Recent Journal Articles: Psychiatry -- Neurotransmitter.net

Recent Articles in Archives of General Psychiatry

McNally RJ
Trauma in childhood.
Arch Gen Psychiatry. 2007 Dec;64(12):1451. [Abstract]

Saddichha S, Kumar D
Is psychosocial management effective?
Arch Gen Psychiatry. 2007 Dec;64(12):1451; author reply 1452-3. [Abstract]

Dickerson BC, Sperling RA, Hyman BT, Albert MS, Blacker D
Clinical prediction of Alzheimer disease dementia across the spectrum of mild cognitive impairment.
Arch Gen Psychiatry. 2007 Dec;64(12):1443-50.
OBJECTIVE: To determine whether clinical assessment methods that grade the severity of impairments within the spectrum of mild cognitive impairment (MCI) can predict clinical course, particularly among very mildly impaired individuals who do not meet formal MCI criteria as implemented in clinical trials. DESIGN: Cohort. SETTING: Community volunteers. PARTICIPANTS: From a longitudinal study of normal (Clinical Dementia Rating [CDR] = 0; n = 77) and mildly impaired (CDR = 0.5; n = 167) participants with 5 or more annual clinical assessments, baseline level of cognitive impairment in daily life was graded using CDR sum of boxes (CDR-SB) and level of cognitive performance impairment was graded using neuropsychological test scores. MAIN OUTCOME MEASURES: Five-year outcome measures included (1) probable Alzheimer disease (AD) diagnosis and (2) clinical "decline" (CDR-SB increase > or = 1.0). Logistic regression models were used to assess the ability of baseline measures to predict outcomes in the full sample and separately in the subjects who did not meet formal MCI criteria as implemented in a multicenter clinical trial (n = 125; "very mild cognitive impairment" [vMCI]). RESULTS: The presence of both higher CDR-SB and lower verbal memory and executive function at baseline predicted greater likelihood of probable AD and decline. Five-year rates of probable AD and decline in vMCI (20%, AD; 49%, decline) were intermediate between normal participants (0%, AD; 28%, decline) and participants with MCI (41%, AD; 62%, decline). Within vMCI, likelihood of probable AD was predicted by higher CDR-SB and lower executive function. CONCLUSIONS: Even in very mildly impaired individuals who do not meet strict MCI criteria as implemented in clinical trials, the degree of cognitive impairment in daily life and performance on neuropsychological testing predict likelihood of an AD diagnosis within 5 years. The clinical determination of relative severity of impairment along the spectrum of MCI may be valuable for trials of putative disease-modifying compounds, particularly as target populations are broadened to include less impaired individuals. [Abstract]

Reed PL, Anthony JC, Breslau N
Incidence of drug problems in young adults exposed to trauma and posttraumatic stress disorder: do early life experiences and predispositions matter?
Arch Gen Psychiatry. 2007 Dec;64(12):1435-42.
CONTEXT: Most estimated associations of posttraumatic stress disorder (PTSD) with DSM-IV drug dependence and abuse are from cross-sectional studies or from prospective studies of adults that generally do not take into account suspected causal determinants measured in early childhood. OBJECTIVE: To estimate risk for incident drug disorders associated with prior DSM-IV PTSD. DESIGN: Multiwave longitudinal study of an epidemiologic sample of young adults first assessed at entry to first grade of primary school in the fall semesters of 1985 and 1986, with 2 young adult follow-up assessments. SETTING: Mid-Atlantic US urban community. PARTICIPANTS: Young adults (n = 988; aged 19-24 years) free of clinical features of DSM-IV drug use disorders at the first young adult assessment and therefore at risk for newly incident drug use disorders during the 1-year follow-up period. MAIN OUTCOME MEASURES: During the 12-month interval between the 2 young adult follow-up assessments, newly incident (1) DSM-IV drug abuse or dependence; (2) DSM-IV drug abuse; (3) DSM-IV drug dependence; and (4) emerging dependence problems (1 or 2 newly incident clinical features of DSM-IV drug dependence), among subjects with no prior clinical features of drug use disorders. RESULTS: Prior PTSD (but not trauma only) was associated with excess risk for drug abuse or dependence (adjusted relative risk, 4.9; 95% confidence interval, 1.6-15.2) and emerging dependence problems (adjusted relative risk, 4.9; 95% confidence interval, 1.2-20.1) compared with the no-trauma group controlling for childhood factors. Subjects with PTSD also had a greater adjusted relative risk for drug abuse or dependence compared with subjects exposed to trauma only (adjusted relative risk, 2.0; 95% confidence interval, 1.1-3.8) controlling for childhood factors. CONCLUSIONS: Association of PTSD with subsequent incident drug use disorders remained substantial after statistical adjustment for early life experiences and predispositions reported in previous studies as carrying elevated risk for both disorders. Posttraumatic stress disorder might be a causal determinant of drug use disorders, possibly representing complications such as attempts to self-medicate troubling trauma-associated memories, nightmares, or painful hyperarousal symptoms. [Abstract]

Galea S, Brewin CR, Gruber M, Jones RT, King DW, King LA, McNally RJ, Ursano RJ, Petukhova M, Kessler RC
Exposure to hurricane-related stressors and mental illness after Hurricane Katrina.
Arch Gen Psychiatry. 2007 Dec;64(12):1427-34.
CONTEXT: Uncertainty exists about the prevalence, severity, and correlates of mental disorders among people exposed to Hurricane Katrina. OBJECTIVE: To estimate the prevalence and associations between DSM-IV anxiety-mood disorders and hurricane-related stressors separately among prehurricane residents of the New Orleans metropolitan area and the remainder of the areas in Alabama, Louisiana, and Mississippi affected by Katrina. DESIGN: Community survey. SETTING AND PARTICIPANTS: A probability sample of 1043 English-speaking prehurricane residents of the areas affected by Hurricane Katrina was administered via telephone survey between January 19 and March 31, 2006. The survey assessed hurricane-related stressors and screened for 30-day DSM-IV anxiety-mood disorders. MAIN OUTCOME MEASURES: The K6 screening scale of anxiety-mood disorders and the Trauma Screening Questionnaire scale for posttraumatic stress disorder (PTSD), both calibrated against blinded structured clinical reappraisal interviews to approximate the 30-day prevalence of DSM-IV disorders. RESULTS: Prehurricane residents of the New Orleans metropolitan area were estimated to have a 49.1% 30-day prevalence of any DSM-IV anxiety-mood disorder (30.3% estimated prevalence of PTSD) compared with 26.4% (12.5% PTSD) in the remainder of the sample. The vast majority of respondents reported exposure to hurricane-related stressors. Extent of stressor exposure was more strongly related to the outcomes in the New Orleans metropolitan area subsample than the remainder of the sample. The stressors most strongly related to these outcomes were physical illness/injury and physical adversity in the New Orleans metropolitan area subsample and property loss in the remainder of the sample. Sociodemographic correlates were not explained either by differential exposure or reactivity to hurricane-related stressors. CONCLUSIONS: The high prevalence of DSM-IV anxiety-mood disorders, the strong associations of hurricane-related stressors with these outcomes, and the independence of sociodemographics from stressors argue that the practical problems associated with ongoing stressors are widespread and must be addressed to reduce the prevalence of mental disorders in this population. [Abstract]

Feusner JD, Townsend J, Bystritsky A, Bookheimer S
Visual information processing of faces in body dysmorphic disorder.
Arch Gen Psychiatry. 2007 Dec;64(12):1417-25.
CONTEXT: Body dysmorphic disorder (BDD) is a severe psychiatric condition in which individuals are preoccupied with perceived appearance defects. Clinical observation suggests that patients with BDD focus on details of their appearance at the expense of configural elements. This study examines abnormalities in visual information processing in BDD that may underlie clinical symptoms. OBJECTIVE: To determine whether patients with BDD have abnormal patterns of brain activation when visually processing others' faces with high, low, or normal spatial frequency information. DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: Twelve right-handed, medication-free subjects with BDD and 13 control subjects matched by age, sex, and educational achievement. Intervention Functional magnetic resonance imaging while performing matching tasks of face stimuli. Stimuli were neutral-expression photographs of others' faces that were unaltered, altered to include only high spatial frequency visual information, or altered to include only low spatial frequency visual information. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes in the BDD and control groups during tasks with each stimulus type. RESULTS: Subjects with BDD showed greater left hemisphere activity relative to controls, particularly in lateral prefrontal cortex and lateral temporal lobe regions for all face tasks (and dorsal anterior cingulate activity for the low spatial frequency task). Controls recruited left-sided prefrontal and dorsal anterior cingulate activity only for the high spatial frequency task. CONCLUSIONS: Subjects with BDD demonstrate fundamental differences from controls in visually processing others' faces. The predominance of left-sided activity for low spatial frequency and normal faces suggests detail encoding and analysis rather than holistic processing, a pattern evident in controls only for high spatial frequency faces. These abnormalities may be associated with apparent perceptual distortions in patients with BDD. The fact that these findings occurred while subjects viewed others' faces suggests differences in visual processing beyond distortions of their own appearance. [Abstract]

Klump KL, Burt SA, McGue M, Iacono WG
Changes in genetic and environmental influences on disordered eating across adolescence: a longitudinal twin study.
Arch Gen Psychiatry. 2007 Dec;64(12):1409-15.
CONTEXT: Previous research suggests substantial increases in genetic effects on disordered eating across adolescence. Unfortunately, these studies were cross-sectional and focused primarily on early (age 11 years) vs late (age 17 years) adolescence. OBJECTIVE: To examine longitudinal changes in genetic and environmental influences on disordered eating across early, mid, and late adolescence. DESIGN AND SETTING: Population-based study of female same-sex twins. PARTICIPANTS: Seven hundred seventy-two female adolescent twins from the Minnesota Twin Family Study assessed at ages 11, 14, and 18 years. MAIN OUTCOME MEASURES: Disordered eating symptoms (ie, body dissatisfaction, weight preoccupation, binge eating, and the use of compensatory behaviors) were assessed with the total score from the Minnesota Eating Behavior Survey. RESULTS: Biometric model-fitting indicated significant changes in genetic and shared environmental effects across early to mid adolescence. Although genetic factors accounted for a negligible proportion (6%) of variance at age 11 years, genes increased in importance and accounted for roughly half of the variance (46%) in disordered eating at ages 14 and 18 years. Shared environmental influences decreased substantially across these same ages. CONCLUSIONS: Findings highlight the transition from early to mid adolescence as a critical time for the emergence of a genetic diathesis for disordered eating. The increase in genetic effects during this developmental stage corroborates previous research implicating puberty in the genetic etiology of eating disorders. [Abstract]

Procopio M, Marriott P
Intrauterine hormonal environment and risk of developing anorexia nervosa.
Arch Gen Psychiatry. 2007 Dec;64(12):1402-7.
CONTEXT: Anorexia nervosa (AN) is approximately 10 times more common in females than in males. The reasons for this difference are not yet understood. Several mechanisms have been hypothesized as possible causes. OBJECTIVE: To determine whether the different hormonal environments to which male and female fetuses are exposed in utero might contribute to the increased risk of developing AN in females. DESIGN, SETTING, AND PARTICIPANTS: The study is based on a large population-based cohort of Swedish twins. The strategy used is to compare the prevalence for AN between same-sex and opposite-sex twins. RESULTS: The study shows that the risk of developing AN in female twins is higher than in male twins, as expected. The only exception is male members of opposite-sex pairs, who have a higher risk of developing the illness when compared with other males (P = .62 for narrow diagnostic criteria and P = .60 for broad diagnostic criteria). In fact, their risk is at a level that is not statistically significantly different from that of females from such a pair. A plausible explanation for this phenomenon is that in pregnancies bearing a female fetus, a substance is produced, probably hormonal, that increases the risk of having AN in adulthood. Because the male half of an opposite-sex twin pair would also be exposed to this substance, it could account for the observed elevated risk in males with female twins. The most likely candidates are sex steroid hormones. CONCLUSIONS: The results of our study are compatible with the hypothesis that intrauterine exposure to sex hormones might influence neurodevelopment, affecting the risk of developing AN in adult life. This might be a factor contributing to the higher risk of developing AN in females. [Abstract]

Kubzansky LD, Thurston RC
Emotional vitality and incident coronary heart disease: benefits of healthy psychological functioning.
Arch Gen Psychiatry. 2007 Dec;64(12):1393-401.
CONTEXT: The potentially toxic effects of psychopathology and poorly regulated emotion on physical health have long been considered, but less work has addressed whether healthy psychological functioning may also benefit physical health. Emotional vitality--characterized by a sense of energy, positive well-being, and effective emotion regulation--has been hypothesized to reduce risk of heart disease, but no studies have examined this relationship. OBJECTIVES: To examine whether emotional vitality is associated with reduced risk of coronary heart disease (CHD). Secondary aims are to consider whether effects are independent of negative emotion and how they may occur. DESIGN: A prospective population-based cohort study. SETTING: National Health and Nutrition Examination Survey I and follow-up studies (a probability sample of US adults). PARTICIPANTS: Six thousand twenty-five men and women aged 25 to 74 years without CHD at baseline, followed up for a mean 15 years after the baseline interview. MAIN OUTCOME MEASURES: Measures of incident CHD were obtained from hospital records and death certificates. During the follow-up period, 1141 cases of incident CHD occurred. RESULTS: At the baseline interview (1971-1975), participants completed the General Well-being Schedule from which we derived a measure of emotional vitality. Compared with individuals with low levels, those reporting high levels of emotional vitality had multivariate-adjusted relative risks of 0.81 (95% confidence interval, 0.69-0.94) for CHD. A dose-response relationship was evident (P < .001). Significant associations were also found for each individual emotional vitality component with CHD, but findings with the overall emotional vitality measure were more reliable. Further analyses suggested that one way in which emotional vitality may influence coronary health is via health behaviors. However, the effect remained significant after controlling for health behaviors and other potential confounders, including depressive symptoms or other psychological problems. CONCLUSION: Emotional vitality may protect against risk of CHD in men and women. [Abstract]

Arabia G, Grossardt BR, Geda YE, Carlin JM, Bower JH, Ahlskog JE, Maraganore DM, Rocca WA
Increased risk of depressive and anxiety disorders in relatives of patients with Parkinson disease.
Arch Gen Psychiatry. 2007 Dec;64(12):1385-92.
CONTEXT: Relatives of patients with Parkinson disease (PD) have an increased risk of PD and other neurologic disorders; however, their risk of psychiatric disorders remains uncertain. OBJECTIVE: To study the risk of depressive disorders and anxiety disorders among first-degree relatives of patients with PD compared with first-degree relatives of controls. DESIGN, SETTING, AND PARTICIPANTS: In a population-based, historical cohort study, we included 1000 first-degree relatives of 162 patients with PD and 850 first-degree relatives of 147 controls. Both patients with PD and controls were representative of the population of Olmsted County, Minnesota. MAIN OUTCOME MEASURES: Documentation of psychiatric disorders was obtained for each relative separately through a combination of telephone interviews with the relatives (or their proxies) and review of their medical records from a records-linkage system (family study method). Psychiatric disorders were defined using clinical criteria from the DSM-IV or routine diagnoses. RESULTS: We found an increased risk of several psychiatric disorders in first-degree relatives of patients with PD compared with first-degree relatives of controls (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.21-1.95; P <.001). In particular, we found an increased risk of depressive disorders (HR, 1.45; 95% CI, 1.11-1.89; P = .006) and anxiety disorders (HR, 1.55; 95% CI, 1.05-2.28; P = .03). The results were consistent in analyses that adjusted for type of interview, excluded relatives who developed parkinsonism, or excluded relatives who developed both a depressive disorder and an anxiety disorder. CONCLUSION: These findings suggest that depressive disorders and anxiety disorders may share familial susceptibility factors with PD. [Abstract]

Agerbo E
High income, employment, postgraduate education, and marriage: a suicidal cocktail among psychiatric patients.
Arch Gen Psychiatry. 2007 Dec;64(12):1377-84.
CONTEXT: Studies dating back over 100 years have shown that the risk of suicide in the general population is associated with low income, unemployment, educational underachievement, and singleness. However, little is known about the association between suicide risk and these factors in psychiatric patients. OBJECTIVE: To estimate the association between suicide risk, socioeconomic position, and marital status in psychiatric patients. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of all first-ever psychiatric patients aged 16 to 65 years admitted from 1981 to 1998, with administrative longitudinal data on income, labor market affiliation, educational attainment, and marital and cohabitational status (96,369 patients, 256,619 admissions, and 2727 suicides). MAIN OUTCOME MEASURES: Suicide risks after hospital discharge were depicted using Kaplan-Meier product-limit methods. Hazard ratios (HRs) for suicide from Cox proportional hazards regression and case-crossover/individually stratified analyses were calculated while adjusting for overall social drift. RESULTS: Using Cox proportional hazards regression, compared with patients in the highest income quartile, the suicide HR decreased from 0.90 (95% confidence interval [CI], 0.79-1.02) in the third lowest to 0.83 (95% CI, 0.73-0.93) in the second lowest and to 0.68 (95% CI, 0.61-0.76) in the lowest income group. Compared with the fully employed, the HR for unemployed patients was 0.85 (95% CI, 0.77-0.93); for social benefits' recipients, 0.58 (95% CI, 0.48-0.70); and for disability or age pensioners, 0.63 (95% CI, 0.55-0.71). Compared with postgraduate education, HRs (95% CIs) associated with a bachelor's degree, vocational school, or primary school education were 0.82 (0.67-1.02), 0.66 (0.55-0.80), and 0.54 (0.44-0.65), respectively. The HRs (95% CIs) for widowed, divorced, and never-married patients were 1.07 (0.89-1.30), 0.74 (0.66-0.84), and 0.88 (0.79-0.98), respectively. Using individually stratified analyses, HRs (95% CIs) for transition into the third lowest, the second lowest, and the lowest income quartile were 1.19 (0.76-1.86), 1.47 (0.92-2.34), and 1.84 (1.14-2.97), respectively. The HRs (95% CIs) for patients who became unemployed, social benefits' recipients, disability or age pensioners, widowed patients, and divorced patients were 1.41 (1.01-1.95), 1.73 (1.06-2.80), 1.45 (0.91-2.30), 2.59 (0.76-8.89), and 1.86 (1.07-3.21), respectively. CONCLUSIONS: Suicide risk is generally associated with low income, unemployment, educational underachievement, and singleness, but this study suggests that the opposite is true among psychiatric patients. However, loss of income, labor market status, and marriage increase the suicide risk. [Abstract]

Hippisley-Cox J, Vinogradova Y, Coupland C, Parker C
Risk of malignancy in patients with schizophrenia or bipolar disorder: nested case-control study.
Arch Gen Psychiatry. 2007 Dec;64(12):1368-76.
CONTEXT: There is conflicting evidence on whether people with schizophrenia have a different risk of cancer from that of the general population. OBJECTIVE: To determine the risk of 6 common cancers in patients with schizophrenia or bipolar disorder. DESIGN: Population-based, nested, case-control study. SETTING: A total of 454 practices contributing to the QRESEARCH general practice database. PARTICIPANTS: We analyzed 40,441 incident cases of 6 cancers (breast, colon, rectal, gastroesophageal, prostate, and respiratory) and up to 5 controls per case matched by single year of age, sex, general practice, and calendar time. MAIN OUTCOME MEASURES: Odds ratios (ORs) for cancer risk associated with schizophrenia and bipolar disorder, adjusting for smoking, body mass index, socioeconomic status, comorbidities, and prescribed medications, including antipsychotics. RESULTS: For breast cancer, we identified 10,535/50,074 cases/controls; colon cancer, 5108/24,458; rectal cancer, 3248/15,552; gastroesophageal cancer, 3854/18,477; prostate cancer, 10,190/48,748; and respiratory cancer, 7506/35,981. After adjustment, patients with schizophrenia had a 190% increased colon cancer risk (adjusted OR, 2.90; 95% confidence interval [CI], 1.85-4.57), a marginal increased breast cancer risk (adjusted OR, 1.52; 95% CI, 1.10-2.11), and a 47% decreased respiratory cancer risk (adjusted OR, 0.53, 95% CI, 0.34-0.85). Patients with schizophrenia taking antipsychotics had a 308% increased colon cancer risk (adjusted OR, 4.08; 95% CI, 2.43-6.84). Patients with bipolar disorder had cancer risks similar to patients with neither condition after adjustment. CONCLUSIONS: Patients with schizophrenia have a significantly higher risk of colon cancer and a lower risk of respiratory cancer compared with patients without schizophrenia after adjustment for confounders. In contrast, the risks of cancer in patients with and without bipolar disorder are similar, suggesting that residual confounding is unlikely to explain the findings. The increased risk of colon cancer is particularly marked in patients with schizophrenia who take antipsychotic medications. [Abstract]

Gur RE, Loughead J, Kohler CG, Elliott MA, Lesko K, Ruparel K, Wolf DH, Bilker WB, Gur RC
Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia.
Arch Gen Psychiatry. 2007 Dec;64(12):1356-66.
CONTEXT: Deficits in emotion processing are prominent in schizophrenia, and flat affect is resistant to treatment and portends poor outcome. Investigation of the underlying neural circuitry can elucidate affective dysfunction. OBJECTIVE: To examine the brain circuitry for facial emotion processing, dissecting response to task demands from effects of the appearance of facial expressions. DESIGN: A facial emotion identification task was presented during high-field (4-T) magnetic resonance imaging. Blood oxygenation level-dependent changes were contrasted for task compared with a scrambled face baseline (blocked analysis) and for the appearance of each of the following 4 target expressions compared with neutral faces (event related): happy, sad, anger, and fear. SETTING: Participants from the Schizophrenia Research Center underwent a functional magnetic resonance imaging study at the University of Pennsylvania Medical Center. PARTICIPANTS: Patients with DSM-IV-defined schizophrenia (n = 16) and healthy controls (n = 17) were recruited from the community. MAIN OUTCOME MEASURES: The percentage of signal change for each contrast and performance and clinical symptom severity ratings. RESULTS: Patients showed reduced limbic activation compared with controls for the emotion identification task. However, event-related analysis revealed that whereas in controls greater amygdala activation was associated with correct identifications of threat-related (anger and fear) expressions, patients showed the opposite effect of greater limbic activation, portending misidentifications. Furthermore, greater amygdala activation to the presentation of fearful faces was highly correlated with greater severity of flat affect. CONCLUSIONS: Abnormal amygdala activation in schizophrenia in response to presentation of fearful faces is paradoxically associated with failure to recognize the emotion and with more severe flat affect. This finding suggests that flat affect in schizophrenia relates to overstimulation of the limbic system. [Abstract]

Toulopoulou T, Picchioni M, Rijsdijk F, Hua-Hall M, Ettinger U, Sham P, Murray R
Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples.
Arch Gen Psychiatry. 2007 Dec;64(12):1348-55.
CONTEXT: The use of endophenotypes, biological traits that increase the liability to a disorder, represents one strategy to facilitate the detection of susceptibility genes for complex behavioral disorders such as schizophrenia. Establishing that a candidate trait is both heritable and linked genetically to schizophrenia is integral to its validity as an endophenotypic marker. Neurocognitive deficits are among the most promising indicators of increased risk for schizophrenia; however, it is not clear to what extent these deficits are genetically linked to the disorder. OBJECTIVES: To quantify the genetic and environmental contributions to the variability of selected neurocognitive measures and to estimate the genetic relationship between these and schizophrenia. DESIGN: Genetic model fitting to monozygotic and dizygotic twin data. SETTING: United Kingdom psychiatric research institute. PARTICIPANTS: Two hundred sixty-seven monozygotic and dizygotic twins concordant and discordant for schizophrenia, and healthy monozygotic and dizygotic control twin pairs. MAIN OUTCOME MEASURES: The heritabilities of intelligence, working memory, processing speed, perceptual organization, and verbal comprehension were estimated, and the genetic relationship between each of these and schizophrenia was quantified. RESULTS: Genetic influences contributed substantially to all of the cognitive domains, but intelligence and working memory were the most heritable. A significant correlation was found between intelligence and schizophrenia (r = -0.61; 95% confidence interval, -0.71 to -0.48), with shared genetic variance accounting for 92% of the covariance between the two. Genetic influences also explained most of the covariance between working memory and schizophrenia. Significant but lesser portions of covariance between the other cognitive domains and schizophrenia were also found to be genetically shared. Environmental effects, although separately linked to neurocognition and schizophrenia, did not generally contribute to their covariance. CONCLUSION: Genomewide searches using factorial designs stratifying for levels of intelligence and working memory will assist in the search for finding quantitative trait loci for schizophrenia. [Abstract]

Harris JC
The Water-lily pond--symphony in green.
Arch Gen Psychiatry. 2007 Dec;64(12):1347. [Abstract]

Manev H, Manev R
5-lipoxygenase as a possible biological link between depressive symptoms and atherosclerosis.
Arch Gen Psychiatry. 2007 Nov;64(11):1333. [Abstract]

Stewart JC, Janicki DL, Muldoon MF, Sutton-Tyrrell K, Kamarck TW
Negative emotions and 3-year progression of subclinical atherosclerosis.
Arch Gen Psychiatry. 2007 Feb;64(2):225-33.
CONTEXT: Although depression, anxiety, and hostility/anger have each been associated with an increased risk of coronary artery disease, these overlapping negative emotions have not been simultaneously examined as predictors of the progression of subclinical atherosclerosis. OBJECTIVE: To evaluate the relative importance of depressive symptoms, anxiety symptoms, and hostility/anger in predicting subclinical atherosclerotic progression over a 3-year period. Design/ SETTING: The Pittsburgh Healthy Heart Project, an ongoing prospective cohort study of healthy, older men and women from the general community. At baseline, questionnaires were administered to assess depressive symptoms, anxiety symptoms, hostility, anger experience, and anger expression. Mean carotid intima-media thickness was assessed by B-mode ultrasonography during the baseline and 3-year follow-up visits. PARTICIPANTS: Of the 464 adults enrolled in the project, 324 (69.8%) were included in this report because they had complete baseline and follow-up data. Main Outcome Measure Three-year change in mean carotid intima-media thickness. RESULTS: Regression analyses indicated that higher depressive symptoms at baseline were associated with greater 3-year change in carotid intima-media thickness (DeltaR(2) = 0.026, P = .002), even after taking into account demographic factors, cardiovascular risk factors, medication use, medical conditions, and other correlated negative emotions. Measures of anxiety symptoms, hostility, anger experience, and anger expression were each unrelated to intima-media thickness change. Post hoc analyses examining depressive symptom clusters showed that the somatic-vegetative symptoms of depression (DeltaR(2) = 0.027, P = .002), but not the cognitive-affective symptoms, were positively associated with intima-media thickness change. CONCLUSION: Our findings suggest that the somatic-vegetative features of depression, but perhaps not anxiety and hostility/anger, may play an important role in the earlier stages of the development of coronary artery disease. [Abstract]

King-Hele SA, Abel KM, Webb RT, Mortensen PB, Appleby L, Pickles AR
Risk of sudden infant death syndrome with parental mental illness.
Arch Gen Psychiatry. 2007 Nov;64(11):1323-30.
CONTEXT: Sudden infant death syndrome is the leading cause of postneonatal death in developed countries. Little is known about risks linked with parental mental illness per se or how such risks are modified by specific psychiatric conditions and by maternal vs paternal psychopathological abnormalities. OBJECTIVE: To investigate cause-specific postneonatal death, including sudden infant death syndrome, in infants whose parents had been admitted as psychiatric inpatients. DESIGN: National cohort study. SETTING: The entire Danish population. Patients All of the singleton live births registered from January 1, 1973, to December 31, 1998. Linkage to the national psychiatric register enabled identification of all of the parental admissions from April 1, 1969, onward. MAIN OUTCOME MEASURE: All of the cases of sudden infant death syndrome in the postneonatal period classified via national mortality registration between January 1, 1973, and December 31, 1998. RESULTS: Psychiatric admission history in either parent doubled the risk of sudden infant death syndrome, but there was no difference in risk whether infants were exposed to maternal or paternal admission. Risk was particularly high if both parents had been admitted for any psychiatric disorder (relative risk, 6.9; 95% confidence interval, 4.1-11.6). Among specific parental disorders, the greatest risk was associated with admission for alcohol- or drug-related disorders (mothers: relative risk, 5.0; 95% confidence interval, 3.4-7.5; fathers: relative risk, 2.5; 95% confidence interval, 1.7-3.8). Contrary to prior expectation, parental schizophrenia and related disorders did not confer higher risks than other parental disorders that resulted in admission. CONCLUSIONS: Infants whose parents have been admitted for psychiatric treatment are at greater risk for sudden infant death syndrome. However, risks may be lower than previously thought with maternal schizophrenia and related disorders. Clinicians should be aware of particularly high risks if both parents have received any psychiatric inpatient treatment or if either parent (but the mother especially) was admitted with an alcohol- or drug-related disorder. [Abstract]

Kendler KS, Myers J, Prescott CA
Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.
Arch Gen Psychiatry. 2007 Nov;64(11):1313-20.
CONTEXT: Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. OBJECTIVE: To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. DESIGN: Lifetime history by structured clinical interview. SETTING: General community. PARTICIPANTS: Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. RESULTS: Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. CONCLUSIONS: The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence appear to be specific to those substances. [Abstract]

C�t� SM, Boivin M, Nagin DS, Japel C, Xu Q, Zoccolillo M, Junger M, Tremblay RE
The role of maternal education and nonmaternal care services in the prevention of children's physical aggression problems.
Arch Gen Psychiatry. 2007 Nov;64(11):1305-12.
CONTEXT: Physical violence is an important health problem, and low maternal education is a significant risk for the development of chronic physical aggression (PA). We hypothesized that nonmaternal care (NMC) services could prevent the development of childhood PA problems, depending on the age at which the services are initiated. Method Children who followed a trajectory of atypically frequent PA between 17 and 60 months of age among a population sample of 1691 Canadian families were identified. Maternal education and NMC were considered in predicting group membership while controlling for confounding family characteristics. RESULTS: Children of mothers with low education levels (ie, no high school diploma) were less likely to receive NMC. Those who did receive such care had significantly lower risk of a high PA trajectory. Results from logistic regressions indicated that NMC reduced the risk of high PA, especially when initiated before age 9 months (odds ratio, 0.20; 95% confidence interval, 0.05-0.90). Children of mothers who graduated from high school were less at risk of PA problems, and NMC had no additional protective effect. CONCLUSIONS: Nonmaternal care services to children of mothers with low levels of education could substantially reduce their risk of chronic PA, especially if provided soon after birth. Because children most likely to benefit from NMC services are less likely to receive them, special measures encouraging the use of NMC services among high-risk families are needed. [Abstract]

D'Onofrio BM, Van Hulle CA, Waldman ID, Rodgers JL, Rathouz PJ, Lahey BB
Causal inferences regarding prenatal alcohol exposure and childhood externalizing problems.
Arch Gen Psychiatry. 2007 Nov;64(11):1296-304.
CONTEXT: Existing research on the neurobehavioral consequences of prenatal alcohol exposure (PAE) has not adequately accounted for genetic and environmental confounds. OBJECTIVE: To examine the association between PAE and offspring externalizing problems in a large representative sample of families in the United States using measured covariates and a quasi-experimental design to account for unmeasured genetic and environmental confounds. DESIGN: This study combines information from the National Longitudinal Survey of Youth and the Children of the National Longitudinal Survey of Youth. The analyses statistically controlled for measured characteristics of the mothers and families and exposure to other prenatal psychoactive substances. In the primary analyses, siblings differentially exposed to prenatal alcohol were compared. SETTING AND PARTICIPANTS: Women were recruited from the community using a stratified and clustered probability sample and were followed longitudinally. The sample included 8621 offspring of 4912 mothers. MAIN OUTCOME MEASURES: Maternal report of conduct problems (CPs) and attention/impulsivity problems (AIPs) during childhood (ages 4-11 years) using standardized assessments related to psychiatric diagnoses. RESULTS: There was an association between PAE and offspring CPs that was independent of confounded genetic and fixed environmental effects and the measured covariates. The CPs in children of mothers who drank daily during pregnancy were 0.35 SD greater than those in children whose mothers never drank during pregnancy. Although AIPs were associated with PAE when comparing unrelated offspring, children whose mothers drank more frequently during pregnancy did not have more AIPs than siblings who were less exposed to alcohol in utero. Additional subsample analyses suggested that maternal polysubstance use during pregnancy may account for the associations between PAE and AIPs. CONCLUSION: These results are consistent with PAE exerting an environmentally mediated causal effect on childhood CPs, but the relation between PAE and AIPs is more likely to be caused by other factors correlated with maternal drinking during pregnancy. [Abstract]

Peterson BS, Choi HA, Hao X, Amat JA, Zhu H, Whiteman R, Liu J, Xu D, Bansal R
Morphologic features of the amygdala and hippocampus in children and adults with Tourette syndrome.
Arch Gen Psychiatry. 2007 Nov;64(11):1281-91.
CONTEXT: Limbic portions of cortical-subcortical circuits are likely involved in the pathogenesis of Tourette syndrome (TS). They are anatomically, developmentally, neurochemically, and functionally related to the basal ganglia, and the basal ganglia are thought to produce the symptoms of tics, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder that commonly affect persons with TS. OBJECTIVE: To study the morphologic features of the hippocampus and amygdala in children and adults with TS. DESIGN: A cross-sectional, case-control study using anatomical magnetic resonance imaging. SETTING: University research center. PARTICIPANTS: A total of 282 individuals (154 patients with TS and 128 controls) aged 6 to 63 years. MAIN OUTCOME MEASURES: Volumes and measures of surface morphologic features of the hippocampus and amygdala. RESULTS: The overall volumes of the hippocampus and amygdala were significantly larger in the TS group. Surface analyses suggested that the increased volumes in the TS group derived primarily from the head and medial surface of the hippocampus (over the length of the dentate gyrus) and the dorsal and ventral surfaces of the amygdala (over its basolateral and central nuclei). Volumes of these subregions declined with age in the TS group but not in controls, so the subregions were significantly larger in children with TS but significantly smaller in adults with TS than in their control counterparts. In children and adults, volumes in these subregions correlated inversely with the severity of tic, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder symptoms, suggesting that enlargement of the subregions may have a compensatory and neuromodulatory effect on tic-related symptoms. CONCLUSION: These findings are consistent with the known plasticity of the dentate gyrus and with findings from previous imaging studies suggesting the presence of failed compensatory plasticity in adults with TS who have not experienced the usual decline in symptoms during adolescence. [Abstract]

Ashtari M, Cottone J, Ardekani BA, Cervellione K, Szeszko PR, Wu J, Chen S, Kumra S
Disruption of white matter integrity in the inferior longitudinal fasciculus in adolescents with schizophrenia as revealed by fiber tractography.
Arch Gen Psychiatry. 2007 Nov;64(11):1270-80.
CONTEXT: There is increasing evidence that schizophrenia is characterized by abnormalities in white matter. OBJECTIVE: To investigate the integrity of white matter tracts in adolescents with schizophrenia. DESIGN: Cross-sectional, case-control, whole-brain, voxel-based analysis and fiber tractography using diffusion tensor magnetic resonance imaging. SETTING: University research institute. PARTICIPANTS: Forty-four individuals (age range, 11-18 years), 23 with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 21 demographically similar healthy controls. MAIN OUTCOME MEASURES: Fractional anisotropy, trace, and radial diffusivity of diffusion tensor and quantitative tractography. RESULTS: Voxelwise analysis revealed that adolescents with schizophrenia had reduced fractional anisotropy within the left inferior temporal (P < .001) and occipital (P < .001) regions. Tractography was performed to extract the left and the right inferior longitudinal fasciculi (ILF). Measuring the mean diffusion indices along the left ILF, patients had significantly reduced fractional anisotropy (P < .001) as well as significantly increased radial diffusivity (P < .001) and trace (P = .003) after adjusting for differences in a measure thought to reflect premorbid intelligence, Wide Range Achievement Test 3 reading scores. Exploratory analyses revealed that patients with a history of visual hallucinations had lower fractional anisotropy in the left ILF (P = .02) than patients without visual hallucinations. CONCLUSION: Our findings, which benefited from greater image resolution and methodological control than previous studies conducted in adolescents with schizophrenia, provide strong evidence for lower white matter integrity in the left ILF, particularly for patients with a history of visual hallucinations. [Abstract]

Rosenheck RA, Leslie DL, Sindelar JL, Miller EA, Tariot PN, Dagerman KS, Davis SM, Lebowitz BD, Rabins P, Hsiao JK, Lieberman JA, Schneider LS
Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease.
Arch Gen Psychiatry. 2007 Nov;64(11):1259-68.
CONTEXT: Second-generation antipsychotics (SGAs) are prescribed for psychosis, aggression, and agitation in Alzheimer disease (AD). OBJECTIVE: To conduct a cost-benefit analysis of SGAs and placebo (taken to represent a "watchful waiting" treatment strategy) for psychosis and aggression in outpatients with AD. DESIGN: Randomized placebo-controlled trial of alternative SGA initiation strategies. SETTING: Forty-two outpatient clinics. PARTICIPANTS: Outpatients with AD and psychosis, aggression, or agitation (N = 421). Intervention Participants were randomly assigned to treatment with olanzapine, quetiapine fumarate, risperidone, or placebo with the option of double-blind rerandomization to another antipsychotic or citalopram hydrobromide or open treatment over 9 months. MAIN OUTCOME MEASURES: Monthly interviews documented health service use and costs. The economic perspective addressed total health care and medication costs. Costs of study drugs were estimated from wholesale prices with adjustment for discounts and rebates. Quality-adjusted life-years (QALYs) were assessed with the Health Utilities Index Mark 3 and were supplemented with measures of functioning, activities of daily living, and quality of life. Primary analyses were conducted using all available data. Secondary analyses excluded observations after the first medication change (ie, phase 1 only). Cost-benefit analysis was conducted using the net health benefits approach in a sensitivity analysis in which QALYs were valued at $50,000 per year and $100,000 per year. RESULTS: Average total health costs, including medications, were significantly lower for placebo than for SGAs, by $50 to $100 per month. There were no differences between treatments in QALYs or other measures of function. Phase 1-only analyses were broadly similar. Net-benefit analysis showed greater net health benefits for placebo as compared with other treatments, with probabilities ranging from 50% to 90%. CONCLUSIONS: There were no differences in measures of effectiveness between initiation of active treatments or placebo (which represented watchful waiting) but the placebo group had significantly lower health care costs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00015548. [Abstract]

Alden A, Brennan P, Hodgins S, Mednick S
Psychotic disorders and sex offending in a Danish birth cohort.
Arch Gen Psychiatry. 2007 Nov;64(11):1251-8.
CONTEXT: Psychotic disorders are associated with an increased risk of aggressive behavior and violent crime. Whether there is also an association with sex offending is unknown. OBJECTIVES: To estimate the lifetime prevalence of arrests for sexual offenses (with and without physical aggression) among men and women with psychotic disorders, the moderating effects of comorbid personality disorders and substance use disorders, and the prevalence rates for 4 specific psychotic disorders. DESIGN: We examined official records of arrests for sexual offenses with and without physical aggression to compare persons hospitalized with a psychotic disorder with those who had never been hospitalized. SETTING: Denmark. PARTICIPANTS: All 358,180 persons born from January 1, 1944, through December 31, 1947, in Denmark. Main Outcome Measure Official arrest records. RESULTS: Among the men, 2.2% were hospitalized with psychotic disorders. These men committed 8.4% of the physically aggressive sexual offenses and 9.0% of the non-physically aggressive sexual offenses of the men in the cohort. Compared with men who had never been hospitalized, men with psychotic disorders without a personality disorder or a substance use disorder were not at increased risk of arrest for physically aggressive sexual offenses but were 3 times more likely to have been arrested for non-physically aggressive sexual offenses. Psychotic disorders with comorbid personality disorders or substance use disorders were associated with a 6-fold increased risk of physically aggressive sex offending and a 3- to 5-fold increased risk of non-physically aggressive sex offending. CONCLUSIONS: Psychotic disorders comorbid with personality disorders and substance use disorders are associated with an increased risk of sex offending with and without physical aggression. Mental health policy and practice need to take account of these findings to improve functional outcome among persons with psychotic disorders. [Abstract]

Greenwood TA, Braff DL, Light GA, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RE, Gur RC, Mintz J, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Schork NJ
Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia.
Arch Gen Psychiatry. 2007 Nov;64(11):1242-50.
CONTEXT: Exploration of the genetic architecture of specific endophenotypes may be a powerful strategy for understanding the genetic basis of schizophrenia. OBJECTIVE: To characterize the genetic architecture of some key endophenotypic measures selected for their reported heritabilities in schizophrenia. DESIGN: Family-based heritability study. SETTING: Seven sites across the United States. PARTICIPANTS: At the time of these initial data analyses, the members of 183 nuclear families ascertained through probands with schizophrenia had been assessed for these endophenotypes. MAIN OUTCOME MEASURES: Variance component models were used to assess the heritability of and the environmental and genetic correlations among the endophenotypes. The Consortium on the Genetics of Schizophrenia assesses the neurophysiologic measures of prepulse inhibition of acoustic startle, P50 event-related potential suppression, and the antisaccade task for eye movements and the neurocognitive measures of the Continuous Performance Test (Degraded Stimulus version), the California Verbal Learning Test, the Letter-Number Sequencing test, and 6 measures from the University of Pennsylvania Computerized Neurocognitive Battery. The heritabilities of these 12 measures are the focus of this article. RESULTS: All of the endophenotypes and the University of Pennsylvania Computerized Neurocognitive Battery measures were found to be significantly heritable (P < or = .005), with heritabilities ranging from 24% to 55%. Significant environmental and genetic correlations were also observed between many of the endophenotypic measures. CONCLUSION: This is the first large-scale, multisite, family-based heritability study of a collection of endophenotypes for schizophrenia and suggests that endophenotypes are important measures to consider in characterizing the genetic basis of schizophrenia. [Abstract]

Haenschel C, Bittner RA, Haertling F, Rotarska-Jagiela A, Maurer K, Singer W, Linden DE
Contribution of impaired early-stage visual processing to working memory dysfunction in adolescents with schizophrenia: a study with event-related potentials and functional magnetic resonance imaging.
Arch Gen Psychiatry. 2007 Nov;64(11):1229-40.
CONTEXT: Working memory (WM) deficits in patients with schizophrenia have mainly been associated with prefrontal dysfunction. However, the contribution of perceptual deficits and abnormalities in sensory areas has not been explored. The present study closes this important gap in our understanding of WM dysfunction in schizophrenia by monitoring neural activity during WM encoding and retrieval with event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI). OBJECTIVE: To investigate the neurophysiological changes that contribute to WM impairment in early-onset schizophrenia at perceptual and cognitive stages using the ERP components P1, P3a, P370, and P570 and fMRI data from extrastriate visual areas. DESIGN: We conducted the study between June 1, 2003, and December 20, 2006. Electroencephalographic and fMRI data were acquired separately during a visual delayed discrimination task. Participants encoded up to 3 abstract shapes that were presented sequentially for 600 milliseconds each and decided after a 12-second delay whether a probe matched 1 of the sample stimuli. SETTING: Between-group study at an inpatient psychiatric hospital and outpatient psychiatric facilities. PARTICIPANTS: Seventeen adolescents with early-onset schizophrenia according to DSM-IV criteria and 17 matched controls participated in the study. MAIN OUTCOME MEASURES: Amplitude of the ERP components P1, P3a, P370, and P570 and the fMRI signal from extrastriate visual areas. RESULTS: The P1 amplitude was reduced in patients during encoding and retrieval. The P1 amplitude increased with WM load during encoding only in controls. In this group, a stronger P1 amplitude increase predicted better WM performance. The P1 reduction was mirrored by reduced activation of visual areas in patients in fMRI. The P370 amplitude during encoding and retrieval was also reduced in patients. CONCLUSIONS: The P1 amplitude reduction indicates an early visual deficit in adolescents with schizophrenia. Our findings suggest that P1 is of particular relevance for successful WM encoding. Early visual deficits contribute to impaired WM in schizophrenia in addition to deficits in later memory-related processes. [Abstract]

Harris JC
Beata Beatrix.
Arch Gen Psychiatry. 2007 Nov;64(11):1228. [Abstract]

Wilson RS, Schneider JA, Arnold SE, Bienias JL, Bennett DA
Conscientiousness and the incidence of Alzheimer disease and mild cognitive impairment.
Arch Gen Psychiatry. 2007 Oct;64(10):1204-12.
CONTEXT: The personality trait of conscientiousness has been related to morbidity and mortality in old age, but its association with the development of Alzheimer disease is not known. OBJECTIVE: To test the hypothesis that a higher level of conscientiousness is associated with decreased risk of Alzheimer disease. DESIGN: Longitudinal clinicopathologic cohort study with up to 12 years of annual follow-up. SETTING: The Religious Orders Study. PARTICIPANTS: A total of 997 older Catholic nuns, priests, and brothers without dementia at enrollment, recruited from more than 40 groups across the United States. At baseline, they completed a standard 12-item measure of conscientiousness. Those who died underwent a uniform neuropathologic evaluation from which previously established measures of amyloid burden, tangle density, Lewy bodies, and chronic cerebral infarction were derived. MAIN OUTCOME MEASURES: Clinical diagnosis of Alzheimer disease and change in previously established measures of global cognition and specific cognitive functions. RESULTS: Conscientiousness scores ranged from 11 to 47 (mean, 34.0; SD, 5.0). During follow-up, 176 people developed Alzheimer disease. In a proportional hazards regression model adjusted for age, sex, and education, a high conscientiousness score (90th percentile) was associated with an 89% reduction in risk of Alzheimer disease compared with a low score (10th percentile). Results were not substantially changed by controlling for other personality traits, activity patterns, vascular conditions, or other risk factors. Conscientiousness was also associated with decreased incidence of mild cognitive impairment and reduced cognitive decline. In those who died and underwent brain autopsy, conscientiousness was unrelated to neuropathologic measures, but it modified the association of neurofibrillary pathologic changes and cerebral infarction with cognition proximate to death. CONCLUSION: Level of conscientiousness is a risk factor for Alzheimer disease. [Abstract]

Druss BG, Wang PS, Sampson NA, Olfson M, Pincus HA, Wells KB, Kessler RC
Understanding mental health treatment in persons without mental diagnoses: results from the National Comorbidity Survey Replication.
Arch Gen Psychiatry. 2007 Oct;64(10):1196-203.
CONTEXT: Epidemiologic surveys have consistently found that approximately half of respondents who obtained treatment for mental or substance use disorders in the year before interview did not meet the criteria for any of the disorders assessed in the survey. Concerns have been raised that this pattern might represent evidence of misallocation of treatment resources. OBJECTIVE: To examine patterns and correlates of 12-month treatment of mental health or substance use problems among people who do not have a 12-month DSM-IV disorder. DESIGN AND SETTING: Data are from the National Comorbidity Survey Replication, a nationally representative face-to-face US household survey performed between February 5, 2001, and April 7, 2003, that assessed DSM-IV disorders using a fully structured diagnostic interview, the World Health Organization Composite International Diagnostic Interview (CIDI). PARTICIPANTS: A total of 5692 English-speaking respondents 18 years and older. MAIN OUTCOME MEASURES: Patterns of 12-month service use among respondents without any 12-month DSM-IV CIDI disorders. RESULTS: Of respondents who used 12-month services, 61.2% had a 12-month DSM-IV CIDI diagnosis, 21.1% had a lifetime but not a 12-month diagnosis, and 9.7% had some other indicator of possible need for treatment (subthreshold 12-month disorder, serious 12-month stressor, or lifetime hospitalization). The remaining 8.0% of service users accounted for only 5.6% of all services and even lower proportions of specialty (1.9%-2.4%) and general medical (3.7%) visits compared with higher proportions of human services (18.9%) and complementary and alternative medicine (7.6%) visits. Only 26.5% of the services provided to the 8.0% of presumably low-need patients were delivered in the mental health specialty or general medical sectors. CONCLUSIONS: Most services provided for emotional or substance use problems in the United States go to people with a 12-month diagnosis or other indicators of need. Patients who lack these indicators of need receive care largely outside the formal health care system. [Abstract]

Dempster EL, Burcescu I, Wigg K, Kiss E, Baji I, Gadoros J, Tam�s Z, Kennedy JL, Vetr� A, Kovacs M, Barr CL
Evidence of an association between the vasopressin V1b receptor gene (AVPR1B) and childhood-onset mood disorders.
Arch Gen Psychiatry. 2007 Oct;64(10):1189-95.
CONTEXT: Disturbances in stress hormones have been implicated in mood disorders, in particular in the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Arginine vasopressin (AVP) plays a crucial role in modulating the HPA axis under stress and does so through a G protein-coupled receptor, vasopressin V1b receptor (AVPR1b). OBJECTIVE: To determine if genetic variation in AVPR1B could be contributing to vulnerability to mood disorders. DESIGN: We genotyped single nucleotide polymorphisms (SNPs) across the AVPR1B gene in a family-based sample with childhood-onset mood disorders. Six SNPs were genotyped; 2 were novel nonsynonymous polymorphisms, and the other 4 were constituents of a haplotype that was previously shown to be protective against depression. SETTING: Twenty-three mental health facilities in Hungary. PARTICIPANTS: The sample was composed of 382 Hungarian nuclear families ascertained through affected probands with a diagnosis of childhood-onset mood disorder. MAIN OUTCOME MEASURES: Association with childhood-onset mood disorders was tested using the transmission disequilibrium test, which measures the transmission frequency of alleles, or haplotypes, from parents to affected offspring. RESULTS: Two of the AVPR1B SNPs showed association individually (Lys65Asn: chi(2) = 7.81, P = .005; S4: chi(2) = 4.58, P = .03); of particular interest is Lys65Asn, which causes an amino acid change in an intracellular protein domain. Haplotype analysis demonstrated significant overtransmission of the most frequent haplotype (chi(2)(3) = 22.42, P <.001). Furthermore, stratifying the sample by sex established that the association was predominantly in affected females, which is consistent with previous observations. CONCLUSIONS: We have found evidence to implicate the AVPR1B gene in the etiology of mood disorders, particularly in females. Antagonists of AVPR1b exhibit antidepressant qualities; hence, genetic variation in AVPR1B may have implications in HPA axis dysregulation in mood disorders. [Abstract]

Merikangas KR, Ames M, Cui L, Stang PE, Ustun TB, Von Korff M, Kessler RC
The impact of comorbidity of mental and physical conditions on role disability in the US adult household population.
Arch Gen Psychiatry. 2007 Oct;64(10):1180-8.
CONTEXT: There is limited information that accounts for comorbidity on the impact of role disability associated with a wide range of mental and physical disorders in population-based samples. OBJECTIVE: To estimate the comparative effects of common mental and physical conditions on role disability in the general population using a novel method that accounts for comorbidity. DESIGN: Direct interviews about physical and mental conditions during the past year. SETTING: The National Comorbidity Survey Replication, a nationally representative series of face-to-face interviews. PATIENTS: A nationally representative sample of adults living in households (N = 5962 respondents, 18 years and older). MAIN OUTCOME MEASURE: Disability in major life roles was assessed with the World Health Organization Disability Assessment Schedule. Simulations that allow for complex interactions among conditions were used to estimate the conditions' effects on disability days, when respondents were completely unable to carry out their usual daily activities because of problems with mental or physical health, in the past 12 months. RESULTS: An estimated 53.4% of US adults have 1 or more of the mental or physical conditions assessed in the survey. These respondents report an average 32.1 more role-disability days in the past year than demographically matched controls, equivalent to nearly 3.6 billion days of role disability in the population. Musculoskeletal disorders and major depression had the greatest effects on disability days. Mental conditions accounted for more than half as many disability days as all physical conditions at the population level. Associations of specific conditions with disability decreased substantially after controlling for comorbidity, suggesting that prior studies, which generally did not control for comorbidity, overestimated disease-specific effects. CONCLUSION: The staggering amount of health-related disability associated with mental and physical conditions should be considered in establishing priorities for the allocation of health care and research resources. [Abstract]

Brotman LM, Gouley KK, Huang KY, Kamboukos D, Fratto C, Pine DS
Effects of a psychosocial family-based preventive intervention on cortisol response to a social challenge in preschoolers at high risk for antisocial behavior.
Arch Gen Psychiatry. 2007 Oct;64(10):1172-9.
CONTEXT: Salivary cortisol levels during social challenge relate to adaptive functioning in children and adults. Low cortisol levels have been related to conduct problems and antisocial behavior. Although studies in rodents implicate early-life social experience in cortisol regulation, no studies with humans have examined the effects of an experimentally manipulated early-life social experience on cortisol regulation. OBJECTIVE: To examine the effects of experimental manipulations of social experience on cortisol response to a social challenge in preschoolers at risk for antisocial behavior. DESIGN: Randomized controlled trial. SETTING: Department of Child and Adolescent Psychiatry, New York University School of Medicine. PARTICIPANTS: Ninety-two preschool-age siblings of youths adjudicated for delinquent acts. Intervention Family-based intervention included 22 weekly group sessions for parents and preschoolers and 10 biweekly home visits conducted during a 6- to 8-month period. MAIN OUTCOME MEASURES: Salivary cortisol levels before and after a social challenge (entry into an unfamiliar peer group). RESULTS: Relative to controls, children in the intervention condition had increased cortisol levels in anticipation of the peer social challenge. Increases were relative to both preintervention cortisol levels during the challenge and cortisol levels in the home, which were not altered by the intervention. CONCLUSIONS: A family-based preventive intervention for children at high risk for antisocial behavior alters stress response in anticipation of a peer social challenge. The experimentally induced change in cortisol levels parallels patterns found in normally developing, low-risk children. [Abstract]

Johnson SC, Ries ML, Hess TM, Carlsson CM, Gleason CE, Alexander AL, Rowley HA, Asthana S, Sager MA
Effect of Alzheimer disease risk on brain function during self-appraisal in healthy middle-aged adults.
Arch Gen Psychiatry. 2007 Oct;64(10):1163-71.
CONTEXT: Asymptomatic middle-aged adult children of patients with Alzheimer disease (AD) recently were found to exhibit functional magnetic resonance imaging (fMRI) deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is yet unknown. This study examines the neural substrates of self-appraisal (SA) in persons at risk for AD. Accurate appraisal of deficits is a problem for many patients with AD, and prior fMRI studies of healthy young adults indicate that brain areas vulnerable to AD such as the anterior mesial temporal lobe and posterior cingulate are involved during SA tasks. OBJECTIVE: To determine whether parental family history of AD (hereafter referred to as FH) or presence of the epsilon4 allele of the apolipoprotein E gene (APOE4) exerts independent effects on brain function during SA. DESIGN: Cross-sectional factorial design in which APOE4 status (present vs absent) was one factor and FH was the other. All participants received cognitive testing, genotyping, and an fMRI task that required subjective SA decisions regarding trait adjective words in comparison with semantic decisions about the same words. SETTING: An academic medical center with a research-dedicated 3.0-T MR imaging facility. PARTICIPANTS: Cognitively normal middle-aged adults (n = 110), 51 with an FH and 59 without an FH. MAIN OUTCOME MEASURE: Blood oxygen-dependent contrast measured using T2*-weighted echo-planar imaging. RESULTS: Parental family history of AD and APOE4 status interacted in the posterior cingulate and left superior and medial frontal regions. There were main effects of FH (FH negative > FH positive) in the left hippocampus and ventral posterior cingulate. There were no main effects of APOE genotype. CONCLUSIONS: Our results suggest that FH may affect brain function during subjective SA in regions commonly affected by AD. Although the participants in this study were asymptomatic and middle-aged, the findings suggest that there may be subtle alterations in brain function attributable to AD risk factors. [Abstract]

Smoller JW, Pollack MH, Wassertheil-Smoller S, Jackson RD, Oberman A, Wong ND, Sheps D
Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study.
Arch Gen Psychiatry. 2007 Oct;64(10):1153-60.
CONTEXT: Previous studies have documented an association of depression and phobic anxiety with cardiovascular morbidity and mortality, but little is known about the cardiovascular sequelae of panic anxiety. OBJECTIVE: To determine whether panic attacks are associated with risk of cardiovascular morbidity and mortality in postmenopausal women. DESIGN: Prospective cohort survey. SETTING: Ten clinical centers of the 40-center Women's Health Initiative. PARTICIPANTS: A total of 3369 community-dwelling, generally healthy postmenopausal women (aged 51-83 years) enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study who completed a questionnaire about occurrence of panic attacks in the previous 6 months. MAIN OUTCOME MEASURES: Cardiovascular/cerebrovascular outcomes (fatal and nonfatal myocardial infarction and stroke