Prensado Menor Formación de Ptas Evaporadores

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Suppression of P50 evoked potential component, schizotypal beliefs and smoking Rodney J. Croft a,b, * , Aneta Dimoska b , Craig J. Gonsalvez b , Adam R. Clarke b a Brain Sciences Institute, Swinburne University of Technology, Hawthorn 3122, Melbourne, Australia b Brain and Behaviour Research Institute, University of Wollongong, Northfields Avenue, Wollongong 2522, Australia Received 10 April 2003; received in revised form 7 March 2004; accepted 21 May 2004 Abstract Suppression of the P50 component of the evoked potential is an electrophysiological index of sensory gating that is blunted in schizophrenia spectrum disorders. Although P50 suppression is thought to be related to symptomatology, this is yet to be shown. The failure to demonstrate this relation has led some to argue that P50 suppression and symptomatology are not related. However, a possible confound has recently been corroborated {i.e., chronic smoking is related to superior P50 suppression [Crawford et al., Neuroscience Letters 317 (2002) 151]}, and a relation has been found in questionnaire-defined individuals with indications of schizotypy {i.e., psychometric schizotypy is related to poor P50 suppression [Croft et al., Biological Psychiatry 50 (2001) 441]}. The present study attempted to replicate and extend both studies by examining P50 suppression, smoking histories, psychometric schizotypy and NEO Five-Factor Inventory (NEO-V) scores in 37 healthy participants. Replicating Crawford et al., P50 suppression was better in the heavier smokers. Providing a partial replication of Croft et al., P50 suppression was inversely related to schizotypy scores in participants who smoked little or not at all; however, P50 suppression was positively related to schizotypy in heavier smokers. Covarying for age and NEO-V scale scores had little effect on these relations. The findings provide evidence of important confounds that would limit our ability to detect P50 suppression/ symptom relations in schizophrenia. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: P50; Event-related potentials; Sensory gating; Schizophrenia; Schizotypy; Unreality 1. Introduction ‘Sensory gating’, which refers to the ability of the brain to modulate its response to sensory stimuli, has been the subject of much research into the schizophrenia spectrum disorders (McGhie and Chapman, 1961; Venables, 1964). As an operational measure of sensory gating, ‘P50 suppression’ defi- cits have also been closely linked to schizophrenia. Measured as an event-related potential, the P50 is a neural response that manifests as a positive deflec- tion over the vertex, occurring approximately 50 ms poststimulus. P50 suppression refers to the tendency of the brain to produce a smaller P50 to the second of two tones (typically separated by 500 ms). Of relevance to schizophrenia is that while normal participants exhibit strong suppression of the P50 response to the second of the two tones, this decrement or ‘gating’ is reduced in schizophrenic 0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2004.05.009 * Corresponding author. Brain Sciences Institute, Swinburne University of Technology, Hawthorn 3122, Melbourne, Australia. Tel.: +61-3-9214-5149; fax: +61-3-9214-5525. E-mail address: [email protected] (R.J. Croft). www.elsevier.com/locate/psychres Psychiatry Research 128 (2004) 53 – 62

Transcript of Prensado Menor Formación de Ptas Evaporadores

www.elsevier.com/locate/psychres

Psychiatry Research 128 (2004) 53–62

Suppression of P50 evoked potential component, schizotypal

beliefs and smoking

Rodney J. Crofta,b,*, Aneta Dimoskab, Craig J. Gonsalvezb, Adam R. Clarkeb

aBrain Sciences Institute, Swinburne University of Technology, Hawthorn 3122, Melbourne, AustraliabBrain and Behaviour Research Institute, University of Wollongong, Northfields Avenue, Wollongong 2522, Australia

Received 10 April 2003; received in revised form 7 March 2004; accepted 21 May 2004

Abstract

Suppression of the P50 component of the evoked potential is an electrophysiological index of sensory gating that is blunted

in schizophrenia spectrum disorders. Although P50 suppression is thought to be related to symptomatology, this is yet to be

shown. The failure to demonstrate this relation has led some to argue that P50 suppression and symptomatology are not related.

However, a possible confound has recently been corroborated {i.e., chronic smoking is related to superior P50 suppression

[Crawford et al., Neuroscience Letters 317 (2002) 151]}, and a relation has been found in questionnaire-defined individuals

with indications of schizotypy {i.e., psychometric schizotypy is related to poor P50 suppression [Croft et al., Biological

Psychiatry 50 (2001) 441]}. The present study attempted to replicate and extend both studies by examining P50 suppression,

smoking histories, psychometric schizotypy and NEO Five-Factor Inventory (NEO-V) scores in 37 healthy participants.

Replicating Crawford et al., P50 suppression was better in the heavier smokers. Providing a partial replication of Croft et al.,

P50 suppression was inversely related to schizotypy scores in participants who smoked little or not at all; however, P50

suppression was positively related to schizotypy in heavier smokers. Covarying for age and NEO-V scale scores had little effect

on these relations. The findings provide evidence of important confounds that would limit our ability to detect P50 suppression/

symptom relations in schizophrenia.

D 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: P50; Event-related potentials; Sensory gating; Schizophrenia; Schizotypy; Unreality

1. Introduction measure of sensory gating, ‘P50 suppression’ defi-

‘Sensory gating’, which refers to the ability of

the brain to modulate its response to sensory

stimuli, has been the subject of much research into

the schizophrenia spectrum disorders (McGhie and

Chapman, 1961; Venables, 1964). As an operational

0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights re

doi:10.1016/j.psychres.2004.05.009

* Corresponding author. Brain Sciences Institute, Swinburne

University of Technology, Hawthorn 3122, Melbourne, Australia.

Tel.: +61-3-9214-5149; fax: +61-3-9214-5525.

E-mail address: [email protected] (R.J. Croft).

cits have also been closely linked to schizophrenia.

Measured as an event-related potential, the P50 is a

neural response that manifests as a positive deflec-

tion over the vertex, occurring approximately 50 ms

poststimulus. P50 suppression refers to the tendency

of the brain to produce a smaller P50 to the second

of two tones (typically separated by 500 ms). Of

relevance to schizophrenia is that while normal

participants exhibit strong suppression of the P50

response to the second of the two tones, this

decrement or ‘gating’ is reduced in schizophrenic

served.

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–6254

patients, their first-degree relatives (Adler et al.,

1982; Siegel et al., 1984; Waldo et al., 1991;

Clementz et al., 1998a) and patients with schizo-

typal personality disorder (Cadenhead et al., 2000).

Furthermore, there is evidence that this P50 sup-

pression deficit may be a genotypic marker for

schizophrenia as it has been linked to chromosome

15q13–14, which in turn has been linked to both

the disorder and other deficits related to the disorder

(Freedman et al., 1997).

However, while schizophrenic symptoms are

thought by some to be related to an inability to filter

out irrelevant stimuli (McGhie and Chapman, 1961;

Venables, 1964) and the P50 suppression deficit has

been implicated as a neural substrate of this process

(Freedman et al., 1997), no clear link between P50

suppression and symptomatology has been demon-

strated in the population (see the inconsistent findings

of Adler et al., 1990; Boutros et al., 1993; Erwin et al.,

1998; Jin et al., 1998; Nagamoto et al., 1999). This

has led some to argue that the P50 suppression deficit

in schizophrenia is not related to the disorder’s symp-

tomatology (Jin et al., 1998).

There are a number of inherent complexities in

schizophrenia research, however, that make it difficult

to explore such relations. For example, patients’

medication history and in-patient lifestyle are likely

confounding factors; it is difficult to obtain valid

measures of patients’ experiences (Light and Braff,

1998) or a broad enough range of P50 suppression

scores to adequately assess the issue, and the possible

link between schizophrenics’ smoking patterns and

P50 suppression. Adler et al., (1998) suggests that

there are many reasons why we might not observe

consistent symptom/P50 suppression relations in

schizophrenic populations. It is thus important to

determine whether these possible confounds are in-

deed likely (the negative argument) and to look for

less direct evidence of such relations (the positive

argument).

In support of the positive argument, we recently

employed nonclinical participants to help clarify this

issue by comparing scores on a psychometric schiz-

otypy scale with P50 suppression. This was based on

the assumptions that psychometric schizotypy is

related to the schizophrenia spectrum and that its

use would overcome the patient-related confounds

discussed above. Consistent with the thesis that poor

P50 suppression is related to symptoms in schizo-

phrenia, we found that poor P50 suppression was

related to schizophrenic-like beliefs and behaviours

in this nonclinical sample (Croft et al., 2001). In

terms of support for the negative argument, Light

and Braff (1998) put forward a strong case, high-

lighting the difficulty of detecting such relations

within a population renowned for inaccurate self-

report, and although not discussed in terms of this

issue, Crawford et al. (2002) found that chronic

smoking was related to superior P50 suppression in

nonclinical participants. This latter demonstration is

important because schizophrenic patients are typical-

ly very heavy smokers, which suggests that even if

there is a P50 suppression/symptom relation in

schizophrenia, it would be difficult to detect because

there are two opposing influences on P50 suppres-

sion (one related to the disorder and one related to

smoking). In support of this link, smoking tempo-

rarily normalises both P50 suppression (Adler et al.,

1993) and certain saccadic intrusion abnormalities

found in schizophrenic patients (Olincy et al., 2003)

with both abnormalities, and schizophrenia linked to

the same gene locus (Freedman et al., 1997). Sim-

ilarly, chronic smoking was found by one group to

be related to greater medication levels in schizo-

phrenic patients, with this smoking group exhibiting

a (nonsignificant) trend to improved P50 suppression

(Ward et al., 1996).

However, to enhance confidence in the findings of

Crawford et al. (2002) and Croft et al. (2001), both

studies need to be replicated and a few issues

clarified. In terms of Croft et al. (2001), we found

that nonclinical participants who had poorer P50

suppression reported more unreality features such as

perceptual anomalies and magical ideation (Gruzelier

and Doig, 1996). We interpreted the psychometric

schizotypy scores as being representative of a schizo-

phrenia spectrum belief set and believe that there is

good evidence in support of this position (Eckblad

and Chapman, 1983; Miller and Chapman, 1983;

Thalbourne, 1994; Gruzelier et al., 1995; Duchene

et al., 1998). However, even if we are justified in this

position, it does not follow that the P50 suppression/

psychometric schizotypy relation corresponds to a

P50 suppression/schizophrenia spectrum relation.

For example, as neuroticism covaries with psycho-

metric schizotypy (e.g., Eysenck and Barrett, 1993;

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–62 55

Lipp et al., 1994), it may be that it is neuroticism and

not schizotypy per se that is responsible for the

relation with P50 suppression. As well as providing

a replication, the present study thus assessed the

relation between P50 suppression and unreality after

covarying for the primary personality dimensions of

the NEO Five-Factor Inventory (NEO-V; Costa and

McCrae, 1991).

With regard to Crawford et al. (2002), their finding

that heavy tobacco smokers had better P50 suppres-

sion than nonsmokers has particular relevance to the

Croft et al. (2001) study, as it demonstrated that an

important confound was not accounted for. That is,

smoking is overrepresented in schizophrenia spectrum

disorders (de Leon et al., 1995), and so we would

expect that coincident with the positive correlation

between poor P50 suppression and psychometric

schizotypy, there would also have been a negative

correlation due to the greater smoking levels in

subjects with high scores on psychometric schizotypy.

Participants’ smoking histories were not obtained in

that study and so it cannot be determined whether

smoking was related to its findings. However, partic-

ipants in that study did score moderately low on

unreality. This raises the possibility that its findings

are not generalisable to psychometric schizotypy as a

whole and instead that the results may be restricted to

moderate levels of schizotypy and any factor repre-

sentative of that group (such as low levels of smok-

ing). The present study thus provides a replication of

the Crawford et al. (2002) findings and furthermore

extends the design to include a range of smoking

histories, offering a more detailed account of the

relation.

2. Methods

2.1. Participants

Participants (16 males, 27 females) were drawn

primarily from an undergraduate psychology student

population. Participants gave written informed con-

sent and were free to withdraw from the study at any

time without penalty. Individuals were excluded on

the basis of self-reported neurological (e.g., severe

head injury, periods of unconsciousness) or psychiat-

ric histories, if they reported the use of illicit sub-

stances at least once a month for the last 6 months or

if they were not fluent in English (due to the use of

English questionnaires). This reduced the sample to

14 males and 23 females, ranging in age from 16 to 33

years (mean = 21.3 years), of which 34 were right-

handed and 3 were left-handed.

2.2. Apparatus and procedure

Upon arrival at the laboratory, participants

completed a consent form and were fitted with

EEG recording apparatus. They then completed a

series of questionnaires including the Personality

Syndrome Questionnaire (PSQ; see below) and the

NEO-V Inventory (Costa and McCrae, 1991).

Participants were then seated in a recording booth

where they performed the P50 paradigm. Partic-

ipants were instructed to count the number of tone

pairs that they heard during the P50 session. The

minimum smoking abstinence period was 2 h. The

experiment was approved by the local ethics

committee.

2.3. EEG data collection

EEG data were recorded from 19 scalp sites (Fp1,

Fp2, Fz, F3, F4, F7, F8, Cz, C3, C4, Pz, P3, P4, T3,

T4, T5, T6, O1, O2; international 10–20 system)

referenced to linked ears using tin electrodes and

grounded midway between Fpz and Fz. Electroocu-

lographic (EOG) data were recorded from above

(E1) and below (E3) the left eye and from the outer

canthi of the left (E5) and right (E6) eyes, and for

later EOG correction, vertical EOG, horizontal EOG

and radial EOG channels were derived as E1–E3,

E5–E6 and (E1 + E3)/2, respectively. Impedances

were below 5 kV at the start of the recording, and

data were continuously digitised at 500 Hz with an

0.01 to 120 Hz bandpass (24 dB/octave roll-off).

2.4. P50 presentation characteristics

Fifty 89-dB click pairs, each with a 500-ms inter-

click interval, were presented through earphones, with

10-s interpair intervals. Clicks were 100-As duration

square waves with near instantaneous rise and fall

times. The paradigm ran continuously and lasted 8 min

and 20 s.

try Research 128 (2004) 53–62

2.5. Assessment of schizotypy and personality traits

We used the same schizotypy scale here as was

used by Croft et al. (2001), the Personality Syndrome

Questionnaire (PSQ). The PSQ was developed by the

laboratory of John Gruzelier at Imperial College,

London, and its psychometric properties have not

yet been published. It separates schizophrenic-like

beliefs and behaviours into active, withdrawn and

unreality scales, has a similar factorial structure to

schizophrenia and has shown similar neuropsycholog-

ical correlates (Gruzelier et al., 1995; Gruzelier and

Doig, 1996; Gruzelier, 1999). Of relevance to the

present discussion is the unreality syndrome, com-

prising items that describe delusional thought, percep-

tual anomalies and magical ideation as characterised

by other scales (Chapman et al., 1978; Eckblad and

Chapman, 1983). Less relevant to the present article is

the active syndrome, comprising items describing

speeded mental or physical activation, and the with-

drawn syndrome, comprising items describing nega-

tive features such as social and emotional withdrawal,

constricted affect and social anxiety. We employed the

NEO-V as a measure of standard personality dimen-

sions because it is widely employed and there is

considerable research demonstrating its reliability

and validity (Costa and McCrae, 1991). It is com-

posed of extroversion, neuroticism, openness, agree-

ableness and conscientiousness scales.

2.6. Signal processing and scoring of event-related

potentials

2.6.1. Signal processing

Data were analyzed offline, rereferenced to com-

mon average, EOG-corrected (Croft and Barry, 2000),

bandpass-filtered (10–49 Hz; 24-dB/octave roll-off),

epoched 100 to 300 ms poststimulus, baseline-cor-

rected and averaged. Before averaging, epochs were

manually inspected and rejected if they were contam-

inated by substantial movement artefact. Averages

were calculated for each participant and for each of

tones 1 and 2 separately.

2.6.2. P50 peak selection and quantification

The P50 peak was identified as the positive peak at

Cz (40 to 80 ms poststimulus) following the Pa wave

(15 to 40 ms poststimulus). Where a Pa component

R.J. Croft et al. / Psychia56

was not visible, the largest positive deflection between

40 and 80 ms was taken to be the P50. In addition to

the above, to be classified as a P50, peaks had to

exhibit fronto-central distributions (manually classi-

fied using topographic maps). To allow comparison,

an automatic peak-detection algorithm was also

employed, where the P50 was defined as the most

positive point at Cz, 40–80 ms. For each of these

methods, the P50 amplitude was defined as the

absolute difference between the P50 peak and the

preceding negative trough (Na). For each of the above

averages, P50 suppression was defined as the ratio of

the P50 amplitudes for tones 2 and 1 (T2/T1; P50

ratio), and as per Clementz et al. (1998b), only Cz

was used for statistical analyses.

3. Results

All statistical tests were nondirectional. Fig. 1

presents grand average waveforms for tones 1 and 2.

The mean P50 ratio and tones 1 and 2 amplitudes

were 0.42 (S.D. = 0.29), 4.2 AV (S.D. = 1.9) and 1.5

AV (S.D. = 0.9), respectively, and each index was

transformed to approximate normality (t_P50r = na-

natural log [P50 ratio], t_tone1 = sqrt [tone 1],

t_tone2 = sqrt [tone 2]). The mean scores for the

active, unreality and withdrawn scales of the PSQ

were 10.2 (S.D. = 3.4), 9.6 (S.D. = 5.2) and 8.7

(S.D. = 5.3), respectively, which are similar to PSQ

norms for active (9.4) and unreality (9.0) but higher

than normal for withdrawn (5.9). Unreality was trans-

formed to approximate normality (t_unreality = sqrt

[unreality]). While participants displayed better sup-

pression in the present (0.42) relative to our previous

study (0.63; Croft et al., 2001), the temporal mor-

phology of the two studies’ waveforms was very

similar. The t_P50r scores did not correlate with age

(r[37] < 0.01, P= 0.982), and there was a trend to

better suppression for females than males (t[35] =

2.00, P= 0.053).

A between-subjects t-test was employed to deter-

mine whether t_P50r was related to smoking histories.

Smoking groups were loosely based on the median

split of reported lifetime consumption of cigarettes,

where the median was ‘six’, but all ‘sixes’ were

included in the lighter smoking group to avoid data

wastage (lighter < 7, median = 0, range = 0–6; heavier

Fig. 1. Evoked potentials to tones 1 and 2 are shown averaged over all participants, along with the scalp distribution of the P50 peak (where

black represents + 2 AVand white � 1 AV). The P50 deflection can be seen as a positive deflection maximal at 60 ms poststimulus onset, where

it is considerably larger for tone 1 than tone 2, and has a fronto-central distribution.

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–62 57

>6, median = 1825, range = 7–51,100 lifetime ciga-

rettes). While none of the lighter smokers had ever

smoked regularly, the heavier smokers varied greatly

in smoking patterns (daily consumption: median = 3.5,

range = 0.1–30.0; duration of use in years: medi-

an = 2.5, range = 0.6–8.0; time since last cigarette:

median = 18 weeks, range = 2 h to 14 years). It may

be noted that only two of the heavier smokers had only

abstained for the minimum requirement of 2 h, with the

next smallest abstinence period being 12 h. It was

found that heavier smokers had smaller t_P50r’s than

lighter smokers (mean = 0.28, S.D. = 0.18 and

mean = 0.53, S.D. = 0.33, respectively; t(35) = 2.63,

P= 0.013). Furthermore, consistent with Crawford et

al. (2002), this effect was related to an enhancement of

tone 1 in the heavier relative to the lighter smokers

(t[35] = 3.31, P= 0.002), with no effect on tone 2

(t[35] = 0.73, P= 0.471). The P50 suppression en-

hancement for heavier smokers was still present when

analysed using the automatic rather than manual peak

detection method (t[35] = 2.51, P= 0.017).

In order to determine whether the particular meth-

od of splitting the groups into lighter and heavier was

important to the results, the groups were reallocated

based on splits at 6, 12, 52 or 112 lifetime cigarettes

(the closest naturally occurring values to the median

split described above) and this made little difference

to the results (P= 0.002, P= 0.012, P= 0.024 and

P= 0.033, respectively). This smoking/t_P50r relation

was found to be linear and strong, irrespective of the

tobacco use index employed (years of use: r[37] =

� 0.40, P= 0.016; cigarettes per day: r[37] =� 0.43,

P= 0.008; total lifetime cigarettes: r[37] =� 0.50,

P= 0.002; Pearson’s correlation; all indexes natural

log-transformed to approximate normality). As can be

seen in Fig. 2, this relation appears to be due to there

being fewer poor P50 suppression ratios with increas-

ing cigarette smoking.

As per Croft et al. (2001), Pearson’s correlation

was employed to determine whether unreality was

related to t_P50r. Across the entire sample, the Croft

et al. (2001) finding of a positive relation between P50

ratio and unreality was not replicated (r[37] = 0.01;

P= 0.963). This finding was not affected by the use of

the automatic rather than the manual peak detection

measure (r[37] =� 0.07, P= 0.674). However, based

on the Crawford et al. (2002) and present findings of

important P50 suppression/smoking relations, these

analyses were also performed for the two smoking

groups separately. In the lighter smokers, there was a

positive relation between t_P50r and t_unreality

(r[20] = 0.54, P= 0.014), and in the heavier smokers,

there was an equally strong but inverted relation

(r[17] =� 0.57, P= 0.018). These findings were not

affected appreciably by the use of the automatic rather

than the manual peak detection measure (r[20] = 0.47,

P= 0.037 and r[17] =� 0.70, P= 0.002, respectively).

These relations were heavily dependent on tone 2

Table 1

Correlations between P50 suppression and personality questionnaire

measures

Combined

sample

(N = 37)

Lighter

smokers

(N= 20)

Heavier

smokers

(N= 17)

Unreality 0.01 (0.96) 0.54 (0.01) � 0.57 (0.02)

Active 0.10 (0.58) 0.36 (0.12) � 0.00 (0.99)

Withdrawn � 0.13 (0.46) 0.36 (0.12) � 0.43 (0.08)

Neuroticism � 0.19 (0.27) 0.23 (0.34) � 0.39 (0.12)

Extroversion 0.19 (0.26) � 0.11 (0.64) 0.37 (0.15)

Openness � 0.02 (0.89) � 0.04 (0.88) 0.20 (0.44)

Agreeableness 0.32 (0.05) 0.10 (0.69) 0.44 (0.08)

Conscientiousness 0.40 (0.02) 0.27 (0.25) 0.58 (0.02)

Pearson’s correlations are shown between P50 suppression scores

and each of the PSQ and NEO-V subscales for the combined sample

and each of the lighter and heavier smoker samples separately.

Significant correlations ( P< 0.05) are in bold italics.

Fig. 2. A scatterplot is shown of participants’ P50 suppression ratios as a function of total lifetime cigarettes smoked (after natural log

transformation).

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–6258

(r[20] = 0.67, P= 0.001 and r[17] =� 0.45, P= 0.068,

respectively), with no tone 1 relations being signifi-

cant (r <0.30, P>0.242).

To help clarify whether the difference between the

present and Croft et al. (2001) results is related to the

higher unreality scores in the present study, a t-test

was employed with total lifetime cigarettes smoked

(log-transformed) as the dependent variable, and un-

reality group as the independent variable. Participants

were grouped into low and high unreality scorers

according to a median split (mean = 5.2 [S.D. = 2.0]

and 13.8 [S.D. = 3.3], respectively), with the low

unreality group exhibiting a mean similar to the mean

of 5.8 in Croft et al. (2001). Suggestive of a link

between the lighter smokers of the present study and

the lower unreality scorers of the Croft et al. (2001)

sample, the low unreality group smoked considerably

less than the high unreality group (mean = 895

[S.D. = 2653] and 7906 [S.D. = 15969] lifetime ciga-

rettes, respectively), although statistically this was

only at trend level (t[35] = 1.81, P= 0.079). Further

to this, t_unreality was related to neuroticism

(r[37] = 0.66, P < 0.001) and t_ratio was related to

conscientiousness (r[37] = 0.37, P= 0.025; all other

combinations were nonsignificant, r[37] < 0.29,

P>0.287); see Table 1.

To determine whether the above tests of P50

suppression/unreality relations were independent of

primary personality factors, the above correlation

analyses were repeated using the ‘primary’ NEO-V

scales as covariates. Across the entire sample, there

was still no observable relation between t_P50r and

t_unreality (r[30] = 0.30, P= 0.092). In the lighter

smokers, there was still a strong relation between

t_P50r and t_unreality (r[13] = 0.56, P= 0.031),

while in the heavier smokers, the strength of the

relation was greatly reduced (r[10] = � 0.21;

P= 0.506). Furthermore, as age (transformed using

natural log; t_age) was related to total cigarettes

consumed in the heavier smokers (r[17] = 0.50,

P= 0.040), t_age was also entered as a covariate to

ensure that it did not affect the main P50 suppres-

sion/unreality relations or the covariate analyses

above. The main analysis was not altered, with P50

suppression positively related to unreality in the

lighter smokers (r[17] = 0.55, P= 0.016) and nega-

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–62 59

tively related to unreality in the heavier smokers

(r[14] =� 0.55, P= 0.028). The covariate analysis

was not altered in the lighter smokers (r[12] = 0.57,

P= 0.033), but the negative relation between P50

suppression and unreality in the heavier smokers

was largely restored with the addition of age as a

covariate (r[9] =� 0.53, P= 0.091).

4. Discussion

The present study has replicated Crawford et al.

(2002) by finding that within a nonclinical sample,

tobacco smoking was related to superior P50 suppres-

sion. This replication was particularly strong given

that differences between the groups’ smoking levels

were far less in the present than in the original study

and that results were consistent in that the effect of

smoking was principally on the tone 1 response in

both studies. It may be noted that as nicotine has a

half-life of 2 h (Benowitz and Jacob, 1999) and only a

2-h abstinence period was required from participants,

the possibility that the smoking/P50 suppression rela-

tion of the present study was due to acute effects of

smoking cannot be discounted. However, Crawford et

al. (2002) were able to show that their effects were not

due to acute smoking effects by demonstrating that

there was no difference between P50 suppression

immediately after smoking and that following pro-

longed abstinence (9–15 h), most participants in the

present study abstained considerably longer than the

minimum 2-h period, and nicotine effects on P50

suppression have been found to be negligible after

30 min (Adler et al., 1993). So although the present

study was not equipped to replicate this aspect of the

Crawford et al. (2002) study, we would presume that

we are observing the same chronic phenomenon.

As more schizophrenic patients smoke, and smoke

far more than nonclinical populations (de Leon et al.,

1995), their smoking behaviour may thus affect their

P50 suppression scores in addition to the effect of the

disorder itself. This complexity suggests that any

relation between P50 suppression and symptomatolo-

gy in schizophrenia will be difficult to identify and

thus that the failure of science to consistently detect

such a relation (e.g., Jin et al., 1998) is not a strong

reason for concluding that P50 suppression is not

related to symptomatology.

This smoking/P50 suppression relation is particu-

larly important when we consider the attempted

replication of a relation between P50 suppression

and unreality. That is, in the lighter smokers, poor

P50 suppression was strongly related to high unre-

ality scores, and in the heavier smokers, the relation

was inverted. While it cannot be determined why the

Croft et al. (2001) study was only replicated within

the lighter smokers, the finding that this group had

similar unreality scores to that of the Croft et al.

(2001) study and that this moderate range of unre-

ality scoring participants smoked less than the higher

scorers of the present study suggests that the relation

only holds for moderate unreality participants or

those who do not regularly smoke. It may be posited

that this may be because the lighter smokers’ P50

suppression scores are the only scores that have not

been heavily affected by smoking and therefore are

the only scores not to have their P50 suppression/

unreality relations masked.

The present study has provided a limited replica-

tion of our previous finding (Croft et al., 2001) of a

relation, within a nonclinical sample, between poor

P50 suppression and psychometric schizotypy. It was

originally argued that this relation provided support

for the proposition that the early sensory gating

deficits and unusual belief systems that characterise

schizophrenia are related. However, as can be seen

in Fig. 3, in the present study, this relation was

restricted to the lighter smokers, corresponding to

similar levels of unreality to those reported in our

previous study and did not extend to high unreality

scorers.

That the relation did not hold at higher levels of

unreality in the present sample is problematic for the

‘positive’ argument that this relation provides support

for a link between symptomatology and poor P50

suppression in schizophrenia. This stems from the

assumption of a continuum moving from low to high

schizotypy and extending beyond this to clinical

populations such as schizotypal personality disorder

and schizophrenia itself. Thus, as the relation holds at

low to moderate but not high levels of schizotypy, this

may suggest that there is no simple extension of the

relation from moderate schizotypy to schizophrenia.

However, due to the strong relation between P50

suppression and smoking in the present study and

the Crawford et al. (2002) study, it may merely be that

Fig. 3. A scatterplot is shown of participants’ P50 suppression ratios (after natural log transformation) as a function of their unreality scores

(after square root transformation), for lighter (empty diamonds and dotted line) and heavier (filled markers and solid line) smokers separately.

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–6260

as with schizophrenia itself, the relation is difficult to

study in samples with higher schizotypy scores and/or

larger smoking histories.

In terms of providing a ‘negative’ argument against

the claim that ‘‘if there was a relation between

schizophrenia symptoms and P50 suppression, then

it would have been detected by now’’, the present

study shows that schizophrenia-like beliefs and

behaviours are heavily dependent on smoking levels.

That is, not only are both P50 suppression and

schizophrenia-like beliefs related to tobacco smoking,

but the relation between the two is also influenced by

tobacco smoking.

It is important to note that the P50 suppression/

unreality relation in the lighter smokers was not

explicable in terms of any of the NEO-V personality

dimensions. Relations were found between P50 sup-

pression and the conscientiousness scale (r = 0.37) and

between unreality and the neuroticism scale (r = 0.66),

but covarying for these dimensions did not affect the

P50 suppression/unreality relation appreciably. Thus,

while replicating the relation between psychometric

schizotypy and neuroticism (Eysenck and Barrett,

1993; Lipp et al., 1994), the present study argues

against the possibility that the relation between P50

suppression and psychometric schizotypy observed in

the lighter smokers/moderate unreality scorers here

and in the moderate unreality scores previously (Croft

et al., 2001) was merely due to standard personality

dimensions. This issue is less clear in relation to the

heavier smokers of the present study, as covarying for

the NEO-V scales did remove the relation, but it was

essentially restored with the addition of age as another

covariate. Furthermore, it may be noted that as unre-

ality scores were independently related to neural

function, this is consistent with other research (Lipp

et al., 1994) suggesting that schizotypy may itself

represent a unique personality dimension.

It is concluded that the present study has repli-

cated the results of Crawford et al. (2002), in that

tobacco smoking was related to stronger P50 sup-

pression, and Croft et al. (2001) in part, in that

psychometric schizotypy was related to poor P50

suppression within the lighter smokers/low to mod-

erate unreality scorers. It was also found that within

the heavier smokers, unreality was related to im-

proved P50 suppression. Together, the complexity

that these findings demonstrate provides strong evi-

dence contrary to the view that ‘‘if there was a

relation between schizophrenia symptoms and P50

suppression, then it would have been detected by

now’’. Furthermore, as findings were not affected by

the statistical removal of NEO-V personality dimen-

sions, this demonstrates that relations between P50

suppression and unreality are not due to other

‘primary’ personality factors.

Acknowledgements

The authors thank John H. Gruzelier, Cognitive

Neuroscience and Behaviour, Imperial College, Lon-

don, for helpful comments regarding interpretation of

the data.

R.J. Croft et al. / Psychiatry Research 128 (2004) 53–62 61

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