Mapping Brain Circuits Provides Clues to Schizophrenia, Earlier Detection of Psychosis

Two regions in the brain have been linked to schizophrenia and psychosis, which may lead to earlier detection of this disorder and symptom, reported an imaging study funded by the National Institute of Mental Health (NIMH) that was published online last month in Biological Psychiatry. Background Patients with schizophrenia experience decreased activity in the prefrontal cortex ( blue, top figure) and excess activity in the basal ganglia (red, bottom figure). The greater the disconnect between these two regions, the higher the level of psychosis seen in these patients. Psychosis is a loss of contact with reality that usually includes false beliefs about what is taking place or who one is (delusions) and seeing or hearing things that aren’t there (hallucinations). Numerous medical problems can cause psychosis such as substance abuse, brain tumors, and certain mental disorders such as schizophrenia and bipolar disorder. Treatment approaches include hospitalization, antipsychotic drugs, and various psychosocial treatments. Too often, psychosis is not diagnosed or treated early enough. The longer this duration of untreated psychosis, the poorer the patient’s long-term functioning and response to treatment. In the United States, the average time between the first onset of psychotic symptoms and the initiation of treatment is about 110 weeks, or over 2 years. Disordered thinking and psychosis often go hand-in-hand in patients with the chronic brain disorder schizophrenia. A popular and long-standing theory in the field implicates the prefrontal cortex, the brain area just behind the forehead that normally supports higher-order capabilities such as prioritizing, categorizing, and strategizing. Damage to this area causes not only disordered thinking but also leads to psychosis from the excess release of the neurotransmitter dopamine into regions deep inside the brain. While this theory offers a compelling explanation for the co-occurrence of these two symptoms in schizophrenia, there have been only a small handful of studies that have directly supported this theory. Identification of the exact circuit(s) involved has so far remained elusive Professional Counselor Continuing Education “Schizophrenia is a very complex condition, involving a constellation of diverse symptoms. This diversity presents both a challenge and a constraint for figuring out the neurobiological root causes of schizophrenia. There is likely not just one lesion but a number of lesions that are present across different brain regions that are the proximal causes for these symptoms.” explained Jong H. Yoon, M.D., at the University of California, Davis, and lead author of the study. Yoon’s study focused on the prefrontal cortex and the basal ganglia. The basal ganglia is a subcortical collection of neuron clusters, including the ventral tegmental area and substantia nigra, which produce the majority of the brain’s dopamine, and the striatum, an important site of action of dopamine. Using functional magnetic resonance imaging (fMRI), the researchers examined the brain activity within the prefrontal cortex and basal ganglia of 18 individuals with schizophrenia and 19 healthy controls. The subjects completed a memory task in which they had to remember images of faces across a brief delay period to determine if subsequently presented faces were the same faces; it was hypothesized that patients with schizophrenia would have more difficulty performing this task. Results of the Study Patients with schizophrenia experienced excess activity in the substantia nigra, decreased activity in the prefrontal cortex, and diminished functional connectivity between these regions, suggesting that communication among these regions was out of sync. Additionally, the higher the level of connectivity between the substantia nigra and the striatum, the higher the level of psychosis seen in the patients with schizophrenia. Significance These findings suggest that the prefrontal cortex-basal ganglia circuit may be a common pathway linking cognitive deficits and psychosis in schizophrenia. It also points to a more widespread use of fMRI in diagnosis and treatment. Compared to other neuroimaging techniques such as positron emission tomography (PET), fMRI yields more detailed images, does not use radiation, and is relatively widely available since most university-based brain imaging centers have this technology. These findings could also lead to the creation of a better animal model of psychosis, of which there currently are few. Biomedical research has shown that early detection and intervention could preempt later stages of diseases. This concept of “treatment as prevention” is seen in the NIMH-supported North American Prodrome Longitudinal Study (NAPLS), which is using biological assessments, such as neuroimaging, to predict who will convert to psychosis and to develop new treatment and prevention approaches. Another NIMH study, Recovery After an Initial Schizophrenia Episode (RAISE), supports the development and testing of two complementary models for early intervention in schizophrenia. Research is also underway to identify genes and environmental elements associated with schizophrenia. What’s Next Because the study involved patients with established illness who are already on antipsychotic medications, it needs replication in patients with schizophrenia who are not medicated and/or in the early phases of illness. The study should also be performed in individuals at high risk of developing psychosis to see if these findings could help identify individuals in the earliest stages of illness when interventions to prevent or significantly ameliorate schizophrenia can be instituted. To obtain greater precision in localizing brain regions, the study also warrants replication with high-resolution fMRI. Furthermore, the techniques in this study could also be applied to other disorders that can have psychosis as one of its symptoms, such as mood disorders, and post-traumatic stress disorder. Reference Yoon JH, Minzenberg MJ, Raouf S, D’Esposito M, Carter CS. Impaired Prefrontal-Basal Ganglia Functional Connectivity and Substantia Nigra Hyperactivity in Schizophrenia. Biological Psychiatry, published online January 14, 2013.

Psychotropic Medications Are Prescribed Appropriately Among U.S. Teens, National Study Finds

Prescribed psychotropic medications are not being misused or overused among U.S. youth, according to a study using nationally representative data sponsored by NIMH. The study was published December 3, 2012, online ahead of print in the Archives of Pediatric and Adolescent Medicine. Background Psychotropic medications affect the brain chemicals associated with mood and behavior. Some studies and media reports have raised concerns about their use among youth. However, much of the concern stems from information found in anecdotal reports, small clinical samples, or insurance databases rather than on representative samples of U.S. youth with clinical assessments of emotional and behavioral disorders. Studies from regional community samples have found widely varying rates, which can lead to skewed perceptions. For example, different studies have found a wide range of stimulant medication use for attention deficit hyperactivity disorder (ADHD)—from 7 percent to 72 percent—likely due to methodological and regional differences. As a result, it has been difficult to get a clear, accurate understanding of medication use among youth. Kathleen Merikangas, Ph.D., of NIMH and colleagues collected information on specific medication use in the National Comorbidity Study-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey from 2004 of more than 10,000 teens ages 13 to 18.The teens were asked questions that helped to ascertain information about mental disorders and service use. A previous report published in October 2010 using data from the NCS-A indicated that about 20 percent of U.S. youth are affected by some type of mental disorder during their lifetime serious enough to affect their functioning. In this most recent analysis, the researchers examined patterns of prescribed medication use among youth who met criteria for a wide range of mental disorders. Psychotropic medications that were examined include antipsychotics, antidepressants, and stimulants Professional Counselor Continuing Education Results of the Study Among those youth who met criteria for any mental disorder, 14.2 percent reported that they had been treated with a psychotropic medication. Teens with ADHD had the highest rates of prescribed medication use at 31 percent, while 19.7 percent of those with a mood disorder like depression or bipolar disorder were taking psychotropic medication. Among those with eating disorders, about 19 percent were taking a psychotropic medication, and 11.6 percent of those with anxiety disorders reported taking medication. Very few youth reported use of antipsychotic medications. They were most frequently used by youth with severe bipolar disorder (1.7 percent) or a neurodevelopmental disorder such as autism (2.0 percent). Approximately 2.5 percent of teens without a diagnosed mental disorder were prescribed a psychotropic medication. Among these youth, 78 percent reported having a previous mental or neurodevelopmental disorder and associated psychological distress or impairment. Significance The data suggest that most adolescent youth who are taking psychotropic medications have serious behavioral, cognitive or emotional disturbances. The findings also showed that youth being treated by a mental health professional were more likely to be receiving appropriate medication as opposed to those being treated within general medicine or other settings. However, more research is needed on medication use among children younger than age 13. Reference Merikangas K, He J, Rapoport J, Vitiello B, Olfson M. Medication use in US Youth with Mental Disorders. Archives of Pediatric and Adolescent Medicine. Online ahead of print Dec 3, 2012.