Brain-Derived Neurotrophic Factor and Suicide in Schizophrenia: Critical Role of Neuroprotective Mechanisms as an Emerging Hypothesis

Abstract

Suicide is a common occurrence in psychiatric disorders and is a cause of increased healthcare utilization worldwide. Schizophrenia is one of the most common psychiatric disorders worldwide and posited to be seen in 1% of the population worldwide. Suicide is a common occurrence in schizophrenia with 25%–30% patients with schizophrenia attempting suicide and 8%–10% completing it. There is a need for valid biological markers to help clinicians identify patients with schizophrenia that may be at a risk of suicide and thus help in them receiving better care and interventions at the earliest even before a suicide attempt occurring. There are clear neurobiological changes at a genetic, neuroimaging, and neurochemical level that occurs in patients with schizophrenia that attempt suicide. There is a new theory that postulates neuronal plasticity and neuroprotection to have a role in the biological changes that ensue when suicidal thoughts and feelings occur in patients with schizophrenia. Neurotrophic growth factors like brain-derived neurotrophic factor (BDNF) have been documented to play a role in the protection of neurons and in the prevention of neurobiological changes that may lead to suicide both in schizophrenia and depression. The present paper presents a commentary that looks at the role of BDNF as a protective factor and neurobiological marker for suicide in schizophrenia.

A Meta-Analysis of Brain-Derived Neurotrophic Factor Effects on Brain Volume in Schizophrenia: Genotype and Serum Levels

“…It is likely, however, that BDNF works synergistically with other neurotrophins, growth factors, and immune response parameters that have similarly shown associations with frontal and hippocampal volume [68][69][70]. The current meta-analysis adds to existing evidence of the status of BDNF as a biomarker of schizophrenia with multiple pleiotropic effects including the incidence of the illness, predisposing factors, cognitive functions, and clinical status [37,50,[71][72][73][74][75][76][77][78][79][80][81].…”

Circulating Levels of Brain‐Derived Neurotrophic Factor and History of Suicide Attempts in Women

“…In addition, although we were able to rule out a number of potential third variable explanations for the observed group difference, we could not rule out all potential influences. For example, we were unable to account for the potential influence of menstrual cycle or contraception use, as this information was not collected, and previous research has suggested a link between circulating BDNF levels and ovarian function (Pluchino et al, 2009). Moreover, we did not have data for the use of medications, including antidepressants, for all participants and previous research supports the involvement of BDNF in antidepressant response (Bj€ orkholm & Monteggia, 2016;Duman, Heninger, & Nestler, 1997;Duman & Monteggia, 2006;Ghosh, Carnahan, & Greenberg, 1994;Monteggia et al, 2004).…”

“…Altered synaptic plasticity, which results in difficulties adapting to environmental stimuli, may play a role in the development and pathogenesis of suicidal behavior (Altshuler, Casanova, Goldberg, & Kleinman, 1990;Bijttebier et al, 2015;Duman, Malberg, Nakagawa, & D'Sa, 2000;Dwivedi, 2012;Fossati, Radtchenko, & Boyer, 2004;Garcia, 2002;Nagy et al, 2015;Minzenberg, Lesh, Niendam, Cheng, & Carter, 2016;Rajkowska, 1997;Torres-Platas et al, 2011). Given the critical involvement of neurotrophins, including brain-derived neurotrophic factor (BDNF), in neuronal plasticity, functioning, and neurogenesis, a number of studies have examined the association between BDNF and suicidal behavior, with the majority of studies yielding results supporting this association (for reviews, see Dwivedi, 2012;Eisen et al, 2015;Shrivastava, De Sousa, & Rao, 2016). There is also evidence of decreased protein and mRNA expression of BDNF in the prefrontal cortex and the hippocampus of individuals who died by suicide, regardless of depression history (Dwivedi et al, 2003;Karege, Vaudan, Schwald, Perroud, & La Harpe, 2005).…”

The Role of Brain-Derived Neurotrophic Factor in the Pathophysiology of Psychiatric and Neurological Disorders

“…Suicide is a common occurrence in schizophrenia with 25%-30% patients attempting suicide and 8%-10% completing it [53]. A growing number of studies implicate BDNF in the pathogenesis of schizophrenia [54,55], and consider it an important element in the protection of neurons and in the prevention of the neurobiological changes that may lead to suicide in this disorder [56].…”