The American Journal of Psychiatry Current Issue

In This Issue

Wed, 01 May 2013 00:00:00 GMT

Chronic Disabling Fatigue in Adolescents

Bleijenberg G, Knoop H. — Wed, 01 May 2013 00:00:00 GMT

T he study by Lamers et al. in this issue (1) is important in several respects. Fatigue in adolescents was investigated in a large representative sample from the general population by structured interviews. The study demonstrated that persistent fatigue without anxiety or depression occurred in 1.4% of the adolescents. This prevalence rate is surprisingly high, and in about 60% of this group the fatigue was associated with substantial disability. Despite these disabilities, the adolescents with persistent fatigue without anxiety or depression generally did not seek help from the health care system. This reflects perhaps the assumption of both adolescents and health care professionals that fatigue is a transient state that will resolve spontaneously. But is that true? Or should more attention be paid to this debilitating symptom? Fatigue indeed occurs frequently in adolescents. It is not unusual that youngsters experiment with extreme behavior, thereby exhausting themselves. Usually the fatigue resolves when the adolescent changes his or her behavior. Fatigue becomes a problem if it persists and leads to disability, such as school absence, or if the adolescent feels continuously unable to be physically active (e.g., participate in sports) and socially involved (e.g., take part in festivities, go out). Then fatigue threatens the adolescent’s social, emotional, and intellectual development. In those instances, fatigue deserves attention from the health care system.

How Should the Psychiatric Profession Respond to the Recent Mass Killings?

Friedman RA, Michels R. — Wed, 01 May 2013 00:00:00 GMT

The horrific school shooting in Newtown, Conn., which took the lives of 20 children and six adults, presents psychiatry with a difficult challenge. How do we as a profession respond to these devastating acts of public violence? What is the best way to bring our expertise—as clinicians, researchers, and educators—to bear on the controversial nexus between guns, violence, and mental illness?

The Neuroepigenetics of Suicide

Akbarian S, Halene T. — Wed, 01 May 2013 00:00:00 GMT

Suicide is considered a major preventable public health problem and is the 10th leading cause of death in the United States for all age groups combined. It is generally accepted that suicide marks the tragic endpoint of a highly complex behavior shaped by social, developmental, and neurobiological factors that translate into a predisposition for the act itself. For example, altered serotonergic activity in the prefrontal cortex, which appears to be partially independent of the changes observed in major depression, is thought to play an important role (1, 2). Furthermore, the concordance rate for serious suicide attempts in monozygotic twins has been reported to be up to 17-fold greater than in dizygotic twins, and heritability estimates for serious suicide attempts are estimated to be as high as 55% (2). On the other hand, recent genome-wide association studies of nearly 9,000 individuals diagnosed with a mood disorder, approximately one-third of whom had a history of attempted suicide, effectively ruled out common genetic variants and polymorphisms of large effect (3). Following this approach, much larger cohorts will be required in order to gain insight into what appears to be a highly polygenic risk architecture.

To Treat or Not to Treat Perinatal Depression With Antidepressant Medication: Effects on Infant Growth

Parry BL. — Wed, 01 May 2013 00:00:00 GMT

The physician managing major depression during pregnancy and lactation must weigh the risks and benefits of treating with antidepressant medication. Investigators examining this question in previous work found that women with major depression during pregnancy were at increased risk for preterm birth and having infants with low birth weight and intrauterine growth restriction (1, 2). Antidepressant use during pregnancy also is associated with adverse outcomes: women treated with a selective serotonin reuptake inhibitor (SSRI) have a two- to threefold greater risk of preterm birth and a higher rate of delivering low-birth-weight infants than do women with no SSRI exposure during pregnancy (3, 4). In a previous study by Wisner et al. (1), preterm birth rates and infant weight, length, and head circumference for women with untreated major depression or SSRI treatment during pregnancy did not differ from those of women with neither major depressive disorder nor SSRI exposure during pregnancy. As Wisner and colleagues note in their article published concurrently with this editorial (5), much of the other investigative work in this area is limited by not having a group of women with untreated major depressive disorder, a group with SSRI or other antidepressant treatment, and a comparison group without major depressive disorder or SSRI exposure during pregnancy to differentiate the effects of treatment on reproductive outcomes. In addition, many of the previous studies did not examine longer-term effects on infant outcomes. The distinguishing feature of the current study by Wisner et al. is that it examines all three groups of women during pregnancy: those with an untreated depression, those with depression receiving SSRIs, and those with neither major depression or antidepressant treatment during pregnancy. Furthermore, the investigators examined women not only during pregnancy (at 20, 30, and 36 weeks gestation) but also for up to a year postpartum (at 2, 12, 26, and 52 weeks). Other strengths of the study include its prospective design, thorough participant (mother and child) assessments of clinical history, and physical examination by raters blind to condition. Thus, this study sets the gold standard as to how to conduct sound methodological investigations in this field so that clinicians and patients have the necessary information to make informed decisions about reproductive choices.

Protecting Confidentiality in Human Research

Adinoff B, Conley RR, Taylor SF, et al. — Wed, 01 May 2013 00:00:00 GMT

The validity of clinical research relies on accurate and truthful data collected without fear of disclosure of sensitive information. To that end, Congress authorized the Secretary of Health and Human Services to issue certificates giving investigators protection as intended by the statute to refuse to disclose the identity of research subjects, even when required by an order of the court. The Certificate of Confidentiality is intended to guarantee that vulnerable research populations can participate in research without fear of disclosure. Some court cases, however, have raised concerns about whether the Certificate provides the promised protections and whether the application procedure is overly cumbersome (1, 2). In addition, the Patriot Act further clouds the security provided to research information presumably secured by the Certificate. At the same time, the National Institutes of Health (NIH) and local institutional review boards have been encouraging, and sometimes requiring, researchers to obtain a Certificate in order to carry out research. These issues have been the focus of several recent symposia at national conferences (3; unpublished 2012 paper of L. Dame; unpublished 2012 paper of T. Zarcone; unpublished 2011 paper of L. Beskow).

The Enigmatic Persistence of Anorexia Nervosa

Walsh B. — Wed, 01 May 2013 00:00:00 GMT

Objective

In this review, based on recent advances in cognitive neuroscience, the author presents a formulation in which the marked persistence of anorexia nervosa can be usefully understood as a well-ingrained maladaptive habit.

Method

The author reviewed the relevant literature on the development and course of anorexia nervosa and interpreted critical features in light of developments in cognitive neuroscience.

Results

Anorexia nervosa is a well characterized disorder with remarkable persistence both across history and among affected individuals. Food restriction, the salient behavioral feature of the disorder, often begins innocently but gradually takes on a life of its own. Over time, it becomes highly entrenched and resistant to change through either psychological or pharmacological treatment. Cognitive neuroscience has described two related but distinct processes that underlie the acquisition of new patterns of behavior, namely, action-outcome and stimulus-response learning. It is likely that both processes are engaged in the development of anorexia nervosa and that stimulus-response learning (that is, habit formation) is critical to the persistence of the dieting behavior.

Conclusions

The formulation of the dieting behavior characteristic of anorexia nervosa as a well-entrenched habit provides a basis for understanding the striking persistence of this disorder. This model helps explain the resistance of anorexia nervosa to interventions that have established efficacy in related disorders and implies that addressing the dieting behavior is critical, especially early in the course of the illness, before it has become ingrained.

Defective Processing Speed and Nonclinical Psychotic Experiences in Children: Longitudinal Analyses in a Large Birth Cohort

Niarchou M, Zammit S, Walters J, et al. — Wed, 01 May 2013 00:00:00 GMT

Objective

Psychotic experiences in children are associated with an elevated risk of developing psychosis. The authors investigated whether the pattern of cognitive deficits present in psychosis also exists in children with psychotic experiences within the general population.

Method

The authors examined the longitudinal relationships between key cognitive domains, selected a priori based on their association with schizophrenia, and onset of psychotic experiences in children from the Avon Longitudinal Study of Parents and Children and whether these associations were independent of one another.

Results

Lower performance in the domains of processing speed at age 8 years (odds ratio=1.24, 95% CI=1.12–1.36) and attention at age 11 (odds ratio=1.14, 95% CI=1.04–1.25) and decline of processing speed between the ages of 8 and 11 (odds ratio=1.29, 95% CI=1.15–1.45) were associated with higher risk of psychotic experiences at age 12. When adjusting for the other cognitive domains, processing speed at age 8 (odds ratio=1.20, 95% CI=1.09–1.33) was the measure most strongly associated with psychotic experiences.

Conclusions

Defective processing speed is a particularly strong predictor of psychotic experiences in children. Furthermore, the pattern of associations between cognition and psychotic experiences in children within the general population is similar to the one between cognition and schizophrenia. These findings have potentially important implications for understanding the pathogenesis of psychotic disorders and the specific deficits that seem to place children at higher risk of psychopathology.

Does Fetal Exposure to SSRIs or Maternal Depression Impact Infant Growth?

Wisner KL, Bogen DL, Sit D, et al. — Wed, 01 May 2013 00:00:00 GMT

Objective

The aim of this study was to compare the growth of infants born to women with antenatal major depressive disorder, either untreated or treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, and infants born to a nondepressed, nonmedicated comparison group across the first year of life.

Method

In this prospective observational study, pregnant women were evaluated at weeks 20, 30, and 36 of gestation, and mother and infant pairs were assessed at 2, 12, 26, and 52 weeks postpartum. Three nonoverlapping groups of women were defined according to their pregnancy exposures: 1) no SSRI and no depression (N=97), 2) SSRI (N=46), and 3) major depression without SSRI (N=31). Maternal demographic and clinical characteristics and newborn outcomes were compared across exposure groups. Infant weight, length, and head circumference were measured by a physician or physician’s assistant who was blind to depression and SSRI exposure status at each postpartum time point.

Results

Both adjusted and unadjusted analyses revealed neither antenatal major depression nor SSRI exposure was significantly associated with infant weight, length, or head circumference relative to nonexposure to either. In addition, the interaction of group and prepregnancy body mass index was also evaluated, and no significant synergistic effect was identified. Similarly, no differential effect of group over time was observed for weight, length, or head circumference.

Conclusions

In utero exposure to major depression or SSRI antidepressants did not affect infant growth with respect to weight, length, or head circumference from birth through 12 months of age.

Effects of News Media Messages About Mass Shootings on Attitudes Toward Persons With Serious Mental Illness and Public Support for Gun Control Policies

McGinty EE, Webster DW, Barry CL. — Wed, 01 May 2013 00:00:00 GMT

Objective

In recent years, mass shootings by persons with serious mental illness have received extensive news media coverage. The authors test the effects of news stories about mass shootings on public attitudes toward persons with serious mental illness and support for gun control policies. They also examine whether news coverage of proposals to prevent persons with serious mental illness from having guns exacerbates the public’s negative attitudes toward this group.

Method

The authors conducted a survey-embedded randomized experiment using a national sample (N=1,797) from an online panel. Respondents were randomly assigned to groups instructed to read one of three news stories or to a no-exposure control group. The news stories described, respectively, a mass shooting by a person with serious mental illness, the same mass shooting and a proposal for gun restrictions for persons with serious mental illness, and the same mass shooting and a proposal to ban large-capacity magazines. Outcome measures included attitudes toward working with or living near a person with serious mental illness, perceived dangerousness of persons with serious mental illness, and support for gun restrictions for persons with serious mental illness and for a ban on large-capacity magazines.

Results

Compared with the control group, the story about a mass shooting heightened respondents’ negative attitudes toward persons with serious mental illness and raised support for gun restrictions for this group and for a ban on large-capacity magazines. Including information about the gun restriction policy in a story about a mass shooting did not heighten negative attitudes toward persons with serious mental illness or raise support for the restrictions.

Conclusions

The aftermath of mass shootings is often viewed as a window of opportunity to garner support for gun control policies, but it also exacerbates negative attitudes toward persons with serious mental illness.

Genome-Wide Linkage Analyses of 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia

Greenwood TA, Swerdlow NR, Gur RE, et al. — Wed, 01 May 2013 00:00:00 GMT

Objective

The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated.

Method

Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 single-nucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigree-wide regression methods.

Results

Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5 for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal Learning Test (8q24), the degraded-stimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23).

Conclusions

Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic studies are needed to assess the biological significance of these results.

Genome-Wide Methylation Changes in the Brains of Suicide Completers

Labonté B, Suderman M, Maussion G, et al. — Wed, 01 May 2013 00:00:00 GMT

Objective

Gene expression changes have been reported in the brains of suicide completers. More recently, differences in promoter DNA methylation between suicide completers and comparison subjects in specific genes have been associated with these changes in gene expression patterns, implicating DNA methylation alterations as a plausible component of the pathophysiology of suicide. The authors used a genome-wide approach to investigate the extent of DNA methylation alterations in the brains of suicide completers.

Method

Promoter DNA methylation was profiled using methylated DNA immunoprecipitation (MeDIP) followed by microarray hybridization in hippocampal tissue from 62 men (46 suicide completers and 16 comparison subjects). The correlation between promoter methylation and expression was investigated by comparing the MeDIP data with gene expression profiles generated through mRNA microarray. Methylation differences between groups were validated on neuronal and nonneuronal DNA fractions isolated by fluorescence-assisted cell sorting.

Results

The authors identified 366 promoters that were differentially methylated in suicide completers relative to comparison subjects (273 hypermethylated and 93 hypomethylated). Overall, promoter methylation differences were inversely correlated with gene expression differences. Functional annotation analyses revealed an enrichment of differential methylation in the promoters of genes involved, among other functions, in cognitive processes. Validation was performed on the top genes from this category, and these differences were found to occur mainly in the neuronal cell fraction.

Conclusions

These results suggest broad reprogramming of promoter DNA methylation patterns in the hippocampus of suicide completers. This may help explain gene expression alterations associated with suicide and possibly behavioral changes increasing suicide risk.

Prevalence and Correlates of Prolonged Fatigue in a U.S. Sample of Adolescents

Lamers F, Hickie I, Merikangas KR. — Wed, 01 May 2013 00:00:00 GMT

Objective

Prolonged fatigue in adolescents has a major impact on social functioning and school attendance. In adults, prolonged fatigue substantially overlaps with mood and anxiety disorders. Extending the data to adolescents, the authors studied the prevalence and correlates of fatigue in a representative U.S. sample.

Method

The participants were 10,123 adolescents ages 13–18 years from the National Comorbidity Survey Adolescent Supplement. They were interviewed about prolonged fatigue, defined as extreme fatigue with at least one associated symptom (pains, dizziness, headache, sleep disturbance, inability to relax, irritability) that does not resolve by resting or relaxing and lasting at least 3 months.

Results

The prevalence of prolonged fatigue was 3.0% (SE=0.3), with 1.4% (SE=0.2) for prolonged fatigue only and 1.6% (SE=0.2) for prolonged fatigue concomitant with a depressive or anxiety disorder. Nearly 60% of the adolescents with prolonged fatigue only had severe or very severe disability, and their rates of poor physical and mental health were comparable to those of adolescents with mood or anxiety disorders only. Adolescents with prolonged fatigue and comorbid mood or anxiety disorders had significantly greater disability, poorer mental health, and more health service use than those with either condition alone.

Conclusions

These findings suggest that prolonged fatigue is associated with disability and is an important clinical entity independent of mood and anxiety disorders in adolescents. Persistent fatigue with a comorbid mood or anxiety state is related to even more functional impairment, suggesting that prolonged fatigue may reflect greater severity of mood and anxiety disorders in adolescents.

The Dutch Bipolar Offspring Study: 12-Year Follow-Up

Mesman E, Nolen WA, Reichart CG, et al. — Wed, 01 May 2013 00:00:00 GMT

Objective

Offspring of bipolar parents have a genetically increased risk of developing mood disorders. In a longitudinal study, the authors followed a bipolar offspring cohort from adolescence into adulthood to determine the onset, prevalence, and early course of mood disorders and other psychopathology.

Method

The Dutch bipolar offspring cohort is a fixed cohort initiated in 1997 (N=140; age range at baseline, 12–21 years). Bipolar offspring were psychiatrically evaluated at baseline and at 1-, 5-, and 12-year follow-ups. Of the original sample, 77% (N=108) were followed for the full 12 years.

Results

Overall, 72% of the bipolar offspring developed a lifetime DSM-IV axis I disorder, 54% a mood disorder, and 13% bipolar spectrum disorders. Only 3% met DSM-IV criteria for bipolar I disorder. In 88% of the offspring with a bipolar spectrum disorder, the illness started with a depressive episode. In total, 24% of offspring with a unipolar mood disorder developed a bipolar spectrum disorder over time. Mood disorders were often recurrent (31%), were complex (comorbidity rate, 67%), and started before age 25.

Conclusions

Even after 12 years of follow-up, from adolescence into adulthood, bipolar I disorder was rare among bipolar offspring. Nevertheless, the risk of developing severe and recurrent mood disorders and other psychopathology was high. Future follow-up of this and other adult bipolar offspring cohorts is essential to determine whether recurrent mood disorders in bipolar offspring reflect the early stages of bipolar disorder.

Ventral Striatum Activity in Response to Reward: Differences Between Bipolar I and II Disorders

Caseras X, Lawrence NS, Murphy K, et al. — Wed, 01 May 2013 00:00:00 GMT

Objective

Little is known about the neurobiology of bipolar II disorder. While bipolar I disorder is associated with abnormally elevated activity in response to reward in the ventral striatum, a key component of reward circuitry, no studies have compared reward circuitry function in bipolar I and bipolar II disorders. Furthermore, associations among reward circuitry activity, reward sensitivity, and striatal volume remain underexplored in bipolar and healthy individuals. The authors examined reward activity in the ventral striatum in participants with bipolar I and II disorders and healthy individuals, the relationships between ventral striatal activity and reward sensitivity across all participants, and between-group differences in striatal gray matter volume and relationships with ventral striatal activity across all participants.

Method

Twenty healthy comparison subjects and 32 euthymic bipolar I (N=17) and bipolar II (N=15) patients underwent a neuroimaging reward paradigm during functional MRI scanning, structural scanning, and completed psychometric and clinical assessments.

Results

Region-of-interest analyses revealed significant ventral striatal activity in all participants during reward anticipation that was significantly greater in bipolar II patients compared with the other groups. Ventral striatal activity during reward anticipation correlated positively with reward sensitivity and fun seeking across all participants. Bipolar II patients had significantly greater left putamen volume than bipolar I patients, and left putamen volume correlated positively with left ventral striatal activity to reward anticipation in all participants.

Conclusions

Abnormally elevated ventral striatal activity during reward anticipation may be a potential biomarker of bipolar II disorder. These findings highlight the importance of adopting a dimensional approach in the study of neural mechanisms supporting key pathophysiological processes that may cut across psychiatric disorders.

Loss of Libido in a Woman With Schizophrenia

Seeman MV. — Wed, 01 May 2013 00:00:00 GMT

Sexual dysfunction is common among women with schizophrenia treated with antipsychotic medication. Multiple factors influence sexual function and reproductive health in this patient population, including the effects of medications on prolactin secretion and the complexities of making contraceptive decisions in the context of a serious mental illness. The author explores the causes and management of loss of libido as illustrated by a case vignette and describes the course and outcome of a clinical intervention that was implemented to alleviate the sexual dysfunction. Possible approaches and potential pitfalls of the intervention are described. Clinicians must be open to discussions regarding sexual concerns, relationships with sexual partners, and reproductive issues with women suffering from schizophrenia. Both patients and clinicians need to be aware of unintended effects of intervention. Opportunities exist for improved education among clinicians to achieve a more proactive approach to sexual health in women receiving antipsychotic medication.

In Whom Does Lithium Work?

Carlson GA. — Wed, 01 May 2013 00:00:00 GMT

To the Editor: In the January issue, Nierenberg et al. (1) try to answer an important question: Does lithium provide mood stabilization to a population of patients with lifetime bipolar I or II disorder who have chronic mood problems? According to the description of the sample, participants experienced an average of eight episodes per year, and although depressive episodes were fewer in number than manic or hypomanic episodes, patient scores on the Mini International Neuropsychiatric Interview at intake suggest that depression rather than mania accounted for more of their difficulties. Improvement in “mood” (it was not specified which mood) was the metric used to ascertain lithium’s success.

Methylfolate as Adjunctive Treatment in Major Depression

Reynolds EH. — Wed, 01 May 2013 00:00:00 GMT

To the Editor: As the principal investigator of the only previous placebo-controlled trial of methylfolate as an adjunctive treatment in major depression 22 years ago (1), I appreciated the new trial by Papakostas et al. (2) in the December 2012 issue confirming the efficacy of the vitamin in some resistant depression.

Relapse of Major Depression in Women Who Continue or Discontinue Antidepressant Medication During Pregnancy

Guille C, Epperson C. — Wed, 01 May 2013 00:00:00 GMT

To the Editor: We applaud Dr. Chaudron’s excellent review of the treatment of depression during pregnancy (1) in the January issue. She has provided a wealth of important information that assists clinicians and their patients in making difficult decisions regarding the use of antidepressant medication during pregnancy and the risks of untreated illness. As Dr. Chaudron astutely points out, decision making can span many months preceding pregnancy and into infancy. Given the breadth and scope of issues that can arise during this time, a single review cannot address them all or provide data to guide all decisions. While the focus of the review is the treatment of depression during pregnancy, a common clinical challenge is whether to continue or discontinue antidepressant medication during pregnancy. We felt this was an important area to further elaborate on, given the prevalence of antidepressant use (2) and currently available conflicting data (3, 4).

Response to Carlson Letter

Nierenberg AA, . — Wed, 01 May 2013 00:00:00 GMT

To the Editor: We appreciate Dr. Carlson’s comments on the main findings from our Lithium Moderate-Dose Use Study (LiTMUS) (1). LiTMUS included treatment-seeking patients who had at least some distress from symptoms in the context of a bipolar I or II diagnosis. Thus, in contrast to the participants included in the Gelenberg et al. study (2), this comparative effectiveness study included the types of patients who would be seen in clinical practice—and therefore the results of the study would be generalizable enough to inform clinicians. Additionally, the question addressed in LiTMUS was not whether or not lithium works, as implied by Dr. Carlson, but whether moderate doses of lithium would minimize side effects and add therapeutic benefit as a part of guideline-informed, evidence-based psychopharmacological treatment. We found that low levels of lithium did not have additive effects apart from a modest decrease in the use of second-generation antipsychotics. The study does not “disprove lithium’s efficacy,” but instead provides evidence that blood levels around 0.4 mEq/L may be insufficient to improve 6-month outcomes for this outpatient sample above and beyond what can be achieved with other medications. Nolen and Weisler (3) recently confirmed the lack of effectiveness for low levels of lithium for maintenance treatment.

Response to Guille and Epperson Letter

Chaudron LH. — Wed, 01 May 2013 00:00:00 GMT

To the Editor: I want to thank Dr. Guille and Dr. Epperson for the complimentary comments and the additional important reference they provided regarding the risk for recurrence of depression during the perinatal period related to antidepressant use. As they point out, the findings by Yonkers et al. (1) highlight the complicated nature of predicting who will or will not have a recurrence of depression and who may or may not require antidepressants during the perinatal period. Drs. Guille and Epperson note that, while controlling for antidepressant use, a history of four or more depressive episodes puts women at high risk for a major depressive episode. In addition, Yonkers et al. identify other risk factors, such as having a depressive episode in the 6 months before pregnancy and being of black race or Hispanic ethnicity. These additional variables, as well as the fact that 16% of the women in the study developed major depression during pregnancy or the postpartum period, underscore the need for further research to more fully understand who is at highest risk for recurrence in the perinatal period and therefore what the risks and benefits of antidepressant treatment are for individual patients with a range of depression severity.

Response to Li and Su Letter

Dieset I. — Wed, 01 May 2013 00:00:00 GMT

To the Editor: We thank Drs. Li and Su for the positive comments and the interest shown in our work, and indeed, we hope that our study will encourage future research on molecular mechanisms of NOTCH4 in bipolar disorder and related disorders.

Up-Regulation of NOTCH4 Gene Expression in Bipolar Disorder: Future Studies

Li M, Su B. — Wed, 01 May 2013 00:00:00 GMT

To the Editor: In the December 2012 issue, Dieset et al. (1) reported significant up-regulation of NOTCH4 gene expression in whole blood in patients with bipolar disorder relative to healthy comparison subjects, and they identified several single-nucleotide polymorphisms (SNPs) that were significantly associated with NOTCH4 expression. This is a nice piece of research, and their findings have encouraged future research on the molecular mechanisms of NOTCH4 in bipolar disorder. However, several lines of their study data await further validation.

American Madness: The Rise and Fall of Dementia Praecox

Fleisher C. — Wed, 01 May 2013 00:00:00 GMT

A surgeon in Chicago performs a laparotomy to cure his son’s psychosis. A celebrity murder trial hinges on a psychiatric diagnosis. An upstart psychiatrist is the first in North America to publicize a method for classifying mental illnesses, only later to repudiate it. Richard Noll brings these and other tales to life in American Madness: The Rise and Fall of Dementia Praecox as he elaborates the history of how psychosis was named, classified, and understood in early 20th-century America.

Black and Blue: The Origins and Consequences of Medical Racism

Primm AB, Griffith EH. — Wed, 01 May 2013 00:00:00 GMT

It is unusual for two African American psychiatrists to review a book, with a provocative title containing the “R” word, for the American Journal of Psychiatry (AJP). The request for an analysis of John Hoberman’s new text, Black and Blue: The Origins and Consequences of Medical Racism, came with a question about whether it warranted review at all in AJP. We agree that not only should a review of a book on this subject be published in AJP, but those in AJP’s audience who have an interest in the intersection of race and health should be introduced to Hoberman’s comprehensive work on this thorny and important subject. In fact, one of Hoberman’s assertions is that editorial gatekeepers have prevented the history of medical racism from being explored in medical literature. So from our vantage point, AJP readers and the medical profession have everything to gain from an honest, intellectual excursion into this subject. This is not to say that the going will be easy, as it requires some effort to follow the author’s wide-ranging argumentation, to sift through his substantial accumulation of data, to evaluate the reasoning he employs, and to weigh the political implications of his conclusions.

Generalized Anxiety Disorder

White H. — Wed, 01 May 2013 00:00:00 GMT

Generalized anxiety disorder is by no means uncommon and often protean; it frequently appears as a complication of medical illness or in association with major depression and other mood disorders. With reported prevalence in the range of 2%–6%, patients with generalized anxiety disorder report levels of disability comparable to or greater than levels reported by patients with serious physical and mental disorders (including depression, arthritis, asthma, and diabetes) (1). Distinguishing generalized anxiety disorder from normal worry is a clinical challenge; patients tend not to self-identify. Given the importance of the disorder, there is certainly need for a simple, straightforward guide for both primary care providers as well as for early-career clinicians and other psychiatric practitioners.

Restoring Mentalizing in Attachment Relationships: Treating Trauma With Plain Old Therapy

Snavely A. — Wed, 01 May 2013 00:00:00 GMT

There is an abundance of manualized approaches for specific diagnoses but a shortage of resources for the generalist psychotherapist whose complex patients rarely fit into any one category. Mentalizing—reflecting on mental states in one’s self and in others—has been identified as a natural human capacity and an integral part of any psychotherapy. Jon G. Allen’s Restoring Mentalizing in Attachment Relationships: Treating Trauma With Plain Old Therapy strives to integrate research and clinical practice to broaden the concept of mentalizing in trauma treatment. He broadly defines trauma as a consequence of mental pain experienced in psychological isolation and focuses specifically on attachment trauma, conceptualized as a defect of mentalizing.

Saint Anthony of Qozhaya’s Cave: A Pioneering Shelter for the Mentally Ill in the Middle East

Bou Khalil R. — Wed, 01 May 2013 00:00:00 GMT

Correction

Wed, 01 May 2013 00:00:00 GMT

The March 2013 CME course on the article “Perinatal Choline Effects on Neonatal Pathophysiology Related to Later Schizophrenia Risk” by Randal G. Ross, M.D. et al. (Am J Psychiatry 2013; 170:290—298) displayed the incorrect wording for the third CME question. The course was taken down and replaced on April 1, 2013, with a course in which the correct question appeared for number 3.

Books Received

Wed, 01 May 2013 00:00:00 GMT

The following books are presented here as a service to our readership to alert them of new titles and as a courtesy to those who have sent copies of these books to the Journal office.