Glutamate Levels May Predict Outcomes of Patients at Risk of Psychosis

Changes in hippocampal function are believed to play a role in the onset of psychosis. A study published today in JAMA Psychiatry suggests that the concentration of the neurotransmitter glutamate and several other metabolites in the hippocampus may offer clues about patients who are most likely to transition to psychosis.

The findings suggest that measuring hippocampal metabolites could help psychiatrists better predict outcomes in patients at risk of developing psychosis.

For the study, Matthijs G. Bossong, Ph.D., of the University Medical Center Utrecht in the Netherlands and colleagues used an imaging technique known as proton magnetic resonance spectroscopy (1 H-MRS) to measure baseline levels of glutamate and several other metabolites in 86 individuals at high risk for psychosis and 30 healthy controls. On the day of the scanning, the researchers used several scales to assess the participants’ functioning as well as symptoms of anxiety and depression. About 18.5 months later, the researchers met face to face with 57 of the 86 participants in the high-risk group to assess whether the patients had transitioned to psychosis; they also assessed the overall functioning in this group.

In total, 12 people in the clinical high-risk group experienced a first episode of psychosis; 19 showed “good overall functioning” (Global Assessment of Function, or GAF, scale equal to or greater than 65), whereas 38 of the 57 had “poor functional outcome” (GAF less than 65), Bossong and colleagues reported. The group of patients who transitioned to psychosis were found to have had significantly higher hippocampal glutamate levels at the start of the study than those patients who did not transition. These patients also had significantly higher levels of the metabolites myo-inositol and creatine than those who did not develop psychosis. Moreover, patients with higher levels of hippocampal glutamate at baseline were found to have lower levels of overall functioning at follow-up, the authors reported.

“The findings indicate that adverse clinical outcomes in individuals at high risk for psychosis may be associated with an increase in baseline hippocampal glutamate levels, as well as an increase in myo-inositol and creatine levels,” the authors wrote.

“Pharmacological treatments that engage glutamatergic targets have been generally unsuccessful for treatment of psychotic, negative, and cognitive symptoms of schizophrenia,” Juan R. Bustillo, M.D., of the University of Mexico and colleagues wrote in an accompanying editorial. “However, because schizophrenia is highly heritable and glutamatergic-associated genes are among the most involved, in vivo glutamate measurements may still assist the delineation of subgroups of patients with vulnerable disease stages.”

For related information, see the Psychiatric News article “Multimodal Approach May Improve Ability to Predict Transition to Psychosis.”

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Antipsychotics May Increase Risk of Pneumonia, Meta-Analysis Suggests

Patients who take antipsychotics may be at an increased risk of pneumonia, according to a systematic review and meta-analysis published in the Journal of Psychopharmacology.

After performing a search of several databases, Olubanke Dzahini, B.Pharm., M.Sc., of the Institute of Pharmaceutical Science at King’s College London and colleagues included 14 studies with a total of 206,899 patients in the meta-analysis. By compiling, comparing, and contrasting data from these studies, the researchers sought to assess the overall risk of pneumonia in patients who took first- or second-generation antipsychotics compared with those who did not take antipsychotics. They also examined the risk of pneumonia in patients who took one of six antipsychotics (clozapine, haloperidol, olanzapine, quetiapine, risperidone, and zotepine) compared with those who did not take these medications.

Compared with those who had not taken antipsychotics, those who took first-generation antipsychotics had a 69% increased risk of pneumonia, and those who took second-generation antipsychotics had a 93% increased risk. Those who had taken any of the antipsychotics included in the analysis had an 83% increased risk of pneumonia. However, the researchers found that antipsychotic use did not significantly affect the fatality rate from pneumonia compared with no antipsychotic use.

When the researchers analyzed the data on the six antipsychotics, they found that patients who took these medications had a significantly increased risk of pneumonia compared with those who did not take the medications.

Although antipsychotic use was associated with a higher risk of pneumonia, the researchers stopped short of claiming causality, citing a lack of data from randomized, controlled trials and a failure of observational studies to control for relevant confounders like tobacco use and weight. Yet they suggested ways that antipsychotics may contribute to risk.

“Antipsychotics could increase the risk of aspiration pneumonia through multiple mechanisms, including specific impairment of the protective swallowing and cough reflexes, sedation, hypersalivation, and changes in pharyngeal and laryngeal muscle tone,” the researchers wrote.

The researchers emphasized the importance of considering patients’ existing risk factors for pneumonia, including older age, chronic respiratory disease, cerebrovascular disease, dysphagia, obesity, and smoking. “Clinicians need to be vigilant for the occurrence of pneumonia in all patients who commence antipsychotics. The potential risk needs to be balanced out against the potential benefits of antipsychotic treatment in an individual,” they wrote.

For related information, see the Psychiatric News article “GI, Pulmonary Illnesses: Most Cited for Hospitalizing Clozapine Patients.”

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APA Speaks Out Against Trump Administration’s Efforts to Undercut Women’s Preventive Care

APA joined four other medical specialty organizations on Thursday to urge the Trump administration to reverse actions taken this week that will limit women’s access to contraception.

The organizations spoke out just one day after the Trump administration issued a pair of federal rules that allow some employers to opt out of a requirement under the Affordable Care Act to provide birth control coverage for their employees. The new rules allow some employers to deny coverage on religious or moral grounds.

“By undercutting women’s access to contraception, a key preventive service, at no out-of-pocket cost in private insurance plans, the final rules conflict with our firmly held belief that no woman should lose the coverage she has today,” they said.

The other four organizations that joined with APA were the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the American College of Physicians.

“These rules create a dangerous new standard for employers to deny their employees coverage based on their own moral objections. This interferes in the personal health care decisions of our patients and inappropriately inserts a patient’s employer into the patient-physician relationship,” they cautioned. Additionally, the rules also “open the door to moral exemptions for other essential physician-recommended preventive services, such as immunizations.”

The groups also warned of the harmful effects of reducing women’s access to contraceptives on public health. “We know that when women have unintended pregnancies, they are more likely to delay prenatal care, resulting in a greater risk of complications during and following pregnancy for both the woman and her child. The final rules reject these facts and the corresponding recommendations of the medical community, jeopardizing many women’s ability to maintain a vital component of their health care,” they said.

“Our organizations, which represent more than 423,000 physicians and medical students, stand together in opposition to the administration’s final rules, the Religious Exemptions and Accommodations for Coverage of Certain Preventive Services Under the Affordable Care Act and the Moral Exemptions and Accommodations for Coverage of Certain Preventive Services Under the Affordable Care Act. … We urge the administration to immediately withdraw these rules and instead focus on policies to expand access to evidence-based health care for all Americans.”

The final rules are set to take effect in January 2019.

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Psychiatrists May Have Greater Obligation to Warn in States With Gun Restraining Order Laws

Psychiatrists practicing in one of the many states that have enacted gun violence restraining order laws may have a greater obligation to warn family members or law enforcement in cases of suicidal patients who own firearms, according to an article published in Psychiatric Services.

In the wake of mass shooting tragedies around the country, 13 states have enacted gun violence restraining order laws, also known as extreme risk protective orders (ERPOs). The first five states to put such laws into effect were Connecticut, followed by Indiana, California, Washington, and Oregon, with the remaining states enacting them in 2018.

These laws allow petitioners to have firearms removed from individuals at risk of harming themselves or others, and more states are considering such an approach, wrote William Frizzell, M.D., and Joseph Chien, D.O., of the Department of Psychiatry at Oregon Health and Science University.

Psychiatrists and mental health professionals should determine how such laws might apply to practices in their states. “From a medical-legal perspective, invoking an ERPO law might be seen as a prudent, and perhaps even expected, intervention for suicidal patients with firearms. It might even be viewed as an extension of Tarasoff-like duties in cases of potential gun violence against others,” Frizzell and Chien wrote.

Because most of these laws are new, research is limited, but existing evidence shows that seizing guns from troubled individuals is associated with a reduction in deaths by suicide and provides a needed “cooling-off period,” Frizzell and Chien wrote. The authors called for more research to clarify the effects of these laws to inform legislators in other states about the potential benefits to public health.

Although the laws vary somewhat by state, all allow law enforcement officials—or in some cases family members—to initiate gun removal from individuals who pose a risk to themselves or others and require a low burden of proof. While most of the laws specifically exclude mental health professionals as potential petitioners, Maryland’s law does permit psychiatrists, licensed psychologists, and certain others to initiate gun removal. Some states make the presence of mental illness a central factor, whereas other states disallow its consideration by courts. Other factors, such as criminal history, history of domestic violence, and history of drug or alcohol abuse may be considered by the courts.

The authors pointed out that psychiatrists and mental health clinicians routinely interface with individuals who make statements about using a firearm to inflict injury, and such professionals should consider their duty to warn and protect in these cases. “In other words, now that there exists a legal mechanism for the removal of firearms … mental health providers implicitly could be obligated to recommend an ERPO or at least inform family or law enforcement if they believe an ERPO petition might be warranted,” Frizzell and Chien wrote.

The authors noted that psychiatrists must weigh the patient’s level of risk for gun violence against other considerations, such as patient confidentiality and Second Amendment rights. “In some cases, advising others about initiating an ERPO may be the clinically correct decision—and could save lives,” they concluded.

For related information, see the Psychiatric News article “Resource Document Offers Clinicians Guidance On Risk-Based Gun Removal Laws.”

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Number of College Students Seeking MH Care Nearly Doubles Over Decade

Over the past decade, the percentage of students at U.S. college campuses seeking mental health care has increased significantly—from 19% in 2007 to 34% in 2017, according to a study published Monday in Psychiatric Services. The most common location for the college students to receive these services was on campus, the study found.

“This study provides the most comprehensive evidence to date regarding upward trends in mental health service utilization on U.S. campuses over the past 10 years,” wrote Sarah Ketchen Lipson, Ph.D., Ed.M., of Boston University School of Public Health and colleagues. “To better meet the mental health care demand from students and reduce strain on existing services, campuses may wish not only to expand capacity but also to increase the use of preventive and digital mental health services, such as those delivered via mobile apps.”

For the study, Lipson and colleagues analyzed 10 years of data collected for the Healthy Minds Study—an annual web-based survey examining mental health, use of mental health services, and related issues among undergraduate and graduate students. Students at participating institutions were randomly recruited to participate in the survey by email and were required to be at least 18 to participate.

Of the 155,026 students (56.5% female; 74.0% white) from 196 campuses included in the sample, 26.9% screened positive for depression, and 8.2% reported suicidal ideation within the past year. Students most commonly reported receiving services for mental health care on campus, with rates increasing from 6.6% in 2007 to 11.8% in the 2016-2017 academic year. The rate of students reporting past-year treatment increased from 18.7% in 2007 to 33.8% in 2016-2017, with similar patterns for both therapy/counseling and medication use. The proportion of students with a diagnosed mental health condition also increased over this period, from 21.9% in 2007 to 35.5% in 2016-2017.

Between 2007 and 2017, students reported less stigma regarding mental illness: the percentage of students who agreed with such statements as “most people think less of a person who has received mental health treatment” (perceived stigma) or “I would think less of a person who has received mental health treatment” (personal stigma) dropped from 64.2% to 46.0% and from 11.4% to 5.7%, respectively.

“The trends revealed in this study have strained counseling centers across the country, given that many are underresourced and operate at full capacity with waitlists for much of the year,” the researchers wrote. “There are a multitude of approaches to consider for alleviating this strain, including universal prevention programs and rapid referral to community treatment.”

For more on what colleges can do to help students seeking mental health care, see the Psychiatric News article “Duck Syndrome, Social Media, and Struggling Together” by Matthew C. Fadus, M.D.

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Negative Thoughts, Fears Linked to Risk of Suicide in Patients With Psychosis

Negative thoughts about psychotic experiences and fears of losing mental control may heighten the risk of suicide in patients with psychosis who were not taking antipsychotics, suggests a report in Schizophrenia Bulletin.

“Overall, our findings emphasize the importance of clinicians promoting a recovery-focused and appropriately optimistic outlook when working with people with psychosis, taking care to avoid providing information that might heighten negative illness appraisals and/or fears of losing mental control,” wrote Paul Hutton, Ph.D., of the Edinburgh Napier University in the United Kingdom and colleagues.

Hutton and colleagues analyzed data on 68 patients in a pilot trial designed to assess the effects of cognitive therapy on individuals with schizophrenia who had not taken antipsychotics for at least six months. At the start of the study and follow-ups at nine and 18 months, the researchers measured the patients’ psychotic symptoms using the Positive and Negative Symptom Scale; they also measured negative beliefs and attitudes using the Personal Beliefs About Experiences Questionnaire and the Metacognitions Questionnaire-30.

The researchers found that symptoms of psychosis were more likely to be linked to suicidal thinking at nine to 18 months when the patients held negative thoughts and fears. Negative thoughts and fears about consequences of symptoms leading to loss of mental control accounted for 37 percent of the association between those symptoms and suicidal thinking, according to the report.

According to the researchers, the findings call for randomized, control trials of special therapies that address negative cognitive beliefs, such as metacognitive therapy, metacognitive reflection and insight therapy, and cognitive analytic therapy to examine their effect on suicidal thinking.

“Consistent with previous findings that fears of mental disintegration are strongly associated with suicide in psychosis, our results suggest that the way people appraise their symptoms and their consequences, including whether they [have] heighten[ed] concerns about losing mental control, may partly determine whether [their symptoms] lead to thoughts of suicide,” Hutton and colleagues wrote.

For related information, see the Psychiatric News article “Upping Our Game Against Suicide” by APA Past President Anita Everett, M.D.

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Gene Risk Scores May Predict Antipsychotic Response in Patients With First-Episode Psychosis

A study published today in AJP in Advance suggests that calculating the polygenic risk score (PRS) of a patient with first-episode psychosis can offer clues as to whether he or she will respond to antipsychotics. A PRS involves adding up the total number of genetic variants associated with schizophrenia risk in an individual’s DNA.

“Polygenic risk scores represent the combined effects of many thousands of genetic variants across the entire genome, and better represent the very complex genetic nature of schizophrenia,” said lead study author Jian-Ping Zhang, M.D., Ph.D., an assistant professor at the Feinstein Institute for Medical Research, in a press release.

Zhang and colleagues first analyzed DNA samples from 510 patients with first-episode psychosis who were participating in one of four clinical trials testing antipsychotic medications (two trials in the United States and two in Europe). The researchers identified how many genetic variants associated with the risk of developing schizophrenia each participant had. The total number of variants was used to calculate a polygenic risk score. They next compared the patients’ PRS score with how well they responded to the assigned antipsychotic (which in these four studies included amisulpride, aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone). The patients were considered to have responded to treatment if they experienced a reduction of 50% or more in total symptom scores from baseline to the 12-week follow-up.

The researchers found that the higher the PRS score a patient had, the more likely he/she would not respond to antipsychotic medication. When the researchers grouped the patients from all of the trials according to high and low PRS scores, they found 60.9% of patients in the low PRS group responded to antipsychotics compared with 52.1% in the high PRS group. The difference was even greater when only the two clinical trials involving people of European ancestry were analyzed; combining these two cohorts, the response rate in the low PRS group was 61.8% compared with 45.8% in the high PRS group.

“The results we found open the door for ‘precision medicine’ approaches to psychiatry, and more specifically, the use of polygene scores as a new technology for the treatment of psychiatric disorders,” said study co-author Todd Lencz, Ph.D., also of the Feinstein Institute, in the press release.

For related information, see the Psychiatric News article “Genetic Variant May Foretell Cognitive Response to Antipsychotics.”

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