Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results.To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms.Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use.Durham Veterans Affairs Medical Center, which is located in proximity to major military bases.Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101).Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging.Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms.These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.

The identification of modifiable predeployment vulnerability factors that increase the risk of combat stress reactions among soldiers once deployed to a war zone offers significant potential for the prevention of posttraumatic stress disorder (PTSD) and other combat-related stress disorders. Adults with anxiety disorders display heightened emotional reactivity to a single inhalation of 35% carbon dioxide (CO(2)); however, data investigating prospective linkages between emotional reactivity to CO(2) and susceptibility to war-zone stress reactions are lacking.To investigate the association of soldiers' predeployment emotional reactivity to 35% CO(2) challenge with several indices of subsequent war-zone stress symptoms assessed monthly while deployed in Iraq.Prospective cohort study of 158 soldiers with no history of deployment to a war zone were recruited from the Texas Combat Stress Risk Study between April 2, 2007, and August 28, 2009.Multilevel regression models were used to investigate the association between emotional reactivity to 35% CO(2) challenge (assessed before deployment) and soldiers' reported symptoms of general anxiety/stress, PTSD, and depression while deployed to Iraq.Growth curves of PTSD, depression, and general anxiety/stress symptoms showed a significant curvilinear relationship during the 16-month deployment period. War-zone stressors reported in theater were associated with symptoms of general anxiety/stress, PTSD, and depression. Consistent with the prediction, soldiers' emotional reactivity to a single inhalation of 35% CO(2)-enriched air before deployment significantly potentiated the effects of war-zone stressors on the subsequent development of PTSD symptoms and general anxiety/stress symptoms but not on the development of depression, even after accounting for the effects of trait anxiety and the presence of past or current Axis I mental disorders.Soldiers' emotional reactivity to a 35% CO(2) challenge may serve as a vulnerability factor for increasing soldiers' risk for PTSD and general anxiety/stress symptoms in response to war-zone stressors.

Although childhood adversities (CAs) are known to be highly co-occurring, most research examines their associations with psychiatric disorders one at a time. However, recent evidence from adult studies suggests that the associations of multiple CAs with psychiatric disorders are nonadditive, arguing for the importance of multivariate analysis of multiple CAs. To our knowledge, no attempt has been made to perform a similar kind of analysis among children or adolescents.To examine the multivariate associations of 12 CAs with first onset of psychiatric disorders in a national sample of US adolescents.A US national survey of adolescents (age range, 13-17 years) assessing DSM-IV anxiety, mood, behavior, and substance use disorders and CAs. The CAs include parental loss (death, divorce, and other separations), maltreatment (neglect and physical, sexual, and emotional abuse), and parental maladjustment (violence, criminality, substance abuse, and psychopathology), as well as economic adversity.Dual-frame household-school samples.In total, 6483 adolescent-parent pairs.Lifetime DSM-IV disorders assessed using the World Health Organization Composite International Diagnostic Interview.Overall, exposure to at least 1 CA was reported by 58.3% of adolescents, among whom 59.7% reported multiple CAs. The CAs reflecting maladaptive family functioning were more strongly associated than other CAs with the onset of psychiatric disorders. The best-fitting model included terms for the type and number of CAs and distinguished between maladaptive family functioning and other CAs. The CAs predicted behavior disorders most strongly and fear disorders least strongly. The joint associations of multiple CAs were subadditive. The population-attributable risk proportions across DSM-IV disorder classes ranged from 15.7% for fear disorders to 40.7% for behavior disorders. The CAs were associated with 28.2% of all onsets of psychiatric disorders.Childhood adversities are common, highly co-occurring, and strongly associated with the onset of psychiatric disorders among US adolescents. The subadditive multivariate associations of CAs with the onset of psychiatric disorders have implications for targeting interventions to reduce exposure to CAs and to mitigate the harmful effects of CAs to improve population mental health.

Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring.To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design.We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding.Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2).Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1,187,360).Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2).The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR](moderate), 1.32 [95% CI, 1.22-1.43]; HR(high), 1.33 [1.17-1.53]) to a narcotics-related conviction (HR(moderate), 2.23 [2.14-2.31]; HR(high), 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant.The association between maternal SDP and offspring substance use/problems is likely due to familial background factors, not a causal influence, because siblings have similar rates of substance use and problems regardless of their specific exposure to SDP.

CONTEXT

Unlike other areas of medicine, psychiatry is almost entirely dependent on patient report to assess the presence and severity of disease; therefore, it is particularly crucial that we find both more accurate and efficient means of obtaining that report.

OBJECTIVE

To develop a computerized adaptive test (CAT) for depression, called the Computerized Adaptive Test-Depression Inventory (CAT-DI), that decreases patient and clinician burden and increases measurement precision. DESIGN Case-control study. SETTING A psychiatric clinic and community mental health center. PARTICIPANTS A total of 1614 individuals with and without minor and major depression were recruited for study. MAIN OUTCOME MEASURES The focus of this study was the development of the CAT-DI. The 24-item Hamilton Rating Scale for Depression, Patient Health Questionnaire 9, and the Center for Epidemiologic Studies Depression Scale were used to study the convergent validity of the new measure, and the Structured Clinical Interview for DSM-IV was used to obtain diagnostic classifications of minor and major depressive disorder.

RESULTS

A mean of 12 items per study participant was required to achieve a 0.3 SE in the depression severity estimate and maintain a correlation of r = 0.95 with the total 389-item test score. Using empirically derived thresholds based on a mixture of normal distributions, we found a sensitivity of 0.92 and a specificity of 0.88 for the classification of major depressive disorder in a sample consisting of depressed patients and healthy controls. Correlations on the order of r = 0.8 were found with the other clinician and self-rating scale scores. The CAT-DI provided excellent discrimination throughout the entire depressive severity continuum (minor and major depression), whereas the traditional scales did so primarily at the extremes (eg, major depression).

CONCLUSIONS

Traditional measurement fixes the number of items administered and allows measurement uncertainty to vary. In contrast, a CAT fixes measurement uncertainty and allows the number of items to vary. The result is a significant reduction in the number of items needed to measure depression and increased precision of measurement.

CONTEXT

Recent evidence from both clinical and population research has pointed to psychotic symptoms as potentially important markers of risk for suicidal behavior. However, to our knowledge, there have been no epidemiological studies to date that have reported data on psychotic symptoms and suicidality in individuals who have been clinically assessed for suicidal behavior.

OBJECTIVES

To explore associations between psychotic symptoms in nonpsychotic adolescents and risk for suicidal behavior in (1) the general population, (2) adolescents with psychiatric disorder, and (3) adolescents with suicidal ideation. DESIGN Two independently conducted case-control clinical interview studies. SETTING Population-based studies in Ireland. PARTICIPANTS Study 1 included 212 adolescents aged 11 to 13 years. Study 2 included 211 adolescents aged 13 to 15 years. Participants were recruited from schools. MAIN OUTCOME MEASURES Suicidal behavior and psychotic symptoms, assessed by semi-structured diagnostic clinical interview.

RESULTS

Psychotic symptoms were associated with a 10-fold increased odds of any suicidal behavior (ideation, plans, or acts) in both the early and middle adolescence studies (odds ratio [OR], 10.23; 95% CI, 3.25-32.26; P < .001 and OR, 10.5; 95% CI, 3.14-35.17; P < .001, respectively). Adolescents with depressive disorders who also experienced psychotic symptoms were at a nearly 14-fold increased odds of more severe suicidal behavior (suicide plans and suicide acts) compared with adolescents with depressive disorders who did not experience psychotic symptoms (OR, 13.7; 95% CI, 2.1-89.6). Among all adolescents with suicidal ideation, those who also reported psychotic symptoms had a nearly 20-fold increased odds of suicide plans and suicide acts compared with adolescents with suicidal ideation who did not report psychotic symptoms (OR, 19.6; 95% CI, 1.8-216.1).

CONCLUSIONS

Psychotic symptoms are strongly associated with increased risk for suicidal behavior in the general adolescent population and in adolescents with (nonpsychotic) psychiatric disorder. In both studies, an absolute majority of adolescents with more severe suicidal behavior (suicidal plans and acts) reported psychotic symptoms when directly questioned about this as part of a psychiatric interview. Assessment of psychotic symptoms should form a key part of suicide risk assessment.

CONTEXT

Neural substrates that may be responsible for the high prevalence of depression in type 1 diabetes mellitus (T1DM) have not yet been elucidated.

OBJECTIVE

To investigate neuroanatomic correlates of depression in T1DM. DESIGN Case-control study using high-resolution brain magnetic resonance images. SETTINGS Joslin Diabetes Center and McLean Hospital, Massachusetts, and Seoul National University Hospital, South Korea. PARTICIPANTS A total of 125 patients with T1DM (44 subjects with ≥1 previous depressive episodes [T1DM-depression group] and 81 subjects who had never experienced depressive episodes [T1DM-only group]), 23 subjects without T1DM but with 1 or more previous depressive episodes (depression group), and 38 healthy subjects (control group). MAIN OUTCOME MEASURES Spatial distributions of cortical thickness for each diagnostic group were compared with the control group using a surface-based approach. Among patients with T1DM, associations between metabolic control measures and cortical thickness deficits were examined.

RESULTS

Thickness reduction in the bilateral superior prefrontal cortical regions was observed in the T1DM-depression, T1DM-only, and depression groups relative to the control group at corrected P < .01. Conjunction analyses demonstrated that thickness reductions related to the influence of T1DM and those related to past depressive episode influence were observed primarily in the superior prefrontal cortical region. Long-term glycemic control levels were associated with superior prefrontal cortical deficits in patients with T1DM (β = -0.19, P = .02).

CONCLUSIONS

This study provides evidence that thickness reduction of prefrontal cortical regions in patients with T1DM, as modified by long-term glycemic control, could contribute to the increased risk for comorbid depression.