The first main objective of this study is 1a. To examine whether striatal [18F]DOPA influx (Ki) values in non-psychotic individuals with ASD are positively related with the total score on the UCLA Loneliness Scale. The second main objective of this…
ID
Source
Brief title
Condition
- Developmental disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Parameters for the first main objective (1a): [18F]DOPA influx (Ki) value and
Degree of loneliness (UCLA Loneliness Scale) in patients with ASD.
Parameter for the second main objective (1b): [18F]DOPA influx (Ki) value in
patients with ASD and healthy control participants.
Secondary outcome
Secondary study parameters are other self-report approximations of social
defeat, used in the secondary objectives 2a and 2b:
1. Degree of ostracism (OES-A).
2. Extent of perceived informal support (ISEL)
3. The desire for acceptance and belonging (Need to belong scale)
4. Degree of exposure to bullying before age 17 (Amended bullying
questionnaire)
5. Size of social network (LSNS)
6. Degree of loneliness (UCLA Loneliness Scale)
The number of sub-clinical psychotic experiences are measured using the PQ-16
(objective 2d).
Other parameters include covariates that might influence dopamine synthesis:
age, sex, smoking status.
Additionally, we will explore the possible confounding effects of factors that
might influence dopamine synthesis and/or social exclusion, such as ADHD
symptoms (ADHD Rating Scale-IV), socioeconomic status (BSMSS), childhood trauma
(JTV), depression (BDI-II), and anxiety (STAI-T).
Background summary
The social defeat hypothesis posits that long-term exposure to the experience
of social defeat (SD) or social exclusion (SE) may lead to increased activity
and/or sensitisation of the mesolimbic dopamine (DA) system and thereby
increase the risk for psychosis/ schizophrenia. The hypothesis may explain the
increased risk for migrants from non-Western countries, individuals with
hearing impairment, low IQ, a history of childhood trauma or a non-heterosexual
orientation. A single-photon emission computed tomography (SPECT) study tested
this hypothesis in young adults with a serious hearing impairment (SHI) and
obtained evidence of DA sensitization in these individuals, because
administration of amphetamine led to a greater striatal dopamine release than
in age-matched normal controls. Individuals with Autism Spectrum Disorder (ASD)
are also vulnerable to social exclusion and at a greatly increased risk to
develop psychosis/schizophrenia. The purpose of this study is to examine
whether the mesolimbic DA system of non-psychotic individuals with ASD is also
sensitized and whether sensitization correlates with social exclusion.
Furthermore, we want to examine if patients with ASD have a higher striatal
dopaminergic activity than healthy controls. To avoid the precipitation of a
psychosis by the administration of amphetamine, it is proposed to conduct a
[18F]DOPA positron emission tomography/computed tomography (PET/CT) study.
Study objective
The first main objective of this study is 1a. To examine whether striatal
[18F]DOPA influx (Ki) values in non-psychotic individuals with ASD are
positively related with the total score on the UCLA Loneliness Scale.
The second main objective of this study is 1b. To examine whether non-psychotic
individuals with ASD have increased striatal [18F]DOPA influx (Ki) values
compared to healthy participants.
Secondary objectives will be to test the following hypotheses:
2a. In non-psychotic individuals with ASD, striatal [18F]DOPA influx values are
positively related to more experiences of being ostracized (OES-A), a greater
discrepancy between the need to belong to others and the perceived availability
of informal support (i.e., a combination of high scores on the Need to Belong
Scale and low scores on the ISEL), a greater severity of bullying experienced
before age 17 (Amended Bullying Questionnaire), and a smaller social network
(LSNS). The purpose of this is to relate other approximations of social defeat
(besides loneliness, see objective 1a) to pre-synaptic striatal dopamine
synthesis.
2b. Compared to healthy participants, non-psychotic individuals with ASD
experience more loneliness (UCLA Loneliness Scale), feelings of being
ostracized (OES-A), a greater discrepancy between the need to belong to others
and the perceived availability of informal support (i.e., a combination of high
scores on the Need to Belong Scale and low scores on the ISEL), a greater
severity of bullying experienced before age 17 (Amended Bullying
Questionnaire), and a smaller social network (LSNS). The purpose of this is to
put the results of 1b in perspective: how socially defeated are individuals
with ASD compared to healthy participants?
2c. Striatal [18F]DOPA influx values in the associative subdivision of the
striatum correlate with measures of social exclusion, not similar values in
other striatal areas.
2d. Striatal [18F]DOPA influx values correlate with the number of sub-clinical
psychotic experiences (PQ-16).
Study design
Cross-sectional.
Intervention
Not applicable.
Study burden and risks
Benefits of this study:
- The study will contribute to our understanding of the aetiology and
neurobiology of psychosis among people who have been socially excluded or
defeated. The first step towards prevention is understanding the biological
mechanisms underlying the increased risk for defeated individuals. If the
results of this study are positive and confirmed by other studies, the
development of drugs to stabilize the mesolimbic dopamine system and thereby
prevent the development of psychosis, is urgently required. Furthermore, mental
health treatment of patients at risk for psychosis, can be focused on reducing
the social exclusion.
- The study may clarify the mechanism whereby people with ASD develop psychotic
disorders.
- Participants who are found to be clinically at ultra-high-risk for psychosis
and participants with high [18F]DOPA influx (Ki) values (upper quartile) may
benefit, because they will be offered CBT, which halves risk for psychosis
within period of 18 months.
Risks of this study:
- Nataf et al. (2006) performed 170 [18F]DOPA PET examinations for the
detection of neuroendocrine tumors. A few of those patients reported a single,
minor adverse effect. They experienced a light and transient burning sensation
at the injection site. This was probably caused by the acidity of the
radiopharmaceutical. To our knowledge, no other side effects have been reported.
- The radiation dose of this study is 3.3 mSv and falls within category IIb
(minor to intermediate). See Appendix K6 for a detailed description of the
radiation dose and accompanying risks.
To avoid the precipitation of a psychosis by the administration of amphetamine,
it is proposed to conduct a [18F]DOPA PET study without amphetamine.
Sandifortdreef 19
Leiden 2333 ZZ
NL
Sandifortdreef 19
Leiden 2333 ZZ
NL
Listed location countries
Age
Inclusion criteria
1. DSM-5 diagnosis of Autism Spectrum Disorder (Patients only, for controls this is an exclusion criterion, see below).
2. Age: 18-30 years.
Exclusion criteria
1. DSM-5 diagnosis of Autism Spectrum Disorder (Healthy controls only)
2. Autism Spectrum Disorder due to a known organic disorder (*Syndromal ASD*, e.g., due to Fragile X syndrome, Klinefelter syndrome, 22q11 deletion syndrome).
3. Neurological disorder (e.g., epilepsy) or evidence of brain damage.
4. History of meningitis.
5. Intellectual disability (IQ<85).
6. Non-affective Psychotic Disorder or Bipolar Disorder (DSM-5: 297.1, 298.8, 295.40, 295.90, 295.70, 292.9, 291.9, 293.81, 293.82, 293.89, 298.9, 296.89, 303.13, 293.83, 296.89, 296.80, 296.4x, 296.5x, 296.7).
7. Social exclusion due to other causes than ASD: visible ethnic minority status, serious physical disability, serious visual or hearing impairment; at discretion of the researcher.
8. Current use of drugs (XTC, cocaine, etc.). Use of cannabis is allowed, but should have been stopped at least one month before the study. Cannabis abuse earlier in life is not allowed.
9. Alcohol- or drug abuse or dependence (DSM-5).
10. Use of an antipsychotic (ever) if prescribed for a psychotic disorder, as a former psychotic disorder is an exclusion criterion. Occasionally, antipsychotics are prescribed against e.g. anxiety or aggression. In these cases:
a) Incidental former use of antipsychotic is allowed, if last use has been more than a year ago.
b) Regular former use of antipsychotic is allowed, if last use has been more than two years ago.
c) Antipsychotic formerly administered as depot medication is allowed, if last injection has been more than two years ago.
11. Use of the antipsychotic quetiapine (ever), if prescribed in relation to a psychotic disorder. However, quetiapine is often prescribed against sleep difficulties and has a low affinity to dopamine receptors. In these cases:
a) Consumption is allowed if previously consumed in a low dose (*50mg), but last use has been more than 3 months ago.
b) Consumption is allowed if previously consumed in a high dose (>50mg), but last use has been more than 6 months ago.
12. Current use of ADHD medication (e.g. methylphenidate). Individuals who have stopped using these drugs for at least one year can participate in the study.
13. Current use of benzodiazepine or promethazine, unless last use has been more than 1 month ago.
14. Current use of other psychotropic drugs. Individuals who have stopped using the drugs for at least 3 months can participate in the study.
15. Smoking during the period of three hours prior to the PET/CT scan and eating or using caffeinated drinks during the period of six hours prior to the PET/CT-scan.
16. Participation in a scientific examination where radiation was used, in the last year.
17. Positive urine drug screen on the day of the PET/CT scan. Participants will be tested on cannabis, amphetamine, XTC, cocaine and opiates.
18. In women: positive pregnancy test on the day of the PET/CT scan and lactation.
19. Metal objects in or around the body.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL54244.058.15 |