Am J Psychiatry recent issues

[In This Issue] In This Issue

2008-05-01

[Editorials] Cost-Effectiveness of Depression Treatment for Adolescents

Norquist, G., McGuire, T. G., Essock, S. M. — 2008-05-01

[Editorials] Does Childhood Treatment of ADHD With Stimulant Medication Affect Substance Abuse in Adulthood?

Volkow, N. D., Swanson, J. M. — 2008-05-01

[Editorials] Psychotherapies and Lasting Change

Levy, K. N. — 2008-05-01

[Editorials] Recognizing Each Other and the Effects of Racial Differences

Bell, C. C. — 2008-05-01

[Images in Neuroscience] Controlling Neuronal Activity

Schneider, M. B., Gradinaru, V., Zhang, F., Deisseroth, K. — 2008-05-01

[Introspections] Doubt

Ablon, S. — 2008-05-01

[Treatment in Psychiatry] Cross-Cultural Evaluation of Maternal Competence in a Culturally Diverse Society

Seeman, M. V. — 2008-05-01

[Clinical Case Conference] Remission From Depression Comorbid With Chronic Illness and Physical Impairment

Turvey, C. L., Klein, D. M. — 2008-05-01

[Images in Psychiatry] Karl Bonhoeffer (1868-1948)

Strohle, A., Wrase, J., Malach, H., Gestrich, C., Heinz, A. — 2008-05-01

[Images in Psychiatry] Dietrich Bonhoeffer (1906-1945)

Strohle, A., Wrase, J., Malach, H., Gestrich, C., Heinz, A. — 2008-05-01

[Reviews and Overviews] Premorbid IQ in Schizophrenia: A Meta-Analytic Review

Woodberry, K. A., Giuliano, A. J., Seidman, L. J. — 2008-05-01

OBJECTIVE: Over the past three decades, there have been significant changes in the diagnostic criteria for schizophrenia as well as changes in measurement of IQ. The last quantitative review of the literature on premorbid IQ in schizophrenia was published more than two decades ago. Since that time, there have been many published studies of data sets pertaining to this issue. The purpose of the present review was to provide an updated meta-analysis of premorbid IQ in individuals who later develop schizophrenia. METHOD: The authors performed a systematic literature search, which yielded 18 studies that met criteria for the meta-analysis. Inclusion criteria were 1) premorbid psychometric measures of IQ in subjects who were later diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder, 2) similar comparison data, and 3) sufficient data for calculation of an effect size. The analogue to the analysis of variance method was used to model between-study variance due to key study-design features. RESULTS: Overall, schizophrenia samples demonstrated a reliable, medium-sized impairment in premorbid IQ. The heterogeneity of effect sizes was minimal and almost exclusively the result of one study. Methodological differences, such as diagnostic criteria, type of IQ measure, sample ascertainment, and age at premorbid testing, contributed minimally to the effect size variance. A cross-sectional analysis of all studies by age and a descriptive review of studies that used repeated measures of IQ in a single sample did not support the presence of a relative decline in IQ during the premorbid period in individuals with schizophrenia. However, all studies with pre- and post-onset testing within the same sample suggested that a significant decline in the IQ of individuals with schizophrenia, relative to comparison subjects, was associated with the onset of frank psychosis. CONCLUSIONS: Years before the onset of psychotic symptoms, individuals with schizophrenia, as a group, demonstrate mean IQ scores approximately one-half of a standard deviation below that of healthy comparison subjects.

[Articles] Cost-Effectiveness of Treatments for Adolescent Depression: Results From TADS

2008-05-01

OBJECTIVE: While the evidence base for treatments for adolescent depression is building, little is known about the relative efficiency of such treatments. Treatment costs are a relevant concern given the competing demands on family and health care budgets. The authors evaluated the cost-effectiveness of three active treatments among adolescents with major depressive disorder. METHOD: Volunteers (N=439) ages 12 to 18 with a primary diagnosis of major depressive disorder participated in a randomized, controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Subjects included those participants who did not drop out and had evaluable outcome and cost data at 12 weeks (N=369). Subjects were randomly assigned to 12 weeks of either fluoxetine alone (10–40 mg/day), CBT alone, CBT combined with fluoxetine (10–40 mg/day), or placebo (equivalent to 10–40 mg/day). Both placebo and fluoxetine were administered double-blind; CBT alone and CBT in combination with fluoxetine were administered unblinded. Societal cost per unit of improvement on the Children’s Depression Rating Scale—Revised and cost per quality-adjusted life year (QALY) were compared. RESULTS: Results ranged from an incremental cost over placebo of $24,000 per QALY for treatment with fluoxetine to $123,000 per QALY for combination therapy treatment. The cost-effectiveness ratio for CBT treatment was not evaluable due to negative clinical effects. The models were robust on a variety of assumptions. CONCLUSIONS: Both fluoxetine and combination therapy are at least as cost-effective in the short-term as other treatments commonly used in primary care (using a threshold of $125,000/QALY). Fluoxetine is more cost-effective than combination therapy after 12 weeks of treatment.

[Articles] Stimulant Therapy and Risk for Subsequent Substance Use Disorders in Male Adults With ADHD: A Naturalistic Controlled 10-Year Follow-Up Study

2008-05-01

OBJECTIVE: The extant literature does not provide definite answers pertaining to whether stimulant treatment increases, decreases, or does not affect the risk for subsequent substance use disorders in youths with attention deficit hyperactivity disorder (ADHD). The authors examined the association between stimulant treatment in childhood and adolescence and subsequent substance use disorders (alcohol, drug, and nicotine) into the young adult years. METHOD: The authors conducted a 10-year prospective follow-up study. One hundred forty male Caucasian children with ADHD, ages 6 to 17, were examined at baseline. Of these, 112 (80%) were reassessed at the 10-year follow-up (mean age at follow-up=22 years). Assessments were made using Cox proportional hazards survival models. All models were adjusted for conduct disorder, since conduct disorder is a potent predictor of subsequent substance use disorders. RESULTS: Of the 112 ADHD subjects who were reassessed at the 10-year follow-up, 82 (73%) had been treated previously with stimulants and 25 (22%) were undergoing stimulant treatment at the time of the follow-up assessment. There were no statistically significant associations between stimulant treatment and alcohol, drug, or nicotine use disorders. CONCLUSIONS: The findings revealed no evidence that stimulant treatment increases or decreases the risk for subsequent substance use disorders in children and adolescents with ADHD when they reach young adulthood.

[Articles] Age of Methylphenidate Treatment Initiation in Children With ADHD and Later Substance Abuse: Prospective Follow-Up Into Adulthood

2008-05-01

OBJECTIVE: Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders. METHOD: The authors conducted a prospective longitudinal study of 176 methylphenidate-treated Caucasian male children (ages 6 to 12) with ADHD but without conduct disorder. The participants were followed up at late adolescence (mean age=18.4 years; retention rate=94%) and adulthood (mean age=25.3; retention rate=85%). One hundred seventy-eight comparison subjects also were included. All subjects were diagnosed by blinded clinicians. The Cox proportional hazards model included the following childhood predictor variables: age at initiation of methylphenidate treatment, total cumulative dose of methylphenidate, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopathology. Separate models tested for the following four lifetime outcomes: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, and stimulant use disorder. Other outcomes included antisocial personality, mood, and anxiety disorders. RESULTS: There was a significant positive relationship between age at treatment initiation and non-alcohol substance use disorder. None of the predictor variables accounted for this association. Post hoc analyses showed that the development of antisocial personality disorder explained the relationship between age at first methylphenidate treatment and later substance use disorder. Even when controlling for substance use disorder, age at stimulant treatment initiation was significantly and positively related to the later development of antisocial personality disorder. Age at first methylphenidate treatment was unrelated to mood and anxiety disorders. CONCLUSIONS: Early age at initiation of methylphenidate treatment in children with ADHD does not increase the risk for negative outcomes and may have beneficial long-term effects.

[Articles] Association of the Neurotrophic Tyrosine Kinase Receptor 3 (NTRK3) Gene and Childhood-Onset Mood Disorders

2008-05-01

OBJECTIVE: Genome scans have revealed significant evidence for linkage of depression to chromosome 15q25.3-q26.2. The gene for neurotrophic tyrosine kinase receptor 3 (NTRK3), the receptor for neurotrophin-3 (trkC) and a key gene in neurotrophin signaling, is located within this region and, given evidence for synaptic plasticity as a mechanism in mood disorders, was considered a prime candidate. The authors investigated NTRK3 as a susceptibility gene for childhood-onset mood disorders. METHOD: The study sample consisted of 603 families with 723 affected children and adolescents diagnosed with a mood disorder with onset of the first episode by age 15. The authors genotyped 18 polymorphic markers across the NTRK3 gene in this sample and tested for association. RESULTS: Results identified significant evidence for association for five of the markers using the transmission disequilibrium test. Four of the five markers were located in a region of strong linkage disequilibrium and were highly correlated. Haplotype results provided significant evidence for association to haplotypes composed of markers located in two haplotype blocks. CONCLUSIONS: The results for NTRK3 as well as the authors’ previous finding for association to brain-derived neurotrophic factor in this sample support synaptic plasticity as a mechanism contributing to mood disorders that begin during childhood and adolescence and specifically implicate the NTRK3 gene as a contributing factor in the 15q-linked region.

[Articles] A 6-Week Randomized, Placebo-Controlled Trial of CP-316,311 (a Selective CRH1 Antagonist) in the Treatment of Major Depression

Binneman, B., Feltner, D., Kolluri, S., Shi, Y., Qiu, R., Stiger, T. — 2008-05-01

OBJECTIVE: The corticotropin-releasing hormone (CRH) system is implicated in the pathogenesis of several psychiatric disorders, including major depressive disorder. This study was designed to evaluate the safety and efficacy of CP-316,311, a selective nonpeptide antagonist of corticotropin-releasing hormone type 1 (CRH₁) receptors, in the treatment of recurrent major depressive disorder. METHOD: Of a total of 167 patients with recurrent major depression who were screened, 123 were randomly assigned to receive 400 mg of CP-316,311 twice daily, or 100 mg of sertraline daily, or placebo in a 6-week fixed-dose, double-blind, double-dummy, parallel-group, placebo- and sertraline-controlled trial. The primary efficacy analysis compared the change in score from baseline to endpoint on the 17-item Hamilton Depression Rating Scale (HAM-D) between the CP-316,311 and placebo groups. A group sequential design was used to support early trial termination based on efficacy or futility at a planned interim analysis. RESULTS: The evaluable data set for the interim analysis included 28 patients in the CP-316,311 group, 31 patients in the placebo group, and 30 patients in the sertraline group. In the interim analysis, the change from baseline in the HAM-D score at the final visit was not significantly different between the CP-316,311 and placebo groups, while change from baseline between the sertraline and placebo groups was significantly different. Given these results, futility was declared for CP-316,311 and the trial was terminated. CONCLUSIONS: Although CP-316,311 was safe and well tolerated in this study population, it failed to demonstrate efficacy in the treatment of major depression.

[Articles] A Randomized, Controlled Trial of Cognitive-Behavioral Therapy for Augmenting Pharmacotherapy in Obsessive-Compulsive Disorder

2008-05-01

OBJECTIVE: Although serotonin reuptake inhibitors (SRIs) are approved for the treatment of obsessive-compulsive disorder (OCD), most OCD patients who have received an adequate SRI trial continue to have clinically significant OCD symptoms. The purpose of this study was to examine the effects of augmenting SRIs with exposure and ritual prevention, an established cognitive-behavioral therapy (CBT) for OCD. METHOD: A randomized, controlled trial was conducted at two academic outpatient clinics to compare the effects of augmenting SRIs with exposure and ritual prevention versus stress management training, another form of CBT. Participants were adult outpatients (N=108) with primary OCD and a Yale-Brown Obsessive Compulsive Scale total score ≥16 despite a therapeutic SRI dose for at least 12 weeks prior to entry. Participants received 17 sessions of CBT (either exposure and ritual prevention or stress management training) twice a week while continuing SRI pharmacotherapy. RESULTS: Exposure and ritual prevention was superior to stress management training in reducing OCD symptoms. At week 8, significantly more patients receiving exposure and ritual prevention than patients receiving stress management training had a decrease in symptom severity of at least 25% (based on Yale-Brown Obsessive Compulsive Scale scores) and achieved minimal symptoms (defined as a Yale-Brown Obsessive Compulsive Scale score ≤12). CONCLUSIONS: Augmentation of SRI pharmacotherapy with exposure and ritual prevention is an effective strategy for reducing OCD symptoms. However, 17 sessions were not sufficient to help most of these patients achieve minimal symptoms.

[Articles] 8-Year Follow-Up of Patients Treated for Borderline Personality Disorder: Mentalization-Based Treatment Versus Treatment as Usual

Bateman, A., Fonagy, P. — 2008-05-01

OBJECTIVE: This study evaluated the effect of mentalization-based treatment by partial hospitalization compared to treatment as usual for borderline personality disorder 8 years after entry into a randomized, controlled trial and 5 years after all mentalization-based treatment was complete. METHOD: Interviewing was by research psychologists blind to original group allocation and structured review of medical notes of 41 patients from the original trial. Multivariate analysis of variance, chi-square, univariate analysis of variance, and nonparametric Mann-Whitney statistics were used to contrast the two groups depending on the distribution of the data. RESULTS: Five years after discharge from mentalization-based treatment, the mentalization-based treatment by partial hospitalization group continued to show clinical and statistical superiority to treatment as usual on suicidality (23% versus 74%), diagnostic status (13% versus 87%), service use (2 years versus 3.5 years of psychiatric outpatient treatment), use of medication (0.02 versus 1.90 years taking three or more medications), global function above 60 (45% versus 10%), and vocational status (employed or in education 3.2 years versus 1.2 years). CONCLUSIONS: Patients with 18 months of mentalization-based treatment by partial hospitalization followed by 18 months of maintenance mentalizing group therapy remain better than those receiving treatment as usual, but their general social function remains impaired.

[Articles] The Other-Race Effect in Face Processing Among African American and Caucasian Individuals With Schizophrenia

2008-05-01

OBJECTIVE: Studies of emotion recognition abilities in schizophrenia show greater impairment for non-Caucasians with schizophrenia compared with Caucasians. These studies, however, included only Caucasian faces as stimuli. There is evidence from healthy individuals for a performance disadvantage on face memory and emotion recognition when processing faces from a different ethnicity. The authors sought to measure the "other-race effect" in schizophrenia, which could account for previous findings and provide information about sensitivity to such social cues in patients. METHOD: The study included 540 participants from four groups: African Americans with schizophrenia (N=135), Caucasians with schizophrenia (N=135), African American community comparison subjects (N=135), and Caucasian community comparison subjects (N=135). All participants completed face recognition and facial emotion identification tasks that included both Caucasian and African American faces as stimuli. RESULTS: Although comparison participants performed better than individuals with schizophrenia across all tasks, both comparison participants and participants with schizophrenia exhibited a strong and significant other-race effect for face memory and emotion recognition. The magnitude of the other-race effect did not differ between these two groups. CONCLUSIONS: These findings reveal an intact other-race effect in patients with schizophrenia and highlight a methodological concern in the measurement of face processing abilities in schizophrenia, namely, that findings of greater impairment in African American patients are spurious when Caucasian faces are used as stimuli. Despite overall impairments in face memory and emotion recognition, the presence of a normative other-race effect in schizophrenia may reflect typical experiences with faces during development.

[Letters to the Editor] Delving Further Into Discontinuation Risk: Addressing the Use of Mood Stabilizers During Pregnancy

ISAKOVICH, N., SMITH, E. — 2008-05-01

[Letters to the Editor] Mood Stabilizer Discontinuation in Pregnant Women With Bipolar Disorder

MAZER-POLINE, C., RIFKIN, A., GEISLER, S., WALCH, T. — 2008-05-01

[Letters to the Editor] Dr. Viguera Replies

VIGUERA,, A. C. — 2008-05-01

[Letters to the Editor] Application of the Seasonal Pattern Assessment Questionnaire in Detecting Seasonal Affective Disorder

GUPTA, N., SHARMA, P. — 2008-05-01

[Letters to the Editor] Ms. Sullivan and Dr. Payne Reply

SULLIVAN, B., PAYNE, T. W. — 2008-05-01

[Letters to the Editor] Argyria as a Result of Somatic Delusions

ANDERSON, E. L., JANOFSKY, J., JAYARAM, G. — 2008-05-01

[Letters to the Editor] Stabilization of Hypomania Following Initiation of Tamoxifen

PALMER, J. T., PAYNE, J. L. — 2008-05-01

[Letters to the Editor] Poor Neonatal Adaptation After in Utero Exposure to Duloxetine

EYAL, R., YAEGER, D. — 2008-05-01

[Letters to the Editor] Cingulate Gyrus Tumor Presenting as Panic Attacks

TAMBURIN, S., CACCIATORI, C., BONATO, C., ZANETTE, G. — 2008-05-01

[Corrections]

2008-05-01

[Book Forum] Changing American Psychiatry: A Personal Perspective

ROBINOWITZ, C. B. — 2008-05-01

[Book Forum] Dialectical Behavior Therapy With Suicidal Adolescents

JACOBSON, G. R. — 2008-05-01

[Book Forum] Magical Moments of Change: How Psychotherapy Turns Kids Around

HARTMANN, L. — 2008-05-01

[Book Forum] Clinical Topics in Addiction: Updates From Advances in Psychiatric Treatment

WOODY, G. E. — 2008-05-01

[Book Forum] The Confabulating Mind: How the Brain Creates Reality

FINEBERG, N. A. — 2008-05-01

[Books Received]

2008-05-01

[In This Issue] In This Issue

2008-04-01

[Editorials] Continuation Treatment With Antidepressants in Child and Adolescent Major Depression

Ryan, N. D. — 2008-04-01

[Editorials] Augmenting Psychotherapy for Borderline Personality Disorder: The STEPPS Program

Silk, K. R. — 2008-04-01

[Editorials] Cannabis, Inhibitory Neurons, and the Progressive Course of Schizophrenia

Freedman, R. — 2008-04-01

[Editorials] Schizophrenia Candidate Genes: Are We Really Coming Up Blank?

Hamilton, S. P. — 2008-04-01

[Editorials] Issues for DSM-V: Night Eating Syndrome

Stunkard, A., Allison, K., Lundgren, J. — 2008-04-01

[Commentary] Treatment of Depression by Maimonides (1138-1204): Rabbi, Physician, and Philosopher

Gesundheit, B., Or, R., Gamliel, C., Rosner, F., Steinberg, A. — 2008-04-01

[Reviews and Overviews] Neurobiology of Aggression and Violence

Siever, L. J. — 2008-04-01

Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of "top-down" control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of "top-down" control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance "top-down" control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.

[Introspections] No Longer Bound by Stigma

Mattox, R. — 2008-04-01

[Education In Psychiatry] Teaching Supportive Psychotherapy to Psychiatric Residents

Douglas, C. J. — 2008-04-01

[Clinical Case Conference] Investigation Into the Cause of Death of a 56-Year-Old Man With Serious Mental Illness

Prochaska, J. J., Schane, R., Leek, D., Hall, S. E., Hall, S. M. — 2008-04-01

[Images in Psychiatry] The Lobotomist

Stewart, D. G., Davis, K. L. — 2008-04-01

[Articles] Fluoxetine Versus Placebo in Preventing Relapse of Major Depression in Children and Adolescents

2008-04-01

OBJECTIVE: The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents. METHOD: After a detailed evaluation, children and adolescents 7–18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children’s Depression Rating Scale—Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children’s Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children’s Depression Rating Scale. RESULTS: Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group. CONCLUSIONS: Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.

[Articles] Systems Training for Emotional Predictability and Problem Solving (STEPPS) for Outpatients With Borderline Personality Disorder: A Randomized Controlled Trial and 1-Year Follow-Up

2008-04-01

OBJECTIVE: Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a 20-week manual-based group treatment program for outpatients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component. The authors compared STEPPS plus treatment as usual with treatment as usual alone in a randomized controlled trial. METHOD: Subjects with borderline personality disorder were randomly assigned to STEPPS plus treatment as usual or treatment as usual alone. Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure. Secondary outcomes included measures of global functioning, depression, impulsivity, and social functioning; suicide attempts and self-harm acts; and crisis utilization. Subjects were followed 1 year posttreatment. A linear mixed-effects model was used in the analysis. RESULTS: Data pertaining to 124 subjects (STEPPS plus treatment as usual [N=65]; treatment as usual alone [N=59]) were analyzed. Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective, cognitive, interpersonal, and impulsive domains. STEPPS plus treatment as usual also led to greater improvements in impulsivity, negative affectivity, mood, and global functioning. These differences yielded moderate to large effect sizes. There were no differences between groups for suicide attempts, self-harm acts, or hospitalizations. Most gains attributed to STEPPS were maintained during follow-up. Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up. The discontinuation rate was high in both groups. CONCLUSIONS: STEPPS, an adjunctive group treatment, can deliver clinically meaningful improvements in borderline personality disorder-related symptoms and behaviors, enhance global functioning, and relieve depression.

[Articles] Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects With Schizophrenia

Hashimoto, T., Bazmi, H. H., Mirnics, K., Wu, Q., Sampson, A. R., Lewis, D. A. — 2008-04-01

OBJECTIVE: Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. METHOD: Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. RESULTS: Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the 1 and subunits of GABA_A receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. CONCLUSIONS: Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.

[Articles] Excessive Brain Volume Loss Over Time in Cannabis-Using First-Episode Schizophrenia Patients

2008-04-01

OBJECTIVE: Cerebral gray matter volume reductions have been found to progress over time in schizophrenia, with larger decreases related to poorer outcome, which has also been associated with cannabis use in schizophrenia patients. Progressive gray matter changes in patients who use cannabis may be more extensive than in those who do not. METHOD: Patients with recent-onset schizophrenia (N=51) and matched healthy subjects (N=31) were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion (T0) and at 5-year follow-up (T5). Nineteen patients used cannabis but no other illicit drugs; 32 patients did not use any drugs during the 5-year follow-up. At T5, clinical outcome was measured. Cumulative amount of antipsychotic medication during the interval was calculated. At T0 and T5, total brain, gray and white matter, and lateral and third ventricle volumes were measured. Univariate analysis of covariance and pairwise comparisons were performed. Result: Schizophrenia patients showed a larger gray matter volume decrease over time than healthy subjects. They also showed larger increases in lateral and third ventricle volumes than healthy subjects and patients who did not use cannabis during follow-up. This decrement was significantly more pronounced in the patients who continued to use cannabis. These differences could not be attributed to outcome or baseline characteristics. CONCLUSIONS: First-episode schizophrenia patients who use cannabis show a more pronounced brain volume reduction over a 5-year follow-up than patients with schizophrenia who do not use cannabis. These results may help explain some of the detrimental effects of cannabis use in schizophrenia.

[Articles] No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics

2008-04-01

OBJECTIVE: The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. METHOD: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3' untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. RESULTS: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. CONCLUSIONS: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.

[Articles] Association of Low Striatal Dopamine D2 Receptor Availability With Nicotine Dependence Similar to That Seen With Other Drugs of Abuse

2008-04-01

OBJECTIVE: All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D₂) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers. METHOD: In vivo D₂/D₃ receptor availability was determined with [ ¹⁸F]fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smokers were scanned twice: first, during a period of usual consumption and second, 24 hours after smoking cessation. RESULTS: Independent of the withdrawal status, the nicotine-dependent smokers displayed significantly less availability of D₂/D₃ receptors within the bilateral putamen functionally covering parts of the dorsal striatum, as compared to the never-smoking subjects. Nicotine craving under the consumption condition correlated positively with D₂/D₃ receptor availability within the ventral striatum but negatively with D₂/D₃ receptor availability within the anterior cingulate and inferior temporal cortex. CONCLUSIONS: Similar to other types of substance abuse, nicotine dependence is associated with low availability of dorsal striatal D₂/D₃ receptors. In contrast to previous findings on abstinent alcohol-dependent patients, nicotine craving seems to be maintained by a region-specific shift in D₂/D₃ receptor availabilities, with higher availability within the ventral striatum but lower availability within the anterior cingulate and inferior temporal cortex.

[Articles] Depression and Ischemic Heart Disease Mortality: Evidence From the EPIC-Norfolk United Kingdom Prospective Cohort Study

2008-04-01

OBJECTIVE: The authors investigated the association between major depressive disorder, including its clinical course, and mortality from ischemic heart disease. METHOD: This was a prospective cohort study of 8,261 men and 11,388 women 41–80 years of age who were free of clinical manifestations of heart disease and participated in the Norfolk, U.K., cohort of the European Prospective Investigation Into Cancer. The authors conducted a cross-sectional assessment of major depressive disorder during the period 1996–2000 and ascertained subsequent deaths from ischemic heart disease through linkage with data from the U.K. Office for National Statistics. RESULTS: As of July 31, 2006, 274 deaths from ischemic heart disease were recorded over a total follow-up of 162,974 person-years (the median follow-up period was 8.5 years). Participants who had major depression during the year preceding baseline assessment were 2.7 times more likely to die from ischemic heart disease over the follow-up period than those who did not, independently of age, sex, smoking, systolic blood pressure, cholesterol, physical activity, body mass index, diabetes, social class, heavy alcohol use, and antidepressant medication use. This association remained after exclusion of the first 6 years of follow-up data. Consideration of measures of major depression history (including recency of onset, recurrence, chronicity, and age at first onset) revealed recency of onset to be associated most strongly with ischemic heart disease mortality. CONCLUSIONS: Major depression was associated with an increased risk of ischemic heart disease mortality. The association was independent of established risk factors for ischemic heart disease and remained undiminished several years after the original assessment.

[Articles] Regional White Matter Hyperintensity Burden in Automated Segmentation Distinguishes Late-Life Depressed Subjects From Comparison Subjects Matched for Vascular Risk Factors

2008-04-01

OBJECTIVE: Segmented brain white matter hyperintensities were compared between subjects with late-life depression and age-matched subjects with similar vascular risk factor scores. Correlations between neuropsychological performance and whole brain-segmented white matter hyperintensities and white and gray matter volumes were also examined. METHOD: Eighty-three subjects with late-life depression and 32 comparison subjects underwent physical examination, psychiatric evaluation, neuropsychological testing, vascular risk factor assessment, and brain magnetic resonance imaging (MRI). Automated segmentation methods were used to compare the total brain and regional white matter hyperintensity burden between depressed patients and comparison subjects. RESULTS: Depressed patients and comparison subjects did not differ in demographic variables, including vascular risk factor, or whole brain-segmented volumes. However, depressed subjects had seven regions of greater white matter hyperintensities located in the following white matter tracts: the superior longitudinal fasciculus, fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, and inferior longitudinal fasciculus. These white matter tracts underlie brain regions associated with cognitive and emotional function. In depressed patients but not comparison subjects, volumes of three of these regions correlated with executive function; whole brain white matter hyperintensities correlated with executive function; whole brain white matter correlated with episodic memory, processing speed, and executive function; and whole brain gray matter correlated with processing speed. CONCLUSIONS: These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.

[Letters to the Editor] Do Adverse Life Events Trigger Atypical Symptoms?

LEVITAN, R. D. — 2008-04-01

[Letters to the Editor] Dr. Keller Replies

KELLER, M. C. — 2008-04-01

[Letters to the Editor] How "Supportive" Is Internet-Based Supportive Psychotherapy?

MARKOWITZ, J. C. — 2008-04-01

[Letters to the Editor] Dr. Litz Replies

LITZ, B. — 2008-04-01

[Letters to the Editor] A Naturalistic Study of Consecutive Agitated Emergency Department Patients Treated With Intramuscular Olanzapine Prior to Consent

2008-04-01

[Letters to the Editor] Improvement in Refractory Obsessive Compulsive Disorder With Dronabinol

SCHINDLER, F., ANGHELESCU, I., REGEN, F., JOCKERS-SCHERUBL, M. — 2008-04-01

[Letters to the Editor] Maintenance Treatment With Transcranial Magnetic Stimulation in a Patient With Late-Onset Schizophrenia

POULET, E., BRUNELIN, J., KALLEL, L., D'AMATO, T., SAOUD, M. — 2008-04-01

[Letters to the Editor] Chest Tightness and Palpitations Associated With Modafinil and Consumption of Free Glutamate

MORGAN, P. T., MALISON, R. T. — 2008-04-01

[Letters to the Editor] Acute Hepatotoxicity Associated With Lamotrigine

MOELLER, K. E., WEI, L., JEWELL, A. D., CARVER, L. A. — 2008-04-01

[Corrections]

2008-04-01

[Corrections]

2008-04-01

[Corrections]

2008-04-01

[Book Forum] Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, Second Edition

SHER, L. — 2008-04-01

[Book Forum] Transgenic and Knockout Models of Neuropsychiatric Disorders

STEVENS, K. E. — 2008-04-01

[Book Forum] Biomedical Ethics: A Multidisciplinary Approach to Moral Issues in Medicine and Biology

LAYDE, J. B. — 2008-04-01

[Book Forum] Growing Up With Autism: Working With School-Age Children and Adolescents

VOLKMAR, F. R. — 2008-04-01

[Books Received]

2008-04-01

[In This Issue] In This Issue

2008-03-03

[Editorials] Critical Parameters for D-Cycloserine Enhancement of Cognitive-Behaviorial Therapy for Obsessive-Compulsive Disorder

Rothbaum, B. O. — 2008-03-03

[Editorials] Anxious Depression and Response to Treatment

Nelson, J. C. — 2008-03-03

[Editorials] Treatment of Rapid-Cycling Bipolar Disorder: Are Antidepressants Mood Destabilizers?

Ghaemi, S. N. — 2008-03-03

[Editorials] Divided Doses for Methadone Maintenance

Adinoff, B. — 2008-03-03

[Editorials] Issues for DSM-V: Internet Addiction

Block, J. J. — 2008-03-03

[Commentary] The Effects of Resident Work-Hour Regulation on Psychiatry

Rabjohn, P. A., Yager, J. — 2008-03-03

[Images in Neuroscience] Cognition in Schizophrenia

Hyman, S. E., Ivleva, E. — 2008-03-03