2014 in Review

Rebecca Birnbaum’s study (1) makes use of the Lieber Institute’s extensive postmortem brain collection, collected over many years at the National Institute of Mental Health by her collaborators Joel Kleinman, Thomas Hyde, and Daniel Weinberger. The study used frontal cortex from normal subjects to identify genes that were expressed at greater levels in fetuses than in individuals who died later in life. Presumably, these genes are particularly concerned with brain development. For autism and schizophrenia, in particular, it is now recognized that some pathological dysfunction is already present at birth in newborns who will later express the full clinical syndrome, as late as adulthood for schizophrenia. Thus, what happens in fetal brain development is an important pathogenic cause of the illness. Birnbaum’s work takes this line of investigation for the first time to the level of the specific genes responsible. For autism 242 possible genes were identified, but for schizophrenia only a handful could be identified. These schizophrenia genes were not among those identified by genome-wide association, but rather those that are present in small chromosomal regions that are deleted in rare individuals with schizophrenia. Birnbaum’s article thus resolves how the complex genetic architecture of these two illnesses is translated, not directly into clinical illness, but rather into pathological brain development that then forms the basis for what will later become illness. It also points to the earliest possible period, fetal development in the maternal uterus, as a target for serious efforts to prevent mental illness entirely. It is sobering that within a few months of intense gene activity, the pattern is set for a lifetime of disability.

This is not Dr. Birnbaum’s first contribution to the Journal. She wrote several years earlier about her father, Dr. Morton Birnbaum, a physician and attorney who in 1960 won a landmark civil rights case that established the right to treatment for patients held involuntarily for mental illness (2). Both Drs. Birnbaum have made radical contributions to patients with mental illness, father leading the way in his era to extend civil rights to ensure their treatment and his daughter in her era, to change the way in which we view the illness’s genetic origins.

Suicide remains a leading cause of death world-wide. In the United States, the rate of suicide increased from 2001 to 2011, the last year for which complete data are available. Furthermore, suicide is arguably the primary cause of mortality within the domain of psychiatric medicine. Although we have learned much about the demographic, social, and behavioral factors associated with higher rates of suicide, prediction of suicide risk at the level of the individual remains a very difficult clinical challenge. Consequently, the study by Guintivano and colleagues (3), which offers promise of a novel biomarker for suicide risk, ranks as a leading contribution in this year’s pages of the Journal. Beginning with unbiased studies of the postmortem human brain, the authors found that epigenetic and genetic variation at a specific location in the SKA2 (spindle and kinetochore associated complex subunit 2) gene was associated with completed suicide. In peripheral blood samples from three independent cohorts of subjects, these same features were also associated with suicidal ideation. Perhaps consistent with the known function of the SKA2 gene product in regulating the function of the glucocorticoid receptor, the investigators found evidence suggesting that epigenetic and genetic variation in SKA2 modulates suppression of the stress hormone cortisol. Finally, the interaction of measures of stress and anxiety with SKA2 epigenetic and genetic variation measured in blood predicted suicidal ideation and attempt with 80% accuracy. This study stands as a tour de force owing to its integration of findings from different types of samples across multiple cohorts of subjects combined with the pursuit of a plausible mechanism linking biological and behavioral measures of suicide risk. Although the findings of this important study merit careful attention, as discussed by the authors the findings must be considered preliminary, with their potential clinical utility awaiting replication in larger, independent studies.

Psychiatrists have countertransferences, that is they are emotionally responsive to their patients. Their reactions may be conscious or unconscious, helpful or unhelpful, and determined by the therapist’s inner life, or by the patient’s. To the extent that they are based on the latter, they provide a potential source of information about the patient, information that can be of diagnostic significance and therapeutic value.

Long viewed primarily as a problem in psychodynamic psychotherapy, the recent emphasis has been on countertransference as a valuable clinical tool. Of course, in order for this to be true it has to be contained, not overwhelming, and to be recognized and understood by the therapist—in other words, to function as a signal.

Much of what is believed in this domain is based on clinical folklore. However, Colli and colleagues (4) report a fascinating empirical study. They invited 203 clinicians to describe individual patients’ personalities and the therapist’s empirical responses to these patients. They found consistent patterns (e.g., clinicians feel fully engaged and engrossed by histrionic patients, while being concerned and cautious lest they self-disclose about their personal lives).

The potential value of such data in the differential diagnosis of personality types is obvious—it reaffirms that the skillful clinical interview not only collects data, it also generates them. The therapeutic value is less clear, but the potential is apparent. For example, studies of specific countertransference responses might lead to criteria for the optimal matching of therapists with patients, to strategies for supervision, and to suggestions for the treatment of patients with specific personality disorders. The study demonstrates that even the most subjective aspects of psychotherapy can be studied and enhanced by systematic empirical research.

More than 25 years ago, advances in brain imaging began to generate enthusiasm. This reflected growing hope for clinically useful biological tests, which could inform diagnosis and treatment. This enthusiasm gradually waned, as few consistently replicated findings emerged. However, enthusiasm may once again begin to grow, as brain imaging research continues to mature. This emerging maturity is illustrated by the wide-scale adoption of standard methods, which supports the collection of increasingly large samples.

Illustrating these encouraging trends, De Wit and colleagues (5) assembled magnetic resonance imaging (MRI) data from six research centers to compare brain structure in more than 400 patients with obsessive-compulsive disorder (OCD) and more than 350 comparison subjects free of psychopathology. The main finding was to demonstrate OCD-related reductions in prefrontal volumes, reductions that lay within regions central to existing pathophysiologic models of OCD. As a result, the study provides a rare instance where neuroimaging data corroborate theory on brain-behavior relationships in a mental illness. From this perspective, excitement reflects the study’s use of brain imaging to tell us that key ideas about an illness have merit, which raises hopes that imaging is converging on approaches that will generate clinically useful measures.

In the February issue, Lineweaver and colleagues (6) described an intriguing analysis testing whether the knowledge of having a genetic risk factor for Alzheimer’s disease can affect one’s self-perception of memory function as well as actual measured memory performance. The study examined older adults who had undergone testing for the apolipoprotein ε4 allele, but one group had been notified of their genotype while another group had not. The investigators discovered that older adults who know they are positive for the ε4 risk factor perceive themselves as having worse memory and also perform worse on objective testing when compared with matched older adults who also have an ε4 allele but are not informed of it prior to testing. This fascinating observation raises new prospects for the future of “resilience” in aging research—through the knowledge that self-perceived successful aging may translate into enhanced function and better outcomes.

Violence toward others is an increasing concern for military veterans, yet predictors of violent outcomes are challenging. Elbogen and colleagues (7) set out to develop a clinical tool for indicating violence risk in military veterans. They used two different veteran populations, each of which had a risk assessment at baseline (using their brief screening tool) and violence assessment at a 12-month endpoint. They found that each of the five individual items included in their proposed screening tool (financial instability, combat experience, alcohol misuse, past violence/arrests, PTSD/anger) made unique contributions to the prediction of violence itself, suggesting that violence risk is multietiological and that no single item accounts for violent behavior. Four of the five risks assessed are dynamic, hence available for modification and management. The accompanying scale, which the authors do not claim is comprehensive, is able to give caregivers a sense of violence risk; hence, it is clinically useful in veteran populations. I like this article because it addresses an important and unmet need of veterans, people who have already provided full commitment to our society and deserve utmost attention. Moreover, this research shows that violence in military veterans is not simple and not dependent on a single factor, but complexly determined.

This year has been one of tremendous growth and development for The Residents’ Journal. As the number of submissions from talented medical students, psychiatry residents, and fellows from across the nation continues to increase, the editorial board is challenged to choose the most thought-provoking, timely, and well-written pieces with clinical utility for trainees. One publication with all of these attributes is Dr. Holly Peek’s review “Playing With Violence: Are Violent Video Games a Risk Factor for Violent Behaviors in Children?” (8). With the recent surge in mass shootings and violent crimes committed by our youth, the public has turned to the field of psychiatry for answers. The Surgeon General and President Obama have echoed this cry for explanation and reform, declaring youth violence as an epidemic that must be curbed. Peek’s review examines the evidence for whether exposure to violent video games is a risk factor for violence in children, and it provides clinicians and public health officials practical treatment guidelines regardless of personal opinion. She discusses the controversial hypothesis that there is a causal relationship between violent video games and violent behaviors in children. Proponents of the general aggression model, a social-cognitive theory, believe that aggressive acts are largely based on the formation of aggression-related scripts and schemas, with little emphasis on genetic diathesis. This contrasts with the more biological “catalyst” model, whose supporters feel a violence-prone personality develops through genetic predisposition that leads to an aggressive temperament. Peek provides a careful discussion of both opinions, highlighting the conclusion shared by both parties that all children are affected in some way by media violence through video game exposure. She leaves the reader with practical treatment approaches to mitigate this problem, emphasizing education provided to both parents and youth regarding critical appraisal of violence in the media. In the end, perhaps education will facilitate healthier processing of violence so that youth will better understand alternative approaches to conflict as well as real consequences of poor decisions. Trainees will certainly benefit from this thought-provoking review, especially as public interest in violent behavior in children continues to grow.