Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum.

A common genetic polymorphism that results in increased activity of the dopamine regulating enzyme COMT (the COMT Val(158) allele) has been found to associate with poorer cognitive performance and increased susceptibility to develop psychiatric disorders. It is generally assumed that this increase in COMT activity influences cognitive function and psychiatric disease risk by increasing dopamine turnover in cortical synapses, though this cannot be directly measured in humans. Here we explore a novel transgenic mouse model of increased COMT activity, equivalent to the relative increase in activity observed with the human COMT Val(158) allele. By performing an extensive battery of behavioral tests, we found that COMT overexpressing mice (COMT-OE mice) exhibit cognitive deficits selectively in the domains that are affected by the COMT Val(158) allele, stimulus-response learning and working memory, functionally validating our model of increased COMT activity. Although we detected no changes in the level of markers for dopamine synthesis and dopamine transport, we found that COMT-OE mice display an increase in dopamine release capacity in the striatum. This result suggests that increased COMT activity may not only affect dopamine signaling by enhancing synaptic clearance in the cortex, but may also cause changes in presynaptic dopamine function in the striatum. These changes may underlie the behavioral deficits observed in the mice and might also play a role in the cognitive deficits and increased psychiatric disease risk associated with genetic variation in COMT activity in humans.

Influence of clerkship on attitudes of medical students toward psychiatry across cultures: United States and Qatar.

OBJECTIVE: To assure adequate treatment for patients with mental illness worldwide, medical schools must impart positive attitudes toward psychiatry. The authors examined the effect of culture on changes in attitudes toward psychiatry among medical students receiving the same psychiatry clerkship curriculum in two different countries. METHODS: A group of 74 students from Weill Cornell Medical College-New York and 32 from Weill Cornell Medical College-Qatar completed pre- and post-clerkship questionnaires assessing their attitudes toward psychiatry. RESULTS: On the pretest, the Qatar students had less positive attitudes than the New York students, as evidenced by lower group mean total scores. During the clerkship, the attitudes of students at both schools improved, but more markedly in Qatar, narrowing the group differences. CONCLUSION: A psychiatry clerkship with a U.S.-derived curriculum had a positive effect on medical students' attitudes toward psychiatry in Qatar, suggesting the usefulness of applying such curricula across cultures.

Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning.

Increased activity of D2 receptors (D2Rs) in the striatum has been linked to the pathophysiology of schizophrenia. To determine directly the behavioral and physiological consequences of increased D2R function in the striatum, we generated mice with reversibly increased levels of D2Rs restricted to the striatum. D2 transgenic mice exhibit selective cognitive impairments in working memory tasks and behavioral flexibility without more general cognitive deficits. The deficit in the working memory task persists even after the transgene has been switched off, indicating that it results not from continued overexpression of D2Rs but from excess expression during development. To determine the effects that may mediate the observed cognitive deficits, we analyzed the prefrontal cortex, the brain structure mainly associated with working memory. We found that D2R overexpression in the striatum impacts dopamine levels, rates of dopamine turnover, and activation of D1 receptors in the prefrontal cortex, measures that are critical for working memory.

Experiential anamnesis and group consensus: an innovative method to teach residents to teach.

OBJECTIVE: Using a novel method, residents generated examples and principles of good medical teaching from their experiences of being taught as medical students. This article describes and evaluates this method of teaching preparation, gives the main teaching principles the residents derived, and provides representative examples of their experiences which illustrate each principle. METHODS: In this 2-hour session, postgraduate year two (PGY-2) psychiatric residents shared their most notable experiences of being taught as medical students with their cohort and a faculty facilitator and, from these experiences, articulated principles of medical teaching for their immediate use as psychiatric clerkship teachers. The residents responded to a survey questionnaire to gauge the value of the method. RESULTS: In 2009, 11 PGY-2 residents recollected 18 experiences of peak or poor teaching and derived five major principles of teaching from them in an affectively intense and cognitively engaging group exercise. The survey results indicated that the session caused residents to feel better prepared for medical student teaching. CONCLUSION: This method of peer group processing mobilized residents' memories of being taught and organized them into practical principles of good teaching.

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability.

The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.

Standards for Psychiatry Clerkship Directors.

The authors review the literature relevant to the position of Psychiatry Clerkship Director (PCD) and propose standards regarding the expectations for this position. The standards address qualifications, duties, and competencies in the areas of leadership, administration, education, mentoring, and scholarship, as well as the resources of time, administrative assistance, budget, and compensation required to carry out these duties. This paper has been endorsed by the Council of the Association of Directors of Medical Student Education in Psychiatry (ADMSEP), by the American Psychiatric Association's Committee on Medical Student Education, and by the Executive Committee of the American Association of Chairmen of Departments of Psychiatry.

Attachment and psychopathology in a community sample.

The Structured Clinical Interview for DSM-III-R (SCID-I) and the Adult Attachment Interview (AAI) were administered to 60 women participating in a study (n=226) of mother-child interaction. These women were not referred to the study for psychiatric care. The 60 women interviewed with the AAI were selected from the first 190 women who completed the SCID-I, so that 30 received a diagnosis and 30 did not. Analyses indicated that psychopathology diagnoses were associated significantly with mental representations of attachment classified in the AAI. The non-autonomous groups had increased likelihood of SCID diagnosis, compared to the autonomous group. While 32% of women with autonomous AAI transcripts received SCID diagnoses, 63% of women with Dismissing, 100% of woman with Preoccupied, and 65% of women with Unresolved transcripts received diagnoses. Secondary analyses indicated that Dismissing classifications were associated with Axis I diagnoses and Preoccupied classifications with affective disorders. Of note was that among women with Unresolved classifications, underlying secure attachment was associated with low risk of psychopathology, while underlying anxious attachment was associated with elevated risk of diagnosis. These findings support the premise from attachment theory that early relationships affect patterns of interpersonal expectations and behavior and affect regulation.

Guidance and differentiation of maternally directed orienting behaviors: probing the origins of filial attachment.

Newborn rats seek and attain contact with their mothers by orienting and primitive locomotor behaviors called maternally-directed orienting behaviors (MDOBs). By 2 days of age MDOBs are elicited specifically by maternal features and are heightened by a period of acute separation from the mother. This behavioral regulation by the mother's presence suggests an early form of filial attachment. To probe for other evidence of filial attachment, two aspects of the controls of MDOBs were investigated: (1) whether MDOBs are goal-corrected in relation to the dam's position and (2) whether the performance of MDOBs can be separated from that of suckling. It was found that, during the first 2 days after birth, MDOBs maintained the pup's ventrum-to-ventrum contact with the dam regardless of her position, suggesting that they are goal-corrected. Evidence was not found for independent controls of nipple grasping (NG), the behavior that initiates suckling, and MDOBs during the first two postnatal days.

Toward a neurobiology of psychotherapy: basic science and clinical applications.

Psychotherapy is used commonly to treat a variety of mental illnesses, yet surprisingly little is known about its biological mechanisms especially in comparison with pharmacotherapy. In this review we survey the current knowledge about changes in brain function following psychotherapeutic intervention that are detectable with current neuroimaging techniques. We also consider the possible role for neuroimaging in refining clinical diagnoses and predicting treatment outcome, which would benefit both clinical decision-making and the cognitive neuroscience of psychotherapy.