Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors.

BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors. METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance. RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset. CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Further evidence of a cumulative effect of social disadvantage on risk of psychosis.

BACKGROUND: A growing body of evidence suggests that indicators of social disadvantage are associated with an increased risk of psychosis. However, only a few studies have specifically looked at cumulative effects and long-term associations. The aims of this study are: To compare the prevalence of specific indicators of social disadvantage at, and prior to, first contact with psychiatric services in patients suffering their first episode of psychosis and in a control sample. To explore long-term associations, cumulative effects, and direction of effects. METHOD: We collected information on social disadvantage from 332 patients and from 301 controls recruited from the local population in South London. Three indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analysed. RESULTS: Across all the domains considered, cases were more likely to report social disadvantage than were controls. Compared with controls, cases were approximately two times more likely to have had a parent die and approximately three times more likely to have experienced a long-term separation from one parent before the age of 17 years. Cases were also more likely than controls to report two or more indicators of adult social disadvantage, not only at first contact with psychiatric services [odds ratio (OR) 9.5], but also at onset of psychosis (OR 8.5), 1 year pre-onset (OR 4.5), and 5 years pre-onset (OR 2.9). CONCLUSIONS: Greater numbers of indicators of current and long-term exposure are associated with progressively greater odds of psychosis. There is some evidence that social disadvantage tends to cluster and accumulate.

Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study.

BACKGROUND: Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis. METHOD: We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire. RESULTS: Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all p FWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation. CONCLUSIONS: Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

Ten-year outcomes in first episode psychotic major depression patients compared with schizophrenia and bipolar patients.

We aimed to investigate long-term outcomes in psychotic major depression patients compared to schizophrenia and bipolar/manic psychosis patients, in an incidence sample, while accounting for diagnostic change. Based on Aetiology and Ethnicity in Schizophrenia and Other Psychoses (ÆSOP and ÆSOP-10), a first episode psychosis cohort was followed-up 10years after first presentation. The Schedules for Clinical Assessment in Neuropsychiatry, WHO Life Chart and Global Assessment of Functioning were used to assess clinical, social and service use outcomes. Seventy-two PMD patients, 218 schizophrenia patients and 70 psychotic bipolar disorder/mania patients were identified at baseline. Differences in outcome between PMD and bipolar patients based on baseline and lifetime diagnosis were minimal. Differences in clinical, social and service use outcomes between PMD and schizophrenia were more substantial with PMD patients showing better outcomes on most variables. However, there was some weak evidence (albeit not quite statistically significant at p<0.05) based on lifetime diagnoses that PMD patients were more likely to attempt suicide (OR 2.31, CI 0.98-5.42, p0.055) and self-harm (OR 2.34, CI 0.97-5.68, p0.060). PMD patients have better social and service use outcomes compared to people with schizophrenia, but may be more likely to attempt suicide or self-harm. This unique profile is important for clinicians to consider in any risk assessment.

Biological and psychosocial risk factors for psychotic major depression.

AIMS: Few studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders. METHODS: Based on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs. RESULTS: Living alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD. CONCLUSIONS: Risk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.

Diagnostic change 10 years after a first episode of psychosis.

BACKGROUND: A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change. METHOD: Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests. RESULTS: Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis. CONCLUSIONS: Diagnoses other than schizophrenia should to be regarded as potentially provisional.

Reappraising the long-term course and outcome of psychotic disorders: the AESOP-10 study.

BACKGROUND: Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare. METHOD: AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews. RESULTS: At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1-4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London. CONCLUSIONS: Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.