ABSTRACT
Brain-derived neurotrophic factor (BDNF) has been studied as a biomarker of major depressive disorder (MDD). Besides diagnostic biomarkers, clinically useful biomarkers can inform response to treatment. We aimed to review all studies that sought to relate BDNF baseline levels, or BDNF polymorphisms, with response to treatment in MDD. In order to achieve this, we performed a systematic review of studies that explored the relation of BDNF with both pharmacological and non-pharmacological treatment. Finally, we reviewed the evidence that relates peripheral levels of BDNF and BDNF polymorphisms with the development and management of treatment-resistant depression.
Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Humans , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/therapeutic use , Biomarkers , Polymorphism, GeneticABSTRACT
BACKGROUND: Approximately 30% of individuals with schizophrenia (SZ) are resistant to conventional antipsychotic drug therapy (AP). Of these, one-third are also resistant to the second-line treatment, clozapine. Treatment resistance and refractoriness are associated with increased morbidity and disability, making timely detection of these issues critical. Variability in treatment responsiveness is partly genetic, but research has yet to identify variants suitable for personalizing antipsychotic prescriptions. METHODS: We evaluated potential associations between response to AP and candidate gene variants previously linked to SZ or treatment response. Two groups of patients with SZ were evaluated: one receiving clozapine (n = 135) and the other receiving another second-generation AP (n = 61). Single-nucleotide polymorphisms (SNPs) in the genes OXT, OXTR, CNR1, DDC, and DRD2 were analyzed. RESULTS: Several SNPs were associated with response vs. resistance to AP or clozapine. CONCLUSIONS: This is the first study of its kind, to our knowledge, in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant SZ in the genes OXT, CNR1, DDC, and DRD2.
Subject(s)
Antipsychotic Agents , Clozapine , Schizophrenia , Humans , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Polymorphism, Single Nucleotide/genetics , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Schizophrenia/geneticsABSTRACT
OBJECTIVE: We aimed to review clinical features and biological underpinnings related to neuroprogression in bipolar disorder (BD). Also, we discussed areas of controversy and future research in the field. METHOD: We systematically reviewed the extant literature pertaining to neuroprogression and BD by searching PubMed and EMBASE for articles published up to March 2016. RESULTS: A total of 114 studies were included. Neuroimaging and clinical evidence from cross-sectional and longitudinal studies show that a subset of patients with BD presents a neuroprogressive course with brain changes and unfavorable outcomes. Risk factors associated with these unfavorable outcomes are number of mood episodes, early trauma, and psychiatric and clinical comorbidity. CONCLUSION: Illness trajectories are largely variable, and illness progression is not a general rule in BD. The number of manic episodes seems to be the clinical marker more robustly associated with neuroprogression in BD. However, the majority of the evidence came from cross-sectional studies that are prone to bias. Longitudinal studies may help to identify signatures of neuroprogression and integrate findings from the field of neuroimaging, neurocognition, and biomarkers.