Recruitment and treatment practices for help-seeking "prodromal" patients

The prodrome of psychosis has become a target for early identification and for treatments that address both symptoms and risk for future psychosis. Interest and activity in this realm is now worldwide. Clinical trials with rigorous methodology have only just begun, making treatment guidelines premature. Despite the sparse evidence base, treatments are currently applied to patients in the new prodromal clinics, usually treatments developed for established psychosis and modified for the prodromal phase. This communication will describe representative samplings of how treatment-seeking prodromal patients are currently recruited and treated in prodromal clinics worldwide. Recruitment includes how prodromal patients are sought, initially evaluated, apprised of their high-risk status, and informed of the risks and benefits of prodromal treatments and how their mental state is monitored over time. The treatment modalities offered (and described) include engagement, supportive therapy, case management, stress management, cognitive behavioral treatment, family-based treatment, antipsychotic pharmacotherapy, and non-antipsychotic pharmacotherapy. References for details are noted.     

The association of insight with psychotic symptoms, depression, and cognition in early psychosis: a 3-year follow-up

Recent research has begun to examine the level of insight following a first episode of psychosis since this may have implications for outcome. Insight was investigated in 278 individuals consecutively admitted to a comprehensive early psychosis treatment program. Insight, symptoms and cognition were assessed on admission and after one, two and three years. Sixty percent had good insight at baseline and this improved significantly to 80% at one year. Insight remained good at years 2 and 3 with 78.6% and 82.8%, respectively, having good insight. A comparison of those with good to those with poor insight revealed that at each assessment point those with poor insight had significantly higher ratings on positive, negative and general psychopathology symptoms (all at p<0.001). Additionally those with good insight had significantly higher levels of depression at baseline (p=0.001). With respect to cognition when using a composite cognitive factor there was a significant advantage for the good insight group at one year (p=0.01). Overall results show that a significant proportion of individuals have good insight following a first episode of psychosis. For this group depression may be a significant concern at least upon initial presentation. Those with poor insight have increased symptoms throughout the first three years and possibly poorer cognitive functioning.     

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

Childhood-onset schizophrenia (COS), defined as onset of psychosis by the age of 12, is a rare and malignant form of the illness, which may have more salient genetic influence. Since the initial report of association between neuregulin 1 (NRG1) and schizophrenia in 2002, numerous independent replications have been reported. In the current study, we genotyped 56 markers (54 single-nucleotide polymorphisms (SNPs) and two microsatellites) spanning the NRG1 locus on 78 COS patients and their parents. We used family-based association analysis for both diagnostic (extended transmission disequilibrium test) and quantitative phenotypes (quantitative transmission disequilibrium test) and mixed-model regression. Most subjects had prospective anatomic brain magnetic resonance imaging (MRI) scans at 2-year intervals. Further, we genotyped a sample of 165 healthy controls in the MRI study to examine genetic risk effects on normal brain development. Individual markers showed overtransmission of alleles to affecteds (P=0.009-0.05). Further, several novel four-marker haplotypes demonstrated significant transmission distortion. There was no evidence of epistasis with SNPs in erbB4. The risk allele (0) at 420M9-1395 was associated with poorer premorbid social functioning. Further, possession of the risk allele was associated with different trajectories of change in lobar volumes. In the COS group, risk allele carriers had greater total gray and white matter volume in childhood and a steeper rate of subsequent decline in volume into adolescence. By contrast, in healthy children, possession of the risk allele was associated with different trajectories in gray matter only and was confined to frontotemporal regions, reflecting epistatic or other illness-specific effects mediating NRG1 influence on brain development in COS. This replication further documents the role of NRG1 in the abnormal brain development in schizophrenia. This is the first demonstration of a disease-specific pattern of gene action in schizophrenia.     

The genetics of childhood-onset schizophrenia: When madness strikes the prepubescent

Stratification by age at onset has been useful for genetic studies across all of medicine. For the past 20 years, the National Institute of Mental Health has been systematically recruiting patients with onset of schizophrenia before age 13 years. Examination of familial transmission of known candidate risk genes was carried out, and a 10% rate of cytogenetic abnormalities was found. Most recently, high-density, array-based scans for submicroscopic rare copy number variations (CNVs) have suggested that this kind of genetic variation occurs more frequently than expected by chance in childhoodonset schizophrenia (COS) and at a higher rate than observed in adult-onset disorder. Several CNVs and cytogenetic abnormalities associated with COS are also seen in autism and mental retardation. Populations with COS may have more salient genetic influence than adult-onset cases. The relationship of rare CNVs to prepsychotic development is being studied further.     

Social and cognitive functioning in psychosis

There is clear evidence that there is a link between cognitive and social functioning in schizophrenia. However, the exact nature of that association is not well established. In this study, three groups were included: 50 first episode of psychosis (FE) subjects, 53 multi-episode schizophrenia subjects (ME) and 55 non-psychiatric controls (NPC). Subjects were assessed on measures of social functioning and a comprehensive cognitive battery. FE subjects were assessed on admission to a comprehensive FE program and one year later. The ME and NPC group had two assessments one year apart. Both the FE and ME subjects were clearly impaired relative to NPCs in cognition and social functioning. In both the patient group and the NPC group cognition predicted performance on a measure of social problem solving and one measure of social functioning but not the other. This study supports the association between cognition and social functioning but indicates that this is a function of how social functioning is conceptualized and assessed.     

Symptom remission in first episode patients

Recently, new remission criteria for schizophrenia has been proposed, based on low symptom severity of core symptoms (the severity criteria), which is sustained over a minimum of 6 months (time criterion). The purpose of this study was to examine, in a secondary analysis, these criteria in a cohort of 240 first episode patients with a mean follow-up of 26.4 months from the Calgary Early Psychosis Program. Eighty-eight subjects (36.7%) met both the severity criteria and time criteria for remission (in-remission group); 47 subjects (19.6%) met only the severity criteria at their most recent assessment (severity only group); 49 (20.4%) subjects had met severity criteria at one or more assessments but did not meet severity or severity and time at the most recent assessment (fluctuating group); and 56 (23.3%) did not meet remission criteria (non-remission group). Those who achieved remission had lower levels of symptoms and higher functioning at baseline and at the final follow-up assessment, improved premorbid functioning, shorter duration of untreated psychosis and increased changes in symptoms over time.     

Outcome after discharge from an early psychosis program

Studies defining the course and outcome of individuals experiencing their first episode (FE) of psychosis generally report an improvement in symptoms and functioning. Today, many FE patients are treated in specialized early psychosis programs. Little is known what happens to these individuals after discharge from these programs back to regular services. We report here on the outcomes of the first 200 subjects admitted to a three year specialized first episode service who could be contacted for assessments between 1 and 2 years after discharge. Approximately 50% of those initially assessed in a first episode service were able to be followed for up to 5 years. Results were that, although there was no further improvement in positive symptoms, there was continued improvement in social functioning and signs of improvement in negative symptoms.     

Facial affect recognition in individuals at clinical high risk for psychosis

Facial affect discrimination and identification were assessed in 86 clinical high-risk individuals and compared with 50 individuals with first-episode psychosis, 53 with multi-episode schizophrenia and 55 non-psychiatric controls. On the identification task the non-psychiatric controls performed significantly better than all other groups, and on discrimination significantly better than both patient groups. Deficits in facial affect recognition appear to be present before the onset of psychosis and may be a vulnerability marker.     

Self-report of family functioning and risk for psychotic disorders in male adolescents with behavioural disturbances

Objective: Previous studies indicate that a poor family environment might affect vulnerability for the later manifestation of psychotic illness. The current study aims to examine family functioning prior to the onset of psychosis. Method: Subjects were 42 948, 17‐year old males with behavioural disturbances who were asked about the functioning of their family by the Israeli Draft Board. Data on later psychiatric hospitalizations were obtained from a National Psychiatric Hospitalization Registry. Results: Poorer self‐reported family functioning was associated with greater risk for later hospitalization for psychosis [adjusted hazard ratio (HR) = 1.16, 95% CI = 1.05–1.27], with a trend in the same direction for schizophrenia (adjusted HR = 1.1, 95% CI = 0.98–1.24). Conclusion: In male adolescents with behavioural disturbances, perceived poorer family functioning is associated with increased risk for non‐affective psychotic disorders and schizophrenia. These data do not enable us to determine if perceived familial dysfunction increases vulnerability for psychosis, if premorbid behavioural abnormalities disrupt family life, or neither.