Subjects, study criteria and design

Average and high scoring schizotypes were recruited from three sites in the United Kingdom (Manchester, London and Cardiff) via an online version of the Schizotypal Personality Questionnaire in its short (Raine et al. 1995) and full version (Raine 1991). Participants were screened using telephone interview to exclude mental health and medical history. The included participants were invited to a screening

appointment at which consent was obtained and the full SPQ was completed again. Volunteers that had a score in the 21-36 range were assigned to the average

schizotypy (AS) group and those scoring 41 or above formed the high schizotypy (HS) group. Other inclusion criteria at the screening visit were age between 18 and 45 years, fluency in the English language, no medical history and body mass index in the range of 18-30. Exclusion criteria were history or presence of mental health disorders (screened for using the Mini-International Neuropsychiatric Interview (MINI;

Sheehan et al., 1998)), daily consumption of more than 5 cigarettes or more than 8 standard caffeinated drinks, history of migraines, significant visual or hearing impairment,

The included participants were invited a day of testing. On the day participants were allowed to take part if the criteria for the study had not been violated and if there had been no prescribed medication in the 14 days prior before or over-the-counter

medicine in the 2 days before. At the onset of the experiment, a nicotine (7 mg) or placebo patch was applied. Three hours later a capsule of either amisulpride (400 mg), risperidone (2 mg) or placebo was administered. Various neuropsychological tests were completed 1.5 hours after the capsule administration. In the current analysis, only participants that had received placebo patch and placebo capsule were included in the analysis (27 HS and 31 AS).

A group of low scoring schizotypes (LS) was recruited in Manchester only. The participants attended a single appointment where the schizotypy status was confirmed (SPQ score of 9 or less) and the same inclusion and exclusion criteria as the ones

Page | 123 described earlier were applied. The included LS participants completed the same battery of neuropsychological tests as the AS and HS but received no treatment. 35 participants were recruited of which 4 were excluded due to SPQ scores out of range and 1 due to medical history.

The demographics of the participants included in the study are presented in table 5.1.

Table 5.1. Demographics of the three study groups

Demographics High schizotypy group: mean ±SD Average schizotypy group: mean ±SD Low schizotypy group: mean ±SD Significance values SPQ 50.1 ± 6.1 27.8 ± 4 3.8 ± 3.1 p < .001 Age 25.3 ± 5.0 23.8 ± 4.6 25.4 ± 5.8 p = .239 IQ 114.2 ± 6.2 114.2 ± 4.9 113.8 ± 6.0 p = .958 Years of education 16.3 ± 2.2 15.5 ± 1.7 17.4 ± 2.6 p = .004 Sex 13 f 14 m 16 f 15 m 15 f 15 m χ2= .125

5.2.2. Task description

Working memory (N-back) task

A series of alphabet letters were presented one at a time on a color monitor. Participants were instructed not to respond until they saw the same letter twice

following one another. The task had three levels of difficulty according to the number of letters in between the two matching letters. In the 1-back condition the two letters followed each other immediately. In the 2-back condition the target letters were separated by one letter and in the three back two letters separated the target letters. Thus participants had to hold in mind one, two or three letters. Consequently, the 1- back condition exerted the lowest load on working memory and the 3-back condition the highest. There was also a baseline condition to control for attending to the task where participants simply needed to respond when they saw the letter ‘X’. The

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Spatial working memory (SWM) task

Treasure chests were presented on a computer screen. The participants were instructed to search for coins in the treasure chests. Only one of the chests contained a coin at any one time and once it had been found it moved to a treasure chest that it had not been present in during the trial. The participants completed trials with 4, 6 and 8 chests and 4 repetitions of each level of the task. A practice trial with only 3 treasure chests was completed to ensure the understanding of the task.

Verbal fluency (VF) task

Letter and category VF and word production were assessed during a succession of one minute periods. For the letter VF test participants were asked to verbally report as many words as they could beginning with the letters F, A and S (FAS condition). The experimenter wrote down the words produced. In the category VF test the categories used were vegetables and animals (category naming condition). Participants were then asked to switch between two categories (fruit and furniture) during the same one minute period (category swap condition).

Salience Attribution Test (SAT)

On this task participants responded quickly to a probe (a black square) in order to win money (possible earnings for the whole task ranging between £5-20). Coloured images of household objects or animals were presented immediately before the probe. One stimulus dimension (e.g. red vs. blue – relevant dimension) very reliably

predicted the availability or non-availability of money while the other (e.g. animals vs. household objects – irrelevant dimension) was not a reliable predictor. The

rewarded stimulus feature (e.g. blue) generally comes to speed responding for reward relative to the unrewarded one (e.g. red), providing a measure of implicit adaptive (i.e. appropriate) salience; participants are usually also able to report this association overtly using visual analogue scales (explicit adaptive salience). If faster

responding/greater reward rating occurs to one of the irrelevant features over the other (e.g. animals faster over household objects), this indicates aberrant salience.

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Eye-tracking (ET) task

Eye-tracking is a technique that allows the recording of the pattern of eye movements in response to task conditions. In the prosaccade task a novel visual target appeared in the periphery and participants had to direct their gaze at it. In the antisaccade task participants had to inhibit the prosaccadic response to a new stimulus and instead look at its mirror image location on the opposite side of the screen. In the Smooth Pursuit Eye Movement (SPEM) paradigm, participants were required to follow a small visual target moving at a constant velocity without moving their head. The participants completed the SPEM task at three target speeds.

Intelligence quotient (IQ)

IQ was determined using the National Adult Reading Test (Nelson et al. 1991), a reading-based estimate of premorbid intelligence. We collected this data to check that the groups have comparable IQ and as a potential covariate of performance. The participant was asked to pronounce irregularly spelt words from a standardized written list. The scores were determined on the basis of the number of correctly pronounced words.

5.2.3. Statistical analysis

Outcome variables

The dependent variables in the N-back task were percentage correct, errors of commission and the reaction times of correct and incorrect responses for each of the four conditions of the task (attention, 1-back, 2-back, 3-back). In the SWM task, 4 outcome measures were extracted for each of the three task levels: time to complete, mean number of choices, mean number of within and between search errors. For all conditions of the VF task the following measures were calculated: mean number of correct words, set and repetition errors, mean number of correct transitions on the category swap condition. The dependent variables in the SAT were reaction time, adaptive and aberrant salience based on reaction time, omission errors and premature responses. In the prosaccade and antisaccade conditions of the ET task, the following variables were calculated: frequency of saccade errors, percentage of corrections after

Page | 126 error, as well as latency, gain and peak velocity of the correct saccades. For SPEM, the saccadic frequency during pursuit was calculated for each target speed.

General description of pre-planned statistical analysis

Before analysis, the data was checked for outliers. For N-back, the criterion for outlier was performance at both the attention and 3-back condition outside the 95%

confidence interval. Participants that had below 20% accuracy on the 3-back condition were also excluded from the analysis. For the VF task, participants were classed as outliers if their number of either set or repetition errors on the FAS

condition were outside the 95% confidence interval. For the SWM task, outliers were identified by visual inspection of boxplots and the extreme values tables produced from SPSS. The dependent variables were entered into a repeated-measures ANOVA (with the exception three VF variables (set errors, repetition errors and mean number of correct transitions) which were entered into univariate ANOVAs) with between- subject factors of group, sex and site. The within-subjects factor was level of difficulty or condition of the task. IQ, age and years of education were added as covariates to the model and were retained if statistically significant. In case of a main effect of level of difficulty, polynomial contrasts were run to determine the character of the relationship. In the case of a main effect of group of schizotypy, polynomial and LSD comparisons were performed to compare the three groups). In case of a group and level interaction, simple contrasts between the different task levels were performed to determine the level of the interaction.

For the SAT only, we performed correlations between the variables and the four subscales of the OLIFE questionnaire. This was based on a previously published data showing a correlation between aberrant salience and the Introvertive Anhedonia subscale.