ReviewOlfaction: A potential cognitive marker of psychiatric disorders
Introduction
About 15% of the global burden of worldwide diseases is attributed to mental disorders (Prince et al., 2007) that are characterized by modified patterns of behaviours, perceptions, cognition, emotions. Depending on their clinical characteristics, psychiatric disorders have various but sometimes severe impact on social skills, relationships, wellbeing, and quality of life. Consequently, they are potentially highly disabling conditions. The understanding of pathophysiological mechanisms of psychiatric disorders is usually addressed at several different levels. Developments in structural and functional neuroimaging techniques have highlighted the potential neuroanatomical substrates of diseases (Abi Dargham et al., 1996, Yatham and Malhi, 2003, Hajek et al., 2005, Campbell and MacQueen, 2006, Gur et al., 2007), while clinically significant impact of drugs modifying neurotransmission gives strong support to the monoamine hypothesis of several psychiatric disorders (Hindmarch, 2002), especially considering psychiatric disorders as the consequences of excess or lack of neurotransmission. Nevertheless, mechanisms of action of psychotropic drugs such as antidepressants or antipsychotics are not fully understood, and it is now widely admitted that apart to enhance or limit neurotransmission, they induce also intracellular effects (Hindmarch, 2002, Yamada and Higuchi, 2002) and that their clinical efficacy can be mediated by neuroplasticity (Malberg et al., 2000, McEwen et al., 2002, Santarelli et al., 2003, Jiang et al., 2005, Yoshimizu and Chaki, 2004). As being a construct of brain activity and related to specific brain areas, cognition has been considered as reflecting cerebral functioning and its modification as a potential mechanism underlying psychiatric disorders. At this time, most of the data on cognitive deficits in psychiatric disorders have focused on memory or executive dysfunctions. This has been particularly well documented in schizophrenia (Dickinson et al., 2004) or in mood disorders (Chamberlain and Sahakian, 2006), in which cognition is also a major therapeutic target (Turkington et al., 2006, Kuyken et al., 2007). In fact cognition gathers a wide range of mental processes like memory, attention, thought process, decision making, language, executive and motor performance. Representations from which action, goal directed behaviour and adaptation to the environment are built, emerge from cognitive activity that roots in sensorial (Mesulam, 1998) and emotional perceptions (Phillips et al., 2003). Until now, researches on cognitive dysfunctions in psychiatric disorders have mainly focused on processes supported by visual or auditory inputs, and less has been done on cognitive functions that are related to olfactory stimuli. Even so, odours have been shown to have a high potential of emotional remembering. This could be explained by the partial overlap of both olfaction and short term memory neuroanatomic substrates (Richardson and Zucco, 1989). Olfactory perception can be experimentally assessed with good reliability by the measurement of several characteristics such as identification of odour, intensity and detection threshold as well as by emotional response (hedonic state) (Alaoui-Ismaili et al., 1997).
Olfactory dysfunction has indeed been investigated in several psychiatric disorders including seasonal affective disorder (Postolache et al., 1999, Postolache et al., 2002), mood disorders (Pause et al., 2001, Gross-Isseroff et al., 1994, Lombion-Pouthier et al., 2006), anorexia nervosa (Kopala et al., 1995c, Fedoroff et al., 1995, Roessner et al., 2005), panic disorder (Kopala and Good, 1996) and psychosis (Corcoran et al., 2005, Hudry et al., 2002, Moberg et al., 2003).
In this paper, the interest of olfaction testing as a potential cognitive marker of psychiatric disorders will be discussed with regard of recent published data, with a particular focus on depression and schizophrenia. Further, in order to assess the specificity of the olfactory markers dysfunction, we will also present research on olfaction alterations in dementia and neurodegenerative disorders that also include cognitive abnormalities. Before detailing these alterations, we will discuss the methods enabling the psychophysical assessment of olfactory perception. As some studies exploring olfactory deficits in psychiatric conditions are based on the assumption that such alterations may be related to the fact that brain areas involved in the processing of olfactory cues partially overlap with the structures having an altered functioning in these pathologies, we will briefly detail the brain circuitry enabling the processing of odours. Then we will describe the alterations observed in schizophrenia, depression and neurodegenerative disease. We will first present data available on schizophrenia, as most studies exploring olfactory deficits in psychiatric conditions examined alterations in this pathology. We will then continue with the studies on olfactory deficits in depression and finish with the studies on neurodegenerative disorders.
Section snippets
Psychophysical assessment of the olfactory perception
Olfactory function has historically been divided into two hierarchical and independent processes, the first being termed as “peripheral” (i.e., acuity or the ability to detect an odour) and the second one being called “central” (i.e., identification, discrimination, memory or the ability to name an odour) (Martzke et al., 1997). Deficits in acuity have been thought to reflect impairment in peripheral processes (defect in processing occurring at the level of the nasal epithelium, e.g.
Brain areas involved in olfaction
In this paper, only process related to functioning of the main olfactory system in humans will be reviewed. Indeed, to our knowledge, no study investigated the alterations of processes related to a dysfunction of the accessory olfactory system in patients suffering from psychiatric conditions or dementia. In the main olfactory system, odour perception results first from the stimulation of olfactory receptors located on specialized neurons (olfactory receptor neurons) from the nasal olfactory
Olfactory alterations in schizophrenia
Because the olfactory system shares a common neural substrate with many of the cognitive and emotion processes that are abnormal in schizophrenia (Turetsky et al., 2003), several authors have used olfactory measures to assess the functional integrity of the brain in patients with schizophrenia. An increasing number of studies have reported evidence that the processing of olfactory information is a cognitive function which is disturbed in patients with schizophrenia (Moberg et al., 1999, Rupp et
Olfactory alterations in depression
Olfactory deficits have been investigated in depression for three main reasons: (a) the olfactory processing at the brain level recruits areas whose functioning is altered in depression (see Table 1), such as the OFC (Drevets, 2007); (b) bilateral olfactory bulbectomy in rodents induces changes in behaviour, as well as in the endocrine, immune and neurotransmitter systems, that are isomorphic to many of those seen in patients with major depression (Song and Leonard, 2005). These alterations are
Olfaction in dementia and other cognitive disorders
A meta-analysis of 43 studies on olfaction in Alzheimer's disease (AD) and Parkinson's disease shows that both identification, recognition and detection threshold are significantly altered in neurodegenerative disorders compared to normal aged controls (Mesholam et al., 1998). Comparing 92 demented patients with 94 control subjects, McShane et al. (2001) have shown that olfactory performances discriminate patients with Senile Dementia of Lewy body type from AD patients (McShane et al., 2001).
Factors, which can influence the olfactory perception
The discrepant results observed in a few studies on olfactory sensitivity in schizophrenia and depression or on identification task in depression can be explained by methodological differences, such as the choice of the evaluation method (methods for odour identification evaluation: UPSIT, ETOC, PST: Pocket Smell test), differences in diagnostic subgroups, differences in odours presentation (unilateral or bilateral), differences in studied odours and differences in subjects. For example, with
General discussion
Taken together, these data indicate that olfactory abnormalities might be a marker of psychiatric conditions, with a specific pattern for each disease. Indeed, no reliable change in odour sensitivity is seen in schizophrenic patients, indicating that these patients show no deficit in the peripheral aspects of odour perception. Thus, no abnormality related to purely sensorial deficits are seen in this pathology. This is not the case of depression, dementia or neurodegenerative disease, as these
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