Currently, there are 11 first-generation antipsychotics (FGA) and 10 second-generation antipsychotics (SGA) available to treat patients with schizophrenia. Clinicians tend to favor SGAs; 75 percent of patients with schizophrenia were prescribed an SGA in 2003. Despite these preferences, there is controversy over the comparative benefits and disadvantages of FGAs and SGAs. A recent review of studies showed few differences of clinical importance between FGAs and SGAs. A total of 263 publications representing 114 primary studies were identified from the literature for inclusion in the analysis. Of these, 110 were randomized clinical trials. A total of 22 drug comparisons were included. All studies were published between 1974 and 2012.

Overall, there was low or insufficient strength of evidence from the studies. Wide variation existed in the ways symptoms were measured. In addition, there were only a small number of studies for specific drug comparisons. Nevertheless, the researchers were able to draw some conclusions. First, when it came to treating core illness symptoms, few differences of clinical importance were observed between FGAs and SGAs and those differences depended on the measure used for the symptoms. The FGA haloperidol appeared to be better than the SGA olanzapine for improving positive symptoms, such as hallucinations, delusions, and thought and movement disorders. However, the level of evidence was stronger for SGAs when it came to treating negative symptoms, such as flat affect and the lack of pleasure in everyday life. In this case, olanzapine was better than haloperidol.

Although the strength of evidence was low regarding medication-associated side effects, there was a higher incidence of developing the metabolic syndrome with olanzapine than for haloperidol. A higher incidence of tardive dyskinesia (repetitive and involuntary movements) was found for the FGA chlorpromazine than for the SGA clozapine. No differences in mortality were found for chlorpromazine versus clozapine or haloperidol versus the SGA aripiprazole.

–Agency for Healthcare Research and Quality

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Research suggests that targeted stimulation of the brain’s prefrontal cortex is a promising treatment for addiction.

Could drug addiction treatment of the future be as simple as an on/off switch in the brain? A study in rats has found that stimulating a key part of the brain reduces compulsive cocaine-seeking and suggests the possibility of changing addictive behavior generally. The study, published in Nature, was conducted by scientists at the Intramural Research Program of the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the University of California, San Francisco.

“This exciting study offers a new direction of research for the treatment of cocaine and possibly other addictions,” said NIDA Director Dr. Nora D. Volkow. “We already knew, mainly from human brain imaging studies, that deficits in the prefrontal cortex are involved in drug addiction. Now that we have learned how fundamental these deficits are, we feel more confident than ever about the therapeutic promise of targeting that part of the brain.”

Compulsive drug-taking, despite negative health and social consequences, has been the most difficult challenge in human drug addiction. NIDA researchers used an animal model of cocaine addiction, in which some rats exhibited addictive behavior by pushing levers to get cocaine even when followed by a mild electric shock to the foot. Other rats did not exhibit addictive responses.

–National Institutes of Health (NIH)

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The mental health effects associated with prolonged solitary confinement demand close consideration and should influence any future policy on use of the practice in U.S. prisons.

Anthony Graves, an exonerated former death-row inmate, spent the majority of his 18 years at a Texas prison in solitary confinement.

“I lived under the rules of a system that is literally driving men out of their minds,” said Graves in describing the inhumane conditions of serving time in a small cell without access to human interaction or proper medical care. “No one can begin to imagine the psychological effects isolation has on another human being.”

According to recent estimates from the Web-based advocacy project Solitary Watch, approximately 82,000 inmates are currently segregated in federal and state prison systems in the United States. And a 2010 study published by the American Academy of Psychiatry and the Law (AAPL) concluded that segregation over prolonged periods of time has the capacity to induce harmful psychological effects such as anxiety, anger, cognitive disturbance, perceptual distortion, obsessive thoughts, paranoia, and psychosis.

The AAPL study also estimated that between 8 percent and 19 percent of current U.S. prisoners suffer from psychiatric disorders, with an additional 15 percent to 20 percent of prisoners requiring some form of psychiatric intervention during incarceration. These individuals, according to AAPL’s findings, often require costly psychiatric hospitalization or crisis-intervention services, and face a heightened risk of suicide.

by Jonathan Wolfe, Psychiatric News

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Shining a light on particular cells in the prefrontal cortex can reduce cocaine addiction in rats, according to a study published April 3 in Nature. The senior scientist was Antonello Bonci, M.D., scientific director of the National Institute on Drug Abuse (NIDA). “Our results can be immediately translated to clinical research settings with humans, and we are planning clinical trials to stimulate this brain region using noninvasive methods,” Bonci reported in a press statement. “By targeting a specific portion of the prefrontal cortex, our hope is to reduce compulsive cocaine-seeking and craving in patients.”

“This exciting study offers a new direction in research for the treatment of cocaine and possibly other addictions,” added NIDA Director Nora Volkow, M.D. “We already knew, mainly from human brain imaging studies, that deficits in the prefrontal cortex are involved in drug addiction. Now that we have learned how fundamental these deficits are, we feel more confident than ever about the therapeutic promise of targeting that part of the brain.”

–Psychiatric News Alert

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Up to twelve chromosome regions may harbor genes for keeping the brain in good working order, reports a new study by Brain & Behavior Research Foundation NARSAD Grantee David Braff, M.D., and his research team. Because problems with certain jobs done by the brain, such as remembering information, have been linked to schizophrenia, pinpointing the genes that help those jobs get done well may be a backdoor route to finding genes that contribute to the disorder.

Problems with certain brain functions, including those related to attention, memory, verbal learning and the ability to suppress a movement were sometimes associated with certain stretches of DNA (molecules that contain heredity encoding information) along the chromosomes. For example, a person’s ability to suppress an eye movement was associated with a region of chromosome 3.

by David Braff, M.D.

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At 7 months of age, children who are later diagnosed with autism take a split second longer to shift their gaze during a task measuring eye movements and visual attention than do typically developing infants of the same age, according to researchers supported by the National Institutes of Health.

The difference between the groups’ test results was 25 to 50 milliseconds on average, the researchers found, too brief to be detected in social interactions with an infant. However, they showed that this measurable delay could be accounted for by differences in the structure and organization of actively developing neurological circuits of a child’s brain.

Efficiently shifting attention early in infancy is thought to be important for later social and cognitive development. Split-second delays, the researchers suggested, could be a precursor to such well known symptoms of autism as difficulty making eye contact or following a parent’s pointing finger, problems that generally emerge after a child turns 1. Typically, autism spectrum disorder (ASD) is not diagnosed until after 3 or 4 years of age.

–National Institutes for Health

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NIMH’s next Twitter Chat will focus on Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strep Infections (PANDAS) and its related syndrome Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). The chat is scheduled for Wednesday, May 8 at 11AM ET. You can find more information about PANDAS and the chat here:http://www.nimh.nih.gov/news/science-news/2013/twitter-chat-on-pandas-pans.shtml

Twitter: NIMH experts will discuss childhood rapid-onset #OCD called #PANDAS & #PANS in a Twitter chat May 8th @ 11am ET: http://1.usa.gov/YjGJd2

Facebook: NIMH will have a second Twitter chat in honor of National Children’s Mental Health Awareness Day on May 8th from 11 a.m. to noon ET on rapid-onset obsessive-compulsive disorder (OCD) in children, which is called Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strep Infections (PANDAS) and its related syndrome Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). For more on the chat and PANDAS/PANS, please visit: http://1.usa.gov/YjGJd2

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Why are rates of schizophrenia and autism higher in males? New evidence implicates an enzyme expressed in the placenta that helps protect the developing fetal brain from adverse effects of maternal stress early in pregnancy. Video: NIMH grantee Tracy Bale, Ph.D., of the University of Pennsylvania, discussed her line of research into how maternal stress might differentially affect the developing male brain during an interview at the 2011 Society for Neuroscience meeting.

Since then, Bale and colleagues discovered in mice that the gene that makes the enzyme, called OGT, is expressed less in placentas of male than in female offspring. Moreover, OGT was also expressed at relatively lower levels in placentas from stressed mothers. When they looked at evidence of its expression in human placentas, they saw a similar pattern of sex differences. Further experiments in mice confirmed that OGT plays a pivotal role in regulating the turning on-and-off of hundreds of brain genes and in protecting the developing brain from insults. The researchers suggest that OGT epigenetically places male fetuses at a disadvantage in adapting to environmental changes – a possible mechanism underlying males’ increased vulnerability to enduring effects of maternal stress on brain development.

–National Institute of Mental Health

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Adults aged 18 or older who experienced any mental illness or who have had a substance use disorder in the past year are more likely to smoke and to smoke more heavily than others according to a new report by the Substance Abuse and Mental Health Services Administration (SAMHSA).

According to the report, adults experiencing any mental illness or a substance use disorder in the past year represent 24.8 percent of the adult population, but that same group used 39.6 percent of all cigarettes smoked by adults.

In terms of rates of cigarette smoking, 38.3 percent of adults experiencing mental illness or substance use disorders were current smokers as opposed to 19.7 percent of those adults without these conditions. That means that the rate of current cigarette smoking among adults experiencing mental illness or substance use disorders is 94 percent higher than among adults without these disorders.

The report reveals that although people with substance use disorders and no mental disorder constitute only 4.9 percent of adults over age 18, they smoked 8.7 percent of all cigarettes. Similarly, although those who had experienced both mental illness and a substance use disorder represented only 3.8 percent of the population in the past year, they smoked 9.5 percent of all cigarettes.

The report defines any mental illness as any diagnosable mental, behavioral, or emotional disorder other than a substance use disorder. The report defines a substance use disorder as dependence on or abuse of alcohol or illicit drugs.

“It has long been a public health priority to develop effective smoking prevention and cessation programs,” said SAMHSA Administrator Pamela S. Hyde. “This report highlights a clear disparity. It shows that people dealing with mental illness or substance abuse issues smoke more and are less likely to quit. We need to continue to strengthen efforts to figure out what works to reduce and prevent smoking for people with mental health conditions,” said Administrator Hyde.

To address the high rates of tobacco use among people with mental or substance use disorders, SAMHSA, in partnership with the Smoking Cessation Leadership Center (SCLC), has developed a portfolio of activities designed to promote tobacco cessation efforts in behavioral health care. SAMHSA and the SCLC launched the 100 Pioneers for Smoking Cessation Campaign, which provides support for mental health and substance abuse treatment facilities and organizations to undertake tobacco cessation efforts. This program has been expanded in conjunction with state Leadership Academies for Wellness and Smoking Cessation, whose goal is to reduce tobacco use among those with behavioral health needs. Participating states bring together policymakers and stakeholders (including leaders in tobacco control, mental health, substance abuse, public health, and consumers) to develop a collaborative action plan.

–SAMHSA

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Five major mental disorders share some of the same genetic risk factors, the largest genome-wide study of its kind has found.  Evidence for such genetic overlap had previously been limited to pairs of disorders.

National Institutes of Health-funded researchers discovered that people with disorders traditionally thought to be distinct – autism, ADHD, bipolar disorder, major depression and schizophrenia – were more likely to have suspect genetic variation at the same four chromosomal sites. These included risk versions of two genes that regulate the flow of calcium into cells.

“These results will help us move toward diagnostic classification informed by disease cause,” said Jordan Smoller, M.D., of Massachusetts General Hospital, Boston, a coordinator of the study, which was supported by NIH’s National Institute of Mental Health. “Although statistically significant, each of these genetic associations individually can account for only a small amount of risk for mental illness, making them insufficient for predictive or diagnostic usefulness by themselves.”

Smoller, Kenneth Kendler, M.D.,, Virginia Commonwealth University, Richmond; Nicholas Craddock, PhD., Cardiff University, England; Stephan Ripke, M.D., Massachusetts General, Patrick Sullivan, M.D., University of North Carolina at Chapel Hill, and colleagues in the Cross-Disorder Group of the Psychiatric Genomics Consortium, report on their findings February 28, 2013 in The Lancet.

Prior to the study, researchers had turned up evidence of shared genetic risk factors for pairs of disorders, such as schizophenia and bipolar disorder, autism and schizophrenia and depression and bipolar disorder. Such evidence of overlap at the genetic level has blurred the boundaries of traditional diagnostic categories and given rise to research domain criteria, or RDoC, an NIMH initiative to develop new ways of classifying psychopathology for research based on neuroscience and genetics as well as observed behavior.

To learn more, the consortium researchers analyzed the five key disorders as if they were the same illness. They screened for evidence of illness-associated genetic variation across the genomes of 33,332 patients with all five disorders and 27,888 controls, drawing on samples from previous consortium mega-analyses.

For the first time, specific variations significantly associated with all five disorders were among several suspect genomic sites that turned up. These included variation in two genes that code for the cellular machinery for regulating the flow of calcium into neurons. Variation in one of these, called CACNA1C, which had previously been implicated in susceptibility to bipolar disorder, schizophrenia and major depression, is known to impact brain circuitry involved in emotion, thinking, attention and memory – functions disrupted in mental illnesses. Variation in another calcium channel gene, called CACNB2, was also linked to the disorders.

Alterations in calcium-channel signaling could represent a fundamental mechanism contributing to a broad vulnerability to psychopathology, suggest the researchers.

They also discovered illness-linked variation for all five disorders in certain regions of chromosomes 3 and 10. Each of these sites spans several genes, and the specific causal factors within them remain elusive. However, one region, called 3p21, which produced the strongest signal of illness association, harbors suspect variations identified in previous genome-wide studies of bipolar disorder and schizophrenia.

–National Institute of Mental Health

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