NIMH Director’s Blog: Tracing the Brain’s Connections

It has become our mantra at NIMH that mental disorders can be addressed as disorders of brain circuits. We frequently use an analogy with heart disease: mental disorders can be thought of as conduction problems or arrhythmias, in contrast to neurodegenerative disorders (Parkinsons, Huntingtons, Alzheimers), which involve loss of tissue similar to the infarctions of ischemic heart disease.

By Dr. T. Insel, NIMH Director

Submitted by SARDAA

More ill Ohio inmates refuse post-prison help

COLUMBUS, Ohio — More mentally ill inmates are refusing help in making the transition from prison to the free world even as advocates are suing Ohio to force the state to do more for them, state records show.

Nearly one in four mentally ill inmates either declined post-release services or never showed up for their prison appointment in the state fiscal year ending in June 2009, according to a review of Department of Mental Health records by The Associated Press.

Reported by ANDREW WELSH-HUGGINS, The Associated Press
Dayton Daily News

Submitted by Darrell H.

Psychotropic Medications Linked to Increased Rates of Obesity

March 8, 2010 (Baltimore, Maryland) — Psychotropic medications, specifically antidepressants and antipsychotics, are associated with higher rates of obesity, new national data suggest.

The research, presented here at the Anxiety Disorders Association of America 30th Annual Conference, shows that the obesity rate among individuals taking antidepressants during the past 12 months was 1.5 times greater compared with individuals not taking these medications. In addition, the obesity rate among subjects taking antipsychotics was more than double.

A collaboration between researchers from the United States and Canada, the study examined the relationship between obesity and specific classes of psychotropic medications, including antidepressants, antipsychotics, anxiolytics, hypnotics, and mood stabilizers, in a large, nationally representative sample of 36,984 participants.

Study subjects were participants in the Canadian Community Health Survey Mental Health and Well-being.

“There are issues that haven’t really been addressed in a population that already is at risk for unhealthy behaviors, since the risk for obesity is added on top of their mental illness,” said first author Candyce D. Tart, MA, doctoral candidate in the Psychology Department at Southern Methodist University, Dallas, Texas.

The preliminary results of the study, with principal investigator Jasper Smits, associate professor and director of the Anxiety Research & Treatment Program at Southern Methodist University, Dallas, Texas, suggest that the increased odds of obesity in mood disorders and anxiety disorders is mediated by psychotropic medication use.

More precisely, the effects of psychotropic medication use appear to be specific to antidepressants and antipsychotics. The investigators found no relationship between mood stabilizers and obesity — a finding that contradicts previous research showing that these drugs are associated with significant weight gain……(

Reported by Crina Frincu-Mallos, PhD
Medscape Medical News

submitted by SARDAA

Early Marijuana Use Heightens Psychosis Risk in Young Adults

March 4, 2010 (Updated with comment March 10, 2010) — Experimenting with marijuana at a young age increases the risk for hallucinations or delusions later in life, a new study shows.

“Early cannabis use increases the risk of psychosis in young adults,” lead investigator John McGrath, MD, from the Queensland Centre for Mental Health Research in Brisbane, Australia, told Medscape Psychiatry.

“Apart from having an increased risk of having a disorder like schizophrenia, the longer the young adults reported since their first cannabis use, the more likely they were to report isolated symptoms of psychosis.”

Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks.

Psychotic disorders are common and typically affect 1 or 2 people of every 100. “Despite our best efforts with treatment, not everyone makes a full recovery,” Dr. McGrath said. “We need to think about prevention. Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks.”

Dr. McGrath says he was surprised that the results were so strong and so consistent.

The study was published online March 1 in Archives of General Psychiatry.

Investigators studied 3800 young adults born at an Australian hospital taking part in the Mater-University Study of Pregnancy.

Prospective studies have already identified an association between marijuana use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables.

Dr. McGrath and his team focused instead on 228 sibling pairs in the prospective birth cohort to reduce the influence of unmeasured residual confounding.

Investigators followed up study participants at ages 5, 14, and 21 years. The researchers assessed first marijuana use and 3 psychosis-related outcomes. These outcomes included nonaffective disease, hallucinations, and the Peters et al delusions inventory score.

Table. Odds Ratio of Psychosis-Related Outcomes With Marijuana Use

Investigators evaluated all associations between duration of marijuana use and psychosis-related outcomes using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up.

The results mirror those of another study published in the November issue of the American Journal of Psychiatry (2009;166:1251–1257). That work suggests a link between daily cannabis or tobacco use and early-onset psychosis.

In that study, investigators looked at 109 patients in a psychiatric unit and found that daily marijuana and tobacco use was common. More than 40% of patients used one or both substances.

Of those who abused cannabis, almost 88% were classified as weekly or daily users before the onset of psychosis.

Escalating Marijuana Use Hastened Psychosis

It is not clear why escalating marijuana use may hasten psychosis, lead investigator Michael Compton, MD, from the Emory University School of Medicine in Atlanta, Georgia, noted in November. However, studies have shown increased cannabinoid receptor density in areas of the brain and elevated levels of endogenous cannabinoids in the blood of some patients with psychosis.

This new study, Dr. McGrath points out, provides additional evidence that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.

Asked by Medscape Psychiatry to comment, Emma Barkus, PhD, from the University of Wollongong in New South Wales, Australia, says the findings are consistent with the substance literature, which suggests that those who are engaging in risk behaviors at the age of 14 years are more likely to persist as they get older.

“Despite the restrictions of the methodologies,” she noted, “such as use of retrospective recall and the pseudoquantification of cannabis exposure, the sample size and the persistence of the findings in the face of controlling for confounding variables and analyses on subsets of participants lend strength to an area of literature which is still fraught with controversy.”

Dr. Barkus says the findings add further support to the role of cannabis use in psychoses in outcomes.

This study was funded by the National Health and Medical Research Council of Australia. Coauthor Dr. Rosa Alati is supported by a National Health and Medical Research Council Career Development Award in Population Health.

Arch Gen Psychiatry. Published online March 1, 2010.

Reported by Allison Gandey
Medscape Medical News

Submitted by SARDAA

Effectiveness of Pharmacotherapy and Behavioral Interventions for Smoking Cessation in Actual Clinical Practice


Objectives: This study evaluated the effectiveness of behavioral interventions (brief counseling, nonspecific psychological support in groups – NSGS and cognitive behavioral group therapy – CBGT) in combination with bupropion SR for smoking cessation in the field, through a smoking cessation clinic.
Methods: Two-hundred-and-five smokers were enrolled in a 19-week course during 2007/2008, and were randomly assigned to: bupropion SR combined with brief counseling (group A), bupropion SR combined with NSGS (group B), bupropion SR combined with CBGT (group C), or CBGT as the only approach (group D).
Results: Continuous abstinence rates at the end of therapy were 53.2% for group A, 62.9% for group B, 50.0% for group C, and 22.2% (p0.05), respectively.
Conclusions: Bupropion SR is an effective aid for smoking cessation in clinical practice. NSGT increased the chances for success at the end of therapy when combined with bupropion SR, while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy. It is suggested that smoking cessation interventions in real-life healthcare settings should be implemented through comprehensive programs using pharmacotherapy where applicable, combined with NSGT, and integrated by specialized healthcare professionals.

Rovina N, Nikoloutsou I, Katsani G, Dima E, Fransis K, Roussos C, Gratziou C. Ther Adv Respir Dis. 2009 Dec;3(6):279-87.

Submitted by SARDAA

Smoking May Be an Independent Risk Factor for Suicidality

March 11, 2010 (Baltimore, Maryland) — Smoking may be an independent risk factor for suicidality, new research suggests.

A longitudinal study presented here at the Anxiety Disorders Association of America 30th Annual Conference shows a strong association between smoking and suicidality in a cohort of 3021 adolescents and young adults aged 14 to 24 years at baseline.

The Early Developmental Stages of Psychopathology study, a prospective, longitudinal study, showed that prior occasional, regular smoking and nicotine dependence were associated with an increased risk for the onset of suicidal ideation, with odds ratios (ORs) ranging from 1.5 to 2.7.

Prior regular smoking and nicotine dependence were also associated with the subsequent first onset of suicide attempts (ORs, 3.1-4.5). According to the investigators led by Roselind Lieb, PhD, preexisting suicidality was not associated with subsequent smoking or nicotine dependence.

“Smoking increases the risk for subsequent suicidality. We have found it is a risk factor independent of other psychopathologies or other drug use,” Dr. Lieb, professor of epidemiology and health psychology, University of Basel, Switzerland, told Medscape Psychiatry.

The study appears to confirm results from a previous 10-year, longitudinal study published in 2005 that showed that current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempts independent of major depression, prior substance use, and suicidal predisposition (Arch Gen Psychiatry. 2005;62:328-334)……….

Author: Crina Frincu-Mallos, PhD
Medscape Medical News

Submitted by SARDAA

Crimes distort reality of schizophrenia

Cedar Rapids, Ia. – A newspaper lying in Steve Miller’s kitchen blared the latest front-page news about a person with schizophrenia. The big black headline announced: “Becker guilty.”

The paper showed a picture of a stone-faced Mark Becker, the 24-year-old Parkersburg man who was convicted last week of murder for shooting his former football coach, Ed Thomas. Iowans read about how Becker assassinated the coach, then screamed gibberish about Satan to the horrified high school students who saw the murder. The media reported how Becker’s defense lawyer tried in vain to blame the killing on the young man’s severe mental illness and the delusions it caused.

What the news stories didn’t provide, Miller said, was a complete picture of schizophrenia. It’s true that a few people with the mental disorder go out of control and commit horrible crimes, he said. But Miller and thousands of other Iowans who have schizophrenia live quiet, unremarkable lives. Few of them talk openly about their experiences, however, so the public learns about the disease only in extreme cases, such as Becker’s.

“Unfortunately, for people who aren’t close to mental illness, who don’t have it in their families, what they see in the headlines becomes their perception,” said Miller, 49.

Experts say about 1 percent of adults have schizophrenia, which would translate to roughly 22,000 Iowans. People with the disease are more likely to be meek and introverted than aggressive and dangerous, psychiatrists say. Studies have shown they’re much more likely to be the victims of violent crime than the perpetrators of it.

But publicity about violent schizophrenia patients drives a cycle of silence and misunderstandings, experts say. Every time the public hears about the illness being linked to a gruesome crime, the stigma surrounding the disease gets stronger. That stigma makes everyday people with mental illnesses even more hesitant to speak openly about their less dramatic experiences……

Story by Tony Leys

Submitted by Darrell H

Lithium Plus Valproate More Likely Than Valproate Alone to Prevent Relapse in Bipolar Disorder

January 6, 2010 — Welcome back lithium.

After losing its luster because of concerns over potentially serious adverse effects, this drug is drawing increasing respect. Results from the Bipolar Affective disorder Lithium/ANti-Convulsant Evaluation (BALANCE) study show that combining valproate with lithium is more likely to prevent relapse in patients with bipolar disorder than valproate alone, with 41% relative benefit for the combination therapy. The benefit was independent of baseline illness severity, lasted for up to 2 years, and was most apparent in prevention of manic relapse. This study, along with other recent research, goes a long way toward putting lithium back on top as the preferred treatment for bipolar disorder, said lead study author John R. Geddes, MD, professor of epidemiological psychiatry and director of the Oxford Clinical Trials Unit for Mental Illness, Department of Psychiatry, University of Oxford, United Kingdom. “We’ve got more evidence purporting the lithium efficacy, safety, and its antisuicidal effects than we’ve ever had before,” Dr. Geddes told Medscape Psychiatry. “So don’t throw lithium away; it’s a highly effective treatment, and if people can tolerate it, then it’s worth trying.” The study was published online December 23, 2009, in The Lancet.
Challenging Guidelines

Although the study could not confirm a benefit of the valproate-lithium combination therapy over lithium alone, its findings should challenge current clinical guidelines that recommend valproate monotherapy as a first-line option for long-term treatment of bipolar disorder. The randomized, open-label trial included 330 men and women 16 years and older with bipolar 1 disorder for whom long-term drug therapy was indicated.
After a 4- to 8-week run-in during which patients received both lithium carbonate and valproate semisodium, subjects were randomly allocated to 1 of 3 groups:
• Continuation of combination lithium plus valproate;
• Switch to lithium monotherapy; or
• Switch to valproate monotherapy.
Study subjects remained on the allocated treatment for 2 years or until treatment failure. Lithium Standard Treatment Lithium, a soft, light metal element, was introduced on the market about 50 years ago. It was the standard maintenance treatment for bipolar disorder for more than 4 decades. However, the drug can be toxic and not all patients can tolerate it.

During the study’s follow-up period, the primary outcome — time to new intervention for an emerging mood episode, including drug treatment or hospital admission — occurred in 59 of 110 patients (54%) receiving combination therapy, 65 of 110 (59%) taking lithium, and 76 of 110 (69%) taking valproate. The hazard ratios for the primary outcome were 0.59 for combination therapy vs valproate, 0.82 for combination therapy vs lithium, and 0.71 for lithium vs valproate. Taking into account baseline severity of disorder, as measured by the number of previous admissions, and the nature of the most recent mood episode did not alter the outcome. The difference between treatments was constant up to 2 years, and exclusion of events occurring in the first 3 months did not significantly change the results.

Hospital Admissions

The risk for hospital admission for participants allocated to combination therapy was significantly lower than forthose allocated to valproate (adjusted hazard ratio of 0.51 for valproate patients compared with combination therapy patients). The benefit of the combination therapy compared with valproate was most apparent for manic relapses, whereas the advantage of lithium compared with valproate was most apparent for depressive relapses. “In terms of prevention of relapse, it’s clear that lithium is better than valproate from this study,” said Dr. Geddes. He added that the results suggest that nonresponders to long-term lithium treatment should continue taking lithium combined with valproate. The effect of adding lithium to valproate was “striking,” and this effect could be even larger in highly adherent patients with optimum therapy, said the study authors. According to Dr. Geddes, the effect was “additive” rather than synergistic.

The 3 groups did not differ in self-harm, quality of life, or global functioning. Most patients who responded — 95% taking lithium, 92% taking valproate, and 100% receiving combination therapy — reported at least 1 nonserious adverse event during follow-up. There were 7 serious adverse events among patients receiving valproate (3 deaths), 5 among those taking lithium (2 deaths), and 4 among those receiving combination therapy (1 death).
Careful Monitoring
Because lithium can have serious adverse effects, patients taking this drug have to be monitored carefully. “Toxicity and overdose [are] very high; so it’s a tricky drug to use,” said Dr. Geddes. However, he said, there is no good evidence of irreversible effects on the kidney, and so it’s not absolutely contraindicated in patients with renal failure. “It just means you have to be cautious.” Dr. Geddes pointed out that lithium is the only drug that reduces suicide in this patient population. Over the years, there has been a major shift away from prescription of lithium, especially in North America. In the United States, lithium prescriptions for outpatients nearly halved between 1992 and 1996 and 1996 and 1999, whereas the rate of prescription of valproate almost tripled, according to background information in the paper. By the start of this trial, valproate “was rapidly taking over” from lithium, with patients only receiving combination therapy after failure of the monotherapy, said Dr. Geddes. A patient with a first or second episode of mania would likely be treated with valproate and continue taking that drug. Indeed, clinical guidelines suggest valproate monotherapy as a first-line long-term therapy. Within that context, the study results are “very important,” said Dr. Geddes. “It suggests that people will do a lot better if they’re treated with lithium plus valproate rather than just be continued on valproate.” Compared with some studies, this randomized trial was more reflective of “the real world” because most patients were recruited from nonteaching centers, said Dr. Geddes. These included 41 sites in the United Kingdom, United States, France, and Italy. A limitation of the study was that treatment allocation was not masked from the investigators or participants. However, patients who had a strong preference for an investigational therapy were excluded from the study. Bipolar disorder is a disabling mental illness that is characterized by episodes of both elevated or irritable mood and depression. It is one of the most important causes of disability for patients between the ages of 15 and 44 years.
Outstanding Work
In an accompanying editorial, Rasmus W. Licht, MD, Mood Disorders Research Unit, Aarhus University Hospital, Risskov, Denmark, praised the BALANCE study, describing it as “outstanding work” and “an impressive example of international collaboration.” He said that even without a placebo group, the study “confirms the long-term efficacy of lithium, not only for the prevention of mania but also for prevention of depression.” On the basis of the study’s results, “the BALANCE group rightly challenges the recommendation by present clinical guidelines that valproate monotherapy is a first-line option for long-term treatment.”
Dr. Geddes has received research funding from the Medical Research Council, Economic and Social Research Council, National Institute for Health Research, and the Stanley Medical Research Institute and has received donations of drugs supplies for trials from Sanofi-Aventis and GlaxoSmithKline. He has acted as an expert witness for Dr Reddys but otherwise has received no payment from drug companies in the past 3 years. For conflict of information on other authors, see the original article. Dr. Licht has served on advisory boards for Bristol-Myers Squibb and AstraZeneca and has received unrestricted grants from GlaxoSmithKline Denmark, honoraria for lectures from Eli Lilly, Jansen-Cilag, GlaxoSmithKline, Bristol-Myers Squibb. and Pfizer, and travel and accommodation fees from Bristol-Myers Squibb.
The Lancet. Published online December 23, 2009.

BY: Pauline Anderson, Medscape Medical News