The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis.

Visual hallucinations in psychosis are under-researched despite associations with increased illness severity, functional impairments, and suicidality in the few existing studies. Further, there are no long-term longitudinal studies, making it impossible to conclude if these associations are state or trait phenomena. In the current prospective longitudinal study, 184 individuals with first-episode psychosis were assessed with semi-structured clinical interviews and self-report questionnaires at baseline and 10-year follow-up. Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH-/+), or never (VH-/-). Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis. At baseline, the VH+/+ group (37.5%), but not VH-/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH-/- group (50%). At follow-up, the VH-/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH-/- group. However, the number of participants who committed multiple suicide attempts during the follow-up period was again significantly higher in the VH+/+ group. There was no association with childhood trauma. Hence, visual hallucinations are associated with impaired functioning and higher symptom severity, but only in the short-term. However, visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course. These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.

A good life with psychosis: rate of positive outcomes in first-episode psychosis at 10-year follow-up.

BACKGROUND: More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. METHODS: FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). RESULTS: In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. CONCLUSIONS: In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.

Long-term course of cognitive functioning in bipolar disorder: A ten-year follow-up study.

INTRODUCTION: Cognitive impairments are common in bipolar disorder (BD), but the long-term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10-year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. METHODS: Fifty-six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10-year follow-up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. RESULTS: BD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short-term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. CONCLUSIONS: We found evidence of long-term cognitive stability or improvement in BD participants from first treatment to 10-year follow-up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

Early identification of treatment non-response in first-episode psychosis.

BACKGROUND: Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery-no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups. METHODS: Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the "Remission in Schizophrenia Working Group" criteria and TR on adaptations of the "Treatment Response and Resistance in Psychosis" (TRRIP) working group criteria. RESULTS: 97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects. CONCLUSION: The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study.

OBJECTIVE: To investigate the trajectories of diminished expression and apathy over 10 years. Further, to explore the effects of baseline- and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. METHODS: 351 participants with a first episode of non-affective psychosis were examined at baseline and invited to follow-up at one year and 10 years. The trajectories of diminished expression and apathy were investigated using linear mixed models. Subsequently, cannabis use and other potential predictors and sources of secondary negative symptoms were added to the model to investigate the respective impact on their trajectories. RESULTS: The severity of both diminished expression and apathy decreased during the follow-up period after the first episode of psychosis, with the most improvement observed from baseline to 1-year follow-up. Cannabis use at baseline was associated with a long-lasting higher symptom load for diminished expression, but not apathy. Introducing persistent cannabis use to the model further strengthened the association with diminished expression. CONCLUSION: Both cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. Our results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

Course of intellectual functioning in schizophrenia and bipolar disorder: a 10-year follow-up study.

BACKGROUND: Intellectual functioning (IQ) is lower in schizophrenia patients compared to healthy controls, with bipolar patients intermediate between the two. Declines in IQ mark the onset of schizophrenia, while stability is generally found post-onset. There are to date few studies on long-term IQ development in bipolar disorder. This study presents 10-year follow-up data on IQ, including premorbid IQ estimates, to track the developmental course from pre-onset levels to long-term outcomes in both patient groups compared to healthy controls. METHODS: We included 139 participants with schizophrenia, 76 with bipolar disorder and 125 healthy controls. Mixed model analyses were used to estimate developmental slopes for IQ scores from estimated premorbid level (NART IQ) through baseline (WASI IQ) measured within 12 months post-onset, to 10-year follow-up (WASI IQ), with pairwise group comparisons. The best fit was found using a model with a breakpoint at baseline assessment. RESULTS: Only the schizophrenia group had significant declines from estimated premorbid to baseline IQ levels compared to controls. When comparing patient groups, schizophrenia patients had steeper declines than the bipolar group. Increases in IQ were found in all groups over the follow-up period. CONCLUSIONS: Trajectories of IQ from premorbid level to 10-year follow-up indicated declines from estimated premorbid level to illness onset in both patient groups, followed by increases during the follow-up period. Schizophrenia patients had a steeper decline than bipolar patients. During follow-up, increases indicate developmental improvement for both patient groups, but with a maintained lag compared to healthy controls due to lower premorbid levels.

Domain-specific cognitive course in schizophrenia: Group- and individual-level changes over 10 years.

Cognitive impairments in schizophrenia are well-documented, present across several cognitive domains and found to be relatively stable over time. However, there is a high degree of heterogeneity and indications of domain-specific developmental courses. The present study investigated the 10-year cognitive course in participants with first-episode schizophrenia (FES) and healthy controls on eight cognitive domains and a composite score, looking at group- and individual-level changes. A total of 75 FES participants and 91 healthy controls underwent cognitive assessment at baseline and follow-up. Linear mixed models were used for group-level analyses and reliable change index (RCI) analyses were used to investigate individual change. The prevalence of clinically significant impairment was explored at both time points, using a cut-off of < -1.5 SD, with significant cognitive impairment defined as impairment on ≥2 domains. Group-level analyses found main effects of group and time, and time by group interactions. Memory, psychomotor processing speed and verbal fluency improved, while learning, mental processing speed and working memory were stable in both groups. FES participants showed deteriorations in attention and cognitive control. Individual-level analyses mainly indicated stability in both FES and controls, except for a higher prevalence of decline in cognitive control in FES. At baseline, 68.8 % of FES participants had clinically significant impairment, compared to 62.3 % at follow-up. We mainly found long-term stability and modest increases in cognition over time in FES, as well as a high degree of within-group heterogeneity. We also found indications of deterioration in participants with worse cognitive performance at baseline.

Cognitive and Global Functioning in Patients With First-Episode Psychosis Stratified by Level of Negative Symptoms. A 10-Year Follow-Up Study.

Negative and cognitive symptoms are core features of schizophrenia that are correlated in cross-sectional designs. To further explore the relationship between these critical symptom dimensions we use a method for stratifying participants based on level and persistence of negative symptoms from absent to sustained levels over a 10-year follow-up period. We investigate associations with cognitive performance and level of global functioning. First-episode psychosis (FEP) participants (n = 102) and healthy controls (n = 116) were assessed at baseline and follow-up. A cognitive battery consisting of 14 tests derived into four domains and a composite score were used in the analyses. FEP participants were stratified based on negative symptom items from the Positive and Negative Syndrome Scale (PANSS-R) into four groups with either no, mild, transitory or sustained symptoms over the 10-year follow-up period. Global functioning was measured with Global Assessment of Functioning Scale-Split version. Multivariate and univariate analyses of variance were used to explore between-group differences in level and course of cognitive performance as global functioning. A multivariate analysis with four cognitive domains as dependent variables, showed significant group differences in performance when including healthy controls and the negative symptom groups. The groups with no and mild negative symptoms outperformed the group with sustained levels of negative symptoms on verbal learning and memory. The group with no negative symptoms also outperformed the group with sustained negative symptoms on the cognitive composite score. Significant improvements on verbal learning and memory, executive functioning and the cognitive composite were detected for the entire sample. No differences in cognitive course were detected. There was a significant improvement in global functioning as measured by the GAF-F over the follow-up period (p < 0.001), without any time x group interactions (p = 0.25). Participants with sustained negative symptoms had a significantly lower level of global functioning at 10-year follow-up with an additional independent effect of the cognitive composite score, compared to all other groups. Individuals with an early illness course characterized by absence of negative symptoms form a group with better cognitive and functional outcomes than the impairments typically associated with schizophrenia. Individuals with sustained levels of negative symptoms on the other hand may require a combined focus on both negative and cognitive symptoms.

Premorbid characteristics of patients with DSM-IV psychotic disorders.

INTRODUCTION: Psychotic disorder not otherwise specified (PNOS) is considered part of the psychosis spectrum, together with schizophrenia spectrum disorders (SSD) and psychotic bipolar spectrum disorders (PBD). The atypical clinical presentations of PNOS conditions may lead to uncertainty regarding treatment choices and expected outcomes. PNOS is understudied, and little is known about patients' premorbid characteristics including premorbid adjustment, prevalence of early cannabis use and childhood trauma. Knowledge about early illness phases can increase our understanding of this diagnostic group. METHODS: We included 1099 participants from the Norwegian TOP-study; 688 with narrow SSD diagnoses (schizophrenia, schizoaffective disorder, schizophreniform disorder), 274 with PBD (psychotic bipolar 1 and bipolar NOS) and 137 with PNOS diagnosed with the SCID-I for DSM-IV. Participants were assessed with the Premorbid Adjustment Scale (PAS) divided into the areas of premorbid academic and social functioning. We obtained information on age at first exposure to cannabis and use of cannabis before the age of 16. The participants also provided information regarding early traumatic experiences using the Childhood Trauma Questionnaire (CTQ). RESULTS: Participants with PNOS and SSD had poorer premorbid academic functioning than those with PBD (F2, 1029 = 7.81, p < 0.001, pη2 = 0.015). Premorbid social adjustment was significantly worse in the SSD group compared to the PBD group (F2, 1024 = 3.10, p = 0.045, pη2 = 0.006), with PNOS in the middle position. Significantly more of the participants with PNOS (17.5%) and SSD (11.5%) used cannabis before the age of 16 compared with PBD (5.3%, Wald χ2 = 6.86, p = 0.03). There were no significant differences between the three groups regarding mean CTQ scores or in the proportion of participants who had experienced at least one type of childhood adversity. CONCLUSIONS: Participants with PNOS appear as more similar to participants with SSD than to those with PBD regarding early premorbid adjustment and early cannabis use. The results indicate that many conditions classified as PNOS have functional impairments and problematic substance use from an early age. The prevalence of childhood adversities are high in all three groups.

The Time is Ripe for a Consensus Definition of Clinical Recovery in First-episode Psychosis: Suggestions Based on a 10-Year Follow-up Study.

OBJECTIVES: A consensus definition of clinical recovery in first-episode psychosis (FEP) is required to improve knowledge about recovery rates in this population. To propose criteria for a future consensus definition, this study aims to investigate rates of clinical recovery when using a standard definition (full psychotic symptom remission and adequate functioning for minimum one year) across both affective and nonaffective FEP groups (bipolar spectrum and schizophrenia spectrum disorders). Second, we aim to explore changes in rates when altering the standard definition criteria. Third, to examine the extent to which healthy controls meet the functioning criteria. STUDY DESIGN: In total, 142 FEP participants and 117 healthy controls preselected with strict criteria, were re-assessed with structured clinical interviews at 10-year follow-up. STUDY RESULTS: A total of 31.7% were in clinical recovery according to the standard definition, with significantly higher recovery rates in bipolar (50.0%) than in schizophrenia spectrum disorders (22.9%). Both groups' recovery rates decreased equally when extending duration and adding affective symptom remission criteria and increased with looser functioning criteria. In healthy controls, 18.8% did not meet the standard criteria for adequate functioning, decreasing to 4.3% with looser criteria. CONCLUSIONS: Findings suggest that clinical recovery is common in FEP, although more in bipolar than in schizophrenia spectrum disorders, also when altering the recovery criteria. We call for a future consensus definition of clinical recovery for FEP, and suggest it should include affective symptom remission and more reasonable criteria for functioning that are more in line with the general population.

Symptom Profiles in Psychotic Disorder Not Otherwise Specified.

Introduction: Approximately 10% of patients with psychotic disorders receive the diagnosis "Psychotic disorder not otherwise specified" (PNOS). However, there is a lack of knowledge about the clinical presentations captured by this diagnosis in the mental health services. Therefore, we examined the symptom profiles of participants with PNOS compared to participants with bipolar disorder (BD) and schizophrenia spectrum disorder (SZ) diagnoses. Methods: We here included 1,221 participants from the Thematically Organized Psychosis-study at Oslo University Hospital; 792 with SZ, 283 with BD, and 146 with PNOS, assessed with SCID-I for DSM-IV. The participants with PNOS were categorized into subgroups based on SCID information. The GAF, PANSS, Alcohol Use Disorders Identification Test (AUDIT), and Drug Use Disorders Identification Test (DUDIT) were used to assess function, clinical symptoms, and substance use. Results: In the PNOS group, 44% did not meet the criteria for any specific psychotic disorder, 35.5% had contradictory information making a specific diagnosis difficult, and 20.5% had inadequate information to make a specific diagnosis. The most frequent reason for a PNOS diagnosis was difficulty ruling out a substance-induced psychotic disorder (n = 41, 28%). Participants with PNOS were younger and more often first-episode than participants with BD and SZ. They were intermediate between BD and SZ for GAF scores (BD>PNOS>SZ) and PANSS scores (BD