Sensory gating and trait anxiety in people with psychotic symptoms.

Impairment in information processing is a central problem in patients with
schizophrenia. Dysfunction in sensory motor gating is considered an operational
measure of information processing. In patients with schizophrenia, dysfunction
in sensory motor gating has been frequently described in terms of a breakdown
of an attentional filter and as impaired selective attention. Impairments in
sensory filters are found in patients with schizophrenia as well as in their
non-affected siblings and in persons with prodromal symptoms (Braff et al.
1978, 1992; Dawson et al. 1993, Grillon et al. 1992; Kumari et al, 2005;
Quednow et al., 2008). In human subjects, sensory motor gating is usually
studied using the eye-blink response of the startle reflex. The contraction of
the eye muscle on a loud auditory, visual/ tactile stimulus (the startle
reflex) is recorded by an electric myograph through dermal electrodes. When the
startling stimulus is preceded by a relatively weak (non-startling) tone, a
normal diminishing of the intensity of the startle response, called prepulse
inhibition (PPI) is expected.
Interest in the prodromal stage of schizophrenia, the period directly preceding
the onset of psychosis, has undergone dramatic increase over the past decade.
The prodromal stage can be defined as the stage of schizophrenia that begins
with the first changes in behaviour and lasts up until the onset of the first
psychotic episode (McGorry et al., 1995). The prodromal period can be
characterized by various mental state features, including non-specific symptoms
such as depressed mood and anxiety as well as sub-threshold or attenuated
psychotic symptoms (Yung AR and McGorry, 1996). Presence of certain *basic
symptoms*, like subjective disturbance of attention, thinking, perception,
speech and motor action, have also been described (Yung et al., 2003). One
important aspect of the prodrome is that it is a period in which intervention
could occur if it would be recognised prospectively. The retrospective term
*prodromal* therefore cannot appropriately be used in prospective
investigations. After all, it is only after someone has a full-blown psychosis
one can say with certainty that the symptoms were prodromal. Instead of
putatively prodromal the subjects are referred to as ultra high risk (UHR).
Research using PPI has shown that sensory motor gating is affected by several
modulating factors such as sex, age, smoking, psychotic symptoms and
anti-psychotic medication. (Swerdlow et al, 1995; Kumari, Checkley and Gray,
1996; Dawson et al.; 2000; Kumari, Soni and Sharma, 2001; Kumari, Aasen and
Sharma, 2004; Kumari et al., 2010). Some findings in the literature also
suggest that emotionional state or trait may similarly affect PPI. (Corr, Tynan
and Kumari, 2002; Ludwig et al., 2002).
For people who have unpleasant and threatening experiences like psychotic
symptoms it is normal to respond with anxiety. However several studies showed
that the tendency to react with anxiety, (defined as high-trait anxiety/
neuroticism) is related to the severity of psychotic symptoms in healthy
controls, people who later became psychotic and in patients with schizophrenia.
(van Os & Jones, 2001; Goodwin, Fergusson & Horwood, 2003; Camisa et al.,
2005;).
A number of lines of evidence point to a role for emotion in sensory motor
gating (Swerdlow et al, 1994, Ludewig et al., 2002, Corr, Tynan and Kumari,
2002; Franklin et al., 2009) For example Swerdlow et al. (1994) and Hoenig et
al. (2005) found that patients with obsessive-compulsive disorder show weaker
PPI than normal individuals. Ludewig et al. (2002) found a negative
relationship between trait anxiety and PPI in persons with a panic disorder.
Knowledge about the relationship between the proneness to worry and experience
anxiety (as measured with STAI-DY and BIS/BAS) and sensory motor gating (as
measured with PPI) in both people at UHR as in patients diagnosed with a
psychotic disorder may be of use in understanding dysfunction in sensory motor
gating in complex disorders like schizophrenia.

Do patients with (recent onset, medicated) psychotic disorder (PDM), in persons
at ultra high risk for later psychosis (UHR), in patients with schizophrenia
who do not use anti-psychotics anymore (PDUM) report higher levels of trait
anxiety (measured by STAI-DY and BIS/BAS) compared to controls with no family
history for psychosis? Is trait anxiety associated with dysfunction in sensory
motor gating, measured by prepulse inhibition of the acoustic startle reflex in
these groups? Is antipsychotic medication of influence on the relation between
trait anxiety and PPI? Does the relationship between trait anxiety and PPI
differ between man and women. The answer to this question may give more insight
into differential symptomatology and its relationship to measures of
attentional function in subgroups of patients (at ultra high risk of) a
psychotic disorder. When subgroups with high trait anxiety related to PPI
disturbances are found, the next step could be to study interventions aimed at
these specific problems.

This is a cross sectional study consisting of 3 independent samples. The first
sample consist of males and females at ultra high risk for developing a
psychosis (UHR). UHR subjects are defined as persons who have had no previous
psychotic episode for more than one week. In addition, each subject had to fall
into one or more of the following groups: 1. Familial risk plus reduced
functioning: Individuals with a DSM-IV schizotypal personality disorder or a
first-degree relative with a history of any DSM-IV psychotic disorder and a
change in mental state or functioning in the individual leading to a reduction
of 30 percent or more on the Global Assessment of Functioning (GAF) Scale. A
*best estimate* derived from an independent interview with the subject and a
close relative, mostly one of the parents, defines the initial baseline of
functioning. 2. Attenuated psychotic symptoms: Presence of at least one of the
ultra high risk symptoms as assessed with the Structured Interview for
Prodromal Symptoms (SIPS) (18). The SIPS is a comprehensive diagnostic tool
designed specifically for the assessment of the whole spectrum of prodromal
signs and symptoms. The scale is composed of 19 items (5 positive, 6 negative,
4 disorganization, 4 general symptoms) each of which is given a score of 0 to
six according to defined criteria. A score between 3 and 5 on the positive
symptoms indicates attenuated psychotic symptoms and a score of 6 indicates a
psychotic state. These symptoms should occur at least several times a week and
should have been present for at least one week. 3. Brief, limited or
intermittent psychotic symptoms (BLIPS): a score of six on one of the positive
items of the SIPS, with duration of less than one week and spontaneous
remission. 4. Basic symptoms: At least two self-perceived deficiencies of
cognition or perception: basic symptoms assessed with the Bonn Scale for the
Assessment of Basic Symptoms - Prediction List (BSABS-P) (19). The BSABS-P
contains 17 selected self-perceived disturbances in cognition and perception
that were found to be predictive for a transition to psychosis over a 10 year
period. Each basic symptom is given a score of 0 to 6 according to frequency of
occurrence. A score of 3 or more on at least 2 of the first 9 items also
indicates an UHR state and makes the subject eligible for the study.
The second sample consists of patients with a recently developed psychotic
disorder. The third sample consists of healthy controls with no family history
of psychosis who are recruited for this study.

Participants will be informed about the procedure. It will be mentioned that
the startling tone is usually experienced as unpleasant but not painful. A
headphone, connected to the PPI program on the computer, will be applied on the
head of the participant. The skin around the right eye is cleaned with alcohol
70%. Two electrodes will be attached to the skin around the right eye (on the
eye muscle) with stickers. Another electrode is placed on the bone behind the
right ear. To inform participants they will hear the background noise and the
startling tone for a brief moment before the start of the trial. Participants
are asked to sit at ease, to look out of the window to the wall in opposite of
the test room for the duration of the test. For 12 minutes participants will
hear alternately the background noise and the startling tone. After the PPI
procedure the participants are requested to fill in self-rating lists
(demographic information, information about hormonal cycle in females, STAI DY,
BIS/BAS) ); the self rating lists will take about 15 minutes. Via venapunction
a bloodsample of 7 ml will be collected.