Brain Region Singled Out for Social Memory, Possible Therapeutic Target for Select Brain Disorders

Researchers have found in mice that a formerly obscure region of the hippocampus called CA2 is important for social memory, the ability of an animal to recognize another of the same species. Identifying the role of this region could be useful in understanding and treating disorders characterized by altered social behaviors such as schizophrenia, bipolar disorder, and autism. Funded in part by the National Institute of Mental Health (NIMH), the study was published last month online in Nature. Background The hippocampus is essential for learning and memory—specifically the storage of knowledge of who, what, where, and when. Clues about the hippocampus’s roles emerged from the famous case of patient HM (Henry Molaison), who had most of his hippocampus removed by surgeons in 1953 to cure his epilepsy. HM became unable to form new memories of people he subsequently worked with for years. Most previous studies of how memory is harnessed have focused on the trisynaptic pathway. In this neural circuit, information that is obtained from the entorhinal cortex—the main interface between the hippocampus and the neocortex or the outermostpart of the brain involved in higher functions such as thought or action—proceeds to the dentate gyrus, the front gate of the hippocampus. Granule neurons from the dentate gyrus then shuttle the information to interneurons and pyramidal cells of the CA3 region of the hippocampus, which then sends the information to the CA1 region, the main source of hippocampal output. Absent from this circuit is the CA2 subfield. “Although the CA2 subregion was discovered over 75 years ago, it has received very little attention,” said Steven A. Siegelbaum, Ph.D., lead author of the study. He ascribes two reasons for the inattention: size and location. CA2 has 10 percent the number of neurons of CA1 or CA3, raising questions about its importance. The region is also squeezed between CA1 and CA3, making it difficult to study with traditional approaches of physical or chemical lesions, which lack the precision to selectively target CA2. To circumvent these problems, Siegelbaum, a neuroscience professor at Columbia University and a Howard Hughes Medical Institute Investigator, and Frederick L. Hitti, an M.D.-Ph.D. student, generated a special transgenic mouse in which the CA2 neurons could be selectively inhibited in adult animals. Once these neurons were inactivated, the mice underwent a series of behavioral tests. Results of the Study Normally when a mouse encounters another mouse it does not know, it gives it a “sniff test” and is more interested in this new mouse versus a familiar acquaintance. The CA2-inactive mouse, however, shows no recognition of mice it has seen before and ends up sniffing indiscriminately familiar and novel mice. The mice showed no loss in the ability to discriminate social or non-social odors, such as food buried deeply in its litterbox. Although a pronounced loss of social memory is seen in the CA2-inactive mice, the mice did not experience changes in other hippocampal-specific behaviors such as spatial and contextual memory, and could still distinguish between novel and familiar inanimate objects. Significance “Because several neuropsychiatric disorders are associated with altered social behaviors, our findings raise the possibility that CA2 dysfunction may contribute to these behavioral changes,” said Siegelbaum. Individuals with schizophrenia and bipolar disorder have lowered numbers of CA2 inhibitory neurons. Similarly, individuals with autism have altered signaling of vasopressin, a social behavior hormone that interacts with a specific class of receptors found predominantly in this region. However, the CA2-inactive mice did not display classic symptoms of autism as they had normal levels of sociability, providing evidence that sociability and social memory involve different brain functions. Techniques such as the one detailed here are examples of research tools that the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN ) Initiative hopes to build upon to further our understanding of the human brain. What’s Next Siegelbaum’s group hopes to use the same genetic technology to examine whether there are changes in CA2 function in mouse models of psychiatric disorders such as autism and schizophrenia. If so, they plan to screen for drugs that restore normal CA2 function and ask whether this drug treatment helps reverse any behavioral changes seen in the mice. Such research offers the possibility of finding new drug targets and approaches for treating the behavioral changes associated with these disorders Alcoholism and Drug Abuse Counselors Continuing Education Reference Hitti FL, Siegelbaum SA. The Hippocampal CA2 Region is Essential for Social Memory. Nature , published online February 23, 2014. Grant 5F30MH098633-02

Survey Finds More Evidence That Mental Disorders Often Begin in Youth

About 8 percent of U.S. teens meet current criteria for having a serious emotional disturbance, according to two NIMH-funded studies published in the April 2012 issue of the Archives of General Psychiatry. Background A September 2010 study using data from the NIMH-funded National Comorbidity Survey-Adolescent Supplement (NCS-A) found that about 20 percent of youth are affected by a mental disorder sometime in their lifetime. The NCS-A is a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. Parents or caregivers were also asked to complete a corroborating questionnaire after teens were interviewed. The NCS-A used criteria established by the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV) to assess for a wide range of mental disorders including mood and anxiety disorders, behavior disorders like attention deficit hyperactivity disorder (ADHD), eating disorders, and substance use disorders. In this most recent analysis, Kathleen Merikangas, Ph.D., of NIMH, Ron Kessler, Ph.D., of Harvard University, and colleagues examined the prevalence of mental disorders, as well as the severity of the disorders, within a 12-month period to estimate the rate of serious emotional disturbances (SED) in youth. SED was defined by the Substance Abuse and Mental Health Administration (SAMHSA) as a “mental, behavioral, or emotional disorder … that resulted in functional impairment which substantially interferes with or limits the child’s role or functioning in family, school, or community activities.” Results of the Study The researchers found that about 8 percent of all respondents had SED. Those with behavior disorders were most likely to be considered to have a severe disorder. Those with three or more coexisting disorders were also more likely to be severely affected. Similar to adults, anxiety disorders were the most common conditions in adolescents. Echoing many other studies, girls were more likely to have a mood or anxiety disorder or eating disorder, while boys were more likely to have a behavior disorder like ADHD or substance use disorder. Contrary to regional studies, this report showed a lower rate of depression among Hispanics compared to whites. Significance The findings in this study reflect the widely held belief that most psychiatric disorders first manifest in childhood or adolescence and tend to persist or recur throughout a person’s life. The researchers conclude that the high prevalence rate of mental disorders in U.S. adolescents underscores the need for more research focused on changing the trajectory of mental disorders in youth. What’s Next More research is needed to better understand the differences in prevalence rates among cultural and ethnic groups in different regions of the country ceus for nurses Citations Kessler R, Avenevoli S, Costello J, Georgiades K, Green JG, Gruber M, He J, Koretz D, McLaughlin K, Petukhova M, Sampson N, Zaslavsky A, Merikangas K. Prevalence, persistence and Sociodemographic correlates of DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement. Archives of General Psychiatry. April 2012; 69(4):372-380. Kessler R, Avenevoli S, Costello J, Green JG, Gruber M, McLaughlin K, Petukhova M, Sampson N, Zaslavsky A, Merikangas K. Severity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement. Archives of General Psychiatry. April 2012; 69(4):381-389.

Intervention Shows Promise in Treating Depression Among Preschoolers

Source: NIMH

A new psychosocial approach shows promise in helping preschoolers with symptoms of depression function better and learn to regulate their emotions, according to an NIMH-funded study published online ahead of print October 31, 2011, in the Journal of Child Psychology and Psychiatry.

Background

Recent studies have shown that symptoms of clinical depression can arise in children as young as 3, and may in fact be an early manifestation of a childhood mood disorder. However, no studies have investigated the best way to treat the disorder among children so young. In addition, many established psychosocial treatments for depression in adults and older youth, such as cognitive behavioral therapy or interpersonal therapy, might not be a good fit to the developmental needs of very young children.

Yet research has shown that very early behavioral interventions can have a significant impact on the trajectory of conduct problems and neuro-developmental disorders like autism or some developmental delays. These findings suggest that very early intervention for a mood disorder could potentially head off depression later in life lpc continuing education

Toward that end, Joan Luby, M.D., of Washington University and colleagues conducted a preliminary pilot study comparing a novel form of psychotherapy called Parent Child Interaction Therapy -Emotion Development (PCIT-ED) with a psycho-educational program. PCIT includes hands-on components aimed at strengthening the parent-child relationship by teaching positive play techniques and coaching parents through the process, and training parents in methods for handling noncompliance and disruptive behavior. PCIT has already been shown to be effective for treating disruptive disorders among preschoolers. The Emotion Development component was designed to help the parent enhance the child’s ability to recognize emotions in self and others and more effectively regulate intense emotions.

The psycho-education program—the control condition—educated parents in small groups about child development. It emphasized emotional and social development but did not include individual coaching or practice sessions with the parents and their children.

The researchers randomly assigned 54 preschoolers (aged 3-7) and their parents to either PCIT-ED or to the psycho-education program. Each program was conducted over a 12-week period.

Results of the Study

After 12 weeks, depression symptoms among the preschoolers significantly declined in both groups. The group receiving PCIT-ED also showed improvements in levels of anxiety, hyperactivity, conduct problems, hostility and inattention, whereas the group receiving the psycho-education program showed improvements in separation anxiety. In addition, the PCIT-ED group showed improvements in a child’s executive functioning and his or her ability to recognize and regulate emotions, compared to the control condition. The PCIT-ED group also reported reduced parenting stress and decreases in maternal depression, whereas the psycho-education group did not.

Significance

The results indicate that PCIT-ED is acceptable to families and may be beneficial. The researchers conclude that a full-scale randomized controlled trial is warranted.

What’s Next

While intriguing, the findings are preliminary only and should be interpreted with caution until further research can be conducted.

Reference

Luby J, Lenze S and Tillman R. A novel early intervention for preschool depression: findings from a pilot randomized controlled trial. Journal of Child Psychology and Psychiatry. Online ahead of print Oct. 31, 2011.