural disturbances in AD. © 1998 John Wiley & Sons, Ltd.     

A case of rapid conversion to psychosis of delusional misidentification associated with derealisation,verbal memory impairment and FDG-PET imaging abnormalities

The delusional misidentification syndromes, occurring within the context of different nosological settings, such as schizophrenia, are psychopathological phenomena related to the experience of depersonalisation/derealisation. Extensive research indicates that individuals meeting specific “prodromal” criteria, such as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or functional decline and family history of schizophrenia have increased risk for impending psychosis. Despite depersonalisation and/or derealisation often precede psychotic onset, they are not included among the prodromal criteria of the Australian–American approach. A 17-year-old boy with acute agitation, violent behaviour and aggression, and dissociative amnesia had a mild verbal memory impairment and temporo-limbic hypometabolism on the positron-emission tomography. The patient was assessed with both the ultra-high risk (UHR) and the basic symptom approaches and was not found to be prodromal with imminent risk of transition to psychosis. He was hospitalised briefly and 2 weeks after discharge he developed delusional misidentification. This case shows that even the integration of both UHR and basic symptoms criteria may give false negatives in the prediction of psychosis, especially in those cases in which a long prodromal phase is absent.     

Patterns of premorbid functioning in first episode psychosis: relationship to 2-year outcome

OBJECTIVE: To determine how different patterns of premorbid functioning relate to outcome longitudinally. METHOD: Premorbid adjustment was assessed in 194 first-episode of psychosis subjects. Positive and negative symptoms, depression, substance misuse and social and cognitive functioning were assessed over 2 years. RESULTS: Four patterns of premorbid adjustment: stable-good, stable-intermediate, poor-deteriorating and deteriorating were identified. Relative to the stable-good group, the deteriorating and poor-deteriorating groups had significantly more positive symptoms at 1-year follow-up but not at 2-year follow-up and significantly more negative symptoms and significantly poorer social functioning at both 1 and 2-years. Only verbal fluency and memory differentiated between the groups with the stable-good group having a superior performance. CONCLUSION: Those who demonstrated poor or deteriorating functioning prior to the onset of acute psychosis have a poorer outcome up to at least 2 years in terms of negative symptoms and social functioning.