Cardiovascular Risk Factors May Predict Brain Changes, Cognitive Decline

A study published this week in the journal Radiology suggests that subtle differences in regional brain volumes that appear to be related to cardiovascular risk factors may potentially serve as an early indicator of cognitive decline before the onset of dementia.

Researchers from the Keck School of Medicine at the University of Southern California, Los Angeles, analyzed data from 1,629 participants in the Dallas Heart Study, aged 25 to 73, to investigate modifiable cardiovascular risk factors (alcohol consumption, smoking, diabetes, and obesity) associated with regional brain volume changes and their association with preclinical deficits in cognitive performance. Participants’ cardiovascular risk factors were evaluated in an initial baseline visit; brain volumes and cognitive function were assessed seven years later by, respectively, magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA).

The results showed that alcohol consumption and diabetes were associated with smaller total brain volume, while smoking and obesity were associated with reduced volumes in the posterior cingulate cortex. Lower hippocampal volume was associated with previous alcohol consumption and smoking, and lower precuneus volume correlated with alcohol consumption, obesity, and high fasting blood glucose numbers.

Low total scores for MoCA were associated with reduced posterior cingulate volume in participants under 50 and with reduced hippocampal and precuneus volumes in those 50 and over.

“Our findings reveal that lower total brain, hippocampal, precuneus, and posterior cingulate volumes are associated with cardiovascular risk factors and with impaired cognitive performance before the onset of clinical dementia. … even in participants younger than 50 years,” the researchers noted. They concluded that subtle differences in regional brain volumes in midlife may serve as a biomarker for brain insult before the onset of dementia.

To read more about associations between brain volume and cognitive function, see the Psychiatric News article, “Study Provides New Details on How Brain Ages.”

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FDA Issues Warning Over Brintellix, Brilinta Confusion

The Food and Drug Administration today issued a warning to health care professionals and patients concerning reports of confusion between the antidepressant Brintellix (vortioxetine) and the anti-blood clotting medication Brilinta (ticagrelor), which has resulted in the wrong medication being prescribed or dispensed.

The FDA has determined that the main reason for the confusion between the two medications—with extremely different indications—is the similarity in the marketed names of the drugs. While Brintellix is used to treat major depressive disorder, Brilinta is used to lower the risk of recurrent heart attacks or death from a heart problem after a heart attack or severe chest pain.

To reduce the risk of name confusion, the FDA recommends that health care professionals include the generic name of the medication (e.g., vortioxetine) in addition to the brand name and the indication for use when prescribing the medication. The FDA also recommends that patients check their prescriptions to ensure that the correct medication was dispensed.

Thus far, no reports made to the FDA regarding the name confusion have indicated that a patient has ingested the wrong medication; however, the agency announced that reports of prescribing and dispensing errors continue.

Researchers Identify, Validate Potential Serum Biomarker Panel for First-Onset Schizophrenia

The ability to firmly diagnose schizophrenia before symptoms of the disease arise can help improve patient outcomes by reducing periods of untreated psychosis. In a paper recently published in Translational Psychiatry, Sabine Bahn, M.D., Ph.D., of the University of Cambridge and colleagues describe the development of a biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples.

The researchers first conducted a meta-analysis of five independent cohorts comprising 331 first-onset drug-naive schizophrenia patients and controls to establish a diagnostic serum biomarker panel, which led to the identification of 26 biomarkers that best discriminated patients and controls. Next, they evaluated the diagnostic performance of the 26-analyte panel using samples from two independent cohorts comprising 93 patients diagnosed with first- or recent-onset schizophrenia and 88 controls, which yielded an area under the curve (AUC) of 0.97 (sensitivity=87%, specificity=97%, accuracy=93%) for schizophrenia detection. Lastly, the researchers tested the predictive performance of the panel before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals.

According to the authors, “The predictive performance achieved by the panel was excellent for identifying U.S. military personnel (AUC: 0.90 [0.86–0.95]) and help-seeking prodromal individuals (AUC: 0.82 [0.71–0.93]) who developed schizophrenia up to two years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 [0.82–0.98]).”

While the authors acknowledged that further validation studies using larger independent pre-onset sample sets are needed, they wrote, “[t]he biomarker panel presented here represents a validated set of biomarkers from which a definitive signature for diagnosis and prediction of schizophrenia in the clinical setting could be developed. Ultimately, further developments of the biomarker panel could form the basis of a low-cost blood test, which can complement DSM-5- or ICD-10-based diagnostic approaches.”

To read more about potential biomarkers for psychiatric illness, see the Psychiatric News article “Potential Biomarker for Suicide Vulnerability Identified.”

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Social Integration Lowers Risk of Suicide in Women, Researchers Say

Being socially well integrated appears to lower the risk of suicide in women, according to a study published online today in JAMA Psychiatry.

To examine the association between social integration and suicide, Alexander Tsai, M.D., Ph.D., of Massachusetts General Hospital and colleagues analyzed data from 72,607 women participating in the Nurses’ Health Study who were surveyed about their social relationships from 1992 to 2010. Social integration was based on a seven-item scale covering “marital status, social network size, frequency of contact with social ties, and participation in religious or other social groups.”

Overall, there were 43 suicides during 1,209,366 person-years of follow-up—a rate the authors noted is lower than suicide rates nationally. After adjustment for age and other variables, the authors determined that women with the highest level of social integration had a hazard ratio for suicide of 0.23 versus 1.0 for women recording the lowest level of social integration.

“Our study strongly suggests that social integration has a protective association against suicide risk for women, even after adjustment for multiple indicators of poor mental health,” the authors wrote. “Interventions aimed at strengthening existing social network structures, or creating new ones, may be valuable programmatic tools in the primary prevention of suicide.”

“[T]he results of their study invite further research to explore whether factors or behaviors that reflect longstanding measures of individual social integration predict a person’s mindset when he or she is suicidal,” wrote Eric Caine, M.D., a professor of psychiatry at the University of Rochester, in an accompanying editorial.

For more in Psychiatric News about suicide, see “Stigma: ‘I Need to Tell You Something I’ve Never Spoken to You About’.”

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Physical Activity May Be Protective Against Suicidality in Bullied Adolescents

Physical activity appears to be inversely related to sadness and suicidality in adolescents and may be protective against suicidality in adolescents who are bullied, according to a report in the Journal of the American Academy of Child and Adolescent Psychiatry.

Using the 2013 National Youth Risk Behavior Survey (N=13,583), researchers from the University of Vermont analyzed the effect of physical activity on odds ratios for sadness, suicidal ideation, and suicide attempts according to whether students were bullied.

Overall, 30.0% of students reported sadness for at least two weeks, 22.2% reported suicidal ideation, and 8.2% reported suicide attempts in the previous 12 months. Bullied students were twice as likely to report feeling sad and three times as likely to report suicidal ideation or attempts.

But students who reported exercising four to five days per week had lower adjusted odds of sadness, suicidal ideation, or suicide attempts than students who exercised one day or less each week. After stratifying by bullying, similar but slightly weaker associations were observed. Overall, exercise for four or more days per week was associated with an approximately 23% reduction in suicidal ideation and attempts in bullied students.

“The consequences of bullying are well described, yet little is known about protective factors that may diminish the negative sequelae,” the researchers stated. “One possible factor, physical activity, improves mental health in general and clinical populations....We hypothesized that physically active students would be less likely to feel sad or report suicidal ideation or attempts, including bullied students."

For related information, see the Psychiatric News article "Effects of Bullying Don't End When School Does."

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Sedentary Lifestyle in Early Adulthood May Contribute to Worse Cognitive Function in Midlife, Study Suggests

A study presented at the 2015 Alzheimer’s Association International Conference, held last week in Washington, suggests that frequencies of physical activity and television viewing in early adulthood may impact cognitive function in midlife.

To investigate whether an association exists between long-term patterns of low physical activity and high television viewing time in early adulthood and cognitive decline in midlife, Kristine Yaffe, M.D. (pictured left), the Roy and Marie Scola Endowed Chair and Vice Chair of Research in Psychiatry at the University of California, San Francisco, and colleagues analyzed data of more than 3,200 individuals, aged 18 to 30. The physical activity and television viewing of the participants were assessed at three or more visits over 25 years. At year 25 of the study, the researchers assessed the participants’ memory, executive function, and processing speed. The investigation was a part of the Coronary Artery Risk Development in Young Adults study.

The researchers found that participants who reported low physical activity (less than 300 kcal/50 min session, three times per week) in more than two-thirds of the follow-up visits had significantly worse cognition in midlife than individuals reporting less frequent physical inactivity—even after adjusting for education, smoking habits, alcohol consumption, body mass index, and hypertension. Participants who reported regularly watching television for more than 4 hours per day throughout the study also had worse midlife cognition than those who reported less television viewing. Those who reported a history of long-term low physical activity and high television viewing were almost two times more likely to have poor cognitive function in midlife.

The researchers said that because global data suggests that levels of physical inactivity and sedentary behavior are increasing, understanding the relationship between physical activity in early adulthood and cognitive decline later in life may be of importance. They concluded that because research indicates that Alzheimer's disease and other dementias develop over several decades, increasing physical activity and reducing sedentary behavior beginning in early adulthood may have a significant public health impact.

An overview of the study by Yaffe is available here.

For more information about the role of physical activity in reducing the onset Alzheimer's disease or other dementias, see the Psychiatric News article "Exercise Found to Reduce Amyloid Plaques in Brain."

Attention-Control Training Found to Improve PTSD Symptoms

Attention-control training is more effective than attention-bias modification at reducing the symptoms of posttraumatic stress disorder (PTSD), according to a study published today in American Journal of Psychiatry in Advance.

Attention-bias modification is designed to shift attention away from perceived threat, whereas attention-control training aims to balance attention between threat and neutral stimuli.

This study compared these two attention strategies in two groups of veterans: one in Israeli Defense Forces veterans and the other in U.S. military veterans. The protocol involved computerized tests focusing the participants’ attention on either neutral or aggressive words.

In both groups, the attention-control training was far more effective in reducing both self-reported and clinician-reported PTSD symptoms in the participants. Attention control, but not attention-bias modification, also reduced the participants’ variability in their attention bias, which is how much they shifted their attention toward or away from threat within a training session.

When the results of both training sessions were combined, the analysis showed that this normalization of attention variability was at least partially responsible for the related improvements in PTSD symptoms. Thus, the authors suggested that balancing these moment-to-moment attention shifts from threat vigilance to threat avoidance may be a preferred treatment strategy.

To learn about another potential approach to treating PTSD, see the Psychiatric News article “Trial of Interpersonal Therapy May Open New Door to Treat PTSD.”

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Many Vietnam Vets Still Have Current PTSD, Study Shows

More than a quarter-million Vietnam War veterans appear to still have current PTSD related to their experience, according to an analysis of survey data appearing in JAMA Psychiatry.

Researchers led by Charles R. Marmar, M.D., from the Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and Traumatic Brain Injury at the New York University Langone Medical Center, New York, and other institutions analyzed data from the National Vietnam Veterans Readjustment Study (NVVRS). That survey consisted of a self-report health questionnaire (n=1,409), a computer-assisted telephone survey health interview (n=1,279), and a telephone clinical interview (n=400) in a representative national sample of veterans who served in the Vietnam theater of operations. A total of 1,839 veterans participated in at least one NVVRS study phase.

Study instruments included the Mississippi Scale for Combat-Related PTSD, PTSD Checklist for DSM-IV supplemented with PTSD Checklist for DSM-5 items (PCL-5+), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and Structured Clinical Interview for DSM-IV, Nonpatient Version.

They found that among male theater veterans, the prevalence of current PTSD ranged from 4.5% based on CAPS-5 criteria to 11.2% using PCL-5+ criteria. Among female veterans, estimates were between 6.1% and 8.7%. Comorbid major depression occurred in 36.7% of veterans with current war-zone PTSD. With regard to the course of PTSD, 16% of theater veterans reported an increase and 7.6% reported a decrease of greater than 20 points in Mississippi Scale for Combat-Related PTSD symptoms.

“Approximately 271,000 Vietnam theater veterans have current full PTSD plus subthreshold war-zone PTSD, one-third of whom have current major depressive disorder, 40 or more years after the war,” the researchers stated. “These findings underscore the need for mental health services for many decades for veterans with PTSD symptoms.”

In an editorial accompanying the study in JAMA Psychiatry, Charles W. Hoge, M.D., of the Center for Psychiatry and Neuroscience at the Walter Reed Army Institute of Research, said, “The study is of vital importance to subsequent generations of war veterans and underscores medical service needs for PTSD and related comorbidities extending decades after service. The study also highlights a need to reconsider changes to the PTSD definition, a definition intimately connected with the Vietnam generation and the foundation for the past 25 years of epidemiologic, neurobiological, and clinical knowledge and evidence-based treatment practices."

For more information see the Psychiatric News article, "Serious Heart Disease Found in Vietnam Vets With PTSD."

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Novel Twist on Fear Extinction Opens New Doors for Research

Something’s better than nothing, at least when using extinction as a means of overcoming fear conditioning, according to Joseph Dunsmoor, Ph.D., Elizabeth A. Phelps, Ph.D., and colleagues from the Psychology Department and Center for Neural Sciences at New York University, writing in the August 1 issue of the journal Biological Psychiatry.

Extinction normally overcomes the association between a benign conditioned stimulus (like a sound or light) and a threatening unconditioned stimulus (like an electric shock) by overlaying a newly learned memory that couples the conditioned stimulus with the absence of threat.

However, that effect often wears off over time, so the researchers used both rats and humans to test another way to extinguish fear. Rather than simply leaving out the shock, they replaced it with a new, nonaversive tone. The goal was to eliminate any ambiguity about the safety or danger of the conditioned stimulus by using the element of surprise to generate “a mismatch between the predicted and received outcome, therefore signaling a clear change in the environment to promote the acquisition of new learning” and “providing a more substantive alternative association for the conditioned stimulus than no shock,” they wrote.

If used in exposure treatments for disorders like anxiety or PTSD, this “novelty-facilitated extinction” may neutralize negative beliefs “by experiencing an unexpectedly mundane event, rather than simply experiencing the absence of a negative event.”

For more in Psychiatric News about fear extinction research, see “Context Is Critical in PTSD Fear Learning.”

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Ultrabrief Pulse ECT Offers Similar Benefit to Standard ECT With Fewer Side Effects

Electroconvulsive therapy (ECT) is known to be a highly efficacious treatment for depression, but it has been associated with cognitive side effects in patients. A meta-analysis of studies published online today in the Journal of Clinical Psychiatry suggests that ultrabrief pulse stimulation is almost as effective as standard brief pulse ECT with fewer side effects.

ECT has historically been administered with brief pulses (1 ms in width). While some studies suggest ECT delivered with ultrabrief pulses (0.25-0.37 ms) may show similar rates of efficacy as the standard method, others have produced conflicting results.

Colleen Loo, M.D., a professor of psychiatry at the University of New South Wales, and colleagues conducted a systematic review of studies comparing brief pulse and ultrabrief pulse right unilateral ECT in patients that reported mood ratings for depression. They identified six studies involving 689 patients (261 receiving brief pulse right unilateral ECT and 428 receiving ultrabrief pulse right unilateral ECT) and used statistical analysis to examine the efficacy and cognitive side effects of brief pulse versus ultrabrief pulse right unilateral ECT.

The analysis revealed that while brief pulse ECT has a small efficacy advantage (reflected in both mean change in mood ratings, remission rates over the ECT course, and one fewer session in the treatment course) over ultrabrief pulse ECT, it was associated with significantly more cognitive side effects in all cognitive domains examined, including global cognition, anterograde learning and recall, and retrograde memory.

"The decision of whether to use BP [brief pulse] or UBP [ultrabrief pulse] RUL [right unilateral] ECT should be made on an individual patient basis and should be based on a careful weighing of the relative priorities of efficacy versus minimization of cognitive impairment," the study authors concluded.

For related information, see the Psychiatric News article “Psychiatrists Discuss Benefits, Risks of ECT.”

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Autoimmune Disorder May Be Linked With Some Cases of Postpartum Psychosis

Previous studies have found that some women who develop psychosis during the postpartum period undergo significant changes in their immune systems. A new study published in AJP in Advance now finds autoimmune encephalitis may underlie about 4% of postpartum psychosis cases and suggests that autoantibody screening should be considered as part of the diagnosis.

Antibody screenings were performed on 96 women who developed postpartum psychosis and 64 healthy postpartum women. Four of the patients with psychosis tested positive for neuronal cell surface antibodies suggestive for encephalitis—two of these patients were identified as having anti-NMDA receptor encephalitis; the other two patients did not test positive for any known brain antigen. In contrast, none of the 64 healthy controls tested positive for any autoimmune activity. This is important as false positives are a major concern when considering clinical screening.

The researchers also found that the women with postpartum psychosis and anti-NMDA receptor autoantibodies exhibited extrapyramidal symptoms with low-dose haloperidol—“a clinical response that is not particularly common among patients with postpartum psychosis,” they noted.

“In patients with acute psychosis during the postpartum period, systematic screening for anti-NMDA receptor autoantibodies should be considered,” the study authors concluded. “The acute onset of severe atypical psychiatric symptoms in young female patients should raise the index of suspicion for anti-NMDA receptor encephalitis, particularly in the setting of neurological symptoms, including extrapyramidal side effects of antipsychotic treatment.”

To read more about the treatment of postpartum psychosis, see the recent AJP article “Treatment of Psychosis and Mania in the Postpartum Period.”

(Bergink et al., AJP in Advance, July 17, 2015)

Study Finds Stimulant Abuse Is Associated With Reduced Brain Volume in Women

Even after a prolonged period of abstinence, women who were previously dependent on stimulants appear to have significantly less gray matter volume in several brain regions compared with women with no history of stimulant abuse, a study published this week in the journal of Radiology reports. In contrast, significant brain volume changes were not seen when comparing men with a similar history of stimulant abuse to those without.

To determine how the brains and behavioral patterns of people previously dependent on stimulants differed across gender lines, researchers from the University of Colorado School of Medicine compared the structural brain magnetic resonance imaging (MRI) exams of 59 men and women who were previously dependent on cocaine, amphetamines, and/or methamphetamine for an average of 15.7 years with those of 68 people with no history of stimulant drug dependence. Participants with past stimulant addictions had been abstinent on average 14 months at the time of the study.

The data showed that women who were previously dependent on stimulants had significantly less gray matter volume in widespread brain regions (including frontal, limbic, and temporal regions) than nondependent women; no differences in gray matter volume were observed between male control subjects and men with stimulant dependence. Lower gray matter volumes in the nucleus accumbens of women with a history of stimulant dependency were associated with the severity of drug abuse, and lower volumes in the frontal and temporal lobes were associated with elevated impulsivity and behavioral tendencies to seek reward.

“These differences between the sexes could reflect a greater neuroanatomic endophenotype in women that predisposes them to stimulant dependence or a vulnerability to morphologic changes that result from stimulant dependence,” the study authors wrote. “Understanding sex differences in both the neuroimaging and clinical course of substance dependence could lead to improved sex-specific or individualized medical treatment and recovery plans.”

To read more on other structural brain changes that are linked to stimulant use, see the Psychiatric News article “Abnormalities Found in Brain Area of Cocaine Addicts.

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Study Finds Only Half of Those With Suicidal Thoughts Seek Mental Health Services

Connecting individuals who are at high risk of suicide to effective mental health treatment can be lifesaving. But, as a study published online Wednesday in Psychiatric Services in Advance found, many with thoughts of suicide fail to access mental health services.

Approximately half of individuals reporting past-year suicide ideation, plans, or attempts reported contact with mental health services (inpatient, outpatient, or psychiatric prescription medication) over the same period, according to an analysis of data from the 2013 National Survey on Drug Use and Health by researchers at Florida State University.

For the study, the researchers examined the sociodemographic characteristics and past-year reports of general health, psychological distress, depression, and mental health service use by adults aged 18 or older, including 2,126 who had reported past-year suicide ideation, 690 who reported they had made past-year suicide plans, and 345 who reported past-year suicide attempts. Findings were compared with those of individuals who reported no past-year suicide ideation (N=35,106).

Those most likely to report contact with mental health services in the past year included females, non-Hispanic whites, those in poor health, and those who reported past-year psychological distress or a past-year diagnosis of a major depressive episode. The authors noted that “no differences in service use across groups emerged on the basis of poverty or marital or health insurance status, with one exception: those with health insurance in the ideation group were more likely to use services than those without insurance.

“Moving forward, efforts must be made to develop and rigorously test programs targeted at increasing service use among suicidal adults,” the authors continued. “Given the correlates of service use identified by this study, effective approaches may involve improving access to care for those without insurance, implementing screening and referral procedures in primary care and emergency department settings, and crafting interventions that are culturally sensitive and acceptable to males.”

For more on efforts to reach patients who may be suicidal, see the Psychiatric News article “Mayo Program Teaches Residents to Empathize With Suicidal Patients.”

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Researchers Report Two Gene Loci Associated With MDD

Researchers have made important strides in recent years in finding genetic loci associated with risk for schizophrenia and autism, but similar steps in depression have remained more elusive.

Now, a group of scientists have reported that a study comparing 5,303 Han Chinese women with recurrent major depressive disorder (MDD) with 5,337 controls revealed two loci on chromosome 10 that contribute to risk of MDD. The findings, published online today in the journal Nature, are the work of Kenneth Kendler, M.D., a professor of psychiatry at Virginia Commonwealth University School of Medicine in Richmond, and other U.S., British, and Chinese colleagues from the CONVERGE consortium.

The team found that one locus lies near the SIRT1 gene and the other in an intron of the LHPP gene. The findings were replicated in a separate cohort of more than 6,000 Han Chinese men and women (including 3,231 cases of recurrent MDD). When the analysis was limited to those with melancholia, a more severe form of MDD, it yielded an increased genetic signal at the SIRT1 locus.

“MDD is most probably highly polygenic, and many additional loci remain to be discovered,” the researchers wrote. “We attribute the discovery and replication of two SNPs associated with MDD in the CONVERGE cohort to the recruitment of cases who were probably more homogeneous and more severely impaired than those collected in previous studies from Western cultures.”

For more in Psychiatric News on psychiatric genetics, see “Revolution in Psychiatric Genetics Rapidly Gains Steam.”

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Study Finds Rates of SGA-Related Neuromotor Side Effects Are Similar in Youth, Adults

Rates of extrapyramidal side effects (EPS) in young people related to use of second-generation antipsychotics (SGA) do not appear to differ from those reported in adults and are particularly low in youth taking quetiapine and olanzapine, according to a report online in the Journal of the American Academy of Child and Adolescent Psychiatry.

Christoph Correll, M.D., of Zucker Hillside Hospital in Glen Oaks, N.Y., and colleagues analyzed data from the Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS was assessed at baseline and four, eight, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders in 342 young people (aged 4 to 19). Drug-induced parkinsonism was defined by incident mean score on the Simpson-Angus Scale (SAS) of more than 0.33, anticholinergic initiation, or an increasing SAS score of two or more in patients with baseline EPS.

Of the cohort, 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were 1.5% for patients taking quetiapine, 13.8% for olanzapine, 16.1% for risperidone, 20.0% for ziprasidone, and 27.3% for aripiprazole. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism.

“Overall rates of drug-induced parkinsonism during second-generation antipsychotic (SGA) treatment were low, indicating that the short-term neuromotor adverse effects of SGAs during routine care are not a major clinical problem,” the researchers stated. “During naturalistic treatment, particularly low rates of drug-induced parkinsonism were found with quetiapine, indicating that youth prone to extrapyramidal adverse effects might benefit from this drug choice.

For related information, see the Psychiatric News article “More Youth Using Antipsychotics Concurrent With Other Medications.”

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People With Depression, Anxiety May Be Less Responsive to Opioids for Chronic Low Back Pain

Opioids are frequently prescribed to treat chronic low back pain, but new research published online in Anesthesiology suggests these drugs may be less effective and more prone to abuse when taken by someone with anxiety or depression.

Chronic low back pain affects an estimated 50 million adults in the United States, and depression or anxiety are common occurrences in patients in response to the chronic pain. In this study, researchers monitored 81 patients with chronic low back pain and varying degrees of depressive or anxiety symptoms (classified as low, medium, or high) over a six-month period; each patient recorded their pain levels and daily dose of medication.

Despite being prescribed a higher average daily dose of morphine, patients with the highest levels of depression and anxiety reported less improvement in back pain (21% vs. 39% pain improvement), a greater rate of opioid misuse (39% vs. 8%), and significantly more frequent and intense side effects from the morphine compared with patients with low levels of depression and anxiety.

“It's important for physicians to identify psychiatric disorders prior to deciding whether to prescribe opioids for chronic back pain as well as treat these conditions as part of a multimodal treatment plan,” study author Ajay Wasan, M.D., of the University of Pittsburgh School of Medicine said in a press release. “Rather than refusing to prescribe opioids, we suggest that these conditions be treated early and preferably before lower back pain becomes chronic.”

To read more about some of the work being done to prevent opioid misuse, see the Psychiatric News article “House Members Consider Best Options for Treatment, Prevention of Opioid Abuse.”

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APA Responds to Inaccuracy in Times Editorial on Psychology, Torture

APA acted to correct a significant inaccuracy in an editorial in yesterday’s New York Times about the American Psychological Association and its policies regarding the involvement of psychologists in the use of torture in the war on terror. The Times corrected the error.

The editorial, titled “Psychologists Who Greenlighted Torture (July 10),” followed an article by Times reporter James Risen on a report commissioned by the American Psychological Association on the subject of psychologists and torture. The editorial originally contained the sentence, “They concluded that psychiatrists could resume assisting in brutal interrogations.”

APA alerted the Times to the error and pointed out that the two professions' ethics differ markedly. On Oct. 19, 2005, then-American Psychiatric Association President Steven Sharfstein, M.D., flew to Guantanamo with the U.S. surgeon general, top military medical officials, and a small group of U.S. medical and psychological leaders. There, he had a frank discussion with them about respecting medical ethics. On his return, the APA Board of Trustees issued a strong statement against psychiatrists' participation in torture as it contravenes physicians' call to do no harm.

After the Times deleted the inaccurate reference, APA President Renée Binder, M.D., and CEO and Medical Director Saul Levin, M.D., M.P.A., sent a letter to the editor in response to the editorial.

"We note that psychiatry determined that psychiatrists could not participate because of our medical ethics.," they wrote. "Psychiatrists, as physicians, take the Hippocratic Oath to 'first do no harm.'

"There is no joy gained from the sad facts of this era. It just means that professional societies have important roles to play in our national affairs. Ethics are as important as ever. And the facts matter.

"Risen’s reporting also reminds us that opposing torture requires vigilance from all concerned parties. We again state our opposition and our hope that such injustices are never repeated."

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Study Examines Association Between SSRIs, Birth Defect Risks

Prenatal use of sertraline may not pose the risk of birth defects in offspring that some previous reports have suggested, according to a study published this week in BMJ.

To estimate the association between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and previously reported offspring birth defects that have been linked to such drug use, researchers from the Centers for Disease Control and Prevention, the University of British Columbia, and Boston University analyzed data from the U.S. National Birth Defects Prevention Study. This analysis included the records of approximately 18,000 mothers of infants with birth defects and 10,000 mothers of infants without birth defects, focusing on the use of citalopram, escitalopram, fluoxetine, paroxetine, or sertraline that occurred at least once in the period from one month prior to conception through the end of the first trimester of pregnancy.

The results showed that though sertraline was the most commonly used SSRI among study participants, none of the five previously reported associations between prenatal use of the drug and birth defects in offspring were confirmed. Additionally, no association with maternal use of citalopram or escitalopram monotherapy was found, except for a marginal association between citalopram and neural tube defects. However, the analysis did confirm heart wall defects and craniosynostosis associated with fluoxetine treatment as well as five previously reported birth defects associated with paroxetine use, including heart defects, problems with brain and skull formation, and abdominal wall effects.

The researchers concluded that “continued scrutiny of the association between SSRIs and birth defects is warranted, and additional studies of specific SSRI treatments during pregnancy are needed to enable women and their health care providers to make more informed decisions about treatment.”

For more information on the prenatal use of SSRIs, see the Psychiatric News article “Certain Cardiac Abnormalities Not Linked to Prenatal Antidepressant Use, Study Finds” and the American Journal of Psychiatry study “SSRI Use During Pregnancy and Risk of Stillbirth and Neonatal Mortality.”

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APA Backs Bill to Increase NIH Funding

APA today expressed support for the 21st Century Cures Act (HR 6), scheduled for a vote tomorrow in the House of Representatives.

“APA shares your goals of modernizing available treatment and improving the discovery, development, and delivery of medical innovations through your proposed reforms and investments in the nation’s research apparatus,” wrote APA President Renée Binder, M.D., and CEO and Medical Director Saul Levin, M.D., M.P.A., in a letter to Rep. Fred Upton (R-Mich.), chair of the House Energy and Commerce Committee, and committee member Rep. Diana DeGette (D-Colo.).

Under the legislation, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) would continue to receive the bulk of their funding over the next five years through the regular annual appropriations process, but with a temporary add-on to be allocated as mandatory spending. Further, the legislation would allocate $1.75 billion each year for five years for a special NIH and Cures Innovation Fund to accelerate biomedical research in critical areas and add $110 million a year for five years to the FDA's budget. The legislation would also change some procedures used by the FDA to approve drugs and medical devices.

“This investment will help rebuild our nation’s biomedical research capacity,” wrote Binder and Levin. “We urge a vote in favor of HR 6 as it heads to the floor of the House of Representatives.”

For more in Psychiatric News about NIH funding, see "Group Pushes House, Senate for More Research Funding."

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Subtle Cues in Young Predict Schizophrenia Risk

Children at high familial risk of schizophrenia may benefit from a wide array of supports that could help reduce the likelihood of developing the illness, said Cindy Liu, Ph.D., of the Department of Psychiatry at Harvard Medical School, and colleagues, in the current issue of the journal Schizophrenia Bulletin.

Often the children born to parents with schizophrenia exhibit visible if subtle signs that can predict later development of psychoses, wrote Liu. These include neuromotor problems and minor physical anomalies; speech, language, or hearing problems; cognitive impairments; and antisocial or externalizing behavior.

Prenatal maternal infection or life stress, obstetric complications, childhood adversity, and life stress may also contribute to risk.

“Targeting [familial high-risk] children and their families may be the most practical strategy for early intervention at this time,” concluded Liu and colleagues. Such interventions might include ensuring continued prenatal care for women with psychoses, increasing social support, enhancing parenting skills, using psychotherapy to reduce cognitive symptoms in parents, and ensuring access to psychiatric, social, educational, and legal resources.

However, they said, “[S]ystematic research is needed to examine the impact of such interventions on preventing psychopathology and functional disability, as well as its cost-effectiveness.”

For more in Psychiatric News about young people at risk for schizophrenia, see "Early Intervention Trial in Youth at Risk for Psychosis Shows Improved Symptoms."

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Meta-Analysis Finds No Association Between Stimulants for ADHD and New, Worsening Tics

Psychostimulant use does not appear to be associated with an onset or worsening of tics in children with with attention-deficit/hyperactivity disorder (ADHD), according to a meta-analysis of studies appearing online in the Journal of the American Academy of Child and Adolescent Psychiatry.

Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics because of fear that tics will develop or worsen as a side effect of treatment. To examine the relationship between psychostimulant use and tics, researchers from several institutions conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD.

They identified 22 studies involving 2,385 children with ADHD for inclusion and used statistical analysis to examine the effects of stimulant type, dosage, duration of use, trial design, and mean age of participants on the measured risk of tics.

The analysis revealed that new onset tics or worsening of tic symptoms were commonly reported in both the psychostimulant and placebo groups, and the risk of new onset or worsening of tics associated with psychostimulant treatment was similar between the two groups. Moreover, type of psychostimulant, dose, and duration of psychostimulant treatment did not affect risk of new onset or worsening of tics.

“When new onset or worsening of tics occurs after the initiation of a psychostimulant medication, it is much more likely to be a result of coincidence than caused by the medication.” the authors wrote. “Using psychostimulant medications in children with ADHD and comorbid tics (or with a family history of tics) should be considered, especially when agents that target both ADHD and tic symptoms (e.g., alpha-2 agonists) have failed.”

For related information, see the Psychiatric News article “ADHD Genes Also Influence Social, Cognitive Behaviors.”

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CBT Reduces Insomnia in Patients With Co-Occurring Psychiatric Conditions

A form of cognitive-behavioral therapy especially developed to treat insomnia (CBT-I) was found to be effective in reducing insomnia symptoms and sleep disturbances, even in cases where the patient has a co-occurring problem such as a psychiatric disorder, according to a new analysis of medical literature published online today in JAMA Internal Medicine.

While a meta-analysis published last month demonstrated that CBT-I—a multicomponent treatment package that usually includes stimulus control, sleep restriction, and cognitive therapy—is a safe and effective treatment option for adults with chronic insomnia, the analysis excluded studies of insomnia comorbid with psychiatric and general medical conditions. For the current study, Jason Ong, Ph.D., of Rush University Medical Center, and colleagues included data from 37 studies and nearly 2,200 participants with insomnia as well as a range of medical conditions (such as depression, alcohol dependence, chronic pain, and cancer).

The researchers found that twice the percentage of patients who received CBT-I achieved remission from insomnia compared with patients in control or comparison groups (36% vs. 17%), and CBT-I improved most sleep parameters with the exception of total sleep time.

CBT-I was also associated with positive effects on the coexisting illness, though the benefits were more pronounced in people with psychiatric disorders compared with other medical problems. The authors suggested this correlation may occur because sleep may be more strongly associated with cognitive-emotional symptoms than physical symptoms.

For more information on sleep and psychiatric disorders, see the Psychiatric News article “Combining Insomnia, Depression Treatment May Improve Outcome” and the FOCUS article “Psychological and Behavioral Treatments for Insomnia,” which was part of an issue devoted to sleep disorders.

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Study Finds Overall Uptick in Youth Prescribed Antipsychotics

From 2006 to 2010, antipsychotic use increased among U.S. adolescents and young adults but not in children 12 and under, according to a study published online Wednesday in JAMA Psychiatry.

Mark Olfson, M.D., M.P.H., a professor of clinical psychiatry at Columbia University, and colleagues retrieved data on antipsychotic prescriptions filled by or for young people (aged 1 to 24 years) in 2006, 2008, and 2010 from the IMS LifeLink LRx Longitudinal Prescription database, which includes about 60 percent of all retail pharmacies in the United States. The researchers then calculated the percentage of young people for whom one or more antipsychotic prescriptions were filled during the study year by sex and age group, and generalized the IMS prevalence to the entire U.S. population of young people, including those who did not fill a prescription.

The percentages of young people whose antipsychotic prescriptions were filled in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children (1 to 6 years), 0.85% and 0.80% for older children (7 to 12 years), 1.10% and 1.19% for adolescents (13 to 18 years), and 0.69% and 0.84% for young adults (19 to 24 years). Further analysis of the 2010 data revealed that across all age groups, males were more likely than females to have filled their antipsychotic prescriptions; among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%).

“In view of evidence of widespread antipsychotic prescribing outside of U.S. Food and Drug Administration–labeled indications and concerns regarding the adverse metabolic effects of second-generation antipsychotics, this decline [in the rate of antipsychotic use among children 12 and under] is a welcome development,” the authors wrote. “Nevertheless, age and sex antipsychotic use patterns suggest that much of the antipsychotic treatment of children and younger adolescents targets age-limited behavioral problems.”

When evaluating treatment options for the youngest children with disruptive behaviors, practice guidelines recommend that “consideration of antipsychotic medications should be limited to those who have severe, sustained, and intractable impairment in multiple settings or who pose safety risks,” the authors noted. They added that if such therapy is initiated, young patients should be continually reassessed to minimize treatment duration. However, as the authors pointed out, children treated with antipsychotics most commonly receive prescriptions from physicians who are not psychiatrists.

“Given the paucity of high-quality empirical evidence supporting the efficacy and safety of antipsychotic treatment in this age group, these treatment patterns raise potential safety concerns and underscore the importance of improving access for young children with severe mental health problems to high-quality, specialized child and adolescent mental health services,” they concluded.

For more on antipsychotic use among children and adolescents and practice guidelines, see the Psychiatric News article “Recent Rise in Youth on Antipsychotics Raises Concerns Among Experts.”

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Childhood Exposure to Violence Highly Prevalent

In the course of a year, four out of ten children experienced some exposure to violence, crime, or abuse, according to a survey of 4,000 young people published online in JAMA Pediatrics June 29.

The researchers analyzed data from the National Survey of Children’s Exposure to Violence (NatSCEV), which is conducted every three years. The most recent study took place in 2014 and asked children aged 0 to 17 (or their caregivers) about physical assault, sexual assault, child maltreatment, property crime, and witnessing violence.

“More than one-third of all youth (37.3%) experienced a physical assault during the study year, primarily at the hands of siblings and peers,” wrote David Finkelhor, Ph.D., a professor of sociology and director of the Crimes against Children Research Center at the University of New Hampshire in Durham, and colleagues. About 15% experienced maltreatment (physical or emotional abuse, neglect, or custodial interference); 6.5% had something stolen; and 24.5% witnessed family or community violence. Overall, 5% experienced a sexual offense; 16% of girls 14 to 17 reported a sexual offense and 4.6% a sexual assault or sexual abuse.

Most concerning to the authors was the fact that 41% of the young people surveyed had more than one direct experience of violence, crime, or abuse.

“Exposures to violence were interrelated in such a way that experiencing one type increased the likelihood of experiencing other types as well,” concluded Finkelhor and colleagues. “Every combination had a significant risk amplification.”

To learn about the association between childhood maltreatment and cognitive deficits, see the AJP study “Neural Correlates of Error Processing in Young PeopleWith a History of Severe Childhood Abuse: An fMRI Study.”

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