Olfactory identification deficits in schizophrenia: correlation with duration of illness

Moberg, Paul J.; Doty, Richard L.; Turetsky, Bruce I.; Arnold, Steven E.; Mahr, Richard N.; Gur, Ruben C.; Bilker, Warren B.; Gur, Raquel E.

doi:10.1176/ajp.154.7.1016

Cited by 102 publications

(12 citation statements)

References 10 publications

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“…Several studies over the past two decades have found that patients with schizophrenia have reduced olfactory function (Kopala et al, 1993; Moberg et al, 1997, 1999). Schizophrenia patients have reduced olfactory discrimination ability (Austin et al, 2004; Tueting et al, 2006) and impaired detection of odor dimensionality (Atanasova et al, 2008).…”

Section: Potential Disadvantages Of Adult Neurogenesismentioning

confidence: 99%

The adaptive significance of adult neurogenesis: an integrative approach

Konefal¹,

Elliot²,

Crespi³

2013

Front. Neuroanat.

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Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts.

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Section: Potential Disadvantages Of Adult Neurogenesismentioning

confidence: 99%

The adaptive significance of adult neurogenesis: an integrative approach

Konefal¹,

Elliot²,

Crespi³

2013

Front. Neuroanat.

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“…Individuals with schizophrenia and those at high risk exhibit deficits in multiple domains of olfactory function including deficits in odor identification (Moberg et al, 1997), odor detection threshold sensitivity (Rupp et al, 2005), odor discrimination (Rupp et al, 2005) and odor memory and odor hedonic judgments (Moberg et al, 2014; Moberg and Turetsky, 2003; Nguyen et al, 2011; Turetsky et al, 2009; Turetsky et al, 2003b). Interestingly, a lesser degree of olfactory dysfunction also may be found among patients’ family members (Moberg et al, 2014) but see (Compton and Chien, 2008; Kamath et al, 2013), suggesting a heritability of this phenotype.…”

Section: Introductionmentioning

confidence: 99%

Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia

Egbujo

Sinclair

Borgmann‐Winter

et al. 2015

Schizophrenia Research

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Multiple lines of evidence suggest altered synaptic plasticity/connectivity as a pathophysiologic mechanism for various symptom domains of schizophrenia. Olfactory dysfunction, an endophenotype of schizophrenia, reflects altered activity of the olfactory circuitry, which conveys signals from olfactory receptor neurons to the olfactory cortex via synaptic connections in the glomeruli of the olfactory bulb. The olfactory system begins with intranasal olfactory receptor neuron axons synapsing with mitral and tufted cells in the glomeruli of the olfactory bulb, which then convey signals directly to the olfactory cortex. We hypothesized that olfactory dysfunction in schizophrenia is associated with dysregulation of synaptic efficacy in the glomeruli of the olfactory bulb. To test this, we employed semi-quantitative immunohistochemistry to examine the olfactory bulbs of 13 postmortem samples from schizophrenia and their matched control pairs for glomerular expression of 5 pre- and postsynaptic proteins that are involved in the integrity and function of synapses. In the glomeruli of schizophrenia cases compared to their matched controls, we found significant decreases in three presynaptic proteins which play crucial roles in vesicular glutamate transport- synapsin IIa (−18.05%, p= 0.019), synaptophysin (−24.08% p=0.0016) and SNAP-25 (−23.9%, p=0.046). Two postsynaptic proteins important for spine formation and glutamatergic signaling were also decreased- spinophilin (−17.40%, p=0.042) and PSD-95 (−34.06%, p=0.015). These findings provide molecular evidence for decreased efficacy of synapses within the olfactory bulb, which may represent a synaptic mechanism underlying olfactory dysfunction in schizophrenia.

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“…Using the University of Pennsylvania Smell Identification Test (UPSIT) (Doty et al, 1984), Moberg et al (1999) report that up to 80% of people with SZ have deficits in odor identification compared to 15% of the general population. The deficits are present early in the disorder and correlate with the duration of the disorder (Moberg et al, 1997; Ugur et al, 2005) apart from aging effects (Kopala et al, 1995). Further findings suggesting that deficits in odor identification might constitute an endophenotype for SZ are that deficits in odor identification are not associated with gender, or state measures such as medication use, smoking, olfactory hallucinations, or clinical symptoms at the onset of illness (Kopala et al, 1989; Kopala et al, 1994; Brewer et al, 2001, 2003; Malaspina and Coleman, 2003; Corcoran et al, 2005; Rupp et al, 2005; Roalf et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: Results from a randomized double blind placebo controlled pilot study

Lee

Wehring

McMahon

et al. 2013

Schizophrenia Research

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Background Deficits in olfactory identification have been widely reported in patients with schizophrenia (SZ) and are associated with negative symptomatology. Adjunctive oxytocin delivered intranasally has been shown to improve some aspects of social cognition as well as positive and negative symptoms in patients with schizophrenia. Given the intranasal delivery route of oxytocin to olfactory pathways and that olfactory abnormalities are a potential endophenotype in SZ, we investigated the effect of intranasal oxytocin on olfactory identification as well as positive and negative symptoms in people with schizophrenia. Methods Individuals with schizophrenia or schizoaffective disorder (n=28; 16 outpatients, 12 inpatients) were randomized to receive adjunctive intranasal oxytocin 20 IU BID or placebo for 3 weeks. Results All 28 participants completed the clinical trial. Odor identification performance significantly improved on the University of Pennsylvania Smell Identification Test (UPSIT) total score and subscore for pleasant smells. UPSIT score (F=5.20, df=1,23, p=0.032) and subscore for pleasant smells (F=4.56, df=1,23, p=0.044), in patients treated with oxytocin were compared to placebo from baseline to endpoint. Global symptomatology as well as positive and negative symptoms were not improved by intranasal oxytocin. In fact, global symptoms, not positive or negative symptoms, improved in the placebo group. Secondary analysis shows that intranasal oxytocin improved negative symptoms in the small group of inpatients. Intranasal oxytocin was well tolerated during the three week trial. Conclusion Adjunctive intranasal oxytocin may improve olfactory identification, particularly in items of positive valence. Larger studies are needed to determine the effects of oxytocin on negative symptoms in SZ.

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Olfactory identification deficits in schizophrenia: correlation with duration of illness

Cited by 102 publications

References 10 publications

The adaptive significance of adult neurogenesis: an integrative approach

The adaptive significance of adult neurogenesis: an integrative approach

Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia

Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: Results from a randomized double blind placebo controlled pilot study

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