Olfaction and Social Drive in Schizophrenia

Malaspina, Dolores; Coleman, Eliza

doi:10.1001/archpsyc.60.6.578

Cited by 91 publications

(72 citation statements)

References 36 publications

(35 reference statements)

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“…With this mouse, it is possible to identify endophenotypes for disease processes in a substantially more controlled manner than is possible in human subject research. Second, olfactory discrimination deficits have been consistently observed in the progression of certain neuropsychiatric disorders (Mesholam et al, 1998;Malaspina and Coleman, 2003), and are considered as potential behavioral endophenotypes for these disorders. However, the mechanisms underlying the observed olfactory deficits are unknown.…”

Section: Discussionmentioning

confidence: 99%

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

Bath¹,

Mandairon²,

Jing³

et al. 2008

J. Neurosci.

145

173

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Neurogenesis, the division, migration, and differentiation of new neurons, occurs throughout life. Brain derived neurotrophic factor (BDNF) has been identified as a potential signaling molecule regulating neurogenesis in the subventricular zone (SVZ), but its functional consequences in vivo have not been well defined. We report marked and unexpected deficits in survival but not proliferation of newly born cells of adult knock-in mice containing a variant form of BDNF [a valine (Val) to methionine (Met) substitution at position 66 in the prodomain of BDNF (Val66Met)], a genetic mutation shown to lead to a selective impairment in activity-dependent BDNF secretion. Utilizing knock-out mouse lines, we identified BDNF and tyrosine receptor kinase B (TrkB) as the critical molecules for the observed impairments in neurogenesis, with p75 knock-out mice showing no effect on cell proliferation or survival. We then localized the activated form of TrkB to a discrete population of cells, type A migrating neuroblasts, and demonstrate a decrease in TrkB phosphorylation in the SVZ of Val66Met mutant mice. With these findings, we identify TrkB signaling, potentially through activity dependent release of BDNF, as a critical step in the survival of migrating neuroblasts. Utilizing a behavioral task shown to be sensitive to disruptions in olfactory bulb neurogenesis, we identified specific impairments in spontaneous olfactory discrimination, but not general olfactory sensitivity or habituation to olfactory stimuli in BDNF mutant mice. Through these observations, we have identified novel links between genetic variant BDNF and adult neurogenesis in vivo, which may contribute to significant impairments in olfactory function.

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Section: Discussionmentioning

confidence: 99%

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

Bath¹,

Mandairon²,

Jing³

et al. 2008

J. Neurosci.

145

173

View full text Add to dashboard Cite

show abstract

“…Thus, disruptions in the olfactory nucleus could conceivable affect these brain areas to produce more widespread alterations in perception and affect. Interestingly, in schizophrenic patients there is considerable evidence of impaired olfaction (Kopala et al, 1993;Moberg et al, 1999;Malaspina and Coleman, 2003), as well as, reduction in the size of the olfactory bulb (Turetsky et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Doat-Meyerhoefer

Hard

Winter

et al. 2005

Pharmacology Biochemistry and Behavior

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Activation of 5-HT 2A receptors has been shown to be an essential component of the discriminative stimulus effects of indoleamine and phenethylamine hallucinogens. The objective of the present study was to determine the neuroanatomical location of the 5HT 2A receptors which may be responsible for the stimulus effects of the phenethylamine hallucinogen [−]2,5-dimethoxy-4-methylamphetamine (DOM). It was hypothesized that brain areas containing altered 5-HT 2A receptor expression in the context of a similar alteration in DOM-induced stimulus control might be important in mediating the stimulus effects of DOM. Fisher 344 rats were treated with either clozapine (25 mg/kg/day) or DOM (2 mg/kg/day) for 7 days, and the consequences of these drug treatment regimens on DOM-induced stimulus control and on 5-HT 2A receptor expression in several brain areas were determined. Chronic administration of clozapine was associated with a wide-spread decrease in levels of 5-HT 2A/2C receptors. Conversely, treatment with DOM had varied effects including a neuroanatomically selective decrease in 5-HT 2A/2C receptors levels that was restricted to the olfactory nucleus. Both chronic treatment with DOM and clozapine decreased the stimulus effects of DOM. The present findings suggest a role for the olfactory nucleus in producing the stimulus effects of DOM.

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“…CrespoFacorro and colleagues 17 found individuals with schizophrenia to demonstrate impairment in apprecia tion of both positive and negative olfactory hedonic ex tremes, with evidence of accompanying neural circuitry dys function, and smell identification deficits have also been linked to diminished social drive in this population. 18 Good and colleagues 19 proposed smell identification test (SIT) per formance in patients with early psychosis as a prospective marker for an illness course characterized by negative and cognitive/disorganized symptoms for those with lower scores versus anxiety/depressive symptoms for those with better scores. This suggests that brain impairments associated with SIT deficits are distinct from those producing anxiety/ depression and that individuals with psychosis may have a course impacted by one of the singular symptom domains.…”

Section: J Psychiatry Neurosci 2015;40(6)mentioning

confidence: 99%

Olfactory performance segregates effects of anhedonia and anxiety on social function in patients with schizophrenia

Cieslak

Walsh‐Messinger

Stanford

et al. 2015

J Psychiatry Neurosci

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Olfaction and Social Drive in Schizophrenia

Cited by 91 publications

References 36 publications

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Olfactory performance segregates effects of anhedonia and anxiety on social function in patients with schizophrenia

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