Extrapyramidal symptoms predict cognitive performance after first-episode psychosis.

Extrapyramidal (EP) symptoms such as tremor, rigidity, and bradykinesia are common side effects of most antipsychotics, and may associate with impaired performance in neurocognitive testing. We studied EP symptoms in first-episode psychosis (FEP; n = 113). Cognitive testing and EP symptoms (three items of the Simpson-Angus Scale) were assessed at baseline and follow-up (mean follow-up time 12 months). Mild EP symptoms were present at treatment onset in 40% of the participants. EP symptoms were related with lower performance in neurocognitive testing at baseline and at follow-up, especially among those with nonaffective psychotic disorder, and especially in tasks requiring speed of processing. No associations between EP symptoms and social cognition were detected. In linear regression models, when positive and negative symptom levels and chlorpromazine equivalents were accounted for, baseline EP symptoms were associated with worse baseline global neurocognition and visuomotor performance. Baseline EP symptoms also longitudinally predicted global, verbal, and visuomotor cognition. However, there were no cross-sectional associations between EP symptoms and cognitive performance at follow-up. In sum, we found both cross-sectional and longitudinal associations between EP symptoms and neurocognitive task performance in the early course of psychosis. Those without EP symptoms at the start of treatment had higher baseline and follow-up neurocognitive performance. Even mild EP symptoms may represent early markers of long-term neurocognitive impairment.

Short-term functional outcome in psychotic patients: results of the Turku early psychosis study (TEPS).

BACKGROUND: Functional recovery of patients with clinical and subclinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known about how these factors predict functional outcomes in the same models. We investigated functional outcomes and their predictors in patients with first-episode psychosis (FEP) or a confirmed or nonconfirmed clinical high risk of psychosis (CHR-P vs. CHR-N). METHODS: Altogether, 130 patients with FEP, 60 patients with CHR-P and 47 patients with CHR-N were recruited and extensively examined at baseline (T0) and 9 (T1) and 18 (T2) months later. Global Assessment of Functioning (GAF) at T0, T1 and T2 and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcomes were predicted using multivariate repeated ANOVA. RESULTS: During follow-up, the GAF score improved significantly in patients with FEP and CHR-P but not in patients with CHR-N. A single marital status, low basic education level, poor work situation, disorganization symptoms, perceptual deficits, and poor premorbid adjustment in patients with FEP, disorganization symptoms and poor premorbid adjustment in patients with CHR-P, and a low basic education level, poor work situation and general symptoms in patients with CHR-N predicted poor functional outcomes. Psychotic symptoms at T1 in patients with FEP and psychotic and depression symptoms at T1 and anxiety symptoms at T2 in patients with CHR-P were associated with poor functioning. CONCLUSIONS: In patients with FEP and CHR-P, poor premorbid adjustment and disorganization symptomatology are common predictors of the functional outcome, while a low education level and poor work situation predict worse functional outcomes in patients with FEP and CHR-N. Interventions aimed at improving the ability to work and study are most important in improving the functioning of patients with clinical or subclinical psychosis.

Neuropsychological performance in patients with substance use disorder with and without mood disorders.

Background: Mood disorders commonly co-occur in patients with substance use disorders (SUD). This combination may increase the risk of pathological effects and impair cognitive functioning.Aim: The aim of the study was to examine the effects of mood and substance use disorders on specific neuropsychological measures.Methods: The participants comprised 164 hospitalised patients, 88 with (SUD + MD) and 76 (SUD-MD) without mood disorders, ranging in age from 19 to 65 years. Their diagnostic assessment was based on a psychiatric interview (ICD-10). Neuropsychological tests were carried out after a minimum of one month of abstinence.Results: Processing speed (p = 0.029), and perceptual reasoning (p = 0.039) were more impaired in the SUD + MD group than in the SUD-MD group. An Analysis of covariance (ANCOVA) controlled for age, education level, learning difficulties and polysubstance use revealed that the groups were most powerfully separated by the Digit Symbol test and the Block Design test.Conclusions: Patients with substance abuse and mood disorders seem to have more deficits in speed processing and perceptual reasoning than substance abuse patients without mood disorders. These processing speed difficulties and perceptual problems may impact prognosis and treatment. The Digit Symbol test and the Block Design test are a fast and sensitive ways to examine treatment effectiveness and monitor treatment progress.

Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function.

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [11C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (VT) of [11C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

Onset Age of Substance Use and Neuropsychological Performance in Hospital Patients.

OBJECTIVE: Several studies have found neurocognitive deficits in adolescents following substance abuse. Predisposing risk factors may further impact vulnerability to neurocognitive deficits. Little is known about the cognitive performance of adult onset substance users compared to earlier onset users. This study aims to explore differences in neuropsychological functioning between early (EOAs) and late onset substance abusers (LOAs) when the effects of confounding factors are controlled. METHOD: Data for this cross-sectional study was collected from hospital patients. A total of 164 patients with substance use disorder (SUD) aged 19 to 65, 76 with single-drug diagnosis and 88 with multidrug diagnosis, underwent neuropsychological tests for verbal capacity, attention, speed of processing, perceptual reasoning, memory and learning, executive functioning, and inhibitory capacity. Associations between regular onset age and neuropsychological measures were analysed using in multi-way ANCOVA, and the effect of age, multiple substance abuse, education level and learning difficulties were controlled. RESULTS: Compared with LOAs, EOAs had weaker performance in the Digit Symbol test for mono-substance users. Meanwhile, compared with EOAs, LOAs had weaker performance in the Delayed Visual Memory test and the Raven test for mono-substance users, and the Block Design test for poly-substance users. From the confounding factors, early onset age of substance use is heightened among individuals with learning disabilities. CONCLUSIONS: Onset age of substance use is related to the deterioration of performance in neuropsychological tests. Premorbid poor learning and inhibitory capacity may be important predisposing risk factors of SUD. Conversely, high level of education may be a protective factor for cognitive performance in patients with SUD.

Amygdala subnucleus volumes in psychosis high-risk state and first-episode psychosis.

Structural and functional abnormalities of the amygdala in schizophrenia have been well documented. Post-mortem studies suggest that the lateral nucleus is particularly affected in schizophrenia. It is not known whether the amygdala subnuclei are differently affected at the time of the first-episode psychosis or already at high-risk state. 75 first-episode psychosis patients (FEP), 45 clinical high-risk patients (CHR) and 76 population controls participated in this cross-sectional case-control study. Participants underwent T1-weighted 3T MRI scans, from which the amygdala was segmented using a newly developed automated algorithm. Because early adverse events increase risk for psychosis and affect the amygdala, we also tested whether experiences of childhood maltreatment associate with the putative amygdala subnuclei abnormalities. Compared to the population controls, FEP had smaller volumes of the lateral, and basal nuclei. In CHR, only the lateral nucleus was significantly smaller compared to the control subjects. Experience of childhood maltreatment was inversely associated with lateral nucleus volumes in FEP but not in CHR. These results show that the lateral and basal nuclei of the amygdala are already affected in FEP. These volumetric changes may reflect specific cellular abnormalities that have been observed in post-mortem studies in schizophrenia in the same subnuclei. Decreased volume of the lateral nucleus in CHR suggest that a smaller lateral nucleus could serve as a potential biomarker for psychosis risk. Finally, we found that the lateral nucleus volumes in FEP may be sensitive to the effects of childhood maltreatment.

A patient with Korsakoff syndrome of psychiatric and alcoholic etiology presenting as DSM-5 mild neurocognitive disorder.

Background: Wernicke's encephalopathy (WE) and Korsakoff syndrome (KS) are underdiagnosed. The DSM-5 has raised the diagnostic threshold by including KS in the major neurocognitive disorders, which requires that the patient needs help in everyday activities. Methods: We report clinical, neuropsychological, and radiological findings from a patient who developed Wernicke-Korsakoff syndrome as a result of alcohol use and weight loss due to major depression. We assess the diagnosis in the context of the scientific literature on KS and according to the DSM-IV and the DSM-5. Results: The patient developed ataxia during a period of weight loss, thus fulfilling current diagnostic criteria of WE. WE was not diagnosed, but the patient partially improved after parenteral thiamine treatment. However, memory problems became evident, and KS was considered. In neuropsychological examination, the Logical Memory test and the Word List test were abnormal, but the Verbal Pair Associates test was normal (Wechsler Memory Scale-III). There were intrusions in the memory testing. The Wisconsin Card Sorting Test was broadly impaired, but the other test of executive functions (difference between Trail Making B and Trail Making A tests) was normal. There was atrophy of the mammillary bodies, the thalamus, the cerebellum, and in the basal ganglia but not in the frontal lobes. Diffusion tensor imaging showed damage in several tracts, including the uncinate fasciculi, the cinguli, the fornix, and the corona radiata. The patient remained independent in everyday activities. The patient can be diagnosed with KS according to the DSM-IV. According to the DSM-5, the patient has major neurocognitive disorders. Conclusions: Extensive memory testing is essential in the assessment of KS. Patients with a history of WE and typical clinical, neuropsychological, and radiological KS findings may be independent in everyday activities. Strict use of the DSM-5 may worsen the problem of Wernicke-Korsakoff syndrome underdiagnosis by excluding clear KS cases that do not have very severe functional impairment.

Longitudinal brain morphology in anti-NMDA receptor encephalitis: a case report with controls.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a severe autoimmune condition, which typically affects young females. The long-term clinical consequences and brain morphology changes after anti-NMDAR encephalitis are not well known. CASE PRESENTATION: We present clinical and neuroimaging follow-up data on a 25-year female patient with typically presenting anti-NMDAR encephalitis. Longitudinal analyses of brain morphology were done using 3 T structural magnetic resonance imaging (sMRI) and Freesurfer analysis at the time of diagnosis and after symptomatic remission. The presented case attained good functional recovery after standard immunoglobulin-corticosteroid treatment but elevated serum NMDAR antibody levels persisted. The patient had no symptomatic relapses during a 3-year clinical follow-up. In the baseline brain sMRI scan there were no marked volume changes. However, a follow-up sMRI after 9 months indicated clear volume reductions in frontal cortical regions compared to matched controls with identical sMRI scans. CONCLUSIONS: This case report of anti-NMDAR encephalitis suggests that despite clinical recovery long-term brain morphological changes can develop in the frontal cortex. Longer clinical and imaging follow-up studies are needed to see whether these frontocortical alterations are fully reversible and if not, can they result in trait vulnerabilities for e.g. neuropsychiatric disorders.

Childhood adversity predicts persistence of suicidal thoughts differently in females and males at clinical high-risk patients of psychosis. Results of the EPOS project.

AIM: Depression and suicidal ideation (SUI) and behaviour are more prevalent in females than males, and common in clinical high-risk (CHR) patients. Childhood adversities and trauma (CAT) are associated with adult depression and SUI. The role of gender as a moderator and depression as a mediator for the effect of CAT on SUI has not been explored in CHR patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for SUI (thoughts of killing themselves) with the Beck Depression Inventory at baseline, 9-month and 18-month follow-ups. At baseline, clinical depression was assessed by the Structured Clinical Interview for DSM-IV (SCID-I), and CAT by the Trauma and Distress Scale (TADS) which includes the five domains of emotional, physical and sexual abuse, emotional and physical neglect. RESULTS: CAT total and all domains except physical neglect predicted SUI over the study period. The effect of CAT on SUI was mediated via clinical depression and concurrent depression symptoms differently for females and males. In females, the effect of emotional abuse and neglect on SUI was mediated via baseline depression. In males, emotional and physical abuse had a direct effect on SUI, and the effect of sexual abuse and emotional neglect was partly mediated via concurrent depression symptoms. CONCLUSIONS: For CHR females, the effect of CAT on adult SUI is mediated via depression, while for males, CAT and its domains have mainly direct effects in maintaining SUI. These gender differences should be taken into account when treating CHR patients with SUI.

Korsakoff Syndrome in Non-alcoholic Psychiatric Patients. Variable Cognitive Presentation and Impaired Frontotemporal Connectivity.

Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI) data are scarce. Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men) with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems. Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient. Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the uncinate fasciculus, may be a feature of non-alcoholic Korsakoff syndrome in psychiatric patients.

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy.

Verbal memory and 5-HT1A receptors in healthy volunteers--A PET study with [carbonyl-(11)C]WAY-100635.

The serotonin 5-HT1A receptor is a putative drug development target in disorders with cognitive and in particular memory deficits. However, previous human positron emission tomography (PET) studies on 5-HT1A receptor binding and memory functions have yielded discrepant results. We explored the association between verbal memory and 5-HT1A receptor binding in 24 healthy subjects (14 male, 10 female, aged 18-41 years). The cognitive tests included the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wisconsin Card Sorting Test (WCST). 5-HT1A receptor binding was measured with PET and the radioligand [carbonyl-(11)C]WAY-100635, which was quantified with the gold standard method based on kinetic modeling using arterial blood samples. We found that global 5-HT1A receptor binding was positively correlated with measures of verbal memory, such that subjects who had higher receptor binding tended to have better verbal memory than subjects who had lower receptor binding. Regional analyses suggested significant correlations in multiple neocortical brain regions and the raphe nuclei. We did not find significant correlations between 5-HT1A receptor binding and executive functions as measured with WCST. We conclude that neocortical as well as raphe 5-HT1A receptors are involved in verbal memory function in man.

Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

BACKGROUND: The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. RESULTS: At baseline, 54.3% of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4%. Depressive, obsessive-compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive-compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. CONCLUSION: Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive-compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

Word list learning in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy.

BACKGROUND/AIMS: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a rare hereditary disease that is characterized by a combination of progressive presenile dementia and sclerosing leukoencephalopathy with bone cysts. No quantitative information on verbal memory functioning in PLOSL patients compared with control subjects is available. METHODS: 23 patients with PLOSL and 23 control subjects were examined with a version of the 10-word list-learning task. Learning curves were compared between the patients and the matched control subjects. RESULTS: Compared with the control subjects, PLOSL patients with moderate or severe dementia were impaired in both learning trials and delayed recall on the 10-word list-learning test. CONCLUSION: Progressive degeneration of brain structures affecting the hippocampus and the medial temporal lobe with advanced PLOSL disease contributes to an inefficient verbal learning process.

Childhood trauma and premorbid adjustment among individuals at clinical high risk for psychosis and normal control subjects.

AIM: Traumatic childhood experiences are associated with psychotic illness and are frequently reported in patients at clinical high risk (CHR) for psychosis. Moreover, deteriorating premorbid functioning from childhood, and through adolescence, is related to greater severity of overall symptomatology and poorer outcomes in patients with psychosis. We studied the prevalence of traumatic childhood experiences and premorbid adjustment and their association with each other in patients at CHR for psychosis and normal control subjects (NCSs). METHODS: A total of 20 CHR patients for psychosis and 30 NCSs aged 14 to 35 participated in the present study. The CHR patients were identified as prodromal to psychosis using the Structured Interview for Prodromal Syndromes/Scale of Prodromal Symptoms. Premorbid adjustment was assessed by using the premorbid adjustment scale (PAS), and self-reported childhood trauma was assessed with the Trauma and Distress Scale (TADS). RESULTS: In CHR patients, TADS and PAS scores were higher than in NCSs. In CHR patients, TADS correlated significantly with the PAS general section and observably, but not significantly, with adolescence and adulthood sections. CONCLUSION: CHR patients reported more childhood trauma experiences and poorer premorbid adjustment than NCSs. In CHR patients, traumatic childhood experiences are associated with poor general premorbid adjustment.

Different vulnerability indicators for psychosis and their neuropsychological characteristics in the Northern Finland 1986 Birth Cohort.

This study is one of very few that has investigated the neuropsychological functioning of both familial and clinical high risk subjects for psychosis. Participants (N = 164) were members of the Northern Finland 1986 Birth Cohort in the following four groups: familial risk for psychosis (n = 62), clinical risk for psychosis (n = 20), psychosis (n = 13), and control subjects (n = 69). The neurocognitive performance of these groups was compared across 19 cognitive variables. The two risk groups did not differ significantly from controls, but differed from the psychosis group in fine motor function. Neuropsychological impairments were not evident in a non-help-seeking high-risk sample.

Differentiating adolescents at clinical high risk for psychosis from psychotic and non-psychotic patients with the Rorschach.

This study was designed to assess cognitive functioning in a clinical sample of adolescents with heterogeneous psychiatric diagnoses, with a specific focus on patients at clinical high risk (CHR) for psychosis. The sample comprised 22 patients identified at CHR for psychosis, 67 psychotic and 187 non-psychotic, non-CHR patients. Neuropsychological assessment was conducted as part of the clinical examination and treatment, including Wechsler Intelligence Scale for Children (WISC)-III and/or Wechsler Adult Intelligence Scale (WAIS)-III measures of verbal comprehension, perceptual organisation, working memory and processing speed, Wisconsin Card Sorting Test (WCST) measures of executive function, and the Rorschach Comprehensive System measures of perceptual and thinking accuracy. Patients at CHR for psychosis did not significantly differ from other patient groups in terms of intellectual or executive functions. The Rorschach Perceptual Thinking Index (PTI) distinguished patients at CHR for psychosis from those diagnosed as having non-psychotic disorders, but not from those diagnosed as psychotic. Our results suggest perceptual and thought disturbance as an important indicator of vulnerability to psychosis.

Cortical dopamine D2/D3 receptors and verbal memory in man.

INTRODUCTION: It has been previously reported that hippocampal dopamine D2/D3 receptors are involved in the regulation of verbal memory and learning in healthy volunteers. We tested this hypothesis further and studied whether cortical dopamine D2/D3 receptor availability in vivo is associated with verbal memory as assessed with the revised Wechsler Memory Scale (WMS-R). METHODS: Forty healthy Finnish subjects were evaluated according to the WMS-R and scanned with positron emission tomography (PET) and dopamine D2/D3 receptor radioligand [(11)C]FLB457 for the measurement of cortical D2/D3 receptor binding. RESULTS: WMS-R verbal memory and learning parameters did not significantly correlate with D2/D3 receptor binding potential (BP(ND)) in the studied cortical regions. CONCLUSIONS: Our findings do not support a major role for cortical D2/D3 receptors in the regulation of verbal memory in healthy individuals.

Perceived negative attitude of others as an early sign of psychosis.

AIM: Risk of psychosis is defined by the presence of positive psychotic-like symptoms, by subtle self-perceived cognitive and perceptual deficiencies, or by decreased functioning with familial risk of psychosis. We studied the associations of psychiatric outpatients' self-reported functioning and interpersonal relationships with vulnerability to and risk of psychosis. METHODS: A total of 790 young patients attending psychiatric outpatient care completed the PROD screen [Heinimaa M, Salokangas RKR, Ristkari T, Plathin M, Huttunen J, Ilonen T, et al. PROD-screen - a screen for prodromal symptoms of psychosis. Int J Meth Psychiatr Res 2003;12:92-04.], including questions on functioning, interpersonal relationships and subtle specific (psychotic-like) and non-specific symptoms. Vulnerability to psychosis was assessed employing the patient's written descriptions of specific symptoms. Of the patients vulnerable to psychosis, those at current risk of psychosis were assessed using the Bonn Scale for Assessment of Basic Symptoms [Schultze-Lutter F, Klosterkötter J. Bonn scale for assessment of basic symptoms - prediction list, BSABS-P. Cologne: University of Cologne; 2002] and the Structured Interview for Positive symptoms [Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002;159:863-65.]. RESULTS: In all, 219 patients vulnerable to and 55 patients at current risk of psychosis were identified. Vulnerability to psychosis was associated with all items of functioning and interpersonal relationships. Current risk of psychosis, however, was associated only with the subjectively reported negative attitude of others. Negative attitude of others was also associated with feelings of reference at both vulnerability and risk levels. CONCLUSION: The subjective experience of negative attitude of others towards oneself may be an early indicator of psychotic development.