9 Oct 2014
October 10, 2014. Like people with schizophrenia, those with severe hearing impairment (SHI) show increased dopamine hypersensitivity in the striatum, reports a new study published online October 1 in JAMA Psychiatry. The findings bolster the social defeat hypothesis of schizophrenia, first suggested in 2005 by lead study author Jean-Paul Selten of the Rivierduinen Institute for Mental Health Care, Leiden, the Netherlands.
The hypothesis originated as a parsimonious explanation for why a variety of risk factors, especially migration and childhood trauma, are associated with schizophrenia (see SRF related news report). It states that long-term exposure to social defeat—the negative experience resulting from being excluded from the societal majority—results in a sensitization of the mesolimbic dopamine system that predisposes one to psychosis (Selten et al., 2013).
Support for the hypothesis comes from animal studies that demonstrated alterations in mesolimbic dopamine release as well as in behavioral responses to amphetamine following chronic social defeat (see SRF related news report). In addition, human imaging studies report elevated presynaptic dopamine function not only in schizophrenia, but also in high-risk individuals (see SRF related news report; SRF news report).
In people with severe hearing impairment (SHI)—a condition associated with an elevated risk for psychosis—communication challenges result in feelings of isolation, making them a unique population for examining the effects of social defeat. In the current study, first author Martin Gevonden and colleagues used single-photon emission computed tomography (SPECT) to assess whether subjects with SHI showed increased dopamine release in the striatum in response to amphetamine and whether their experience on the drug was different from that of healthy controls.
Dexamphetamine and dopamine
A total of 19 subjects in the SHI group, who on average detected about half of the syllables during a loud conversation, were individually matched to a healthy control based on age, smoking, and sex. An initial SPECT scan using a dopamine D2/3 radiotracer showed that its baseline non-displaceable binding potential, a measure of D2/3 receptor availability, did not differ between the two groups. A second scan was performed to measure dopamine release one hour after administration of the amphetamine isomer dexamphetamine sulfate. Subjects with hearing loss displayed a 19 percent decrease in the non-displaceable binding potential between the two scans, while healthy controls had an 11 percent reduction, indicating that SHI subjects released more dopamine than the controls.
Gevonden and colleagues also asked if this increase in dopamine release was associated with measures of social defeat. Not surprisingly, the SHI group scored worse on the UCLA Loneliness Scale and the Social Defeat Scale than the healthy controls at baseline; however, there was no significant correlation between either measure and subsequent dopamine release.
The dexamphetamine experience
The researchers next assessed whether the increase in dopamine release was associated with symptomatology. Self-reported positive, negative, and depressive symptoms, assessed using the Community Assessment of Psychic Experiences (CAPE) questionnaire, did not differ between the two groups either before or after amphetamine treatment. Although they did not measure plasma levels of dexamphetamine, the researchers note that the elevated salivary cortisol levels, as well as increased blood pressure and heart rate, suggest the administered dose was adequate.
Amphetamine altered both groups' affect throughout the two hours following administration, producing changes in euphoria, energy, restlessness, and anxiety. The SHI group experienced a significantly larger drop in euphoria and energy than did controls, and a significant increase in anxiety.
The results of the current study suggest that severe hearing impairment is associated with striatal dopamine hypersensitivity and lend support to the social defeat hypothesis of schizophrenia. However, the authors acknowledge that they "cannot conclude whether or not social exclusion plays a causal role in the observed difference in dopamine functioning or in the previously observed increased risk for psychosis in people with hearing impairment." Future studies with larger sample sizes and alternative populations of socially marginalized people are needed, they added.—Allison Marin.
Gevonden M, Booij, van den Brink W, Heijtel D, van Os J, Selten J-P. Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia. JAMA Psychiatry. 2014 Oct 1. Abstract