Research and treatment approaches to depression

Wong, Ma-Li; Licinio, Júlio

doi:10.1038/35072566

Cited by 558 publications

(331 citation statements)

References 86 publications

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Section: Discussionmentioning

confidence: 99%

“…49,[108][109][110][111][112][113][114][115][116] Recent basic and clinical studies provide evidence for a 'neurotrophin hypothesis' of depression and antidepressive treatments. 111,117,[113][114][115][116] This concept postulates that plasticity-related changes, like hippocampal atrophy in depressed patients, are related to a decreased expression or function of BDNF and/or its high-affinity receptor TrkB. 111,117,[114][115][116]118 These results, together with the antidepressive effects of BDNF in mouse models of depression, 119 and the increased BDNF levels in patients treated with antidepressants, 16 suggest a central role for this neurotrophin and its receptor in the molecular mechanisms of antidepressive therapy.…”

Section: Discussionmentioning

confidence: 99%

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BDNF in schizophrenia, depression and corresponding animal models

2005

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Understanding the etiology and pathogenesis schizophrenia and depression is a major challenge facing psychiatry. One hypothesis is that these disorders are secondary to a malfunction of neurotrophic factors. Inappropriate neurotrophic support during brain development could lead to structural disorganisation in which neuronal networks are established in a nonoptimal manner. Inadequate neurotrophic support in adult individuals could ultimately be an underlying mechanism leading to decreased capacity of brain to adaptive changes and increased vulnerability to neurotoxic damage. Brain-derived neurotrophic factor (BDNF) is a mediator involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system (CNS). In this review, we summarize findings regarding altered BDNF in schizophrenia and depression and animal models, as well as the effects of antipsychotic and antidepressive treatments on the expression of BDNF. Molecular Psychiatry (2005) 10, 345-352.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

BDNF in schizophrenia, depression and corresponding animal models

2005

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“…43 Despite intense studies and the development of various drug therapies, the etiopathogenesis for common human mental disorders such as affective disorders, anxiety and schizophrenia remains poorly understood. 44,45 However, recent clinical observations from patients on IFN-a therapy 10,11 and genetic studies on autoimmune mice 46 suggest a direct link between IFN-a and neuropsychiatric disorders. Therapeutic application of IFN-a presents a wide range of side effects, particularly CNS complications, including depression, anxiety and cognitive abnormalities often leading to the discontinuation of the therapy.…”

Section: Discussionmentioning

confidence: 99%

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

2007

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The prime anti-viral cytokine interferon-a (IFN-a) has been implicated in several central nervous system (CNS) disorders in addition to its beneficial effects. Systemic IFN-a treatment causes severe neuropsychiatric complications in humans, including depression, anxiety and cognitive impairments. While numerous neuromodulatory effects by IFN-a have been described, it remains unresolved whether or not systemic IFN-a acts directly on the brain to execute its CNS actions. In the present study, we have analyzed the genes directly regulated in post-IFN-a receptor signaling and found that intraperitoneal administration of mouse IFN-a, but not human IFN-a, activated expression of several prototypic IFN-stimulated genes (ISGs), in particular signal transducers and activators of transcription (STAT1), IFN-induced 15 kDa protein (ISG15), ubiquitin-specific proteinase 18 (USP18) and guanylate-binding protein 3 (GBP3) in the brain. A similar temporal profile for the regulated expression of these IFN-aactivated ISG genes was observed in the brain compared with the peripheral organs. Dual labeling in situ hybridization combined with immunocytochemical staining demonstrated a wide distribution of the key IFN-regulated gene STAT1 transcripts in the different parenchyma cells of the brain, particularly neurons. The overall response to IFN-a challenge was abolished in STAT1 knockout mice. Together, our results indicate a direct, STAT1-dependent action of systemic IFN-a in the CNS, which may provide the basis for a mechanism in humans for neurological/neuropsychiatric illnesses associated with IFN-a therapy.

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“…Converging evidence suggests that the serotonin system plays a critical role in the pathophysiology of major depression (Wong and Licinio, 2001). During the last decade, genetic variations in the serotonin system have been discovered that might constitute susceptibility factors for the development of depression.…”

Section: Introductionmentioning

confidence: 99%

5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression

Dannlowski

Ohrmann

Bauer

et al. 2007

Neuropsychopharmacol

161

107

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The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. Increased amygdala reactivity has been discussed in the context of major depression. Recent studies reported that amygdala activity during conscious emotion processing is modulated by a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in healthy subjects. In the present study, amygdala reactivity to displays of emotional faces was measured by means of fMRI at 3T in 35 patients with major depression and 32 healthy controls. Conscious awareness of the emotional stimuli was prevented via backward-masking to investigate automatic emotion processing. All subjects were genotyped for the 5-HTTLPR polymorphism. Risk allele carriers (S or L G ) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with life-time psychiatric hospitalization as an index of chronicity. This might indicate that genetic variations of the serotonin transporter could increase the risk for depression chronification via altering limbic neural activity on a preattentive level of emotion processing.

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Research and treatment approaches to depression

Cited by 558 publications

References 86 publications

BDNF in schizophrenia, depression and corresponding animal models

BDNF in schizophrenia, depression and corresponding animal models

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression

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