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Suicidal behavior in depressive disorder: An event-related potential study
Suicidal Behavior in Depressive Disorder: An EventRelated Potential Study Michel Hansenne, William Pitchot, Antonio Gonzalez Moreno, Immacula Urcelay Zaldua, and Marc Ansseau
P300 and contingent negative variation (CNV) were recorded in depressive inpatients with and without history of suicide attempt. The results showed a significant reduction of P200, P300, and CNV and a significant increase of postimperative negative variation (PINV) in patients who had attempted suicide compared to patients with a negative history. Moreover, P300 amplitude was negatively related with the Suicidal Risk and the Hopelessness but not with the Hamilton scales. These results stress the need to differentiate clinical subgroups of patients to assess the psychophysiology of depression, and indicate that patients who attempted suicide exhibit lower cortical resources and poorer cortical performance than patients without history of suicide attempt.
Key Words: P300, contingent negative variation, hopelessness, helplessness, depression, suicide BIoL PS¥CrtIATR¥ 1996;40:116--122
Introduction Contingent negative variation (CNV) and P300 are two well-known event-related potentials (ERPs) that have been widely applied in the psychiatric field (Roth et al 1986; Polich 1992). Several lines of evidence suggest that CNV is constituted by two different components. The first, or early CNV, is related to the orienting response and exhibit a rapid habituation. The second component, or late CNV, has been associated with motor preparation and stimulus anticipation (Rohrbaugh and Gaillard 1983; Brunia 1988). The overall amplitude of the CNV has been related to arousal, attention, and motivation (Tecce 1972). On the From the Psychiatric Unit, CHU Andr6 Vrsale, Montigny-Le-Tilleul, Belgium (MH, IUZ) and Psychiatric Unit, CHU du Sart-Tilman, Liege, Belgium (MH, WP, AGM, MA). Address reprint requests to Michel Hansenne, B.Sc., Psychiatric Unit, CHU du Sart-Tilman, B35, B-4000 Lirge, Belgium. Received September 28, 1994; revised July 11, 1995.
© 1996 Society of Biological Psychiatry
other hand, the variables that modulate the P300 amplitude have been described in a triarchic model (Johnson 1986, 1993), including the subjective probabilities of stimuli, their meaning, and the amount of information delivered. CNV and P300 abnormalities have been reported in several psychiatric disorders, especially in dementia, schizophrenia, and depression (Pfefferbaum et al 1984; Roth et al 1986; Blackwood et al 1987), and more recently in antisocial behavior (Raine and Venables 1987), personality disorder (Kutcher et al 1989), obsessive-compulsive disorder (Towey et al 1990) and posttraumatic stress disorder (McFarlane et al 1993). Concerning depressive disorders, abnormalities of CNV amplitude and duration, as well as reduced P300 amplitude and longer latency, have been reported with some controversies (Levit et al 1973; Roth et al 1986; Thier et al 1986; E1 Massioui and Lesevre 1988). Moreover, the decrease in CNV amplitude has been related to the severity of depres0006-3223/96/$15.00 SSDI 0006-3223(95)00372-N
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sive symptoms (Papart et al 1991) and to central catecholaminergic deficit (Timsit-Berthier 1991). However, the heterogeneity of the samples of depressed patients in these prior studies may have obscured effects that could be specific to only a subgroup of patients and therefore be responsible for the controversial results. Some studies recently reported differences in P300 according to clinical subgroups of depression. Bruder et al (1991) compared a control group with 27 depressed patients in two subgroups: the first with typical depression (melancholic or simple mood reactive depression) and the other with atypical depression (reactivity of mood with preserved pleasure capacity). They found that typical depressive patients exhibited longer P300 latency than controls, whereas atypical depressive patients did not differ. Moreover, longer P300 latency exhibited by the typical group was associated with the rating of insomniac complaints but not with the overall severity of depression as indexed by total scores on the Hamilton scale. In a more recent study (Santosh et al 1994), psychotic depression was associated with a decrease of P300 amplitude as compared to nonpsychotic depression, whereas the mean scores on the Hamilton scale (excluding paranoid features) did not differ between the two groups. In the same direction, our group showed recently a significant reduction of both P300 and CNV amplitudes in patients who had attempted suicide compared with patients who had not. Moreover, a significant correlation was found between the Suicidal Risk scale and P300 amplitude (Hansenne et al 1994). In this study, we postulated that the reduction of cortical activity reported in the suicide attempters group could reflect the concepts of helplessness and hopelessness described in depression and more particularly in relation to suicidal behavior (Seligman 1974; Beck 1986). Ashton et al (1994) had also reported a reduction of CNV in patients who had attempted suicide, with a more marked phenomenon in the subgroup with multiple attempt. Moreover, they found significant relationships between both N100 and P200 components of the auditory evoked potential and measures of suicide intent as assessed by the suicidal items of Montgomery-Asberg Depression Rating Scale (MADSR) in patients with a history of suicide attempts. An earlier study IYom the same group had already demonstrated a relationship between N100 reduction and recent suicide attempts in three depressed patients (Ashton et al 1988). Therefore, the aim of this present study was twofold: first, to replicate our previous findings and those of Ashton et al (1994) in another sample of depressive patients with and without history of suicide attempt and, second, to assess the possible contribution of the hopelessness dimension to these results.
Methods
Subjects The study was conducted in 10 depressive inpatients following a suicide attempt by drug overdose without major medical complications (Psychiatric Unit of the University Hospital Andr6 V6sale, Montigny-le-Tilleul, Belgium). The sample was comprised of six men and four women with a mean age of 43.2 years (_+7.6 years). The patients were matched for age and gender with 10 depressive inpatients without a history of suicide attempts (mean age of 44.1, -+ 7.8 years). All diagnostic assessments of the patients were performed by the same psychiatrist (IUZ). All patients met the criteria for DSM-III-R major depressive disorder (APA 1987). The severity of depression was assessed by the same psychologist (MH) using the Hamilton depression scale. The depressed patients included in our study had at least a score of 18 on the 17-item Hamilton depression scale. The patients were free of medical illness, evidenced by clinical examination, history, electrocardiogram (ECG), electroencephalogram (EEG), chest x-ray, and routine laboratory tests. The control group was 20 nurses recruited from hospital staff, who were not familiar with psychophysiological techniques. The control group was matched for gender, but not for education level or age (36.2 _+ 10.4 years). However, the difference with the patient group was not significant (F = 2.5, p = 0.38). Moreover, all control subjects presented a score lower than 6 on the 17-item Hamilton depression scale.
Psychological Assessment Past history of suicide attempts was assessed by the suicidal risk scale (Plutchick et al 1989) and hopelessness by the Hopelessness scale (Beck et al 1985).
Event-Related Potential Recording Psychophysiological recording was conducted at the end of a drug-free period of at least 1 week for all the patients. For the suicidal attempt group, the recording was sometimes delayed until 3 weeks after the attempt, depending on the need to use minor tranquilizers during the first days of the hospitalization. The subjects were sitting in a sound-attenuated room. For the P300 paradigm, the subjects were tested until a total of 100 trials was obtained after rejecting trials for eye movement or other artifacts. The auditory stimuli were presented with a variable interstimuli interval between 2 and 4 sec. P300 trials contaminated by blinks or large amplitude eye movements were automatically excluded by using a 50 o~V rejection criterion. Smaller eye movements were rejected trial-per-
1 18
BIOL PSYCHIATRY 1996;40:116-122
trial by visual inspection of the electrooculogram (EOG). A similar number of rare trial were rejected among the three groups. According to the classic oddball paradigm, 85% of the stimuli (frequent) were tones of 2000 Hz, 75 dB, and 50 msec duration. The other 15% (rare) were tones of 1000 Hz, 75 dB, and 50 msec duration. A sequence of 100 artefact-free trials contained 16 rare stimulations. The subjects were asked to press a button for the rare stimuli. All the subjects and patients successfully completed the discrimination task. N100, P200, and P300 amplitudes were measured as the difference in voltage between the baseline and the higher point between, respectively, 80 and 140 msec, 160 and 220 msec, and 250 and 650 msec after the stimulus onset. The CNV paradigm consisted of a simple reaction time preceded by a warning stimulus 1 s earlier. The warning stimulus was a tone of 1000 Hz, 75 dB, and 50 msec duration, and the imperative stimuli was a tone of 1000 Hz, 75 dB, stopped by the motor response (reaction time). The intertrial interval was randomized from 5 to 10 sec. The CNV was obtained from 32 artefact-free trials as inspected visually trial-per-trial by EOG tracing. CNV amplitude was measured as the voltage difference between the baseline and the average of the 200 msec preceding the imperative stimulus. PINV amplitude was measured as the voltage difference between the baseline and the average of the 200 ms period from 500 to 700 msec after the imperative stimuli. The EEG was recorded using silver-silver chloride disc electrodes attached with collodion at Cz, using the left earlobe for reference and fight forehead for ground. All sites were cleaned with acetone and abraded to maintain resistance below 3 Kohms. EOG was recorded from above the left eye. Amplifier gains were set at 10,000, with a band pass of 0.05-50 Hz, and digitized at 250 samples/sec for 3000 msec epochs (of which the first 1000 msec were prestimulus activities).
M. H a n s e n n e et al
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Figure 1. Grand mean ERP waveforms and EOG from midline Cz electrode for depressed patients with past history of suicide attempt (lower traces), depressed patients without past history of suicide attempt (median traces), and control group (upper traces).
Statistical Analysis All the analyses were performed using Statgraphics (STSC Inc., 1988). Group differences were assessed by one-way analysis of variance, and the relationships between psychophysiological and clinical data by Pearson correlation coefficients. Paired Student's t-tests were used for subgroup comparisons.
Results Figure 1 shows the grand mean ERPs for each group recorded at Cz. The mean results and standard deviations for each component are presented in Table 1. Baseline to peak measures showed significant difference among
groups for P300 amplitude (F = 14.98, p < 0.001). Moreover, post hoc comparisons indicated that depressed patients with suicide attempts exhibited a lower P300 amplitude than controls (t = 4.87, p < 0.001) and depressed patients with a negative history (t = 6.42, p < 0.0001), whereas depressed patients without suicide attempts did not differ from normal controls (t = 0.4, p = 0.68). However, no differences were present for P300 latency (F = 0.85, p = 0.14). Reaction times were increased in the two clinical groups compared to control (F = 8.8, p < 0.01), but did not differ between them (t = 0.98, p = 0.1). Mean N100 amplitude but not latency was significantly
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119
Table 1. Mean Results, Standard Deviations, and Statistical Values for the Amplitude of Each Component in the Three Groups
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-18.5 --- 4.2" 12.8 ± 3.7 16.8 ± 8.1 -25.3 __+-4.8e
11.53 8.3 28.8 14.98
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different among the three groups ( F = 11.53, p < 0.0001, and F = 0.54, p = 0.25, respectively). Table 1 shows that the control group exhibited a significantly higher N100 compared to depressed patients with (t = 4.06, p < 0.001) or without (t = 3.44, p < 0.001) suicide attempts, whereas no difference existed between the two clinical subgroups (t = 0.81, p = 0.42). Again, mean P200 amplitude but not latency was significantly different between the three groups ( F = 8.3, p < 0.001, and F = 0.68, p = 0.36, respectively). Table 1 shows that depressed patients with history of suicide attempts exhibited significant lower P200 amplitude compared to patients with negative history (t = 3.4, p < 0.001) and controls (t = 3.9, p < 0.0001), whereas the last two groups did not differ (t = 1.17, p = 0.25). Figure 2 shows the grand mean CNV in the three groups. The results are presented in Table 1. Significant differences appears among the groups ( F = 28.8, p < 0.001). Post hoc comparisons indicated differences between controls and depressed patients with (t = 7.6, p < 0.001) and without (t = 4.3, p < 0.001) history of suicide attempts, as well as a difference between the two clinical groups (t = 2.4, p = 0.025). As shown in Figure 2, depressed patients with a positive history exhibited a significant Post Imperative Negative Variation (PINV) compared to patients with a negative history (t = 4.49, p < 0.001) and controls (t = 2.76, p < 0.01). Reaction times were increased in the two clinical groups compared to controls ( F = 6.5, p < 0.01) but did not differ between them (t = 1.54, p = 0.2). Mean scores of the Hopelessness ( F = 72.42, p < 0.0001), Suicidal Risk ( F = 241, p < 0.0001), and Hamilton ( F = 808, p < 0.0001) scales significantly differ among the groups. Post hoc comparisons showed higher scores on the Hopelessness (t = 3.8, p < 0.001) and the Suicidal Risk (t = 3.2, p < 0.001), but not for the Hamilton (t = 1.16, p -- 0.26), scales in depressed patients with a positive history compared to patients with a negative history.
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Figure 2. Grand mean CNV waveforms and EOG from midline Cz electrode for depressed patients with past history of suicide attempt (lower traces), depressed patients without past history of suicide attempt (median traces), and control group (upper traces).
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Among the whole group of depressed patients, significant negative correlations existed between P300 amplitude and Suicidal Risk scale on the one hand (r = -0.65, p = 0.002) and Hopelessness scale on the other hand (r = -0.81, p < 0.001) but not with the Hamilton scale (r = -0.15, p = 0.5). Concerning CNV, no relationships reached the level of significance (r = 0.41, p = 0.07 for the Suicidal Risk scale; r = 0.43, p = 0.06 for the Hopelessness scale; and r = 0.41, p = 0.07 for the Hamilton scale). No significant correlations existed between both N100 and P200 and the three clinical rating scales.
Discussion The present study confirms the significant reduction of P300 amplitude in depressive patients who had attempted suicide compared with those without suicidal history reported by our group in a previous sample (Hansenne et al 1994). Moreover, P300 amplitude is negatively related with the Hopelessness and the Suicidal Risk scales, and P200 amplitude were reduced in patients with a history of suicide attempts. In contrast, P300 latency and the reaction time do not differentiate the two clinical subgroups. Our study likewise confirms the significant reduction of CNV amplitude in depressed patients with a history of suicide attempts compared to depressed patients with a negative history of suicide attempts. In addition to our preliminary report, the present study shows a increased PINV in depressed patients with a history of suicide attempts. However, the results of the present study should be taken with caution since they used only one channel of recording (Cz). Event-related potentials have been related with many psychological variables. More particularly, CNV amplitude has been associated with attention, arousal, motor preparation, time estimation, and cognitive processes (Tecce 1972; Macar 1985), and the variables affecting P300 amplitude have been integrated in a model including stimulus probability, stimulus meaning, and the information delivered by the stimulus (Johnson 1986, 1993). Moreover, P300 latency is correlated with the stimulus evaluation processes (Donchin et al 1986). Recent information processing theories have described both energetic and computational mechanisms. A model providing a synthesis from these different theories has been proposed as an integrative model (Rockstroh et al 1982; Birbaumer et al 1990). This model combines two concepts: cerebral potentiality (negative cortical waves) and cerebral performance (positive cortical waves). Cerebral potentiality refers to the psychophysiological state necessary for any cerebral processes, and cerebral performance covers the input, decoding, storage, and output of information processing. In other words, cerebral potenti-
M. H a n s e n n e et al
ality represents the energetic mechanisms of information processing and cerebral performance the computational ones. According to this integrative model, CNV amplitude represents the cerebral potentiality, and its resolution cerebral performance. Then, a reduced CNV amplitude represents a lower cerebral potentiality in the anticipation task, and a delayed CNV resolution (PINV) suggests a difficulty in reducing the cortical activity for producing an optimal response. Therefore, our results suggest that patients with a history of suicide attempts present a lower cerebral potentiality reflected by lower CNV (or lower energetical resources) and lower cerebral performance reflected by the PINV than patients without previous suicidal attempts. According to the integrative model described before, P300 amplitude has also been associated with cerebral performance, and more particularly with memory processes. The cognitive disturbances described in depression (negative view of the self, the world, and the future) (Beck 1976) normally involve a perturbation of information processing. Our results show that disturbances of cerebral performance are more severe in patients with suicidal attempts. However, the lack of a difference between reaction time or P300 latency between suicidal and nonsuicidal groups does not support our interpretation in terms of a "cortical performance" deficit. A possible explanation for our findings is that suicidal behavior appears in patients with fewer resources to cope with the environment, as indicated by less cerebral potentiality and poor cerebral performance. These alterations of cerebral potentiality and cerebral performance could reflect the concepts of helplessness and hopelessness described in depression (Seligman 1974; Beck 1986). Hopelessness refers to the state that occurs when the individual expects that his or her response leads to negative outcomes, and helplessness exists when he or she does not expect any relationship between responses and results. Both mechanisms represent a noncoping response, and a disturbance of information processing. For Beck (1986), hopelessness is a key psychological factor in suicidal behaviors. He reported that among hospitalized patients, hopelessness was a significant predictor of the severity of suicidal attempts, as well as the extent of suicidal ideation or risk. The relationship between the hopelessness and suicidal risk scores among our sample confirms this point. The present findings show a significant negative relationship between P300 amplitude and both the Hopelessness and Suicidal Risk scores. Similar results had been reported by Bachneff and Engelsmann (1980), who showed a relationship between CNV amplitude and hopelessness and suicidal thoughts as assessed by the Present State Examination. They interpreted these results as a
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consequence of a decreased attention to the imperative stimuli ($2), resulting from the self-absorption and preoccupations of depressed patients with suicidal intent. From a theoretical point of view, P300 amplitude has been related to some psychological variables in normal subjects (Johnson 1986). However, P300 amplitude has never been associated with affective states in depressive disorders. In this study, hopelessness and suicidal risk scores significantly modulate P300 amplitude. These results suggest that, in addition to computational mechanisms, affective states play an important role in P300 amplitude. An association between both the N100 and P200 components of the auditory evoked potential and suicidal intent was first described by Ashton et al (1988), and confirmed recently by the same group (Ashton et al 1994). Our data do not replicate these findings. However, we found a significant decrease of P200 but not N100 in depressed patients with a history of suicide attempts compared to those who did not. One possible reason for this discrepancy may be the difference in the protocol used. Indeed, simple auditory evoked potentials were used by Ashton et al (1988, 1994), although we had used an oddball paradigm. From a psychopharmacological point of view, a large body of findings show that dopaminergic function is impaired in depressive patients with previous suicide attempts (Roy et al 1988, 1992; Roy and Pollack 1994; Agren 1980). Recently, our group reported a lower growth
hormone (GH) response to apomorphine in patients with suicide attempts than in patients without suicidal history (Pitchot et al 1992). On the other hand, the dopamine systems modulate P300 and CNV amplitude (TimsitBerthier 1991; Callaway 1991). For example, dopaminergic agonists such as methylphenidate enhance P300 amplitude in hyperkinetic children and normal subjects (Klormann and Brumaghin 1991), whereas dopaminergic antagonists such as flupentixol reduced P300 amplitude in normal subjects (R6sler et al 1985). Moreover, a recent study by our group (Hansenne et al 1995) showed a significant relationship between P300 amplitude and growth hormone response to apomorphine among depressed patients. In the same manner, CNV amplitude is modulated by dopaminergic agents (Tecce 1991), and correlated with GH response to apomorphine, a dopaminergic agonist (Timsit-Berthier et al 1987). Therefore, the reduction of P300 and CNV amplitudes could reflect the dopaminergic dysfunction linked to suicidal behavior in depression. The major findings of this study are the differences in both CNV and P300 amplitudes in relation to suicidal behavior in depressive patients. Moreover, P300 amplitude appears to be related to the suicidal risk and the hopelessness features of depression but not with the intensity of depression. These results stress the need to differentiate clinical subgroups of patients to assess the psychophysiology of depression.
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E1 Massioui F, Les~vre N (1988): Psychomotor retardation in depressed patients: an event-related study. Neurophysiol Clin 70:46 -55. Hansenne M, Pitchot W, Gonzalez-Moreno A, Gonzalez-Torrecilas J, Mirel J, Ansseau M (1994): Psychophysiological correlates of suicidal behavior in depression: Preliminary results. Neuropsychobiology 30:1-3. Hansenne M, Pitchot W, Gonzalez-Moreno A, Papart P, TimsitBerthier M, Ansseau M (1995): Catecholaminergic functions and P300 amplitude in depressed patients. Electroencephalogr Clin J 96:194-196. Johnson R (1986): A triarchic model of P300 amplitude. Psychophysiology 23:367-384. Johnson R (1993): On the neural generators of the P300 component of the event-related potential. Psychophysiology 30:90-97. Klorman R, Brumaghim JT (1991): Stimulant drugs and ERPs. In Brunia CHM, Mulder G, Verbaten MN (eds): EventRelated Brain Research, EEG suppl. 42. Amsterdam: Elsevier, pp 135-141. Kutcher SP, Blackwood DHR, Gaskell DF, Muir WJ, St Clair DM (1989): Auditory P300 does not differentiate borderline personality disorder from schizotypical personality disorder. Biol Psychiatry 26:766-774. Levit RA, Sutton S, Zubin J (1973): Evoked potential correlates of information processing in psychiatrics patients. Psychol Med 3:487-494. Macar F (1985): Time psychophysics and related models. In Michon JA, Jackson JL (eds): Time, Mind and Behavior. Heidelberg: Springer, pp 112-130. McFarlane AC, Weber DL, Clark CR (1993): Abnormal stimulus processing in postraumatic stress disorder. Biol Psychiatry 34:311-320. Papart P, Ansseau M, Devoitille J-M, Mantanus H, TimsitBerthier M (1991): Contingent negative variation and the severity of depression. In Stefanis CN, Soldatos CR, Rabavilas P (eds): Psychiatry: A World Perspective, Vol 2. Amsterdam, pp 402-408. Pfefferbaum A, Wenegrat BG, Ford JM (1984): Clinical application of P3 component of event-related potentials II. Dementia, depression and schizophrenia. Electroencephalogr Clin Neurophysiol 59:104-124. Pitchot W, Hansenne M, Gonzalez Moreno A, Ansseau M (1992): Suicidal behavior and growth hormone response to apomorphine test. Biol Psychiatry 31 :1213-1219. Plutchick R, van Praag HM, Conte HR, Pilard S (1989): Correlates of suicide and violence risk 1: The suicide risk measure. Compr Psychiatry 30:296-302. Polich J (1992): On the clinical application of P300. Biol Psychiatry 31:647-649. Raine A, Venables PH (1987): Contingent negative variation, P3 evoked potentials, and antisocial behavior. Psychophysiology 24:191-199. Rockstroh B, Elbert T, Lutzenberger W, Birbaumer N (1982): Slow Brain Potentials and Behavior. Baltimore: Munich Urban and Schwarzenberg. Rohrbaugh JW, Gaillard AWK (1983): Sensory and motor aspects of the contingent negative variation. In Gaillard
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P300 and contingent negative variation (CNV) were recorded in depressive inpatients with and without history of suicide attempt. The results showed a significant reduction of P200, P300, and CNV and a significant increase of postimperative negative variation (PINV) in patients who had attempted suicide compared to patients with a negative history. Moreover, P300 amplitude was negatively related with the Suicidal Risk and the Hopelessness but not with the Hamilton scales. These results stress the need to differentiate clinical subgroups of patients to assess the psychophysiology of depression, and indicate that patients who attempted suicide exhibit lower cortical resources and poorer cortical performance than patients without history of suicide attempt.
Key Words: P300, contingent negative variation, hopelessness, helplessness, depression, suicide BIoL PS¥CrtIATR¥ 1996;40:116--122
Introduction Contingent negative variation (CNV) and P300 are two well-known event-related potentials (ERPs) that have been widely applied in the psychiatric field (Roth et al 1986; Polich 1992). Several lines of evidence suggest that CNV is constituted by two different components. The first, or early CNV, is related to the orienting response and exhibit a rapid habituation. The second component, or late CNV, has been associated with motor preparation and stimulus anticipation (Rohrbaugh and Gaillard 1983; Brunia 1988). The overall amplitude of the CNV has been related to arousal, attention, and motivation (Tecce 1972). On the From the Psychiatric Unit, CHU Andr6 Vrsale, Montigny-Le-Tilleul, Belgium (MH, IUZ) and Psychiatric Unit, CHU du Sart-Tilman, Liege, Belgium (MH, WP, AGM, MA). Address reprint requests to Michel Hansenne, B.Sc., Psychiatric Unit, CHU du Sart-Tilman, B35, B-4000 Lirge, Belgium. Received September 28, 1994; revised July 11, 1995.
© 1996 Society of Biological Psychiatry
other hand, the variables that modulate the P300 amplitude have been described in a triarchic model (Johnson 1986, 1993), including the subjective probabilities of stimuli, their meaning, and the amount of information delivered. CNV and P300 abnormalities have been reported in several psychiatric disorders, especially in dementia, schizophrenia, and depression (Pfefferbaum et al 1984; Roth et al 1986; Blackwood et al 1987), and more recently in antisocial behavior (Raine and Venables 1987), personality disorder (Kutcher et al 1989), obsessive-compulsive disorder (Towey et al 1990) and posttraumatic stress disorder (McFarlane et al 1993). Concerning depressive disorders, abnormalities of CNV amplitude and duration, as well as reduced P300 amplitude and longer latency, have been reported with some controversies (Levit et al 1973; Roth et al 1986; Thier et al 1986; E1 Massioui and Lesevre 1988). Moreover, the decrease in CNV amplitude has been related to the severity of depres0006-3223/96/$15.00 SSDI 0006-3223(95)00372-N
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sive symptoms (Papart et al 1991) and to central catecholaminergic deficit (Timsit-Berthier 1991). However, the heterogeneity of the samples of depressed patients in these prior studies may have obscured effects that could be specific to only a subgroup of patients and therefore be responsible for the controversial results. Some studies recently reported differences in P300 according to clinical subgroups of depression. Bruder et al (1991) compared a control group with 27 depressed patients in two subgroups: the first with typical depression (melancholic or simple mood reactive depression) and the other with atypical depression (reactivity of mood with preserved pleasure capacity). They found that typical depressive patients exhibited longer P300 latency than controls, whereas atypical depressive patients did not differ. Moreover, longer P300 latency exhibited by the typical group was associated with the rating of insomniac complaints but not with the overall severity of depression as indexed by total scores on the Hamilton scale. In a more recent study (Santosh et al 1994), psychotic depression was associated with a decrease of P300 amplitude as compared to nonpsychotic depression, whereas the mean scores on the Hamilton scale (excluding paranoid features) did not differ between the two groups. In the same direction, our group showed recently a significant reduction of both P300 and CNV amplitudes in patients who had attempted suicide compared with patients who had not. Moreover, a significant correlation was found between the Suicidal Risk scale and P300 amplitude (Hansenne et al 1994). In this study, we postulated that the reduction of cortical activity reported in the suicide attempters group could reflect the concepts of helplessness and hopelessness described in depression and more particularly in relation to suicidal behavior (Seligman 1974; Beck 1986). Ashton et al (1994) had also reported a reduction of CNV in patients who had attempted suicide, with a more marked phenomenon in the subgroup with multiple attempt. Moreover, they found significant relationships between both N100 and P200 components of the auditory evoked potential and measures of suicide intent as assessed by the suicidal items of Montgomery-Asberg Depression Rating Scale (MADSR) in patients with a history of suicide attempts. An earlier study IYom the same group had already demonstrated a relationship between N100 reduction and recent suicide attempts in three depressed patients (Ashton et al 1988). Therefore, the aim of this present study was twofold: first, to replicate our previous findings and those of Ashton et al (1994) in another sample of depressive patients with and without history of suicide attempt and, second, to assess the possible contribution of the hopelessness dimension to these results.
Methods
Subjects The study was conducted in 10 depressive inpatients following a suicide attempt by drug overdose without major medical complications (Psychiatric Unit of the University Hospital Andr6 V6sale, Montigny-le-Tilleul, Belgium). The sample was comprised of six men and four women with a mean age of 43.2 years (_+7.6 years). The patients were matched for age and gender with 10 depressive inpatients without a history of suicide attempts (mean age of 44.1, -+ 7.8 years). All diagnostic assessments of the patients were performed by the same psychiatrist (IUZ). All patients met the criteria for DSM-III-R major depressive disorder (APA 1987). The severity of depression was assessed by the same psychologist (MH) using the Hamilton depression scale. The depressed patients included in our study had at least a score of 18 on the 17-item Hamilton depression scale. The patients were free of medical illness, evidenced by clinical examination, history, electrocardiogram (ECG), electroencephalogram (EEG), chest x-ray, and routine laboratory tests. The control group was 20 nurses recruited from hospital staff, who were not familiar with psychophysiological techniques. The control group was matched for gender, but not for education level or age (36.2 _+ 10.4 years). However, the difference with the patient group was not significant (F = 2.5, p = 0.38). Moreover, all control subjects presented a score lower than 6 on the 17-item Hamilton depression scale.
Psychological Assessment Past history of suicide attempts was assessed by the suicidal risk scale (Plutchick et al 1989) and hopelessness by the Hopelessness scale (Beck et al 1985).
Event-Related Potential Recording Psychophysiological recording was conducted at the end of a drug-free period of at least 1 week for all the patients. For the suicidal attempt group, the recording was sometimes delayed until 3 weeks after the attempt, depending on the need to use minor tranquilizers during the first days of the hospitalization. The subjects were sitting in a sound-attenuated room. For the P300 paradigm, the subjects were tested until a total of 100 trials was obtained after rejecting trials for eye movement or other artifacts. The auditory stimuli were presented with a variable interstimuli interval between 2 and 4 sec. P300 trials contaminated by blinks or large amplitude eye movements were automatically excluded by using a 50 o~V rejection criterion. Smaller eye movements were rejected trial-per-
1 18
BIOL PSYCHIATRY 1996;40:116-122
trial by visual inspection of the electrooculogram (EOG). A similar number of rare trial were rejected among the three groups. According to the classic oddball paradigm, 85% of the stimuli (frequent) were tones of 2000 Hz, 75 dB, and 50 msec duration. The other 15% (rare) were tones of 1000 Hz, 75 dB, and 50 msec duration. A sequence of 100 artefact-free trials contained 16 rare stimulations. The subjects were asked to press a button for the rare stimuli. All the subjects and patients successfully completed the discrimination task. N100, P200, and P300 amplitudes were measured as the difference in voltage between the baseline and the higher point between, respectively, 80 and 140 msec, 160 and 220 msec, and 250 and 650 msec after the stimulus onset. The CNV paradigm consisted of a simple reaction time preceded by a warning stimulus 1 s earlier. The warning stimulus was a tone of 1000 Hz, 75 dB, and 50 msec duration, and the imperative stimuli was a tone of 1000 Hz, 75 dB, stopped by the motor response (reaction time). The intertrial interval was randomized from 5 to 10 sec. The CNV was obtained from 32 artefact-free trials as inspected visually trial-per-trial by EOG tracing. CNV amplitude was measured as the voltage difference between the baseline and the average of the 200 msec preceding the imperative stimulus. PINV amplitude was measured as the voltage difference between the baseline and the average of the 200 ms period from 500 to 700 msec after the imperative stimuli. The EEG was recorded using silver-silver chloride disc electrodes attached with collodion at Cz, using the left earlobe for reference and fight forehead for ground. All sites were cleaned with acetone and abraded to maintain resistance below 3 Kohms. EOG was recorded from above the left eye. Amplifier gains were set at 10,000, with a band pass of 0.05-50 Hz, and digitized at 250 samples/sec for 3000 msec epochs (of which the first 1000 msec were prestimulus activities).
M. H a n s e n n e et al
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Figure 1. Grand mean ERP waveforms and EOG from midline Cz electrode for depressed patients with past history of suicide attempt (lower traces), depressed patients without past history of suicide attempt (median traces), and control group (upper traces).
Statistical Analysis All the analyses were performed using Statgraphics (STSC Inc., 1988). Group differences were assessed by one-way analysis of variance, and the relationships between psychophysiological and clinical data by Pearson correlation coefficients. Paired Student's t-tests were used for subgroup comparisons.
Results Figure 1 shows the grand mean ERPs for each group recorded at Cz. The mean results and standard deviations for each component are presented in Table 1. Baseline to peak measures showed significant difference among
groups for P300 amplitude (F = 14.98, p < 0.001). Moreover, post hoc comparisons indicated that depressed patients with suicide attempts exhibited a lower P300 amplitude than controls (t = 4.87, p < 0.001) and depressed patients with a negative history (t = 6.42, p < 0.0001), whereas depressed patients without suicide attempts did not differ from normal controls (t = 0.4, p = 0.68). However, no differences were present for P300 latency (F = 0.85, p = 0.14). Reaction times were increased in the two clinical groups compared to control (F = 8.8, p < 0.01), but did not differ between them (t = 0.98, p = 0.1). Mean N100 amplitude but not latency was significantly
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119
Table 1. Mean Results, Standard Deviations, and Statistical Values for the Amplitude of Each Component in the Three Groups
NI00 (IzV) P200 (IzV) P300 (IxV) CNV (txV)
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Depressed withoutSuicide (DwoS)
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-9.7 ± 5.4 2.9 ± 1.8 b 5.3 -+ 4.2c -12.9 -+ 4.7d
-11.4 ± 6.8 9.3 ± 3.2 17.7 -+ 7.4 -17.9 - 3.7
-18.5 --- 4.2" 12.8 ± 3.7 16.8 ± 8.1 -25.3 __+-4.8e
11.53 8.3 28.8 14.98
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C > DwS DwS DwS C >
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37 37 37 37
<0.001 <0.001 <0.001 <0.00l
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different among the three groups ( F = 11.53, p < 0.0001, and F = 0.54, p = 0.25, respectively). Table 1 shows that the control group exhibited a significantly higher N100 compared to depressed patients with (t = 4.06, p < 0.001) or without (t = 3.44, p < 0.001) suicide attempts, whereas no difference existed between the two clinical subgroups (t = 0.81, p = 0.42). Again, mean P200 amplitude but not latency was significantly different between the three groups ( F = 8.3, p < 0.001, and F = 0.68, p = 0.36, respectively). Table 1 shows that depressed patients with history of suicide attempts exhibited significant lower P200 amplitude compared to patients with negative history (t = 3.4, p < 0.001) and controls (t = 3.9, p < 0.0001), whereas the last two groups did not differ (t = 1.17, p = 0.25). Figure 2 shows the grand mean CNV in the three groups. The results are presented in Table 1. Significant differences appears among the groups ( F = 28.8, p < 0.001). Post hoc comparisons indicated differences between controls and depressed patients with (t = 7.6, p < 0.001) and without (t = 4.3, p < 0.001) history of suicide attempts, as well as a difference between the two clinical groups (t = 2.4, p = 0.025). As shown in Figure 2, depressed patients with a positive history exhibited a significant Post Imperative Negative Variation (PINV) compared to patients with a negative history (t = 4.49, p < 0.001) and controls (t = 2.76, p < 0.01). Reaction times were increased in the two clinical groups compared to controls ( F = 6.5, p < 0.01) but did not differ between them (t = 1.54, p = 0.2). Mean scores of the Hopelessness ( F = 72.42, p < 0.0001), Suicidal Risk ( F = 241, p < 0.0001), and Hamilton ( F = 808, p < 0.0001) scales significantly differ among the groups. Post hoc comparisons showed higher scores on the Hopelessness (t = 3.8, p < 0.001) and the Suicidal Risk (t = 3.2, p < 0.001), but not for the Hamilton (t = 1.16, p -- 0.26), scales in depressed patients with a positive history compared to patients with a negative history.
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Figure 2. Grand mean CNV waveforms and EOG from midline Cz electrode for depressed patients with past history of suicide attempt (lower traces), depressed patients without past history of suicide attempt (median traces), and control group (upper traces).
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Among the whole group of depressed patients, significant negative correlations existed between P300 amplitude and Suicidal Risk scale on the one hand (r = -0.65, p = 0.002) and Hopelessness scale on the other hand (r = -0.81, p < 0.001) but not with the Hamilton scale (r = -0.15, p = 0.5). Concerning CNV, no relationships reached the level of significance (r = 0.41, p = 0.07 for the Suicidal Risk scale; r = 0.43, p = 0.06 for the Hopelessness scale; and r = 0.41, p = 0.07 for the Hamilton scale). No significant correlations existed between both N100 and P200 and the three clinical rating scales.
Discussion The present study confirms the significant reduction of P300 amplitude in depressive patients who had attempted suicide compared with those without suicidal history reported by our group in a previous sample (Hansenne et al 1994). Moreover, P300 amplitude is negatively related with the Hopelessness and the Suicidal Risk scales, and P200 amplitude were reduced in patients with a history of suicide attempts. In contrast, P300 latency and the reaction time do not differentiate the two clinical subgroups. Our study likewise confirms the significant reduction of CNV amplitude in depressed patients with a history of suicide attempts compared to depressed patients with a negative history of suicide attempts. In addition to our preliminary report, the present study shows a increased PINV in depressed patients with a history of suicide attempts. However, the results of the present study should be taken with caution since they used only one channel of recording (Cz). Event-related potentials have been related with many psychological variables. More particularly, CNV amplitude has been associated with attention, arousal, motor preparation, time estimation, and cognitive processes (Tecce 1972; Macar 1985), and the variables affecting P300 amplitude have been integrated in a model including stimulus probability, stimulus meaning, and the information delivered by the stimulus (Johnson 1986, 1993). Moreover, P300 latency is correlated with the stimulus evaluation processes (Donchin et al 1986). Recent information processing theories have described both energetic and computational mechanisms. A model providing a synthesis from these different theories has been proposed as an integrative model (Rockstroh et al 1982; Birbaumer et al 1990). This model combines two concepts: cerebral potentiality (negative cortical waves) and cerebral performance (positive cortical waves). Cerebral potentiality refers to the psychophysiological state necessary for any cerebral processes, and cerebral performance covers the input, decoding, storage, and output of information processing. In other words, cerebral potenti-
M. H a n s e n n e et al
ality represents the energetic mechanisms of information processing and cerebral performance the computational ones. According to this integrative model, CNV amplitude represents the cerebral potentiality, and its resolution cerebral performance. Then, a reduced CNV amplitude represents a lower cerebral potentiality in the anticipation task, and a delayed CNV resolution (PINV) suggests a difficulty in reducing the cortical activity for producing an optimal response. Therefore, our results suggest that patients with a history of suicide attempts present a lower cerebral potentiality reflected by lower CNV (or lower energetical resources) and lower cerebral performance reflected by the PINV than patients without previous suicidal attempts. According to the integrative model described before, P300 amplitude has also been associated with cerebral performance, and more particularly with memory processes. The cognitive disturbances described in depression (negative view of the self, the world, and the future) (Beck 1976) normally involve a perturbation of information processing. Our results show that disturbances of cerebral performance are more severe in patients with suicidal attempts. However, the lack of a difference between reaction time or P300 latency between suicidal and nonsuicidal groups does not support our interpretation in terms of a "cortical performance" deficit. A possible explanation for our findings is that suicidal behavior appears in patients with fewer resources to cope with the environment, as indicated by less cerebral potentiality and poor cerebral performance. These alterations of cerebral potentiality and cerebral performance could reflect the concepts of helplessness and hopelessness described in depression (Seligman 1974; Beck 1986). Hopelessness refers to the state that occurs when the individual expects that his or her response leads to negative outcomes, and helplessness exists when he or she does not expect any relationship between responses and results. Both mechanisms represent a noncoping response, and a disturbance of information processing. For Beck (1986), hopelessness is a key psychological factor in suicidal behaviors. He reported that among hospitalized patients, hopelessness was a significant predictor of the severity of suicidal attempts, as well as the extent of suicidal ideation or risk. The relationship between the hopelessness and suicidal risk scores among our sample confirms this point. The present findings show a significant negative relationship between P300 amplitude and both the Hopelessness and Suicidal Risk scores. Similar results had been reported by Bachneff and Engelsmann (1980), who showed a relationship between CNV amplitude and hopelessness and suicidal thoughts as assessed by the Present State Examination. They interpreted these results as a
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consequence of a decreased attention to the imperative stimuli ($2), resulting from the self-absorption and preoccupations of depressed patients with suicidal intent. From a theoretical point of view, P300 amplitude has been related to some psychological variables in normal subjects (Johnson 1986). However, P300 amplitude has never been associated with affective states in depressive disorders. In this study, hopelessness and suicidal risk scores significantly modulate P300 amplitude. These results suggest that, in addition to computational mechanisms, affective states play an important role in P300 amplitude. An association between both the N100 and P200 components of the auditory evoked potential and suicidal intent was first described by Ashton et al (1988), and confirmed recently by the same group (Ashton et al 1994). Our data do not replicate these findings. However, we found a significant decrease of P200 but not N100 in depressed patients with a history of suicide attempts compared to those who did not. One possible reason for this discrepancy may be the difference in the protocol used. Indeed, simple auditory evoked potentials were used by Ashton et al (1988, 1994), although we had used an oddball paradigm. From a psychopharmacological point of view, a large body of findings show that dopaminergic function is impaired in depressive patients with previous suicide attempts (Roy et al 1988, 1992; Roy and Pollack 1994; Agren 1980). Recently, our group reported a lower growth
hormone (GH) response to apomorphine in patients with suicide attempts than in patients without suicidal history (Pitchot et al 1992). On the other hand, the dopamine systems modulate P300 and CNV amplitude (TimsitBerthier 1991; Callaway 1991). For example, dopaminergic agonists such as methylphenidate enhance P300 amplitude in hyperkinetic children and normal subjects (Klormann and Brumaghin 1991), whereas dopaminergic antagonists such as flupentixol reduced P300 amplitude in normal subjects (R6sler et al 1985). Moreover, a recent study by our group (Hansenne et al 1995) showed a significant relationship between P300 amplitude and growth hormone response to apomorphine among depressed patients. In the same manner, CNV amplitude is modulated by dopaminergic agents (Tecce 1991), and correlated with GH response to apomorphine, a dopaminergic agonist (Timsit-Berthier et al 1987). Therefore, the reduction of P300 and CNV amplitudes could reflect the dopaminergic dysfunction linked to suicidal behavior in depression. The major findings of this study are the differences in both CNV and P300 amplitudes in relation to suicidal behavior in depressive patients. Moreover, P300 amplitude appears to be related to the suicidal risk and the hopelessness features of depression but not with the intensity of depression. These results stress the need to differentiate clinical subgroups of patients to assess the psychophysiology of depression.
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