Psychiatry News

Elevated Prefrontal Cortex {gamma}-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  Postmortem studies have found evidence of -aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness.

Objective  To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls.

Design  Case-control study.

Setting  Inpatient psychiatric research unit and associated outpatient clinic.

Participants  Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking.

Methods  Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects.

Main Outcome Measures  The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy.

Results  In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found.

Conclusions  To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.

Categorie: Psychiatry News

A Population-Based Study of Shared Genetic Variation Between Premorbid IQ and Psychosis Among Male Twin Pairs and Sibling Pairs From Sweden [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  The strong association between lower IQ and risk for psychosis has led to the suggestion that the search for genes influencing cognition may provide a useful strategy for examining the genetic origins of psychosis. However, research in this area has generally used designs in which twin pairs are selected by case status and with assessment of IQ after the onset of psychosis rather than longitudinal population-based samples.

Objective  To examine the relationship and shared genetic origin between premorbid IQ and psychotic disorders in a longitudinal population-based cohort.

Design  Genetically informative longitudinal study.

Setting  Population-based cohort in Sweden.

Participants  Individuals were identified from the population-based Swedish Multi-Generation Register and consisted of male sibling (n = 369 960), monozygotic twin (n = 1986), and dizygotic twin (n = 2253) pairs born between January 1951 and December 1976. Their IQs were measured during compulsory military conscription.

Main Outcome Measure  Individuals having a subsequent diagnosis of psychosis were identified via the Swedish National Hospital Discharge Register.

Results  Heritability estimates for IQ and psychosis were similar to previous estimates, approximately 69% and 56%, respectively. However, the phenotypic correlation between IQ and psychosis was only –0.11, of which 91% was due to shared genetic influences. The proportion of genetic variance for psychosis shared with that for IQ was approximately 7%.

Conclusions  Using IQ as a phenotype to identify genes that have an important role in the genetic origin of schizophrenia is unlikely to be a successful strategy. The low correlation seen in this study between premorbid IQ and psychosis vs the higher correlations reported in the literature with postmorbid IQ suggests the correlation between these phenotypes has more to do with the influence that the onset of psychosis has on cognitive functioning than with shared genetic origin.

Categorie: Psychiatry News

Self-reported Attenuated Psychotic Symptoms as Forerunners of Severe Mental Disorders Later in Life [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  It has been suggested that attenuated psychotic symptoms (APSs) reported by people who do not have psychotic disorders signal risk for later severe mental illness.

Objective  To investigate this suggestion using follow-up assessments of hospitalization for clinical diagnoses of nonaffective psychotic and other psychiatric disorders.

Design  Longitudinal cohort study of self-reported APSs with outcome assessment of severe mental illness obtained through linkage with a national hospitalization case registry.

Setting  Israel.

Participants  A stratified full probability sample of 4914 persons aged 25 to 34 years who were screened for psychopathology in the 1980s.

Main Outcome Measure  Subsequent psychiatric hospitalization was ascertained using the psychiatric hospitalization registry, with a mean follow-up of 24 years.

Results  After removing subjects with diagnosable psychotic disorders at baseline, 57.2% of the remaining sample reported at least 1 weak (infrequent) APS and 14.3% reported at least 1 strong (frequent) APS in the year preceding the assessment. Self-reported APSs predicted risk of later hospitalization for nonaffective psychotic disorders, mostly during the 5 years after baseline (adjusted odds ratio = 4.31; 95% CI, 2.21-8.41; positive predictive value = 1.27%; population attributable risk fraction = 33%). Also, APSs increased the risk of later hospitalization for other psychiatric disorders, albeit to a lesser extent (adjusted odds ratio = 2.21; 95% CI, 1.02-4.82).

Conclusions  Self-reported APSs signal risk for later nonaffective psychotic disorders but are not clinically useful as predictors. The difference between these population-based data and the high-risk literature in terms of the positive predictive value (1% vs 10%, respectively) and the time window of transition (5 years vs 12 months, respectively) can be attributed to the selective enrichment strategies that produce high-risk samples.

Categorie: Psychiatry News

Polypharmacy With Antipsychotics, Antidepressants, or Benzodiazepines and Mortality in Schizophrenia [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  Polypharmacy is widely used in the treatment of schizophrenia, although it is believed to have major adverse effects on the well-being of patients.

Objective  To investigate if the use of benzodiazepines, antidepressants, or multiple concomitant antipsychotics is associated with increased mortality among patients with schizophrenia.

Design  Registry-based case linkage study.

Setting  Academic research.

Patients  We linked national databases of mortality and medication prescriptions among a complete nationwide cohort of 2588 patients hospitalized in Finland for the first time with a diagnosis of schizophrenia between January 1, 2000, and December 31, 2007.

Main Outcome Measures  Hazard ratios (HRs) were computed for all-cause mortality during the use of antipsychotics, antidepressants, or benzodiazepines in outpatient care, adjusting for the effects of sociodemographic and clinical variables, geographic location, and current and past pharmacological treatments.

Results  Compared with antipsychotic monotherapy, concomitant use of 2 or more antipsychotics was not associated with increased mortality (HR, 0.86; 95% CI, 0.51-1.44). Similarly, antidepressant use was not associated with a higher risk for mortality (HR, 0.57; 95% CI, 0.28-1.16) and was associated with markedly decreased suicide deaths (HR, 0.15; 95% CI, 0.03-0.77). However, benzodiazepine use was associated with a substantial increase in mortality (HR, 1.91; 95% CI, 1.13-3.22), and this was attributable to suicidal deaths (HR, 3.83; 95% CI, 1.45-10.12) and to nonsuicidal deaths (HR, 1.60; 95% CI, 0.86-2.97). In total, 826 of 904 patients (91.4%) who used benzodiazepines had purchased prescriptions that contained more than 28 defined daily doses, violating treatment guidelines.

Conclusions  Benzodiazepine use was associated with a marked increase in mortality among patients with schizophrenia, whereas the use of an antidepressant or several concomitant antipsychotics was not. Antidepressant use was associated with decreased suicide deaths. The literature indicates that long-term use of benzodiazepines among patients with schizophrenia is more prevalent in other countries (eg, the United States) compared with Finland, which suggests that benzodiazepine use may contribute to mortality among this patient population worldwide.

Categorie: Psychiatry News

Lifetime History of Depression and Anxiety Disorders as a Predictor of Quality of Life in Midlife Women in the Absence of Current Illness Episodes [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  It is unknown whether a history of depression, anxiety disorders, or comorbid depression and anxiety affects subsequent health-related quality of life (HRQOL) during midlife in women when vasomotor symptoms (VMS) and sleep disturbance commonly disrupt QOL.

Objectives  To evaluate whether previous affective illness is associated with low HRQOL during midlife in the absence of current illness episodes and whether low HRQOL is explained by VMS or sleep disruption.

Design  Longitudinal, community-based study.

Setting  Western Pennsylvania.

Participants  A total of 425 midlife women in the Study of Women's Health Across the Nation who completed the Structured Clinical Interview for DSM-IV (SCID) and the 36-Item Short Form Health Survey (SF-36) annually during 6 years of follow-up.

Main Outcome Measures  Scores on the SF-36 scales of social functioning (SF), role-emotional (RE), role-physical (RP), body pain (BP), and vitality.

Results  Ninety-seven women (22.8%) had comorbid affective illness histories, 162 (38.1%) had previous depression only, and 21 (4.9%) had previous anxiety only. Those with comorbid illness histories and depression alone were more likely to report low HRQOL on the SF, RE, RP, and BP domains (odds ratio [OR] = 2.31-3.54 and 1.59-2.28, respectively) than were women with neither disorder. After adjustment for VMS and sleep disturbance, the comorbid group continued to have low HRQOL on these domains (OR = 2.13-3.07), whereas the association was significant on SF and BP only for the depression-alone group (OR = 2.08 and 1.95, respectively). Compared with women with neither disorder, the anxiety-only group had low HRQOL on the RP domain (OR = 2.60). Sleep disturbance, but not VMS, was independently associated with low HRQOL on all the domains except RE.

Conclusions  A history of both depression and anxiety has the most robust negative effect on HRQOL in women during midlife, an association not explained by VMS or sleep disturbance. For the depression-alone group, sleep disturbance may partially explain the negative impact of previous affective illness on HRQOL. Sleep disturbance remains an independent correlate of low HRQOL.

Categorie: Psychiatry News

Midlife vs Late-Life Depressive Symptoms and Risk of Dementia: Differential Effects for Alzheimer Disease and Vascular Dementia [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia.

Objective  To clarify the timing and nature of the association between depression and dementia.

Design  We examined depressive symptoms assessed in midlife (1964-1973) and late life (1994-2000) and the risks of dementia, Alzheimer disease (AD), and vascular dementia (VaD) (2003-2009) in a retrospective cohort study. Depressive symptoms were categorized as none, midlife only, late life only, or both. Cox proportional hazards models (age as timescale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD, or VaD.

Setting  Kaiser Permanente Medical Care Program of Northern California.

Participants  Thirteen thousand five hundred thirty-five long-term Kaiser Permanente members.

Main Outcome Measure  Any medical record diagnosis of dementia or neurology clinic diagnosis of AD or VaD.

Results  Subjects had a mean (SD) age of 81.1 (4.5) years in 2003, 57.9% were women, and 24.2% were nonwhite. Depressive symptoms were present in 14.1% of subjects in midlife only, 9.2% in late life only, and 4.2% in both. During 6 years of follow-up, 22.5% were diagnosed with dementia (5.5% with AD and 2.3% with VaD). The adjusted hazard of dementia was increased by approximately 20% for midlife depressive symptoms only (hazard ratio, 1.19 [95% CI, 1.07-1.32]), 70% for late-life symptoms only (1.72 [1.54-1.92]), and 80% for both (1.77 [1.52-2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a 2-fold increase in AD risk (hazard ratio, 2.06 [95% CI, 1.67-2.55]), whereas subjects with midlife and late-life symptoms had more than a 3-fold increase in VaD risk (3.51 [2.44-5.05]).

Conclusions  Depressive symptoms in midlife or in late life are associated with an increased risk of developing dementia. Depression that begins in late life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.

Categorie: Psychiatry News

Effect of Purpose in Life on the Relation Between Alzheimer Disease Pathologic Changes on Cognitive Function in Advanced Age [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  Purpose in life is associated with a substantially reduced risk of Alzheimer disease (AD), but the neurobiologic basis of this protective effect remains unknown.

Objective  To test the hypothesis that purpose in life reduces the deleterious effects of AD pathologic changes on cognition in advanced age.

Design  A longitudinal, epidemiologic, clinicopathologic study of aging was conducted that included detailed annual clinical evaluations and brain autopsy.

Participants  Two hundred forty-six community-based older persons from the Rush Memory and Aging Project participated.

Main Outcome Measures  Purpose in life was assessed via structured interview, and cognitive function was evaluated annually and proximate to death. On postmortem examination, 3 indexes of AD pathologic features were quantified: global AD pathologic changes, amyloid, and tangles. The associations of disease pathologic changes and purpose in life with cognition were examined using linear regression and mixed models.

Results  Purpose in life modified the association between the global measure of AD pathologic changes and cognition (mean [SE] parameter estimate, 0.532 [0.211]; P = .01), such that participants who reported higher levels of purpose in life exhibited better cognitive function despite the burden of the disease. Purpose in life also reduced the association of tangles with cognition (parameter estimate, 0.042 [0.019]; P = .03), and the protective effect of purpose in life persisted even after controlling for several potentially confounding variables. Furthermore, in analyses examining whether purpose in life modified the association between AD pathologic effects and the rate of cognitive decline, we found that higher levels of purpose in life reduced the effect of AD pathologic changes on cognitive decline (parameter estimate, 0.085 [0.039]; P = .03).

Conclusion  Higher levels of purpose in life reduce the deleterious effects of AD pathologic changes on cognition in advanced age.

Categorie: Psychiatry News

Cost-effectiveness of a Multicondition Collaborative Care Intervention: A Randomized Controlled Trial [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  Patients with depression and poorly controlled diabetes mellitus, coronary heart disease (CHD), or both have higher medical complication rates and higher health care costs, suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life.

Objective  To evaluate the cost-effectiveness of a multicondition collaborative treatment program (TEAMcare) compared with usual primary care (UC) in outpatients with depression and poorly controlled diabetes or CHD.

Design  Randomized controlled trial of a systematic care management program aimed at improving depression scores and hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) levels.

Setting  Fourteen primary care clinics of an integrated health care system.

Patients  Population-based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD.

Intervention  Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors.

Main Outcome Measures  Blinded assessments evaluated depressive symptoms, SBP, and HbA1c at baseline and at 6, 12, 18, and 24 months. Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months. Health plan accounting records were used to assess medical service costs. Quality-adjusted life-years (QALYs) were assessed using a previously developed regression model based on intervention vs UC differences in HbA1c, LDL-C, and SBP levels over 24 months.

Results  Over 24 months, compared with UC controls, intervention patients had a mean of 114 (95% CI, 79 to 149) additional depression-free days and an estimated 0.335 (95% CI, –0.18 to 0.85) additional QALYs. Intervention patients also had lower mean outpatient health costs of $594 per patient (95% CI, –$3241 to $2053) relative to UC patients.

Conclusions  For adults with depression and poorly controlled diabetes, CHD, or both, a systematic intervention program aimed at improving depression scores and HbA1c, SBP, and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs.

Trial Registration  clinicaltrials.gov Identifier: NCT00468676

Categorie: Psychiatry News

A Randomized Controlled Trial of Risperidone, Lithium, or Divalproex Sodium for Initial Treatment of Bipolar I Disorder, Manic or Mixed Phase, in Children and Adolescents [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents.

Objective  To investigate which medication to administer first to antimanic medication–naive subjects.

Design, Setting, and Participants  The Treatment of Early Age Mania (TEAM) study recruited 6- to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patient-choice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments.

Interventions  Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg).

Main Outcome Measures  Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement–Mania and the Modified Side Effects Form for Children and Adolescents.

Results  There were 279 antimanic medication–naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics: 100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; 21 = 16.9, P < .001) and vs divalproex sodium (68.5% vs 24.0%; 21 = 28.3, P < .001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (21 = 6.4, P = .011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F1,212 = 45.5, P < .001; F1,212 = 39.1, P < .001; and F1,213 = 191.4, P < .001, respectively) and vs divalproex sodium (F1,212 = 34.7, P < .001; F1,212 = 45.3, P < .001; and F1,213 = 209.4, P < .001, respectively). The thyrotropin level increased in subjects taking lithium (t62 = 11.3, P < .001).

Conclusions  Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects.

Trial Registration  clinicaltrials.gov Identifier: NCT00057681

Categorie: Psychiatry News

Association of Leptin With Food Cue-Induced Activation in Human Reward Pathways [Original Article]

Archives of General Psychiatry - Lun, 05/07/2012 - 20:50

Context  Overlapping neurobiological pathways between obesity and addiction disorders are currently in discussion. Whereas the hypothalamic regulation of energy homeostasis by endocrine feedback signals has been widely investigated, its interplay with mesolimbic reward-associated pathways represents a rich field of future research.

Objective  To assess changes in regional brain activation in response to food-related cues in association with body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and the plasma concentration of the appetite-regulating peptide leptin.

Design  Case-control study.

Setting  Academic addiction and brain imaging center, Central Institute of Mental Health, Mannheim, Germany.

Participants  Twenty-one obese subjects (BMI >30) and 23 age- and sex-matched nonobese control subjects (BMI 18.5-24.0) recruited by advertisements.

Main Outcome Measures  Regional brain activation (blood oxygen level–dependent response) in response to visual cue presentation and association of the brain activation with BMI and plasma leptin concentration.

Results  Significant positive relationships were observed for food cue–induced brain activations in the ventral striatum in association with the plasma concentration of leptin (r = 0.27; P = .04) and with BMI (r = 0.47; P = .001).

Conclusions  Data suggest a physiological role of satiety factors in modulating the responsivity of mesolimbic circuits to food cues. Moreover, an altered homeostatic feedback regulation of reward pathways might explain addictionlike behavior and the inability of obese patients to adapt food intake to physiological needs.

Categorie: Psychiatry News

Reduced Dopamine Receptor Sensitivity as an Intermediate Phenotype in Alcohol Dependence and the Role of the COMT Val158Met and DRD2 Taq1A Genotypes [Original Article]

Archives of General Psychiatry - Lun, 04/02/2012 - 20:50

Context  Alcohol dependence is a common neuropsychiatric disorder with high heritability. However, genetic association studies on alcohol dependence are often troubled by nonreplication. The use of intermediate phenotypes may help make clear the mode of action of various candidate genes and improve the reproducibility of genetic association studies.

Objective  To test central dopamine receptor sensitivity as an intermediate phenotype for alcohol dependence, specifically evaluating the hypothesis that the dopaminergic genes COMT Val158Met and DRD2 Taq1A affect dopamine receptor sensitivity.

Design  Case-control pharmacogenetic challenge study.

Setting  Patients with alcohol dependence admitted for detoxification were compared with healthy control subjects matched for age and level of education.

Participants  Patients (n = 110) were a consecutive sample, whereas controls (n = 99) were recruited through advertisements in regional newspapers.

Intervention  A dopamine challenge test was subcutaneously administered using the dopamine agonist apomorphine hydrochloride (0.005 mg/kg).

Main Outcome Measures  Outcome measures were plasma growth hormone levels and results of a continuous performance task.

Results  Central dopamine receptor sensitivity is reduced in alcohol dependence, and this is modulated by dopaminergic genes. Specifically, DRD2 Taq1A genotype affected dopamine receptor sensitivity as measured by plasma growth hormone levels, and COMT Val158Met genotype affected dopamine receptor sensitivity as measured by performance on a continuous performance task. In a logistic regression analysis, reduced dopamine receptor sensitivity on both measures predicted alcohol dependence, without an additive effect of the COMT Val158Met and DRD2 Taq1A genotypes.

Conclusions  COMT Val158Met and DRD2 Taq1A may affect the intermediate phenotype of central dopamine receptor sensitivity. COMT Val158Met and DRD2 Taq1A may confer their risk of alcohol dependence through reduced dopamine receptor sensitivity in the prefrontal cortex and hindbrain, respectively.

Categorie: Psychiatry News

Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder [Original Article]

Archives of General Psychiatry - Lun, 04/02/2012 - 20:50

Context  The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders.

Objectives  To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences.

Design  Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling.

Setting  The Netherlands Twin Register and University Medical Center Utrecht.

Participants  A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13 MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44 MZ and 39 DZ).

Main Outcome Measures  Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness.

Results  Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume.

Conclusions  Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots.

Categorie: Psychiatry News

Dorsolateral Prefrontal Cortex Activation During Emotional Anticipation and Neuropsychological Performance in Posttraumatic Stress Disorder [Original Article]

Archives of General Psychiatry - Lun, 04/02/2012 - 20:50

Context  Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates.

Objective  To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation.

Design  Case-control, cross-sectional study.

Setting  General community and hospital and community psychiatric clinics.

Participants  Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women.

Main Outcome Measures  We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance.

Results  Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed.

Conclusions  During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.

Categorie: Psychiatry News
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