BDNF in schizophrenia, depression and corresponding animal models

Angelucci, Francesco; Brené, Stefan; Mathé, Aleksander A.

doi:10.1038/sj.mp.4001637

Cited by 498 publications

(307 citation statements)

References 118 publications

(153 reference statements)

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“…Likewise, with regard to a possible SLC6A4-BDNF interaction in OCD, comorbidity in particular with major depressive disorder, might also help explain the lack of replication in our study with the previous strong finding of a protective effect of the BDNF Met66 allele in OCD by Hall et al (2003). TheV66M polymorphism has been reported in several studies as significantly associated with different depressive disorders (Angelucci et al, 2005), and well as with schizophrenia (Neves-Pereira et al, 2005), and anorexia nervosa (Ribases et al, 2004).…”

Section: Discussionsupporting

confidence: 39%

A Large Case–Control Study of Common Functional SLC6A4 and BDNF Variants in Obsessive–Compulsive Disorder

Wendland

Kruse

Cromer

et al. 2007

Neuropsychopharmacol

101

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Both serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) genes have shown positive associations with obsessive-compulsive disorder (OCD) and some other psychiatric disorders, but these results have not been consistently replicated. To explore the hypothesis that this variability might result from the effects of differing combinations of overlooked variants within SLC6A4 together with small OCD and control sample sizes, we studied three common functional polymorphisms (5-HTTLPR, STin2, and the newly discovered SNP, rs25531) in the largest sample size of OCD patients (N ¼ 347) and controls (N ¼ 749) ever investigated. During methods development, we found evidence for potential SLC6A4 genotyping problems with earlier methodology, a third possible contributor to variability in earlier studies. A fourth possible explanation might be SLC6A4 Â BDNF interactions, which prompted us to investigate combined genotypes of BDNF V66M with the three SLC6A4 loci. Except for a nominal association with rs25531 alone, which did not survive correction for multiple comparisons, we found no evidence for any of these other variants being associated alone or together with OCD, and we therefore also examined clinical OCD subtypes within the sample to evaluate clinical heterogeneity. Subgroups based on the age of OCD onset, gender, familiality, factor analysis-derived symptom dimensions, or comorbidity with other psychiatric disorders failed to identify SLC6A4-or BDNF-associated phenotypes, with one exception of overall number of comorbid anxiety disorders being significantly associated with 5-HTTLPR/rs25531. We conclude that despite their attractiveness as candidate genes in OCD, our data provide no support for association in this large OCD patient sample and point toward the need to examine other genes as candidates for risk determinants in OCD.

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Section: Discussionsupporting

confidence: 39%

A Large Case–Control Study of Common Functional SLC6A4 and BDNF Variants in Obsessive–Compulsive Disorder

Wendland

Kruse

Cromer

et al. 2007

Neuropsychopharmacol

101

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“…One possible involvement could be through opiate's interference with the neurotrophines (eg, BDNF) supporting neuronal survival (Weickert et al, 2003;Angelucci et al, 2005) with consequential damage of mesolimbic dopaminergic neurons (Sklair-Tavron et al, 1996). Furthermore, similarly to methadone-maintained patients (Willenbring et al, 1989;Zador et al, 1996), exaggerated opioidergic activity could enhance hedonic preference (ie, liking) for sweet and fatty foods (Doyle et al, 1993;Pecina and Berridge, 1995;.…”

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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“…Under baseline conditions, BDNF and its receptor trkB are densely expressed in the hippocampal formation (Conner et al., 1997; Phillips et al., 1991; Quartu et al., 1999, 2013; Webster, Herman, Kleinman, & Weickert, 2006; Yan, Radeke, et al., 1997; Yan, Rosenfeld, et al., 1997), one of the key regions implicated in depression‐linked maladaptive neuronal plasticity (Dias, Banerjee, Duman, & Vaidya, 2003; Malberg, Eisch, Nestler, & Duman, 2000; Vaidya, Siuciak, Du, & Duman, 1999). Accordingly, the hippocampal volume is reduced in patients with post‐traumatic stress disorder (Angelucci, Brene, & Mathe, 2005), and with depression associated with the BDNF Met polymorphism, which is known to be less active than its normal variant (Autry & Monteggia, 2012). The hippocampus is functionally parcelled along its longitudinal septo‐temporal axis into the dorsal and ventral subregions: the dorsal hippocampus is preferentially involved in spatial learning and memory, while the ventral hippocampus plays a central role in the control of the stress response and anxiety (Tanti & Belzung, 2013).…”

Section: Introductionmentioning

confidence: 99%

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

et al. 2017

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IntroductionThe selective breeding of Roman High‐ (RHA) and Low‐Avoidance (RLA) rats for, respectively, rapid versus poor acquisition of the active avoidance response has generated two distinct phenotypes differing in many behavioral traits, including coping strategies to aversive conditions. Thus, RLA rats are considered as a genetic model of vulnerability to stress‐induced depression whereas RHA rats are a model of resilience to that trait. Besides the monoamine hypothesis of depression, there is evidence that alterations in neuronal plasticity in the hippocampus and other brain areas are critically involved in the pathophysiology of mood disorders.Materials and MethodsWestern blot (WB) and immunohistochemistry were used to investigate the basal immunochemical occurrence of brain‐derived neurotrophic factor (BDNF) and its high‐affinity tyrosine‐kinase receptor trkB in the dorsal and ventral hippocampus of adult RHA and RLA rats.Results WB analysis indicated that the optical density of BDNF‐ and trkB‐positive bands in the dorsal hippocampus is, respectively, 48% and 25% lower in RLA versus RHA rats. Densitometric analysis of BDNF‐ and trkB‐like immunoreactivity (LI) in brain sections showed that BDNF‐LI is 24% to 34% lower in the different sectors of the Ammon's horn of RLA versus RHA rats, whereas line‐related differences are observed in the dentate gyrus (DG) only in the ventral hippocampus. As for trkB‐LI, significant differences are observed only in the dorsal hippocampus, where density is 23% lower in the DG of RLA versus RHA rats, while no differences across lines occur in the Ammon's horn.ConclusionThese findings support the hypothesis that a reduced BDNF/trkB signaling in the hippocampus of RLA versus RHA rats may contribute to their more pronounced vulnerability to stress‐induced depression.

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BDNF in schizophrenia, depression and corresponding animal models

Cited by 498 publications

References 118 publications

A Large Case–Control Study of Common Functional SLC6A4 and BDNF Variants in Obsessive–Compulsive Disorder

A Large Case–Control Study of Common Functional SLC6A4 and BDNF Variants in Obsessive–Compulsive Disorder

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

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