The trajectory of cognitive functioning following first episode mania: a 12-month follow-up study

OBJECTIVES: Cognitive deficits are apparent in the early stages of bipolar disorder; however, the timing and trajectory of cognitive functioning following a first episode of mania remains unclear. The aim of this study was to assess the trajectory of cognitive functioning in people following a first episode of mania over a 12-month period, relative to healthy controls. METHOD: The cohort included 61 participants who had recently stabilised from a first treated manic episode, and 21 demographically similar healthy controls. These groups were compared on changes observed over time using an extensive cognitive battery, over a 12-month follow-up period. RESULTS: A significant group by time interaction was observed in one measure of processing speed (Trail Making Test - part A,) and immediate verbal memory (Rey Auditory Verbal Learning Test - trial 1), with an improved performance in people following a first episode of mania relative to healthy controls. On the contrary, there was a significant group by time interaction observed on another processing speed task pertaining to focussed reaction time (Go/No-Go, missed go responses), with first episode of mania participants performing significantly slower in comparison with healthy controls. Furthermore, a significant group by time interaction was observed in inhibitory effortful control (Stroop effect), in which healthy controls showed an improvement over time relative to first episode of mania participants. There were no other significant interactions of group by time related to other measures of cognition over the 12-month period. CONCLUSION: Our findings revealed cognitive change in processing speed, immediate memory and one measure of executive functioning over a 12-month period in first episode of mania participants relative to healthy controls. There was no evidence of change over time for all other cognitive domains. Further studies focussed on the at-risk period, subgroup analysis, and the effects of medication on the cognitive trajectory following first episode of mania are needed.

Spurious precision : variability in procedural validity of diagnostic procedures in psychotic disorders and implications for research and treatment

Very few studies have quantified the level of agreement among alternative diagnostic procedures that use a common set of fixed operational criteria. The authors examined the procedural validity of four independent methods of assigning DSM-III-R diagnoses of psychotic disorders. METHOD: The research was conducted as a satellite study to the DSM-IV Field Trial for Schizophrenia and Related Psychotic Disorders. The setting was the National Health and Medical Research Council Schizophrenia Research Unit's Early Psychosis Prevention and Intervention Centre, which focuses on first-episode psychosis. Consecutively admitted patients (N = 50) were assessed by independent raters who used four different procedures to determine a DSM-III-R diagnosis. These procedures were 1) the diagnostic instrument developed for the DSM-IV field trial, 2) the Royal Park Multidiagnostic Instrument for Psychosis, 3) the Munich Diagnostic Checklists, and 4) a consensus DSM-III-R diagnosis assigned by a team of clinician researchers who were expert in the use of diagnostic criteria. RESULTS: Concordance between pairs of diagnostic procedures was only moderate. Corresponding levels of percent agreement, however, ranged from 66% to 76%, with converse misclassification rates of 24%-34% (assuming one procedure to be "correct"). CONCLUSIONS: These findings have significant research and clinical implications. Despite the introduction of operationally defined diagnoses, there remained an appreciable level of differential classification or misclassification arising from variability in the method of assigning the diagnostic criteria rather than the criteria themselves. Such misclassification may impede neurobiological research and have harmful clinical effects on patients with first-episode psychosis.

The procedural validity of retrospective case note diagnosis

Objective: Deriving diagnoses from retrospective case note examination is a common practice in psychiatric research. The Operational Criteria (OPCRIT) diagnostic checklist is essentially a checklist built up of operational criteria defined by a comprehensive glossary and is designed to assign reliable diagnoses from case notes. However, the validity of such a procedure compared with procedures involving prospective assessment has never been tested. We examined the procedural validity of the OPCRIT diagnostic system in relation to four other diagnostic procedures mostly employing prospectively gathered information.

Method: Three experienced psychopathology raters rated the case notes and clinical abstracts, using the OPCRIT method of diagnostic assignment, of 50 subjects who had participated in an early procedural validity study as an adjunct to the DSM-IV Field Trial for psychotic disorders. The setting was the Early Psychosis Prevention and Intervention Centre (EPPIC), which focuses on first episode psychosis.

Results: The pairwise concordance with the other procedures for DSM-III-R diagnoses assigned by OPCRIT using ratings derived from either the clinical abstracts or the case notes was found to be only poor to moderate when compared with the pairwise concordance of the four other procedures. The per cent agreement between OPCRIT clinical abstracts diagnoses and the other procedures ranged from 49% to 60% with kappa values between 0.30 and 0.45, and for OPCRIT case note diagnoses and the other procedures the per cent agreement range was between 44% and 57% and the kappa values were between 0.35 and 0.49.

Conclusions: The procedural validity of diagnoses assigned via the application of checklists of operational criteria to case notes and clinical abstracts alone is unacceptably poor. Such sources need to be buttressed by other data, particularly direct patient interview and informant material.

Managing risks of violence in a youth mental health service: a service model description

There is a significant relationship between experiencing a severe mental illness, particularly psychosis, and exhibiting violent or offending behaviour. Reducing, if not preventing, the risks of violence among patients of mental health services is clinically warranted, but models to address this are limited

Can a targeted psychological intervention be effective for young people following a first manic episode? Results from an 18-month pilot study

Aim: There is a scarce literature describing psychological interventions for a young, first-episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population.

Methods: The study was an open-label design, drawn from a larger pharmacotherapy trial. All participants in the pharmacotherapy trial were offered a manualized psychological intervention in addition to case management. Inclusion in the psychotherapy group was based on participant's choice, and on completion of four or more of the eight modules offered. All clinical files were audited to ensure accuracy of group allocation. Forty young people aged 15 to 25 years old who had experienced a manic episode with psychotic features were recruited into the study, with 20 people in the combined treatment as usual plus psychotherapy group (P+TAU), and an equal number of matched control participants who received treatment as usual (TAU) within the same service. All participants were prescribed antipsychotic and mood-stabilizing medication. Symptomatic, functional and relapse measures were taken both at baseline and at 18-month follow-up.

Results: Manic symptoms improved significantly for both groups, with no differences between groups. Depression scores and overall symptom severity were significantly lower in the P + TAU group. No differences were evident between groups with regard to numbers or type of relapse. The P + TAU group had significantly better social and occupational functioning after 18 months.

Conclusion: This study suggests that a manualized psychological intervention targeted to a first-episode population can be effective in reducing depression and overall symptom severity, and can improve functional outcome following a first episode of psychotic mania.

Relationship between membrane fatty acids and cognitive symptoms and information processing in individuals at ultra-high risk for psychosis

Cognitive symptoms and impairment are central to schizophrenia and often an early sign of this condition. The present study investigated biological correlates of cognitive symptoms and performance in individuals at ultra-high risk (UHR) for psychosis. The study sample comprised 80 neuroleptic-naïve UHR individuals aged 13-25 years. Associations among erythrocyte membrane fatty acid levels, measured by gas chromatography, and cognitive functioning were investigated in UHR patients. Subjects were divided into terciles based on their scores on the cognitive factor of the Positive and Negative Syndrome Scale. The Zahlen-Verbindungs Test (ZVT) (the number-combination test) was also used as a measure of information-processing speed. Exploratory analysis was conducted to investigate the relationship between membrane fatty acid levels with the size of the intracranial area (ICA), a neurodevelopmental measure relevant to schizophrenia, in half of subjects (n=40) using magnetic resonance imaging. The adjusted analysis revealed that omega-9 eicosenoic and erucic acid levels were significantly higher, but omega-3 docosahexaenoic acid levels were significantly lower, in the cognitively impaired than in the cognitively intact group. We found a significant negative association of eicosenoic, erucic, and gamma-linoleic acids with ZVT scores. A negative association between ICA and membrane levels of eicosenoic acid was also found. This is the first study to demonstrate the relationship between membrane fatty acids and cognitive function in neuroleptic-naïve subjects at UHR for psychosis. The study findings indicate that abnormalities in membrane fatty acids may be associated with the neurodevelopmental disruption associated with the cognitive impairments of individuals at UHR for psychosis.

Niacin skin sensitivity is increased in adolescents at ultra-high risk for psychosis

BACKGROUND: Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders.

METHODS: We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics.

RESULTS: Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling.

CONCLUSIONS: Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

Youth mental health first aid: a description of the program and an initial evaluation

BACKGROUND: Adolescence is the peak age of onset for mental illness, with half of all people who will ever have a mental illness experiencing their first episode prior to 18 years of age. Early onset of mental illness is a significant predictor for future episodes. However, adolescents and young adults are less likely than the population as a whole to either seek or receive treatment for a mental illness. The knowledge and attitudes of the adults in an adolescent's life may affect whether or not help is sought, and how quickly. In 2007, the Youth Mental Health First Aid Program was launched in Australia with the aim to teach adults, who work with or care for adolescents, the skills needed to recognise the early signs of mental illness, identify potential mental health-related crises, and assist adolescents to get the help they need as early as possible. This paper provides a description of the program, some initial evaluation and an outline of future directions.

METHODS: The program was evaluated in two ways. The first was an uncontrolled trial with 246 adult members of the Australian public, who completed questionnaires immediately before attending the 14 hour course, one month later and six months later. Outcome measures were: recognition of schizophrenia or depression; intention to offer and confidence in offering assistance; stigmatising attitudes; knowledge about adolescent mental health problems and also about the Mental Health First Aid action plan. The second method of evaluation was to track the uptake of the program, including the number of instructors trained across Australia to deliver the course, the number of courses they delivered, and the uptake of the YMHFA Program in other countries.

RESULTS: The uncontrolled trial found improvements in: recognition of schizophrenia; confidence in offering help; stigmatising attitudes; knowledge about adolescent mental health problems and application of the Mental Health First Aid action plan. Most results were maintained at follow-up. Over the first 3 years of this program, a total of 318 instructors were trained to deliver the course and these instructors have delivered courses to 10,686 people across all states and territories in Australia. The program has also spread to Canada, Singapore and England, and will spread to Hong Kong, Sweden and China in the near future.

CONCLUSIONS: Initial evaluation suggests that the Youth Mental Health First Aid course improves participants' knowledge, attitudes and helping behaviour. The program has spread successfully both nationally and internationally.

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics : meta-analysis and implications

The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.

Evidence and implications for early intervention in bipolar disorder

Aims: To review the evidence that supports early intervention in the treatment of bipolar disorder.

Background: Bipolar disorder is a pleomorphic condition, with varying manifestations that are determined by a number of complex factors including the ‘‘stage’’ of illness. It is consequently a notoriously difficult illness to diagnose and as a corollary is associated with lengthy delays in recognition and the initiation of suitable treatment.

Methods: A literature search was conducted using MEDLINE augmented by a manual search.

Results: Emerging neuroimaging data suggests that, in contrast to schizophrenia, where at the time of a first-episode of illness there is already discernible volume loss, in bipolar disorder, gross brain structure is relatively preserved, and it is only with recurrences that there is a sequential, but marked loss of brain volume. Recent evidence suggests that both pharmacotherapy and psychotherapy are more effective if instituted early in the course of bipolar disorder, and that with multiple episodes and disease progression there is a noticeable decline in treatment response.

Conclusions: Such data supports the notion of clinical staging, and the tailored implementation of treatments according to the stage of illness. The progressive nature of bipolar disorder further supports the concept that the first episode is a period that requires energetic broad-based treatment, with the hope that this could alter the temporal trajectory of the illness. It also raises hope that prompt treatment may be neuroprotective and that this perhaps attenuates or even prevents the neurostructural and neurocognitive changes seen to emerge with chronicity. This highlights the need for early identification at a population level and the necessity of implementing treatments and services at a stage of the illness where prognosis is optimal.

Clinical characteristics and management of bipolar disorder in women across the life span

Though prevalent in both genders, specific consideration needs to be given when treating a woman suffering from bipolar disorder over her lifetime. Bipolar disorder is a serious and incapacitating illness affecting an estimated 5% of women. The first episode of illness in women is usually a depressive episode. Female gender has been associated with greater axis-one comorbidity, more depressive episodes, rapid cycling and mixed affective states. Special consideration is required for the treatment of bipolar disorder during reproductive events. More studies are required to better understand the course, outcome and gender-specific treatment strategies of this disorder.

Predominant polarity as a course specifier for bipolar disorder: a systematic review

ABSTRACT