The pernicious course of schizophrenia has spurred efforts to identify and effectively treat this condition as early as possible. This assertive therapeutic stance is supported by epidemiologic data suggesting a substantial time lag between onset of illness and therapeutic intervention, and by neurobiologic data suggesting that brain changes present in first-episode psychosis are comparable to those in chronic schizophrenia. The proposal that atypical antipsychotic medications may prevent illness deterioration and/or be a restorative intervention is an appealing, but as yet unproven, hypothesis. Major challenges to maximizing treatment outcomes in first-episode schizophrenia include optimizing timing and effectiveness of pharmacologic interventions, service coordination, and access to care. We present data on the onset and presentation of first-episode schizophrenia and emerging findings about the neurobiology of first episodes, review nonpharmacologic and pharmacologic management, and summarize clinical research data on use of atypical antipsychotics in first-episode patients.
"The study of first-episode psychosis (FEP) is particularly advantageous in understanding the neurobiology of schizophrenia in part because of the opportunity to minimize the potential impact of confounds, such as illness duration, medication effects, and the psychiatric and medical comorbidities that are associated with chronicity of illness (Buckley and Evans 2006). Only a few studies have reported the decreased serum or plasma BDNF levels in first-episode patients with schizophrenia (Buckley et al. 2007; Rizos et al. 2008). "
[Show abstract][Hide abstract] ABSTRACT: There is accumulating evidence that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of patients with schizophrenia. Clinical studies show reductions in BDNF in schizophrenic patients treated with first generation antipsychotics or second generation antipsychotics. However, there have been few systematic studies to examine the relationship between BDNF levels and psychopathology in first-episode and drug-naïve patients with schizophrenia.
Serum BDNF levels were determined using enzyme-linked-immunosorbent assay (ELISA) in the serum of 88 never-medicated first-episode and 90 healthy controls subjects matched for age and gender. The schizophrenia symptomatology and the depressive symptoms were assessed by the positive and negative syndrome scale (PANSS) and the Hamilton rating (HAMD) scale for depression.
The results showed that BDNF levels were significantly lower in first-episode patients with schizophrenia than in healthy control subjects (9.0 +/- 4.2 ng/ml vs 12.1 +/- 2.2 ng/ml; F = 37.6; df = 1, 176; p < 0.0001). A significant positive correlation between BDNF levels and PANSS positive subscore was observed (r = 0.29; df = 88; p = 0.008). Furthermore, higher BDNF levels were observed in patients with paranoid subtype of schizophrenia. However, no significant correlation between BDNF and HAMD total score was found.
Low BDNF levels at the onset of psychosis suggest that it may contribute to the pathogenesis of schizophrenia and perhaps, could be a candidate biological marker for positive symptoms.
[Show abstract][Hide abstract] ABSTRACT: The goal of the Roadmap is to provide guidance on how to use currently available antipsychotics to achieve best outcomes for patients with serious mental illness. The Roadmap orientation is that clinicians often make treatment decisions based on their underlying model of the illness. The Roadmap therefore begins with a review of two theoretical models often used by clinicians who treat patients with severe mental illness (Section II). The "maintenance model" emphasizes achieving clinical stability; once the patient is stable, this model gives priority to relapse prevention and maintenance of stability. The "recovery model" also aims for achieving stability, but it places more emphasis on achieving further gains in physical and emotional health once stability is achieved. While a simplification, these models are based on different assumptions about the course and outcome of schizophrenia and the potential risks and benefits of different pharmacologic treatment options. These treatment models serve as the framework for the Roadmap recommendations, which are based on the clinical and psychopharmacologic research literature as well as expert consensus on questions not definitively answered in that literature.
On the basis of results of an initial survey and a roundtable meeting, a panel of 10 experts developed a list of psychopharmacologic topics not adequately addressed by the evidence-based literature, but which clinicians who use antipsychotic medications need to understand. These questions were posed in a survey to a larger panel of 32 experts, 27 (84%) of whom responded. Results of this survey and data from the literature were then used to develop recommendations for applying psychopharmacologic principles to individualize treatment for patients with severe mental illness.
Recommendations are presented to help clinicians make informed decisions about choice of medication, dosing, and switching strategies, based on the pharmaco-dynamic and pharmacokinetic properties of different antipsychotics (Section III); diagnosis, prominent symptoms, and treatment history (Section IV); the patient's age, gender, and psychosocial characteristics (Section V); and the patient's medical conditions whether related to antipsychotic treatment or not (Section VI). The final section illustrates how to apply the principles presented in the first six sections in real-world clinical situations.
The experts reached a high level of consensus on many key questions about treatment strategies. The Roadmap recommendations provide guidance for clinicians on how to fine-tune their psychopharmacologic strategies with antipsychotics to achieve the best outcomes for each individual patient.
The Journal of Clinical Psychiatry 02/2007; 68 Suppl 7(Suppl):1-48. · 5.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is much interest, derived from current neurochemical, genetic, and therapeutic research, in the role of brain neurotrophins in schizophrenia. Neurotrophins play key roles in neuronal development and differentiation (i.e., promoting dendritogenesis and synaptogenesis), and in orchestrating the neuronal response to stress/noxious stimuli. Additionally, neurotrophins are modulators across monominergic (dopamine and serotonin), gabaergic and cholinergic systems. These roles focus on important areas of the etiopathophysiology of schizophrenia. Clinical studies show reductions in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NFG) in schizophrenic patients as compared to normal control subjects, as well as differences in patients receiving first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs). We now report on BDNF levels in subjects with first-episode psychosis in comparison with normal healthy controls. Compared to normal controls (N=14; 290.5+/-38.81 pg/ml), first-episode psychotic patients showed significant reduction (N=15; 135+/-21.77 pg/ml; P=0.001; f=12.873) in plasma BDNF. Additionally, plasma BDNF levels showed a significant negative correlation (N=13' r=0.584, P=0.0362) only with positive symptom scores at base line and no significant correlations were found with any of the cognitive performance test battery or motor function test scores. Low BDNF levels at the onset of psychosis suggest that it may contribute to the pathogenesis of schizophrenia and/or perhaps could be a helpful neurobiological marker for possible early treatment intervention.
Schizophrenia Research 04/2007; 91(1-3):1-5. DOI:10.1016/j.schres.2006.12.026 · 3.92 Impact Factor
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