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Odour recognition memory and odour identification in patients with mild and severe major depressive disorders
Psychiatry Research 190 (2011) 217–220
Contents lists available at SciVerse ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Odour recognition memory and odour identification in patients with mild and severe major depressive disorders Gesualdo M. Zucco ⁎, Fabiola Bollini Department of General Psychology, University of Padova, Via Venezia 8, 35100 Padova, Italy
a r t i c l e
i n f o
Article history: Received 17 May 2011 Received in revised form 17 July 2011 Accepted 30 August 2011 Keywords: Major Depressive Disorder Olfactory identification Olfactory recognition Disease progression
a b s t r a c t Olfactory deficits, in detection, recognition and identification of odorants have been documented in ageing and in several neurodegenerative and psychiatric conditions. However, olfactory abilities in Major Depressive Disorder (MDD) have been less investigated, and available studies have provided inconsistent results. The present study assessed odour recognition memory and odour identification in two groups of 12 mild MDD patients (M age 41.3, range 25–57) and 12 severe MDD patients (M age, 41.9, range 23–58) diagnosed according to DSM-IV criteria and matched for age and gender to 12 healthy normal controls. The suitability of olfactory identification and recognition memory tasks as predictors of the progression of MDD was also addressed. Data analyses revealed that Severe MDD patients performed significantly worse than Mild MDD patients and Normal controls on both tasks, with these last groups not differing significantly from one another. The present outcomes are consistent with previous studies in other domains which have shown reliable, although not conclusive, impairments in cognitive function, including memory, in patients with MDD, and highlight the role of olfactory identification and recognition tasks as an important additional tool to discriminate between patients characterised by different levels of severity of MDD. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Olfactory deficits, in detection, recognition and identification of odorants, have been documented in several neurodegenerative (e.g., Alzheimer's, Parkinson's, Multiple System Atrophy, Korsakov's, Huntington's; see Doty, 2003; Hawkes, 2003; Kovacs, 2004 for reviews) and psychiatric conditions (e.g., Schizophrenia, Anorexia and Bulimia nervosa, Alcoholic/Drug addiction, Major Depression; see, Moberg et al., 1999; Atanasova et al., 2008 for reviews). Olfaction in Major Depressive Disorder (MDD), however, has not often been investigated and available studies have provided inconsistent results. Olfactory thresholds were found to have be increased (LombionPouthier et al., 2006; Pollatos et al., 2007), to be reduced (Postolache et al., 2002,) or to be the same (Thomas et al., 2002) as thresholds in healthy controls; excepting preliminary studies by Moberg et al. (1986), and by Sreenivasan et al. (1987), recognition memory remains uninvestigated, with data suggesting decreased performance (the first, however, on an unspecified odour recognition task, and the second on a matching to sample task); for odour identification some have find no difference between MDD and controls (e.g., Lombion-Pouthier et al., 2006; Pentzek et al., 2007; Swiecicki et
⁎ Corresponding author at: Dipartimento di Psicologia Generale, Via Venezia, 8, 35100 Padova, Italy. Tel.: +39 49 8276678; fax: +39 49 827 6500. E-mail address: [email protected] (G.M. Zucco). 0165-1781/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.08.025
al., 2009), while others have found poorer odour identification ability (Serby et al., 1990). Several factors may account for these inconsistencies between studies, as for example, the severity of the pathology, the medication status, the age of the participants, the task characteristics, and the participants' motivation (see Elliott, 1998; Rose and Ebmeier, 2006), that – if not carefully controlled before investigations – may impact on the experimental outcomes. A further source of variation concerns the homogeneity of the MDD samples (Amsterdam et al., 1987; Kopala et al., 1994; Duff et al., 2002). In the current study we sought to address these limitations, by testing odour recognition memory and odour identification abilities in two groups of unmedicated MDD patients well characterised as to the severity of the pathology and comparable for age to the matched normal controls. According to findings in other domains than olfaction (see, e.g., Cassens et al., 1990; Ravnkilde et al., 2002; Porter et al., 2003), we predicted that the patients would show odour recognition and identification impairment (i.e., high level deficits) as a function of the severity of their disease, with Severe MDD performing worse relative to the Mild MDD and healthy controls. As a further step we aimed at investigating whether olfactory identification and recognition tasks may be an adjunctive clinical tool to discriminate between patients characterised by differing degrees of MDD as possible predictors of disease progression. This is a picture that is well established for several other neurodegenerative and pathological conditions (cf. Moberg et al., 1987; Wenning et al.,
218
G.M. Zucco, F. Bollini / Psychiatry Research 190 (2011) 217–220
1995; Nordin and Murphy, 2002; Doty, 2003; Zucco et al., 2006; Zucco, 2011) where olfactory identification and recognition memory deficits are prominent. 2. Methods 2.1. Participants Two groups of 12 Mild MDD patients aged on average 41.3± (SD) 6.4 years (range, 25–57 years) and 12 Severe MDD patients aged on average 41.9± (SD) 6.2 years (range, 23–58 years), matched for age and gender to 12 Normal Controls aged on average 39.8 ± (SD) 7.1 years (range, 23–53), participated in the study. In all groups both sexes were equally represented. The patients were diagnosed according to DSM-IV (1994) criteria at the Psychiatric Clinic of the University Hospital of Pisa (I) by trained M.D. clinicians using an unstructured interview. They were in good health and free of major medical illness. The patients also had no history of major olfactory pathologies, and they were not taking drugs that may affect olfactory function. Exclusion criteria were related to conditions causing temporary or permanent alterations to the sense of smell (e.g., current allergic rhinitis, polyposis, viral infection, nasal trauma, head injury), neurological disorder that might affect cognitive function, age over 60, drug or alcohol abuse, smoking habits (mainly non-smokers were tested; 1–2 per group were occasional smokers). All the patients were un-medicated at the time of testing. They were well motivated to take part in the test. The 12 healthy volunteers were recruited among the staff personnel. They had neither personal nor family history of psychiatric disorders nor history of major olfactory pathologies. All the participants provided informed consent before their participation in the study. The study was conducted in accordance with the Declaration of Helsinki for experimentation with human subjects.
age and gender of the participants was not included as a variable in the following analyses, since it had no influence on test performance as ascertained by an (unreported) set of prior analyses. As the identification and memory tests were significantly correlated, overall [r (36) = 0.82, P b 0.0001], and within each group [Severe MDD group, r (12) = 0.75, P b 0.005; Mild MDD group, r (12) = 0.69, P b 0.02; Control group, r (12) = 0.60, p b 0.05], they were analysed together to maximise power. The number of correct responses were analysed by a two-way mixed-design analysis of variance (ANOVA), with factors “Groups” (Severe MDD patients vs. Mild MDD patients vs. Controls) and “Tasks” (Recognition vs. Identification). The analysis revealed a significant effect of both factors, Groups: [F (2,33) = 15.89, P b 0.001] and Tasks: [F (1, 33) = 13.64, P b 0.001]. The mean scores and standard deviations for each group in function of the two tasks were as follows: Severe MDD patients (Recognition: M = 7.3, SD = 1.08; Identification: M = 8.21, SD = 1.05); Mild MDD patients (Recognition: M = 8.91, SD = 0.66; Identification: M = 9.33 SD = 0.65); Controls (Recognition: M = 9.33, SD = 0.77; Identification: M = 9.58, SD = 0.51). Pair-wise post-hoc comparison using Tukey's test (P b 0.01) showed for both identification and recognition tasks significantly worse performance in the Severe MDD group compared to both the Mild MDD and the Normal Control groups (these last two did not differ significantly from one another).
2.2. Procedures and materials Participants underwent an odour identification and an odour recognition task of suprathreshold common odorants comparable for subjective intensities, as based on prior laboratory comparisons. Some of the odorants were drawn from household items (e.g., garlic, shoe-polish, coffee), while others were essences and essential oils (Kart laboratories, Lausanne, Switzerland). Ten odorants served as target and 30 as distractors (see Table 1). The odorants were dissolved in mineral oil, in distilled water or neat, and contained in small test glasses (height 15 cm) fitted with rubber lids connected to a cotton swab wrapped around the end of a stick. Test tubes were covered with white paper to prevent participants from having visual cues. Substances were replaced every 48 h, so that their concentration was kept constant. On the recognition task each trial comprised the presentation of a target odorant and a recognition set of four odorants. Each participant smelled for about 4 s the target, randomly chosen from the set of 10. About 3–4 s after that, the participant was presented, one at a time, four test tubes one of which contained the previously sniffed odorant, and he/she was asked to recognise the target. The stimuli added to the target for each recognition trial were the associated distractors (see Table 1). Interstimulus intervals; 6 s induration, between odour presentations were used to avoid carry-over adaptation effects. Between trials a 20–25 s rest was provided. On the identification task the participant had to smell for about 4 s an odorant randomly selected from the set of 10, while the examiner read aloud four alternative verbal labels. Each participant had to identify the correct label for the odorant. During both tasks participants were required to close their eyes. The distance between the stimulus and the subject's nose was kept constant (i.e., the odorants were kept approximately 2 cm in front of both nostrils). The experiment took place in one quiet, well-ventilated room. The order of tasks was counterbalanced among participants. Responses were scored for accuracy. The participants' scores ranged from 0 to 10. Each test procedure lasted about 20 min per participant.
4. Discussion The present study was aimed at assessing odour recognition memory and odour identification in two groups of MDD patients matched for age and gender to a group of healthy normal controls. The two groups of patients were well characterised as to age, severity of depression (mild and severe) and medication status. It has been documented that these factors, if not carefully controlled for, may bias results. We were also interested to address the suitability of olfactory identification and recognition tasks as tools for assessment and diagnosis of MDD and predictors of MDD progression. The data of this study support our hypothesis of a depressionassociated olfactory impairment. Such a deficit appears to depend from the severity of the disease. Indeed, only the Severe MDD group showed impaired performance relative to Mild MDD patients and healthy Normal Controls on both tasks, suggesting that identification and odour memory deficits would emerge when the depressive disorder is already self-evident or at a late stage. Interestingly, all groups performed slightly worse on the recognition task (see Fig. 1); but, while this effect was quite small in the two groups of Mild MDD patients and Normal Controls, it was more accentuated in the Severe MDD group (7.30 versus 8.25). This could suggest that odour memory might be
3. Results
10
Table 1 Odorants used. Targets
Distracters
Aniseed Cinnamon Coffee Garlic Ink Lavender Marsala Liquor Mint Petrol Shoe-polish cream
Anchovy paste Banana Boot grease Camphor Chocolate Clove Denatured alcohol Dish washing liquid Fennel Honey
Jasmine Juniper Lemon Licorice Mustard Onion Oregano Paint Pine Rose
Rum Sulphur Strawberry Tar Tobacco Tomato Turpentine Vanilla Vinegar Violet
9
Mean correct responses (%)
The mean (±95% confidence interval) number of correct recognition and identification scores for each group are depicted in Fig. 1. The
8 7 6
MDD severe
5
MDD mild
4
Controls
3 2 1 0
Recognition
Identification
Fig. 1. Number of correct recognition and identification scores (mean ± 95% confidence interval) for MDD severe, MDD mild, and controls participants.
G.M. Zucco, F. Bollini / Psychiatry Research 190 (2011) 217–220
affected to a larger extent than other olfactory processes (e.g., identification) in severe MDD patients, an outcome that would seem worthy of further investigation. The present results are also consistent with studies in other domains which have revealed reliable, although not conclusive, impairments in cognitive function, including memory in patients with MDD. Ravnkilde et al. (2002), for instance, have shown that depressed patients exhibit widespread deficiencies in verbal shortterm memory, semantic tasks and attention, while a specific impairment of working memory function and attention was observed by Rose and Ebmeier (2006). Visual and verbal memory deficits in depressed people were demonstrated by Cassens et al. (1990), while Porter et al. (2003) found deficits in spatial working memory, in several other verbal and visual memory tasks, and in semantic tasks (see also, Bazin et al., 1994; Isley et al., 1995; Bearden et al., 2006). Although we cannot exclude that our group of Severe MDD patients exhibited impairment in verbal and semantic memory, we suggest that such deficiencies probably could not have affected the patients' olfactory performances. First, the odour identification test was cognitively quite easy to handle as the patients were required to select a label, amongst the four provided to a given odorant. This is clearly less demanding than, e.g., free or serial recall of lists of words, a task not always performed correctly by depressed people. Second, since the stimuli we have used were common, identifiable odorants, we asked both groups of MDD patients to provide a short definition of 20 words, 10 of which were the names of the target odorants, while the others were the names of common objects. All the patients performed this test without difficulty. This suggests that the deficiencies in olfactory identification and memory probably could not be the results of difficulties in the verbal domain but rather in olfaction per se (see, e.g., Møller et al., 2004, who found that when uncommon, unnameable odorants are used, elderly people – whose verbal memory defects are known – may recognise them as well as young people). Therefore, the poor performance exhibited by the group of severe MDD patients is very probably olfactory selective. As to the reasons for the cognitive impairments in depression and mood disorders, a single cause has yet to be identified, although more general biological and/or psychological underlying mechanisms have been suggested. These include volume reductions in sub-cortical and medial temporal regions, abnormal activation in brain regions such as the amygdala, prefrontal and anterior cingulate cortex (these structures are also involved in odour perception and processing), elevated levels of corticosteroids, reduced attention capacity and reduced motivation in testing (see, Soares and Mann, 1997; Pause et al., 2001; Bearden et al., 2006; Rose and Ebmeier, 2006; Pollatos et al., 2007). The odour identification and recognition memory tests used here suggest their suitability for the assessment of specific olfactory deficits in MDD patients, as has been found for several other neurodegenerative and pathological conditions. Accordingly, such tests may represent an important additional tool, in clinical and experimental contexts, to assess the disease progression in patients characterised by differing degrees of MDD. Indeed, the stage in between patients with mild and severe MDD disorders has here emerged to be a crucial cut-off from olfactory normality to pathology. These tests are easy to use, require a short testing time, and can be found in more widespread standardised forms (e.g., UPSIT and Sniffin' Sticks; see, Doty et al., 1984, 1996; Hummel et al., 1997; Zucco, 2011). In conclusion, the present outcomes underline the need to address the clinical dimensions of MDD in the arrangement of the experimental samples. In particular, the severity of the disease, if not carefully taken into account, may significantly affect the likelihood of detecting significant effects. The current findings also indicated the suitability of olfactory identification and recognition memory tasks for the assessment of MDD severity and thus the potential usefulness of incorporating such testing procedures in the routine clinical examination.
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Acknowledgments We would like to thank Professor Remo Job and three anonymous referees for helpful comments on an earlier draft.
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Zucco, G.M., 2011. Olfactory performance assessed via a new odour recognition test. Reliability and normative data. Journal of Cognitive Psychology 23 (1), 1–7. Zucco, G.M., Amodio, P., Gatta, A., 2006. Olfactory deficits in patients affected by minimal hepatic encephalopathy: a pilot study. Chemical Senses 31 (3), 273–278.
Contents lists available at SciVerse ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Odour recognition memory and odour identification in patients with mild and severe major depressive disorders Gesualdo M. Zucco ⁎, Fabiola Bollini Department of General Psychology, University of Padova, Via Venezia 8, 35100 Padova, Italy
a r t i c l e
i n f o
Article history: Received 17 May 2011 Received in revised form 17 July 2011 Accepted 30 August 2011 Keywords: Major Depressive Disorder Olfactory identification Olfactory recognition Disease progression
a b s t r a c t Olfactory deficits, in detection, recognition and identification of odorants have been documented in ageing and in several neurodegenerative and psychiatric conditions. However, olfactory abilities in Major Depressive Disorder (MDD) have been less investigated, and available studies have provided inconsistent results. The present study assessed odour recognition memory and odour identification in two groups of 12 mild MDD patients (M age 41.3, range 25–57) and 12 severe MDD patients (M age, 41.9, range 23–58) diagnosed according to DSM-IV criteria and matched for age and gender to 12 healthy normal controls. The suitability of olfactory identification and recognition memory tasks as predictors of the progression of MDD was also addressed. Data analyses revealed that Severe MDD patients performed significantly worse than Mild MDD patients and Normal controls on both tasks, with these last groups not differing significantly from one another. The present outcomes are consistent with previous studies in other domains which have shown reliable, although not conclusive, impairments in cognitive function, including memory, in patients with MDD, and highlight the role of olfactory identification and recognition tasks as an important additional tool to discriminate between patients characterised by different levels of severity of MDD. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Olfactory deficits, in detection, recognition and identification of odorants, have been documented in several neurodegenerative (e.g., Alzheimer's, Parkinson's, Multiple System Atrophy, Korsakov's, Huntington's; see Doty, 2003; Hawkes, 2003; Kovacs, 2004 for reviews) and psychiatric conditions (e.g., Schizophrenia, Anorexia and Bulimia nervosa, Alcoholic/Drug addiction, Major Depression; see, Moberg et al., 1999; Atanasova et al., 2008 for reviews). Olfaction in Major Depressive Disorder (MDD), however, has not often been investigated and available studies have provided inconsistent results. Olfactory thresholds were found to have be increased (LombionPouthier et al., 2006; Pollatos et al., 2007), to be reduced (Postolache et al., 2002,) or to be the same (Thomas et al., 2002) as thresholds in healthy controls; excepting preliminary studies by Moberg et al. (1986), and by Sreenivasan et al. (1987), recognition memory remains uninvestigated, with data suggesting decreased performance (the first, however, on an unspecified odour recognition task, and the second on a matching to sample task); for odour identification some have find no difference between MDD and controls (e.g., Lombion-Pouthier et al., 2006; Pentzek et al., 2007; Swiecicki et
⁎ Corresponding author at: Dipartimento di Psicologia Generale, Via Venezia, 8, 35100 Padova, Italy. Tel.: +39 49 8276678; fax: +39 49 827 6500. E-mail address: [email protected] (G.M. Zucco). 0165-1781/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.08.025
al., 2009), while others have found poorer odour identification ability (Serby et al., 1990). Several factors may account for these inconsistencies between studies, as for example, the severity of the pathology, the medication status, the age of the participants, the task characteristics, and the participants' motivation (see Elliott, 1998; Rose and Ebmeier, 2006), that – if not carefully controlled before investigations – may impact on the experimental outcomes. A further source of variation concerns the homogeneity of the MDD samples (Amsterdam et al., 1987; Kopala et al., 1994; Duff et al., 2002). In the current study we sought to address these limitations, by testing odour recognition memory and odour identification abilities in two groups of unmedicated MDD patients well characterised as to the severity of the pathology and comparable for age to the matched normal controls. According to findings in other domains than olfaction (see, e.g., Cassens et al., 1990; Ravnkilde et al., 2002; Porter et al., 2003), we predicted that the patients would show odour recognition and identification impairment (i.e., high level deficits) as a function of the severity of their disease, with Severe MDD performing worse relative to the Mild MDD and healthy controls. As a further step we aimed at investigating whether olfactory identification and recognition tasks may be an adjunctive clinical tool to discriminate between patients characterised by differing degrees of MDD as possible predictors of disease progression. This is a picture that is well established for several other neurodegenerative and pathological conditions (cf. Moberg et al., 1987; Wenning et al.,
218
G.M. Zucco, F. Bollini / Psychiatry Research 190 (2011) 217–220
1995; Nordin and Murphy, 2002; Doty, 2003; Zucco et al., 2006; Zucco, 2011) where olfactory identification and recognition memory deficits are prominent. 2. Methods 2.1. Participants Two groups of 12 Mild MDD patients aged on average 41.3± (SD) 6.4 years (range, 25–57 years) and 12 Severe MDD patients aged on average 41.9± (SD) 6.2 years (range, 23–58 years), matched for age and gender to 12 Normal Controls aged on average 39.8 ± (SD) 7.1 years (range, 23–53), participated in the study. In all groups both sexes were equally represented. The patients were diagnosed according to DSM-IV (1994) criteria at the Psychiatric Clinic of the University Hospital of Pisa (I) by trained M.D. clinicians using an unstructured interview. They were in good health and free of major medical illness. The patients also had no history of major olfactory pathologies, and they were not taking drugs that may affect olfactory function. Exclusion criteria were related to conditions causing temporary or permanent alterations to the sense of smell (e.g., current allergic rhinitis, polyposis, viral infection, nasal trauma, head injury), neurological disorder that might affect cognitive function, age over 60, drug or alcohol abuse, smoking habits (mainly non-smokers were tested; 1–2 per group were occasional smokers). All the patients were un-medicated at the time of testing. They were well motivated to take part in the test. The 12 healthy volunteers were recruited among the staff personnel. They had neither personal nor family history of psychiatric disorders nor history of major olfactory pathologies. All the participants provided informed consent before their participation in the study. The study was conducted in accordance with the Declaration of Helsinki for experimentation with human subjects.
age and gender of the participants was not included as a variable in the following analyses, since it had no influence on test performance as ascertained by an (unreported) set of prior analyses. As the identification and memory tests were significantly correlated, overall [r (36) = 0.82, P b 0.0001], and within each group [Severe MDD group, r (12) = 0.75, P b 0.005; Mild MDD group, r (12) = 0.69, P b 0.02; Control group, r (12) = 0.60, p b 0.05], they were analysed together to maximise power. The number of correct responses were analysed by a two-way mixed-design analysis of variance (ANOVA), with factors “Groups” (Severe MDD patients vs. Mild MDD patients vs. Controls) and “Tasks” (Recognition vs. Identification). The analysis revealed a significant effect of both factors, Groups: [F (2,33) = 15.89, P b 0.001] and Tasks: [F (1, 33) = 13.64, P b 0.001]. The mean scores and standard deviations for each group in function of the two tasks were as follows: Severe MDD patients (Recognition: M = 7.3, SD = 1.08; Identification: M = 8.21, SD = 1.05); Mild MDD patients (Recognition: M = 8.91, SD = 0.66; Identification: M = 9.33 SD = 0.65); Controls (Recognition: M = 9.33, SD = 0.77; Identification: M = 9.58, SD = 0.51). Pair-wise post-hoc comparison using Tukey's test (P b 0.01) showed for both identification and recognition tasks significantly worse performance in the Severe MDD group compared to both the Mild MDD and the Normal Control groups (these last two did not differ significantly from one another).
2.2. Procedures and materials Participants underwent an odour identification and an odour recognition task of suprathreshold common odorants comparable for subjective intensities, as based on prior laboratory comparisons. Some of the odorants were drawn from household items (e.g., garlic, shoe-polish, coffee), while others were essences and essential oils (Kart laboratories, Lausanne, Switzerland). Ten odorants served as target and 30 as distractors (see Table 1). The odorants were dissolved in mineral oil, in distilled water or neat, and contained in small test glasses (height 15 cm) fitted with rubber lids connected to a cotton swab wrapped around the end of a stick. Test tubes were covered with white paper to prevent participants from having visual cues. Substances were replaced every 48 h, so that their concentration was kept constant. On the recognition task each trial comprised the presentation of a target odorant and a recognition set of four odorants. Each participant smelled for about 4 s the target, randomly chosen from the set of 10. About 3–4 s after that, the participant was presented, one at a time, four test tubes one of which contained the previously sniffed odorant, and he/she was asked to recognise the target. The stimuli added to the target for each recognition trial were the associated distractors (see Table 1). Interstimulus intervals; 6 s induration, between odour presentations were used to avoid carry-over adaptation effects. Between trials a 20–25 s rest was provided. On the identification task the participant had to smell for about 4 s an odorant randomly selected from the set of 10, while the examiner read aloud four alternative verbal labels. Each participant had to identify the correct label for the odorant. During both tasks participants were required to close their eyes. The distance between the stimulus and the subject's nose was kept constant (i.e., the odorants were kept approximately 2 cm in front of both nostrils). The experiment took place in one quiet, well-ventilated room. The order of tasks was counterbalanced among participants. Responses were scored for accuracy. The participants' scores ranged from 0 to 10. Each test procedure lasted about 20 min per participant.
4. Discussion The present study was aimed at assessing odour recognition memory and odour identification in two groups of MDD patients matched for age and gender to a group of healthy normal controls. The two groups of patients were well characterised as to age, severity of depression (mild and severe) and medication status. It has been documented that these factors, if not carefully controlled for, may bias results. We were also interested to address the suitability of olfactory identification and recognition tasks as tools for assessment and diagnosis of MDD and predictors of MDD progression. The data of this study support our hypothesis of a depressionassociated olfactory impairment. Such a deficit appears to depend from the severity of the disease. Indeed, only the Severe MDD group showed impaired performance relative to Mild MDD patients and healthy Normal Controls on both tasks, suggesting that identification and odour memory deficits would emerge when the depressive disorder is already self-evident or at a late stage. Interestingly, all groups performed slightly worse on the recognition task (see Fig. 1); but, while this effect was quite small in the two groups of Mild MDD patients and Normal Controls, it was more accentuated in the Severe MDD group (7.30 versus 8.25). This could suggest that odour memory might be
3. Results
10
Table 1 Odorants used. Targets
Distracters
Aniseed Cinnamon Coffee Garlic Ink Lavender Marsala Liquor Mint Petrol Shoe-polish cream
Anchovy paste Banana Boot grease Camphor Chocolate Clove Denatured alcohol Dish washing liquid Fennel Honey
Jasmine Juniper Lemon Licorice Mustard Onion Oregano Paint Pine Rose
Rum Sulphur Strawberry Tar Tobacco Tomato Turpentine Vanilla Vinegar Violet
9
Mean correct responses (%)
The mean (±95% confidence interval) number of correct recognition and identification scores for each group are depicted in Fig. 1. The
8 7 6
MDD severe
5
MDD mild
4
Controls
3 2 1 0
Recognition
Identification
Fig. 1. Number of correct recognition and identification scores (mean ± 95% confidence interval) for MDD severe, MDD mild, and controls participants.
G.M. Zucco, F. Bollini / Psychiatry Research 190 (2011) 217–220
affected to a larger extent than other olfactory processes (e.g., identification) in severe MDD patients, an outcome that would seem worthy of further investigation. The present results are also consistent with studies in other domains which have revealed reliable, although not conclusive, impairments in cognitive function, including memory in patients with MDD. Ravnkilde et al. (2002), for instance, have shown that depressed patients exhibit widespread deficiencies in verbal shortterm memory, semantic tasks and attention, while a specific impairment of working memory function and attention was observed by Rose and Ebmeier (2006). Visual and verbal memory deficits in depressed people were demonstrated by Cassens et al. (1990), while Porter et al. (2003) found deficits in spatial working memory, in several other verbal and visual memory tasks, and in semantic tasks (see also, Bazin et al., 1994; Isley et al., 1995; Bearden et al., 2006). Although we cannot exclude that our group of Severe MDD patients exhibited impairment in verbal and semantic memory, we suggest that such deficiencies probably could not have affected the patients' olfactory performances. First, the odour identification test was cognitively quite easy to handle as the patients were required to select a label, amongst the four provided to a given odorant. This is clearly less demanding than, e.g., free or serial recall of lists of words, a task not always performed correctly by depressed people. Second, since the stimuli we have used were common, identifiable odorants, we asked both groups of MDD patients to provide a short definition of 20 words, 10 of which were the names of the target odorants, while the others were the names of common objects. All the patients performed this test without difficulty. This suggests that the deficiencies in olfactory identification and memory probably could not be the results of difficulties in the verbal domain but rather in olfaction per se (see, e.g., Møller et al., 2004, who found that when uncommon, unnameable odorants are used, elderly people – whose verbal memory defects are known – may recognise them as well as young people). Therefore, the poor performance exhibited by the group of severe MDD patients is very probably olfactory selective. As to the reasons for the cognitive impairments in depression and mood disorders, a single cause has yet to be identified, although more general biological and/or psychological underlying mechanisms have been suggested. These include volume reductions in sub-cortical and medial temporal regions, abnormal activation in brain regions such as the amygdala, prefrontal and anterior cingulate cortex (these structures are also involved in odour perception and processing), elevated levels of corticosteroids, reduced attention capacity and reduced motivation in testing (see, Soares and Mann, 1997; Pause et al., 2001; Bearden et al., 2006; Rose and Ebmeier, 2006; Pollatos et al., 2007). The odour identification and recognition memory tests used here suggest their suitability for the assessment of specific olfactory deficits in MDD patients, as has been found for several other neurodegenerative and pathological conditions. Accordingly, such tests may represent an important additional tool, in clinical and experimental contexts, to assess the disease progression in patients characterised by differing degrees of MDD. Indeed, the stage in between patients with mild and severe MDD disorders has here emerged to be a crucial cut-off from olfactory normality to pathology. These tests are easy to use, require a short testing time, and can be found in more widespread standardised forms (e.g., UPSIT and Sniffin' Sticks; see, Doty et al., 1984, 1996; Hummel et al., 1997; Zucco, 2011). In conclusion, the present outcomes underline the need to address the clinical dimensions of MDD in the arrangement of the experimental samples. In particular, the severity of the disease, if not carefully taken into account, may significantly affect the likelihood of detecting significant effects. The current findings also indicated the suitability of olfactory identification and recognition memory tasks for the assessment of MDD severity and thus the potential usefulness of incorporating such testing procedures in the routine clinical examination.
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Acknowledgments We would like to thank Professor Remo Job and three anonymous referees for helpful comments on an earlier draft.
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