Archives of general psychiatry最新文献

Context: Converging evidence from electrophysiological studies suggests that in individuals with schizophrenia, electroencephalographic frontal fast oscillations are reduced. It is still unclear whether this reduction reflects an intrinsic deficit of underlying cortical/thalamocortical circuits and whether this deficit is specific for frontal regions. Recent electrophysiological studies in healthy individuals have established that, when perturbed, different brain regions oscillate at a specific, intrinsically generated dominant frequency, the natural frequency.

Objective: To assess the natural frequency of the posterior parietal, motor, premotor, and prefrontal cortices in patients with schizophrenia and healthy control subjects.

Design: High-density electroencephalographic recordings during transcranial magnetic stimulation of 4 cortical areas were performed. Several transcranial magnetic stimulation–evoked electroencephalographic oscillation parameters, including synchronization, amplitude, and natural frequency, were compared across the schizophrenia and healthy control groups.

Setting: Wisconsin Psychiatric Institute and Clinic, University of Wisconsin–Madison.

Participants: Twenty patients with schizophrenia and 20 age-matched healthy control subjects.

Main outcome measures: High-density electroencephalographic measurements of transcranial magnetic stimulation–evoked activity in 4 cortical areas, scores on the Positive and Negative Syndrome Scale, and performance scores (reaction time, accuracy) on 2 computerized tasks (word memory [Penn Word Recognition Test] and facial memory [Penn Facial Memory Test]).

Results: Patients with schizophrenia showed a slowing in the natural frequency of the frontal/prefrontal regions compared with healthy control subjects (from an average of a 2-Hz decrease for the motor area to an almost 10-Hz decrease for the prefrontal cortex). The prefrontal natural frequency of individuals with schizophrenia was slower than in any healthy comparison subject and correlated with both positive Positive and Negative Syndrome Scale scores and reaction time on the Penn Word Recognition Test.

Conclusions: These findings suggest that patients with schizophrenia have an intrinsic slowing in the natural frequency of frontal cortical/thalamocortical circuits, that this slowing is not present in parietal areas, and that the prefrontal natural frequency can predict some of the symptoms as well as the cognitive dysfunctions of schizophrenia.

Context: The endocannabinoid system has been implicated in stress adaptation and the regulation of mood in rodent studies, but few human association studies have examined these links and replications are limited.

Objectives: To examine whether a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood physical abuse on lifetime anhedonia and depression and to replicate this interaction in an independent sample.

Design, setting, and participants: Genetic association study in 1041 young US women with replication in an independent Australian sample of 1428 heroin-dependent individuals as cases and 506 participants as neighborhood controls.

Main outcome measures: Self-reported anhedonia and depression (with anhedonia).

Results: In both samples, individuals who experienced childhood physical abuse were considerably more likely to report lifetime anhedonia. However, in those with 1 or more copies of the minor allele of rs1049353, this pathogenic effect of childhood physical abuse was attenuated. Thus, in participants reporting childhood physical abuse, although 57.1% of those homozygous for the major allele reported anhedonia, only 28.6% of those who were carriers of the minor allele reported it (P=.01). The rs1049353 polymorphism also buffered the effects of childhood physical abuse on major depressive disorder; however, this influence was largely attributable to anhedonic depression. These effects were also noted in an independent sample, in which minor allele carriers were at decreased risk for anhedonia even when exposed to physical abuse.

Conclusions: Consistent with preclinical findings, a synonymous CNR1 polymorphism, rs1049353, is linked to the effects of stress attributable to childhood physical abuse on anhedonia and anhedonic depression. This polymorphism reportedly resides in the neighborhood of an exon splice enhancer; hence, future studies should carefully examine its effect on expression and conformational variation in CNR1, particularly in relation to stress adaptation.

Context: Prior research suggests that drug abuse (DA) is strongly influenced by both genetic and familial environmental factors. No large-scale adoption study has previously attempted to verify and integrate these findings.

Objective: To determine how genetic and environmental factors contribute to the risk for DA.

Design: Follow-up in 9 public databases (1961-2009) of adopted children and their biological and adoptive relatives.

Setting: Sweden.

Participants: The study included 18 115 adopted children born between 1950 and 1993; 78,079 biological parents and siblings; and 51,208 adoptive parents and siblings.

Main outcome measures: Drug abuse recorded in medical, legal, or pharmacy registry records.

Results: Risk for DA was significantly elevated in the adopted offspring of biological parents with DA (odds ratio, 2.09; 95% CI, 1.66-2.62), in biological full and half siblings of adopted children with DA (odds ratio, 1.84; 95% CI, 1.28-2.64; and odds ratio, 1.41; 95% CI, 1.19-1.67, respectively), and in adoptive siblings of adopted children with DA (odds ratio, 1.95; 95% CI, 1.43-2.65). A genetic risk index (including biological parental or sibling history of DA, criminal activity, and psychiatric or alcohol problems) and an environmental risk index (including adoptive parental history of divorce, death, criminal activity, and alcohol problems, as well as an adoptive sibling history of DA and psychiatric or alcohol problems) both strongly predicted the risk for DA. Including both indices along with sex and age at adoption in a predictive model revealed a significant positive interaction between the genetic and environmental risk indices.

Conclusions: Drug abuse is an etiologically complex syndrome strongly influenced by a diverse set of genetic risk factors reflecting a specific liability to DA, by a vulnerability to other externalizing disorders, and by a range of environmental factors reflecting marital instability, as well as psychopathology and criminal behavior in the adoptive home. Adverse environmental effects on DA are more pathogenic in individuals with high levels of genetic risk. These results should be interpreted in the context of limitations of the diagnosis of DA from registries.

Context: Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to pregnant women, but knowledge about their unintended effects on child health is scarce.

Objective: To examine the effects of maternal SSRI use during pregnancy on fetal growth and birth outcomes.

Design: The study was embedded in the Generation R Study, a prospective population-based study from fetal life onward.

Participants: Seven thousand six hundred ninety-six pregnant women were included. Selective serotonin reuptake inhibitor use was assessed by questionnaires in each trimester and verified by pharmacy records. Using depressive symptom scores from the Brief Symptom Inventory, 7027 pregnant mothers (91.3%) had no or low depressive symptoms, 570 pregnant mothers (7.4%) had clinically relevant depressive symptoms and used no SSRIs, and 99 pregnant mothers (1.3%) used SSRIs.

Main outcome measures: Fetal ultrasonography was performed in each trimester. We determined fetal body and head growth with repeated assessments of body and head size. The birth outcomes studied were preterm birth, small for gestational age, and low birth weight.

Results: Fetuses from mothers with prenatal depressive symptoms showed reduced body growth (β=-4.4 g/wk; 95% CI: -6.3 to -2.4; P<.001) and head growth (β=-0.08 mm/wk; 95% CI: -0.14 to -0.03; P=.003). Mothers using SSRIs during pregnancy had fewer depressive symptoms than mothers in the clinical symptom range. Prenatal SSRI use was not associated with reduced body growth but was associated with reduced fetal head growth (β=-0.18 mm/wk; 95% CI: -0.32 to -0.07; P=.003). The SSRI-exposed children were at higher risk for preterm birth (odds ratio=2.14; 95% CI: 1.08 to 4.25; P=.03).

Conclusions: Untreated maternal depression was associated with slower rates of fetal body and head growth. Pregnant mothers treated with SSRIs had fewer depressive symptoms and their fetuses had no delay in body growth but had delayed head growth and were at increased risk for preterm birth. Further research on the implications of these findings is needed.

Context: Disruption of frontal-subcortical and limbic networks is hypothesized to have a key role in late-life depression (LLD) and can be examined using magnetic resonance imaging (MRI) techniques. Gray matter can be examined using T1-weighted MRI, white matter using T2-weighted MRI and diffusion tensor imaging, and functional connectivity in resting-state networks using functional MRI. Although independent MRI studies have supported gray and white matter abnormalities in frontosubcortical and limbic networks and increased functional connectivity in the default-mode network in depression, no study has concurrently examined gray matter, white matter, and functional connectivity.

Objective: To examine whether results of different MRI techniques are complementary, multimodal MRI was used to compare gray matter, white matter, and resting-state networks between LLD and control groups.

Design: Cross-sectional, case-control, multimodal MRI analysis.

Setting: University research department.

Participants: Thirty-six recovered participants with LLD (mean age, 71.8 years) and 25 control participants (mean age, 71.8 years).

Main outcome measures: Gray matter was examined across the whole brain using voxel-based morphometry. Subcortical gray matter structures were also automatically segmented, and volumetric and shape analyses were performed. For white matter analysis, fractional anisotropy, axial diffusivity, and radial diffusivity values were examined using tract-based spatial statistics. For resting-state network analysis, correlation coefficients were compared using independent components analysis followed by dual regression.

Results: White matter integrity was widely reduced in LLD, without significant group differences in gray matter volumes or functional connectivity.

Conclusions: The present work strongly supports the hypothesis that white matter abnormalities in frontal-subcortical and limbic networks play a key role in LLD even in the absence of changes in resting functional connectivity and gray matter. Factors that could contribute to the lack of significant differences in gray matter and functional connectivity measures, including current symptom severity, medication status, and age of participants with LLD, are discussed.

Context: Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited.

Objective: To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth.

Design: Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled.

Setting: Swedish national health registers.

Participants: All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n = 169), (2) other antipsychotics (n = 338), or (3) no antipsychotics (n = 357,696).

Main outcome measures: Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference.

Results: Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]).

Conclusions: Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.