Prevalence of item level negative symptoms in first episode psychosis diagnoses

The relevance of negative symptoms across the diagnostic spectrum of the psychoses remains uncertain. The purpose of this study was to report on prevalence of item and subscale level negative symptoms across the first episode psychosis (FEP) diagnostic spectrum in an epidemiological sample, and to ascertain whether items and subscales were more prevalent in a schizophrenia spectrum diagnoses group compared to an 'all other psychotic diagnoses' group. We measured negative symptoms in 330 patients presenting with FEP using the Scale for Assessment of Negative Symptoms (SANS), and ascertained diagnosis using the Structured Clinical Interview for DSM IV. Prevalence of SANS items and subscales were tabulated across all psychotic diagnoses, and logistic regression analysis determined which items and subscales were predictive of schizophrenia spectrum diagnoses. SANS items were most prevalent in schizophrenia spectrum conditions but frequently presented in other FEP diagnoses, particularly substance induced psychotic disorder and Major Depressive Disorder. Brief psychotic disorder and bipolar disorders had low levels of negative symptoms. SANS items and subscales which significantly predicted schizophrenia spectrum diagnoses, were also frequently present in some of the other psychotic diagnoses. Conclusions: SANS items have high prevalence in FEP, and while commonest in schizophrenia spectrum conditions are not restricted to this diagnostic subgroup.     

Incidence and diagnostic diversity in first‐episode psychosis

Reay R, Mitford E, McCabe K, Paxton R, Turkington D. Incidence and diagnostic diversity in first‐episode psychosis. Objective: To investigate the incidence and range of diagnostic groups in patients with first‐episode psychosis (FEP) in a defined geographical area. Method: An observational database was set up on all patients aged 16 years and over presenting with FEP living in a county in Northern England between 1998 and 2005. Results: The incidence of all FEP was 30.95/100 000. The largest diagnostic groups were psychotic depression (19%) and acute and transient psychotic disorder (19%). Fifty‐four per cent of patients were aged 36 years and over. Patients with schizophrenia spectrum disorder only accounted for 55% of cases. Conclusion: This clinical database revealed marked diversity in age and diagnostic groups in FEP with implications for services and guidelines. These common presentations of psychoses are grossly under researched, and no treatment guidelines currently exist for them.     

Diagnostic stability 2 years after treatment initiation in the early psychosis intervention programme in Singapore

OBJECTIVE: To evaluate the diagnostic stability of psychotic disorders over a 2 year period in patients presenting with first-episode psychosis. METHODS: One hundred and fifty-four patients were recruited from an early psychosis intervention programme (EPIP). They were diagnosed by the attending psychiatrist using the Structured Clinical Interview for DSM-IV Axis I at first contact (baseline) and after 24 months. The diagnoses were classified into the following categories: schizophrenia spectrum disorders (schizophrenia, schizophreniform disorder and schizoaffective disorder), affective psychosis (bipolar and major depressive disorders with psychotic symptoms), and other non-affective psychosis (delusional disorder, psychosis not otherwise specified and brief psychotic disorder). Two measures of stability, the prospective and the retrospective consistency were determined for each diagnosis. RESULTS: The diagnoses with the best prospective consistency were schizophrenia (87.0%) and affective psychosis (54.5%). The shift into schizophrenia spectrum disorder was the most frequent diagnostic change. Duration of untreated psychosis was found to be the only significant predictor of shift. CONCLUSION: It is difficult to make a definitive diagnosis at first contact. The clinical need to review the diagnosis throughout the period of follow up is emphasized.     

Executive functioning correctly classified diagnoses in patients with first-episode psychosis: evidence from a 2-year longitudinal study

Few studies have analysed factors that predict the ultimate clinical diagnosis in first-episode psychosis (FEP), and none has included cognitive factors. Eighty-six FEP patients and 34 healthy controls were recruited and followed up for two years. Positive and negative symptoms, depression, mania, duration of untreated psychosis (DUP), premorbid functioning, functional outcome and neurocognition were assessed over 2 years. Logistic regression models revealed that Wisconsin Card Sorting Test correctly distinguished the patients ultimately diagnosed with schizophrenia (87%) from those with bipolar disorder (80%) and those with other psychoses (85%), for an overall correct-diagnosis rate of 84.4%. The prediction was stable despite the inclusion of clinical and affective symptoms, DUP, clinical impression, and functional outcome scores. Results highlight the importance of reconsidering neurocognition as a diagnostic criterion for psychosis and schizophrenia.     

Panic attacks in psychosis

OBJECTIVE: To determine the prevalence, psychiatric comorbidity and suicidal ideation associated with co-occurring non-affective psychosis and panic attacks, compared with non-affective psychosis without panic attacks, in the general population. METHOD: Data were drawn from the National Comorbidity Survey (n = 8098). Statistical analyses were used to identify differences in sociodemographic characteristics, psychiatric comorbidity, suicidal ideation, and familial psychopathology between those with non-affective psychoses with and without panic, as well as to identify correlates of non-affective psychosis and panic. RESULTS: Co-occurring panic attacks and non-affective psychosis, compared with non-affective psychosis without panic, was associated with elevated psychiatric comorbidity and increased odds of suicidal ideation. CONCLUSION: Consistent with clinical findings, these data suggest that panic attacks commonly co-occur with psychosis in the community. Results indicate that the co-occurrence of panic and psychosis is associated with increased likelihood of psychiatric comorbidity and suicidality. These findings need replication.     

White-matter hyperintensities in first-episode psychosis

BACKGROUND: White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. AIMS: To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. METHOD: T(2)-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons. RESULTS: There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. CONCLUSIONS: White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings.     

Negative symptoms in first episode non-affective psychosis

OBJECTIVE: To determine the prevalence of negative symptoms and to examine secondary sources of influence on negative symptoms and the role of specific negative symptoms in delay associated with seeking treatment in first episode non-affective psychosis. METHOD: One hundred and ten patients who met Diagnostic Statistical Manual-IV (DSM-IV) criteria for a first episode of schizophrenia spectrum psychoses were rated for assessment of negative, positive, depressive and extrapyramidal symptoms, the premorbid adjustment scale and assessment of demographic and clinical characteristics including duration of untreated psychosis (DUP). RESULTS: Alogia/flat affect and avolition/anhedonia were strongly influenced by parkinsonian and depressive symptoms, respectively. A substantial proportion (26.8%) of patients showed at a least moderate level of negative symptoms not confounded by depression and Parkinsonism. DUP was related only to avolition/anhedonia while flat affect/alogia was related to male gender, diagnosis of schizophrenia, age of onset and the length of the prodrome. CONCLUSION: Negative symptoms that are independent of the influence of positive symptoms, depression and extra pyramidal symptoms (EPS) are present in a substantial proportion of first episode psychosis patients and delay in seeking treatment is associated mainly with avolition and anhedonia.     

Clinical and sociodemographic comparison of people at high‐risk for psychosis and with first‐episode psychosis

Zimbrón J, Ruiz de Azúa S, Khandaker GM, Gandamaneni PK, Crane CM, González‐Pinto A, Stochl J, Jones PB, Pérez J. Clinical and sociodemographic comparison of people at high‐risk for psychosis and with first‐episode psychosis. Objective: To compare clinical and sociodemographic characteristics previously associated with psychosis, between individuals at high‐risk for psychosis (HR) and patients experiencing a first episode psychosis (FEP), to achieve a better understanding of factors associated with psychosis. Method: Cross‐sectional comparison of 30 individuals at HR with 30 age‐gender matched FEP, presenting to an early intervention service for psychosis. Participants were followed‐up for 2 years to establish the proportion of HR who made the transition into FEP. Results: Both groups showed similar socio‐clinical characteristics, including immigration status, employment history, marital status, family history of psychotic illness, self‐harm and alcohol and drug use. The HR group had a lower level of education, higher burden of trauma, earlier onset of psychiatric symptoms and a longer delay in accessing specialised services. A younger onset of symptoms was associated with a longer delay in accessing services in both groups. After a 2 year follow‐up, only three (10%) of the HR group made a transition into FEP. Conclusion: The similarities observed between individuals at HR and those with FEP suggest that known variables associated with psychosis may be equally prevalent in people at HR who do not develop a psychotic disorder.     

Affective dimensions as a diagnostic tool for bipolar disorder in first psychotic episodes

ObjectiveTo examine the predictive diagnostic value of affective symptomatology in a first-episode psychosis (FEP) sample with 5 years’ follow-up.MethodAffective dimensions (depressive, manic, activation, dysphoric) were measured at baseline and 5 years in 112 FEP patients based on a factor structure analysis using the Young Mania Rating Scale and Hamilton Depression Rating Scale. Patients were classified as having a diagnosis of bipolar disorder at baseline (BDi), bipolar disorder at 5 years (BDf), or “other psychosis”. The ability of affective dimensions to discriminate between these diagnostic groups and to predict a bipolar disorder diagnosis was analysed.ResultsManic dimension score was higher in BDi vs. BDf, and both groups had higher manic and activation scores vs. “other psychosis”. Activation dimension predicted a bipolar diagnosis at 5 years (odds ratio = 1.383; 95% confidence interval, 1.205–1.587; P = 0.000), and showed high levels of sensitivity (86.2%), specificity (71.7%), positive (57.8%) and negative predictive value (90.5%). Absence of the manic dimension and presence of the depressive dimension were both significant predictors of an early misdiagnosis.ConclusionThe activation dimension is a diagnostic predictor for bipolar disorder in FEP. The manic dimension contributes to a bipolar diagnosis and its absence can lead to early misdiagnosis.     

Major self-mutilation in the first episode of psychosis

Major self-mutilation (MSM) is a rare but catastrophic complication of severe mental illness. Most people who inflict MSM have a psychotic disorder, usually a schizophrenia spectrum psychosis. It is not known when in the course of psychotic illness, MSM is most likely to occur. In this study, the proportion of patients in first episode of psychosis (FEP) was assessed using the results of a systematic review of published case reports. Histories of patients who had removed an eye or a testicle, severed their penis, or amputated a portion of a limb and were diagnosed with a schizophrenia spectrum psychosis were included. A psychotic illness was documented in 143 of 189 cases (75.6%) of MSM, of whom 119 of 143 (83.2%) were diagnosed with a schizophrenia spectrum psychosis. The treatment status of a schizophrenia spectrum psychosis could be ascertained in 101 of the case reports, of which 54 were in the FEP (53.5%, 95% confidence interval = 43.7%-63.2%). Patients who inflict MSM in FEP exhibited similar symptoms to those who inflict MSM later in their illness. Acute psychosis, in particular first-episode schizophrenia, appears to be the major cause of MSM. Although MSM is extremely uncommon, earlier treatment of psychotic illness may reduce the incidence of MSM.     

Long-term effects of a community intervention for early identification of first-episode psychosis

Objective: To assess whether an Early Case Identification Program (ECIP) for first‐episode psychosis (FEP), which showed no significant short‐term effects, has a delayed impact on duration of untreated psychosis (DUP). Method: Using a historical control design, FEP patients were assessed on clinical variables over three consecutive phases, 2 years prior, 2 years during and 3 years after implementation of the ECIP. Additional analyses were conducted on non‐affective and schizophrenia spectrum psychoses cases only. Results: There was no overall significant difference in DUP across the three phases. For cases treated within the first year of illness a nonsignificant reduction in DUP to less than 2 months observed during the active phase was sustained post‐ECIP. Conclusion: In some jurisdictions community‐wide early case detection may fail to have an immediate or delayed effect on DUP, especially for cases who normally present for treatment with DUP >1 year.     

Diagnostic specificity and predictors of neurological soft signs in schizophrenia, bipolar disorder and other psychoses over the first 4 years of illness

BACKGROUND: Neurological soft signs (NSS) are well described among patients with schizophrenia, the neurology of other psychoses is relatively unexplored and few comparative studies have prospectively examined these signs in first-episode patients. METHODS: We assessed neurological functioning in 242 patients presenting with a first episode of psychosis (in accordance with DSM-IV diagnosis) using the Condensed Neurological Examination (CNE). We sought to determine whether NSS were specific to patients with schizophrenia, bipolar affective disorder and other forms of psychosis. We also examined the factors associated with and predictive of neurodysfunction at first presentation and at 4 year follow-up. RESULTS: NSS were not specific to any diagnostic group. Neurological functioning was closely associated with psychopathology and mixed-handedness at first presentation. At follow-up there was a statistically significant improvement in neurological functioning. Persistent neurodysfunction at this stage was related to enduring negative symptoms and associated with poorer outcome. DISCUSSION: Schizophrenia and bipolar disorder are indistinguishable in terms of neurodysfunction at presentation. At presentation and 4 years NSS closely parallel psychopathology and mixed-handedness indicating that NSS may be a function of these factors or possibly an independent factor operates equally upon both symptoms and neurological function.     

Neonatal levels of acute phase proteins and later risk of non-affective psychosis

Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log₂-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85–0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78–0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32–0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.     

Regional gray matter volume deficits in adolescents with first-episode psychosis

ObjectiveThe current study combined baseline voxel-based morphometry and 1-year clinical follow-up assessments to examine whether and where regional gray matter (GM) volumes differed between a control group and diagnostic subgroups of early-onset first-episode psychosis (FEP).MethodMagnetic resonance imaging brain scans were obtained from 70 patients with early-onset FEP, and 51 non-FEP controls. Early-onset FEP was defined as age younger than 18 years and a duration of positive symptoms of less than 6 months. The age range of the sample was 7 to 18 years. After a 1-year follow-up, patients were stratified into three subgroups: schizophrenia (n = 25), bipolar I disorder (n = 20), and other psychoses (n = 25). Regional GM volumes of each patient subgroup were compared with those of the control group.ResultsA follow-up diagnosis of schizophrenia was associated with GM volume deficits in the left medial and left middle frontal gyrus; bipolar I disorder was related to a GM volume deficit in the left medial frontal gyrus; and not having a follow-up diagnosis of schizophrenia or bipolar disorder was associated with smaller bilateral GM volumes in the insula and right middle occipital gyrus.ConclusionsLeft medial frontal GM volume deficits were common in the groups with schizophrenia and bipolar I disorder, which may point to shared underlying pathological findings.     

Diagnostic stability 18 months after treatment initiation for first-episode psychosis

OBJECTIVES: (1) Assessment of diagnostic stability of psychotic disorders or psychotic mood disorders from 6 weeks to 18 months after initiation of treatment in a representative first-episode psychosis (FEP) sample. (2) Comparison between those patients who shifted from DSM-IV schizophreniform disorder to schizophrenia or schizo-affective disorder and those whose diagnosis of schizophreniform disorder remained stable. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from patients' medical records (MRs) using a standardized questionnaire. Seven hundred four MRs were available, 36 of which were excluded owing to nonpsychotic diagnoses or a psychotic disorder due to a general medical condition. Of the remaining 668 patients, 176 (26.3%) were lost to follow-up. Four hundred ninety-two subjects were analyzed. Strategies to assure validity and reliability of diagnoses were applied. RESULTS: The same diagnosis was made at baseline (< or = 6 weeks after admission into EPPIC) and 18 months for 69.9% of the patients. Among the most consistent diagnoses were schizophrenia (97.3%), schizoaffective disorder (94.1%), and bipolar disorder (83.2%); the least stable, as expected, was schizophreniform disorder (40.0%). In subjects with schizophreniform disorder at baseline, the best predictors of a shift from schizophreniform disorder to schizophrenia or schizoaffective disorder were a higher baseline Clinical Global Impressions-Severity of Illness scale score and lower premorbid Global Assessment of Functioning score, although the variance accounted for was small (R2 = .07). CONCLUSIONS: A longitudinally based diagnostic process in FEP samples is needed, especially in schizophreniform disorder and bipolar disorder. However, a thorough initial assessment of patient and family by a specialized team of investigators regarding the kind and duration of patient symptoms may lead to high diagnostic stability, especially in schizophrenia and schizoaffective disorder, even in a FEP sample with a relatively short duration of untreated psychosis.     

Illicit substance use and its correlates in first episode psychosis

Mazzoncini R, Donoghue K, Hart J, Morgan C, Doody GA, Dazzan P, Jones PB, Morgan K, Murray RM, Fearon P. Illicit substance use and its correlates in first episode psychosis. Objective: To determine if substance use (particularly cannabis) is more frequent among first episode psychosis patients and associated with a more problematic clinical presentation. Method: All first episode psychosis (FEP) patients presenting to secondary services were recruited from London and Nottingham, over 2 years, in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study broad framework. Clinical and sociodemographic variables were assessed using a set of standardized instruments. A schedule was created to retrospectively collate substance use data from patients, relatives and clinicians. Results: Five hundred and eleven FEP were identified. They used three to five times more substances than general population. Substance use was associated with poorer social adjustment and a more acute mode of onset. Cannabis use did not affect social adjustment, but was associated with a more acute mode of onset. Conclusion: Cannabis has a different impact on FEP than other substances. Large epidemiological studies are needed to disentangle cannabis effect.     

Sleep loss and postpartum psychosis

Postpartum psychosis is a rare but severe psychiatric disorder. Its diagnostic status remains controversial, but several studies have shown that the majority of patients who develop psychosis immediately following childbirth suffer from bipolar disorder. The pathophysiology of postpartum psychosis is poorly understood, but factors such as primiparity, difficult labor, genetic predisposition, and hormonal changes have been suggested as etiological factors. This paper reviews the literature on the relationship of sleep disruption and postpartum psychosis. It is argued that sleep loss resulting from the interaction of various putative causal factors may be the final common pathway in the development of psychosis in susceptible women. Clinical significance of these findings, including strategies to prevent postpartum psychosis, are discussed and suggestions are made for future research directions.     

EEG abnormalities and 3-year outcome in first episode psychosis

Objective: This study assesses the relationship of EEG to several aspects of 3 year symptomatic and functional outcome in first episode psychosis. Method: A total of 117 patients with first episode psychosis had their baseline EEG classified by modified Mayo Clinic criteria as normal, essentially normal or dysrhythmia. Socio‐demographic variables, duration of illness and of untreated psychosis and premorbid adjustment were also recorded. Positive and negative symptoms of psychoses, depression, anxiety and global functioning were rated on entry and after 3 years of treatment. Results: Patients with a dysrhythmic EEG at entry into treatment showed significantly greater persistence in both positive and negative symptoms of psychoses as well as anxiety and depression over 3 years. These findings were independent of duration of untreated illness or premorbid adjustment. Conclusion: An abnormal baseline EEG in patients with first episode psychosis is associated with a poorer symptomatic outcome at 3‐year follow‐up.     

Risk of schizophrenia and other non-affective psychosis among individuals exposed to head injury: Case control study

Studies of the risk of schizophrenia and related non-affective psychoses among individuals exposed to head injury have reported conflicting findings. The diagnostic specificity of reported associations remains unclear and the effects of sex, genetic vulnerability and timing of exposures are also uncertain. The authors used a comprehensive range of data derived from the linkage of several Swedish registers to investigate associations of head injury with schizophrenia and other non-affective psychoses. We carried out a nested case control study drawn from a cohort of 785,051 men and women born between 1973 and 1980. After head injury exposure, there was a small increase in the risk (OR 1.37 (CI 1.14–1.66)) of non-schizophrenic, non-affective psychoses but not schizophrenic disorder (OR 1.10 CI 0.82 to 1.47). There was no critical period effect for exposures in early childhood, the association with non-affective psychosis being observed only in those exposed to head injury after age 10. There was no evidence that associations differed in males and females or in those with, and those without, a family history of psychosis. We conclude that it is unlikely that head injury causes schizophrenia. There is a small but significant risk of non-schizophrenic psychotic disorders but this is not associated with early age of injury or family history of psychosis. Further research is needed to clarify the potential roles of social and biological intermediary factors.     

Longitudinal changes in brain structure following the first episode of psychosis

Both schizophrenia and bipolar disorder have been associated with progressive changes in grey matter (GM) volume. However, the temporal trajectories of these changes are poorly understood. The aim of this study was to assess longitudinal changes in grey matter volume subsequent to the first episode of schizophrenia and of affective psychoses. Adolescent patients with a first episode psychosis (n = 26) were scanned twice using magnetic resonance imaging, at first presentation and after a 3-year follow-up period. An age-matched group of healthy volunteers (n = 17) was scanned at the same time points. Within-group and between-group changes in regional grey matter volume were examined using voxel-based morphometry. There were significant group by time interactions (p_FDRcorr < 0.05) in the frontal, temporal, parietal, cerebellar cortex, and in the thalamus, mainly reflecting longitudinal reductions in the controls but not in the patients. Subdivision of the patient group revealed that there were similar longitudinal reductions in patients with affective psychoses as in the controls but no volumetric changes in patients with schizophrenia. Psychosis with onset in adolescence or early adulthood may be associated with a delay or a loss of longitudinal reductions in regional grey matter volume that normally occur at this stage of development. These changes may be specific to schizophrenia.