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A miscellany from NEJM Journal Watch.
October 10, 2014
Reviews of Note
Barbara Geller, MD, Joel Yager, MD, Jonathan Silver, MD
Concussion, transference interpretations, anxiety disorders in children, how to study and prevent suicide, the etiology of psychiatric disorders, and mitochondrial transfer techniques for severe genetic disease
In an occasional column, NEJM Journal Watch Psychiatry editors comment briefly on review articles.
Concussion: Two concise and critical research reviews. Giza and Hovda, who performed essential work informing our knowledge of the postconcussion neurometabolic cascade, now provide an update.1 They review current knowledge of the acute pathophysiology of concussion (ionic flux, glutamate release, the “energy crisis,” cytoskeletal damage, axonal dysfunction, altered neurotransmission, inflammation, and cell death) and relate these processes to symptoms. For example, ionic flux may be linked to postconcussion migraines; the energy crisis is related to the greater vulnerability to a second concussion before this process normalizes, and altered neurotransmission and axonal dysfunction relates to slowed cognition. The authors also hypothesize about how these processes can result in more chronic brain dysfunction. This paper is important for anyone who sees patients with concussion.
Yuh and colleagues review current research and practical uses of neuroimaging.2 Acute computerized tomography is indicated in those with loss of consciousness >30 seconds, prolonged or deteriorating level of consciousness, severe headache, or worsening symptoms. Structural magnetic resonance imaging (MRI) has a role in those with subacute or chronic mild traumatic brain injury (mTBI) with persistent symptoms or deficits, because hemorrhagic axonal injury, small contusions, and small extra-axial collections are correlated with prognosis. The most sensitive MRI sequence is susceptibility-weighted imaging in machines with higher (3 T) magnetic fields. Other research techniques (e.g., diffusion tensor imaging, functional MRI, and MR spectroscopy) are not diagnostic, showing only group differences at this point, and cannot be used for individual cases. Single-photon emission computerized tomography (SPECT) and positron emission tomography (PET) may be supportive of the diagnosis of mTBI, but are not themselves diagnostic. We await the refinement of these techniques to have sufficient sensitivity and specificity to help with diagnosis and prognosis for individual patients.
What roles do transference and transference interpretation play in psychotherapy outcomes? This author examines studies of transference work in psychotherapy (almost exclusively in studies of psychodynamic psychotherapy).3 Evidence from naturalistic and experimental studies shows that transference reactions and how they are handled can benefit, or harm, psychotherapy outcomes. Although the experimental studies are too heterogeneous to permit meta-analysis, the author interprets overall findings to support the contention that transference interpretation has specific therapeutic value over and above “common factors,” particularly in the treatment of women with interpersonal difficulties and more-severe personality pathology.
Treating anxiety disorders in children and adolescents. This review of treatment options for children and adolescents with a variety of anxiety disorders4 finds evidence for the effectiveness of selective serotonin reuptake inhibitors for children and cognitive-behavioral therapy (CBT). Pharmacotherapy studies typically have included children aged ≥6 or ≥7 years, and no evidence as yet exists for CBT prior to age 7. Combination treatments utilizing both approaches have been more effective than either one singly. Clearly, family involvement and education in treatments are essential in all cases.
Ways to understand and prevent suicide. These authors note that over 1 million deaths by suicide occur per year, a number greater than from war and homicide; yet too little is done to address this problem.5 Further, many cultural and interpersonal barriers impede studying and reporting suicidality; e.g., attempters are imprisoned in India and Singapore. The authors have developed a multifaceted proposal to combat high suicide rates — make suicide a coded category in nosological schema, such as the DSM; target research into the neurobiological basis of suicide; provide greater funding for research, especially as a domain across diagnoses, such as through the Research Domain Criteria project at the National Institute of Mental Health; and institute preventive measures, such as increased efforts to help general practitioners — often the only clinicians who see these patients — recognize patients with suicidality.
Toward a more scientific psychiatry. In a measured analysis, one of psychiatry's most thoughtful scholars considers contemporary research into the etiology of psychiatric disorders.6 After reviewing 197 recent articles in 12 major psychiatric journals, Kendler classifies the field into three categories (biological, psychology, and environmental), each of which have various sublevels (5 biological subcategories, 4 psychological subcategories, and 3 environmental subcategories). He shows how these various sublevels relate to one another, how often individual investigations extend within and across these levels, and what implications the resulting multilevel pluralism holds for our conceptual models and future work. Kendler advocates for intensive search for risk factors and causal mechanisms within and across levels and, ultimately, for tracing these pathways back to the mental experiences of our patients. Overall, he disdains the tunnel vision that has occasionally afflicted psychiatric research (i.e., that there is only one valid approach), settling instead for our “dappled causal world of psychiatric disorders.”
Mitochondrial transfer to evade severe genetic disease. Impaired mitochondrial function and mitochondrial DNA expression occur in autism spectrum disorder and other inherited brain and muscle diseases. This reporter details one investigational approach to correct these anomalies.7 First, eggs are removed from both a mutation-carrying mother and a donor. The nuclear DNA is removed from the donor ova, leaving healthy mitochondrial DNA. Then, DNA from the mutation carrier's egg is transferred to the donor's, and the egg is implanted in the mutation carrier. In nonhuman primates, this method yields successful pregnancies and apparently normal offspring. But many questions remain about whether other DNA damage could occur during the procedures and whether the offspring themselves will be fertile. While bioethicists are examining critical and controversial issues related to the new technology, teams in both the U.S. and U.K. are advocating for human trials.
Citation(s):
Giza CC and Hovda DA.The new neurometabolic cascade of concussion. Neurosurgery 2014 Oct; 75:S24. (http://dx.doi.org/10.1227/NEU.0000000000000505)
PubMed abstract (Free)
Yuh EL et al. Imaging concussion: A review. Neurosurgery 2014 Oct; 75:S50. (http://dx.doi.org/10.1227/NEU.0000000000000491)
PubMed abstract (Free)
Høglend P.Exploration of the patient-therapist relationship in psychotherapy. Am J Psychiatry 2014 Oct; 171:1056. (http://dx.doi.org/10.1176/appi.ajp.2014.14010121)
PubMed abstract (Free)
Mohatt J et al. Treatment of separation, generalized, and social anxiety disorders in youths. Am J Psychiatry 2014 Jul; 171:741. (http://dx.doi.org/10.1176/appi.ajp.2014.13101337)
PubMed abstract (Free)
Aleman A and Denys D.A road map for suicide research and prevention. Nature 2014 May 22; 509:421. (http://www.ncbi.nlm.nih.gov/pubmed/24860882)
CrossRefPubMed abstract (Free)
Kendler KS.The structure of psychiatric science. Am J Psychiatry 2014 Sep; 171:931. (http://dx.doi.org/10.1176/appi.ajp.2014.13111539)
PubMed abstract (Free)
Callaway E.Reproductive medicine: The power of three. Nature 2014 May 22; 509:414. (http://dx.doi.org/10.1038/509414a)
PubMed abstract (Free)