Latest Articles Include:
- This Month in Archives of General Psychiatry
- Arch Gen Psychiatry 66(4):347 (2009)
- Hagia Sophia (Divine Wisdom)
- Arch Gen Psychiatry 66(4):353-354 (2009)
- Neurobiology of Wisdom: A Literature Overview
- Arch Gen Psychiatry 66(4):355-365 (2009)
Context Wisdom is a unique psychological trait noted since antiquity, long discussed in humanities disciplines, recently operationalized by psychology and sociology researchers, but largely unexamined in psychiatry or biology. Objective To discuss recent neurobiological studies related to subcomponents of wisdom identified from several published definitions/descriptions of wisdom by clinical investigators in the field, ie, prosocial attitudes/behaviors, social decision making/pragmatic knowledge of life, emotional homeostasis, reflection/self-understanding, value relativism/tolerance, and acknowledgment of and dealing effectively with uncertainty. Data Sources Literature focusing primarily on neuroimaging/brain localization and secondarily on neurotransmitters, including their genetic determinants. Study Selection Studies involving functional neuroimaging or neurotransmitter functioning, examining human (rather than animal) subjects, and identified via a PubMed ! search using keywords from any of the 6 proposed subcomponents of wisdom were included. Data Extraction Studies were reviewed by both of us, and data considered to be potentially relevant to the neurobiology of wisdom were extracted. Data Synthesis Functional neuroimaging permits exploration of neural correlates of complex psychological attributes such as those proposed to comprise wisdom. The prefrontal cortex figures prominently in several wisdom subcomponents (eg, emotional regulation, decision making, value relativism), primarily via top-down regulation of limbic and striatal regions. The lateral prefrontal cortex facilitates calculated, reason-based decision making, whereas the medial prefrontal cortex is implicated in emotional valence and prosocial attitudes/behaviors. Reward neurocircuitry (ventral striatum, nucleus accumbens) also appears important for promoting prosocial attitudes/behaviors. Monoaminergic activity (especially dopaminergic and serotonergic), in! fluenced by several genetic polymorphisms, is critical to cert! ain subcomponents of wisdom such as emotional regulation (including impulse control), decision making, and prosocial behaviors. Conclusions We have proposed a speculative model of the neurobiology of wisdom involving frontostriatal and frontolimbic circuits and monoaminergic pathways. Wisdom may involve optimal balance between functions of phylogenetically more primitive brain regions (limbic system) and newer ones (prefrontal cortex). Limitations of the putative model are stressed. It is hoped that this review will stimulate further research in characterization, assessment, neurobiology, and interventions related to wisdom. - Progressive Gray Matter Reduction of the Superior Temporal Gyrus During Transition to Psychosis
- Arch Gen Psychiatry 66(4):366-376 (2009)
Context Longitudinal magnetic resonance imaging studies have shown progressive gray matter reduction in the superior temporal gyrus during the earliest phases of schizophrenia. It is unknown whether these progressive processes predate the onset of psychosis. Objective To examine gray matter reduction of the superior temporal gyrus over time in individuals at risk for psychosis and in patients with first-episode psychosis. Design Cross-sectional and longitudinal comparisons. Setting Personal Assessment and Crisis Evaluation Clinic and Early Psychosis Preventions and Intervention Centre. Participants Thirty-five ultrahigh-risk individuals (of whom 12 later developed psychosis [UHRP] and 23 did not [UHRNP]), 23 patients with first-episode psychosis (FEP), and 22 control subjects recruited from the community. Main Outcome Measures Volumes of superior temporal subregions (planum polare, Heschl gyrus, planum temporale, and rostral and caudal regions) were measured! at baseline and follow-up (mean, 1.8 years) and were compared across groups. Results In cross-sectional comparisons, only the FEP group had significantly smaller planum temporale and caudal superior temporal gyrus than other groups at baseline, whereas male UHRP subjects also had a smaller planum temporale than controls at follow-up. In longitudinal comparison, UHRP and FEP patients showed significant gray matter reduction (approximately 2%-6% per year) in the planum polare, planum temporale, and caudal region compared with controls and/or UHRNP subjects. The FEP patients also exhibited progressive gray matter loss in the left Heschl gyrus (3.0% per year) and rostral region (3.8% per year), which were correlated with the severity of delusions at follow-up. Conclusions A progressive process in the superior temporal gyrus precedes the first expression of florid psychosis. These findings have important implications for underlying neurobiologic features of emerging psychot! ic disorders and emphasize the importance of early interventio! n during or before the first episode of psychosis. - Organization of Cognitive Control Within the Lateral Prefrontal Cortex in Schizophrenia
- Arch Gen Psychiatry 66(4):377-386 (2009)
Context Cognitive control is highly affected in schizophrenia, but its overall functional architecture remains poorly understood. A recent study demonstrated that, in healthy subjects, cognitive control is functionally organized within the lateral prefrontal cortex (LPFC) as a cascade of representations ranging from premotor to anterior LPFC regions according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur. Objective To determine the functional hierarchical organization of cognitive control within the LPFC in patients with schizophrenia. Design Case-control study. Setting Hospital-based research units. Participants Fifteen schizophrenic patients and 14 controls. Main Outcome Measures Behavioral performance and regional brain activity as measured by functional magnetic resonance imaging during a task, varying the amount of information conveyed by episodic and contextual signals. Results In patients and healthy con! trols, activity in caudal LPFC regions varied as episodic and contextual signals, whereas rostral LPFC regions only exhibited an episodic effect. However, patients made more errors than controls when information conveyed by contextual and episodic signals increased. These impairments were related to hypoactivation in caudal LPFC regions and hyperactivation in rostral LPFC regions, respectively. Activation in caudal LPFC regions negatively correlated with the disorganization syndrome score of patients. Conclusions In schizophrenic patients, the architecture of cognitive control follows the cascading organization from rostral LPFC regions to caudal LPFC and premotor regions depending on the temporal framing of action and events. We found, however, that immediate contextual signals insufficiently bias the caudal LPFC activity required to select the appropriate behavioral representation. This specific deficit could thus alter the internal consistency of schizophrenic patients! ' behavior. To compensate for this weakening of contextual inf! luence, schizophrenic patients may inefficiently use temporal episodic information through higher activation in rostral LPFC regions. - Treatment of Depression After Coronary Artery Bypass Surgery: A Randomized Controlled Trial
- Arch Gen Psychiatry 66(4):387-396 (2009)
Context There has been little research on the treatment of depression after coronary artery bypass surgery. Objective To test the efficacy of 2 nonpharmacological interventions for depression after coronary artery bypass surgery compared with usual care. Design A 12-week, randomized, single-blind clinical trial with outcome evaluations at 3, 6, and 9 months. Setting Outpatient research clinic at Washington University School of Medicine, St Louis, Missouri. Patients One hundred twenty-three patients who met the DSM-IV criteria for major or minor depression within 1 year after surgery. Intervention Twelve weeks of cognitive behavior therapy or supportive stress management. Approximately half of the participants were taking nonstudy antidepressant medications. Main Outcome Measure Remission of depression, defined as a score of less than 7 on the 17-item Hamilton Rating Scale for Depression. Results Remission of depression occurred by 3 months in a higher pr! oportion of patients in the cognitive behavior therapy (71%) and supportive stress-management (57%) arms than in the usual care group (33%) ({chi}22 = 12.22, P = .002). Covariate-adjusted Hamilton scores were lower in the cognitive behavior therapy (mean [standard error], 5.5 [1.0]) and the supportive stress-management (7.8 [1.0]) arms than in the usual care arm (10.7 [1.0]) at 3 months. The differences narrowed at 6 months, but the remission rates differed again at 9 months (73%, 57%, and 35%, respectively; {chi}22 = 12.02, P = .003). Cognitive behavior therapy was superior to usual care at most points on secondary measures of depression, anxiety, hopelessness, stress, and quality of life. Supportive stress management was superior to usual care only on some of the measures. Conclusions Both cognitive behavior therapy and supportive stress management are efficacious for treating depression after coronary artery bypass surgery, relative to usual care. Cognitive behavior th! erapy had greater and more durable effects than supportive str! ess management on depression and several secondary psychological outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00042198 - Childhood Predictors of Completed and Severe Suicide Attempts: Findings From the Finnish 1981 Birth Cohort Study
- Arch Gen Psychiatry 66(4):398-406 (2009)
Context To our knowledge, no prospective, population-based study in existence examines predictive associations between early or middle childhood psychopathologic disorders and later completed suicides. Objective To study predictive associations between childhood psychopathologic disorders at the age of 8 years and later completed suicides and severe suicide attempts. Design Birth cohort study of individuals 8 to 24 years old. Setting Finland. Participants The sample includes 5302 Finnish people born in 1981 who were examined at the age of 8 years to gather information about psychopathologic conditions, school performance, and family demographics from parents, teachers, and children. Main Outcome Measures National register-based lifetime information about completed suicides and suicide attempts that prompted hospital admission. Results Of all 24 deaths among males between 8 and 24 years of age, 13 were suicides, whereas of 16 deaths among females, only 2 we! re suicides. Fifty-four males and females (1%) had either completed suicide or made a serious suicide attempt, defined as a suicide attempt that prompted hospital admission. Of 27 males with completed or serious suicide attempts, 78% screened positive on parent or teacher Rutter scales at the age of 8 years, whereas of 27 females only 11% screened positive. Among males, completed or serious suicide attempt outcome was predicted at the age of 8 years by living in a nonintact family; psychological problems as reported by the primary teacher; or conduct, hyperkinetic, and emotional problems. However, self-reports of depressive symptoms at the age of 8 years did not predict suicide outcome. No predictive associations between the study variables measured at the age of 8 years and suicide outcome were found among females. Male suicide outcome was predicted most strongly by comorbid conduct and internalizing problems. Conclusions Most males who completed suicide and/or made seri! ous suicide attempts in adolescence or early adulthood had psy! chiatric problems by the age of 8 years, indicating a trajectory that persists throughout their lives. However, female severe suicidality is not predicted by psychopathologic disorders at the age of 8 years. The results give additional support to the importance of early detection and treatment of psychiatric problems in males. - A Haplotype Containing Quantitative Trait Loci for SLC1A1 Gene Expression and Its Association With Obsessive-Compulsive Disorder
- Arch Gen Psychiatry 66(4):408-416 (2009)
Context Recent evidence from linkage analyses and follow-up candidate gene studies supports the involvement of SLC1A1, which encodes the neuronal glutamate transporter, in the development of obsessive-compulsive disorder (OCD). Objectives To determine the role of genetic variation of SLC1A1 in OCD in a large case-control study and to better understand how SLC1A1 variation affects functionality. Design A case-control study. Setting Publicly accessible SLC1A1 expression and genotype data. Patients Three hundred twenty-five OCD probands and 662 ethnically and sex-matched controls. Interventions Probands were assessed with the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive Compulsive Scale, and the Saving Inventory-Revised. Six single-nucleotide polymorphisms (SNPs) were genotyped. Multiple testing corrections for single-marker and haplotype analyses were performed by permutation. Results Gene expression of SLC1A1 is heritable in lymphoblas! toid cell lines. We identified 3 SNPs in or near SLC1A1 that correlated with gene expression levels, 1 of which had previously been associated with OCD. Two of these SNPs also predicted expression levels in human brain tissue, and 1 SNP was further functional in reporter gene studies. Two haplotypes at 3 SNPs, rs3087879, rs301430, and rs7858819, were significantly associated with OCD after multiple-testing correction and contained 2 SNPs associated with expression levels. In addition, another SNP correlating with SLC1A1 gene expression, rs3933331, was associated with an OCD-hoarding subphenotype as assessed by 2 independent, validated scales. Conclusions Our case-control data corroborate previous smaller family-based studies that indicated that SLC1A1 is a susceptibility locus for OCD. The expression and genotype database-mining approach we used provides a potentially useful complementary approach to strengthen future candidate gene studies in neuropsychiatric and other d! isorders. - Tracing the Flow of Knowledge: Geographic Variability in the Diffusion of Prazosin Use for the Treatment of Posttraumatic Stress Disorder Nationally in the Department of Veterans Affairs
- Arch Gen Psychiatry 66(4):417-421 (2009)
Context Passive diffusion of new medical innovations is an important mechanism by which knowledge transitions from research to clinical practice. Preliminary evidence has emerged about the effectiveness of the {alpha}1-adrenergic blocker prazosin hydrochloride in the treatment of nightmares and hyperarousal among patients with posttraumatic stress disorder (PTSD). This treatment has been neither widely accepted nor the subject of active dissemination efforts, and its efficacy was discovered in a discrete geographic location. Objectives To evaluate the pace and reach of the passive dissemination of a promising technology within a national health care system. Design Geographic surveillance data study. Setting Academic research. Patients We tracked the use of prazosin in the treatment of patients diagnosed as having PTSD in the Department of Veterans Affairs during fiscal years 2004 (n = 203 414) and 2006 (n = 319 670). Main Outcome Measure The percentage of pa! tients diagnosed as having PTSD who received a prescription for prazosin. Results Whereas 37.6% of patients with PTSD treated within the Veterans Affairs Puget Sound Health Care System, Tacoma, Washington, in 2004 were prescribed prazosin, only 18.2% were treated with prazosin at medical centers up to 499 miles (to convert miles to kilometers, multiply by 1.6) away, 6.7% at centers 500 to 999 miles away, 4.0% at centers 1000 to 2499 miles away, and 1.9% at centers 2500 miles away or farther. Adjusting for patient characteristics, patients with PTSD treated up to 499 miles from Puget Sound were about 49% less likely in 2006 and about 63% less likely in 2004 to be prescribed prazosin than their counterparts treated within Puget Sound, while those who were treated 2500 miles away or farther were about 94% less likely in 2006 and about 97% less likely in 2004 to be treated with prazosin than patients within Puget Sound. Conclusion Passive diffusion of a new treatment can be! rapid in the immediate area in which it is developed, but the! geographic gradient of use seems to be steep and enduring even when cost and organizational barriers are minimal. - Response to Corticotropin-Releasing Hormone Infusion in Cocaine-Dependent Individuals
- Arch Gen Psychiatry 66(4):422-430 (2009)
Context Corticotropin-releasing hormone (CRH), through the hypothalamic pituitary adrenal axis and other brain stress systems, is involved in the emotional dysregulation associated with cocaine dependence. Little is known about the response of cocaine-dependent individuals to CRH administration. Objective The primary objective was to examine the hypothalamic-pituitary-adrenal axis and the subjective and physiologic response to CRH in cocaine-dependent individuals and controls. Design A case-control study. Setting Subjects were admitted to a General Clinical Research Center for testing and abstinence was verified with a urine drug screening. Participants Participants were male controls (n = 23), female controls (n = 24), cocaine-dependent men (n = 28), and cocaine-dependent women (n = 25). Individuals with dependence on other substances (except caffeine or nicotine) or with major depression, posttraumatic stress disorder, bipolar disorder, or psychotic or eatin! g disorders were excluded. Intervention Subjects received 1 {micro}g/kg of CRH intravenously. Main Outcome Measures Primary outcomes included plasma corticotropin levels, cortisol levels, and heart rate and subjective measurements. Results Cocaine-dependent individuals exhibited higher stress (P < .001) and craving for CRH compared with controls. A positive correlation (rs = 0.51; P < .001) between stress and craving was found in cocaine-dependent subjects. Intravenous CRH elevated heart rates in all groups; however, cocaine-dependent women demonstrated a significantly higher heart rate at all time points (P = .05). Women had higher cortisol responses to CRH (P = .03). No effect of cocaine status was observed. The corticotropin response to CRH was independent of sex and cocaine dependence. Cortisol and corticotropin were positively correlated in the controls and cocaine-dependent men, but not in cocaine-dependent women (rs = 0.199; P = .4). Conclusions There is an i! ncreased subjective and heart rate response to CRH and a relat! ionship between stress and craving in cocaine-dependent individuals. The lack of difference in hypothalamic pituitary adrenal axis response between the cocaine-dependent and control groups suggests that the heart rate and subjective responses in the cocaine group may be mediated by sensitization of nonhypothalamic stress-responsive CRH systems. - Association of Nicotine Addiction and Nicotine's Actions With Separate Cingulate Cortex Functional Circuits
- Arch Gen Psychiatry 66(4):431-441 (2009)
Context Understanding the mechanisms underlying nicotine addiction to develop more effective treatment is a public health priority. Research consistently shows that nicotine transiently improves multiple cognitive functions. However, using nicotine replacement to treat nicotine addiction yields generally inconsistent results. Although this dichotomy is well known, the reasons are unclear. Imaging studies showed that nicotine challenges almost always involve the cingulate cortex, suggesting that this locus may be a key region associated with nicotine addiction and its treatment. Objective To identify cingulate functional circuits that are associated with the severity of nicotine addiction and study how nicotine affects them by means of region-specific resting-state functional magnetic resonance imaging. Design Double-blind, placebo-controlled study. Setting Outpatient clinics. Participants Nineteen healthy smokers. Intervention Single-dose (21- or 35-mg) nico! tine patch. Main Outcome Measures Correlation of nicotine addiction severity and cingulate resting-state functional connectivity, and effects of short-term nicotine administration on connectivity strength. Results Clearly separated pathways that correlated with nicotine addiction vs nicotine's action were found. The severity of nicotine addiction was associated with the strength of dorsal anterior cingulate cortex (dACC)-striatal circuits, which were not modified by nicotine patch administration. In contrast, short-term nicotine administration enhanced cingulate-neocortical functional connectivity patterns, which may play a role in nicotine's cognition-enhancing properties. Conclusions Resting-state dACC-striatum functional connectivity may serve as a circuit-level biomarker for nicotine addiction, and the development of new therapeutic agents aiming to enhance the dACC-striatum functional pathways may be effective for nicotine addiction treatment. - Modulation of Mediotemporal and Ventrostriatal Function in Humans by {Delta}9-Tetrahydrocannabinol: A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis
- Arch Gen Psychiatry 66(4):442-451 (2009)
Context Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives To investigate the effects of 2 main psychoactive constituents of C sativa, {Delta}9-tetrahydrocannabinol ({Delta}9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of {Delta}9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting University research center. Participants Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had ! used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results {Delta}9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of {Delta}9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. {Delta}9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, whic! h was directly correlated with concurrently induced psychotic ! symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion The modulation of mediotemporal and ventrostriatal function by {Delta}9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively. - Psychiatry Without Psychotherapy?
- Arch Gen Psychiatry 66(4):452 (2009)
- "Familiality" or Heritability
- Arch Gen Psychiatry 66(4):452-a-453 (2009)
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