Late-Onset Neutropenia in Long-Term Clozapine Use and Its Management Utilizing Prophylactic G-CSF.

This case outlines recurrent neutropenia after fourteen years of successful clozapine use. The patient has a diagnosis of treatment-resistant schizophrenia which has been complicated by sensitivity to side effects of haloperidol and past failure of antipsychotics to manage her symptoms. It was necessary for our patient to follow a complicated treatment path involving close monitoring of blood levels, admissions, the initiation of lithium and the regular use of filgrastim (Neupogen), granulocyte colony stimulating factor (G-CSF). Following a failure of rescue filgrastim to increase her neutrophil levels, a management protocol was designed with input from the on-site hematology team. This protocol involved the use of filgrastim on a regular prophylactic basis. This management plan has worked for the patient who has been able to continue use of clozapine and has not suffered from any neutropenic episodes in over six months.

Does the ability to sustain attention underlie symptom severity in schizophrenia?

An association between deficits in executive control, particularly inhibitory control, and more severe negative and disorganised symptoms of schizophrenia has been widely reported. The importance of more basic aspects of attention, often referred to as 'vigilant' or 'sustained' attention, to this relationship remains unclear. This study examined the contribution of sustained attention to symptom severity using the Sustained Attention to Response Task (SART) in 69 patients with schizophrenia. We found that negative and disorganised symptom severity scores were correlated with sustained attention, working memory, and psychomotor speed. The ability to sustain attention significantly predicted variance in negative symptom severity but not disorganised symptoms, which were instead predicted by working memory performance. These data suggest that this component of attention at least partly explains variance in negative symptoms.

Is "clinical" insight the same as "cognitive" insight in schizophrenia?

Poor insight is associated with impaired cognitive function in psychosis. Whether poor clinical insight overlaps with other aspects of self-awareness in schizophrenia, such as cognitive self-awareness, is unclear. We investigated whether awareness of clinical state ("clinical insight") and awareness of cognitive deficits ("cognitive insight") overlap in schizophrenia in a sample of 51 stabilized patients with chronic schizophrenia. Cognitive insight was assessed in terms of the agreement between subjective self-report and neuropsychological assessment. Patients who show good cognitive insight did not necessarily show good clinical insight. By contrast, self-report and objective neuropsychological assessment only correlated for patients in the intact clinical insight group and not for those in the impairment clinical insight group. We conclude that while good cognitive insight may not be necessary for good clinical insight, good cognitive awareness is at least partly reliant on the processes involved in clinical insight.

Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.

The kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-gamma), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-gamma was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine/tryptophan) was significantly higher in the patient group compared with controls (P < 0.05). IFN-gamma measures did not differ between groups (P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.

Functional dyspepsia: are psychosocial factors of relevance?

The pathogenesis of Functional Dyspepsia (FD) remains unclear, appears diverse and is thus inadequately understood. Akin to other functional gastrointestinal disorders, research has demonstrated an association between this common diagnosis and psychosocial factors and psychiatric morbidity. Conceptualising the relevance of these factors within the syndrome of FD requires application of the biopsychosocial model of disease. Using this paradigm, dysregulation of the reciprocal communication between the brain and the gut is central to symptom generation, interpretation and exacerbation. Appreciation and understanding of the neurobiological correlates of various psychological states is also relevant. The view that psychosocial factors exert their influence in FD predominantly through motivation of health care seeking also persists. This appears too one-dimensional an assertion in light of the evidence available supporting a more intrinsic aetiological link. Evolving understanding of pathogenic mechanisms and the heterogeneous nature of the syndrome will facilitate effective management. Co-morbid psychiatric illness warrants treatment with conventional therapies. Acknowledging the relevance of psychosocial variables in FD, the degree of which is subject to variation, has implications for assessment and management. Available evidence suggests psychological therapies may benefit FD patients particularly those with chronic symptoms. The rationale for use of psychotropic medications in FD is apparent but the evidence base to support the use of antidepressant pharmacotherapy is to date limited.

An analysis of clinicians' verbal behaviors in a community reintegration program for traumatic brain injury survivors.

The authors present an analysis of clinician verbal behaviors in the Community Reintegration Program, a treatment program for traumatic brain injury survivors. Experienced clinicians from different allied health professions were videotaped as they provided group treatment. Each clinician's verbal behaviors were coded using an adaptation of the Clinical Interaction Analysis System, a reliable system for describing verbal behaviors. Clinicians then participated in a structured interview with the investigators; during the interview, clinicians reviewed their treatment tape and stated what treatment goals they were working on during each utterance. The majority of the clinicians' behaviors fell into two categories: clinician-initiated discourse and explanation. Chi-square analyses revealed that these two categories occurred significantly more frequently than other coded categories. These two verbal codes predominated regardless of the goal being addressed and regardless of the professional background of the treating clinician.

Sensitivity and specificity of a two-question screening tool for depression in a specialist palliative care unit.

OBJECTIVES: The primary objective in this study is to determine the sensitivity and specificity of a two-item screening interview for depression versus the formal psychiatric interview, in the setting of a specialist palliative in-patient unit so that we may identify those individuals suffering from depressive disorder and therefore optimise their management in this often-complex population. METHODS: A prospective sample of consecutive admissions (n = 167) consented to partake in the study, and the screening interview was asked separately to the formal psychiatric interview. RESULTS: The two-item questionnaire, achieved a sensitivity of 90.7% (95% CI 76.9-97.0) but a lower specificity of 67.7% (95% CI 58.7-75.7). The false positive rate was 32.3% (95% CI 24.3-41.3), but the false negative rate was found to be a low 9.3% (95% CI 3.0-23.1). A subgroup analysis of individuals with a past experience of depressive illness, (n = 95), revealed that a significant number screened positive for depression by the screening test, 55.2% (16/29) compared to those with no background history of depression, 33.3% (22/66) (P = 0.045). CONCLUSION: The high sensitivity and low false negative rate of the two-question screening tool will aid health professionals in identifying depression in the in-patient specialist palliative care unit. Individuals, who admit to a previous experience of depressive illness, are more likely to respond positively to the two-item questionnaire than those who report no prior history of depressive illness (P = 0.045).