3 Apr 2016
The Fifth Schizophrenia International Research Society (SIRS) conference got underway in balmy Florence, Italy, on Saturday evening, April 2. With about 1,800 attendees hailing from 54 countries gathering at the Firenza Fiera Conference Center, the meeting was the biggest—and most exclusive—ever: SIRS President Rene Kahn of the University Medical Center Utrecht in the Netherlands mentioned in his opening remarks that only one-third of submitted abstracts had been accepted. The keynote speech followed, with Susannah Cahalan, author of Brain on Fire, sharing her story of being struck down, and recovering from, NMDA receptor autoimmune encephalitis. Though the condition is thought to be a rare cause of psychosis, her story had several clinicians wondering afterward whether they had missed such a condition in some of their patients.
On Sunday, April 3, plenary speaker Jeff Conn of Vanderbilt University in Nashville, Tennessee, kicked off the science of the meeting. He gave an update on his efforts to develop positive allosteric modulators (PAMs) for receptors, which would potentiate the response of a receptor when it binds to its native neurotransmitter, but which would not activate the receptor by itself. This kind of amplification of naturally occurring signaling might avoid some of the troublesome side effects that come with drugs that directly activate or block receptors. With a pharma-like pipeline in place at Vanderbilt to develop and test new compounds, Conn reported on a PAM selective for the M1 subtype of the muscarinic receptor that had pro-cognitive effects (Ghoshal et al., 2016) and may be tested in a clinical trial as early as this September. An M4 PAM in mice had antipsychotic effects stemming from decreased dopamine release in the striatum. He also mentioned designing modulators to improve the function of metabotropic glutamate receptors hampered by schizophrenia-related mutations (e.g., Cho et al., 2014).
After a coffee break, Til Wykes of King's College London in the UK gave an expansive overview of psychological treatments in her plenary talk to a full house. She said that clinicians should take a cue from what people with schizophrenia say they wish for in their recovery—independence, life skills, work, and fulfilling relationships. She focused on the evidence for cognitive therapies, arguing that cognitive behavioral therapy in particular, recently controversial, stands as an effective approach and warned that meta-analyses need to be careful to choose appropriate studies and to not mix up outcomes. She also grappled with negative studies: Do they nullify an entire approach, or do they say something more specific about how a therapy was delivered or to whom it was given? Wykes also provided a glimpse of new innovations such as avatar therapy, virtual reality approaches, and computerized cognitive therapies, yet cautioned against "digital exclusion" of people with severe mental illness who may not have the needed devices or data plans for these approaches.
Trauma complicates things
On Sunday afternoon, a symposium offered new data on the confusing relationship between trauma, psychosis, and outcomes. Following up on his meta-analysis that found childhood adversity to be a risk factor for psychosis (Varese et al., 2012), Filippo Varese of the University of Manchester in the UK proposed that the quality of attachment to one's parents or feelings of dissociation could determine how a person reacts to trauma. Consistent with this, his recent meta-analysis found an association between dissociation and hearing voices (Pilton et al., 2015).
Martine Van Nierop of Maastricht University in the Netherlands explored the idea that childhood trauma may contribute to the co-morbid symptoms such as anxiety or depression that often accompany a psychotic disorder. In healthy controls, she found that people with childhood trauma report more subclinical symptoms of depression, anxiety, mania, or psychosis. In those with a psychiatric disorder, the ones with childhood trauma and co-morbid symptoms in these domains have worse outcomes, more severe symptoms, and increased substance abuse. The connection might be mediated by stress reactivity: in a separate study of the general population, those with childhood trauma were more sensitive to stress than those who did not report abuse, though their levels of cortisol, a stress hormone, did not differ.
Child abuse may not necessarily doom people to repeated psychotic episodes, according to data from Helen Fisher of King's College London. She described a 10-year follow-up study of more than 100 people first enrolled in the AESOP (Aetiology and Ethnicity of Schizophrenia and Other Psychoses) study at their first episode of psychosis. When contacted a decade later, of those with a psychotic disorder (62 percent of whom had schizophrenia), one-third reported severe child abuse. This subgroup was less likely to fall ill with another psychotic episode; however, they still faced substantial challenges, as they were more likely to have attempted suicide, be unemployed, and have more severe non-psychosis symptoms than those not reporting abuse.
Treating PTSD-like symptoms can bring benefits to people with psychotic disorders, reported Mark Van der Gaag of VU University Amsterdam in Oegstgeest in the Netherlands. Noting that people with psychosis are usually excluded from trauma trials, he described the results of his Treating Trauma in Psychosis Trial (T.TIP) in which 16 percent of those screened met full criteria for PTSD. This subgroup consisted of people with schizophrenia (95 percent) who had been sick for an average of 17 years; 60 percent had attempted suicide. "This is the most ill population I've ever worked with," he said. Two common treatments for PTSD—exposure therapy and eye movement desensitization (in which therapists wag a finger in front of patients to distract them while they conjure up traumatic memories)—worked for this subgroup, and 60 percent lost their PTSD diagnosis. "Schizophrenia patients are human beings and respond to these therapies like human beings, too," Van der Gaag said.
Robin Murray of King's College London wrapped up the session as the discussant. He urged researchers to collect DNA in these trauma studies, noting that genetics could be mediating some of the effects. For example, parents with mental illness may be more likely to abuse their children, or children with atypical development due to genetic variation may be more prone to bullying, or how people react to adversity may depend on their genes. He ended by acknowledging the inherent difficulty of talking about childhood trauma as a risk factor for psychosis without returning to the bad old days when parents were often blamed. "How are we going to address the question of childhood trauma without offending the people who are outstanding parents?" he asked.—Michele Solis.