Adolescent immaturity in attention-related brain engagement to emotional facial expressions.

Selective attention, particularly during the processing of emotionally evocative events, is a crucial component of adolescent development. We used functional magnetic resonance imagining (fMRI) with adolescents and adults to examine developmental differences in activation in a paradigm that involved selective attention during the viewing of emotionally engaging face stimuli. We evaluated developmental differences in neural activation for three comparisons: (1) directing attention to subjective responses to fearful facial expressions relative to directing attention to a nonemotional aspect (nose width) of fearful faces, (2) viewing fearful relative to neutral faces while attending to a nonemotional aspect of the face, and (3) viewing fearful relative to neutral faces while attention was unconstrained (passive viewing).

Development and Reliability of a Method for Using Magnetic Resonance Imaging for the Definition of Regions of Interest for Positron Emission Tomography.

Although positron emission tomography (PET) provides important physiological information, a major limitation of this technique is poor anatomical resolution. Combining the superior anatomical resolution of magnetic resonance imaging (MRI) with the physiologic information of PET could be an important advance for clinical and research applications of PET. The purpose of this study was to develop reliable methods for using MRI in the definition of brain regions of interest (ROIs) for application to coregistered PET brain images.

Assessment of the hypothalamic-pituitary-adrenal axis over a 24-hour diurnal period and in response to neuroendocrine challenges in women with and without childhood sexual abuse and posttraumatic stress disorder.

Background: Preclinical studies showed that early stress results in long-term alterations in the hypothalamic-pituitary-adrenal (HPA) axis. We performed a comprehensive assessment of the HPA axis in women with and without a history of early childhood sexual abuse and posttraumatic stress disorder (PTSD).

Methods: Fifty-two women with and without a history of early childhood sexual abuse and PTSD underwent a comprehensive assessment of the HPA axis, including measurement of cortisol in plasma every 15 min over a 24-hour period and cortisol and corticotropin (ACTH) following corticotropin-releasing factor (CRF) and ACTH challenge.

Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder.

Background: Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy.

The psychobiology of resilience and vulnerability to anxiety disorders: implications for prevention and treatment.

Much of the research on the neurobiology of human anxiety disorders has focused on psychopaihological abnormalities in patients with anxiety disorders. While this line of research is obviously important, more investigation is needed to elucidate the psychobiology of resilience to extreme stress. Study of the psychobiology of resilience has the potential to identify neurochemical, neuropeptide, and hormonal mediators of vulnerability and resilience to severe stress.

Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients.

Ethanol is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. Ethanol dependence upregulates NMDA receptors and contributes to crosstolerance with selective NMDA receptor antagonists in animals. This study evaluated whether recovering ethanol-dependent patients show evidence of a reduced level of response to the effects of the NMDA receptor antagonist, ketamine.

Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life.

Objectives: To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research.

Participants: The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy.

Evidence: (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates.

Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI.

Objective: This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness.

Method: Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging.

Results: Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group.

Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression.

Context: We previously used positron emission tomography (PET) measurement of brain metabolism with 18fluorodeoxyglucose to show that patients receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion-induced return of depressive symptoms have an acute decrease in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients with depression in remission while taking norepinephrine reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion of norepinephrine and dopamine using alpha-methylparatyrosine (AMPT).

Objective: To assess brain metabolic correlates of AMPT administration in patients with depression in remission while receiving NRIs.

A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices.

Background: Abnormalities in prefrontal and anterior cingulate cortices are implicated in disturbances of attention, cognition, and impulse regulation in bipolar disorder. Acute episodes have been associated with dysfunction in these brain regions, and more enduring trait-related dysfunction has been implicated by volumetric and cellular abnormalities in these regions. The relative contributions of prefrontal regions to state and trait disturbances in bipolar disorder, however, have not been defined.

Researching the pathophysiology of pediatric bipolar disorder.

We suggest that the core feature of bipolar disorder (BPD) is marked state fluctuations. The pathophysiology of switches into depressed, irritable, and extreme positive valence states requires study, with the latter deserving particular focus because it represents a pathognomonic feature of BPD in both adults and children. Hypotheses regarding the pathophysiology of pediatric BPD must account for these marked state fluctuations as well as for specific developmental aspects of the illness.

Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse.

Background: Animal studies have shown that early stressors result in lasting changes in structure and function of brain areas involved in memory, including hippocampus and frontal cortex. Patients with childhood abuse-related posttraumatic stress disorder (PTSD) have alterations in both declarative and nondeclarative memory function, and imaging studies in PTSD have demonstrated changes in function during stimulation of trauma-specific memories in hippocampus, medial prefrontal cortex, and cingulate. The purpose of this study was to assess neural correlates of emotionally valenced declarative memory in women with early childhood sexual abuse and PTSD.

MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder.

Objective: Animal studies have suggested that early stress is associated with alterations in the hippocampus, a brain area that plays a critical role in learning and memory. The purpose of this study was to measure both hippocampal structure and function in women with and without early childhood sexual abuse and the diagnosis of posttraumatic stress disorder (PTSD).

Method: Thirty-three women participated in this study, including women with early childhood sexual abuse and PTSD (N=10), women with abuse without PTSD (N=12), and women without abuse or PTSD (N=11).

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression.

There is growing evidence from neuroimaging and ostmortem studies that severe mood disorders, which have traditionally been conceptualized as neurochemical disorders, are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that recent preclinical studies have shown that critical molecules in neurotrophic signaling cascades (most notably cyclic adenosine monophosphate [cAMP] response element binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen activated protein [MAP] kinases) are long-term targets for antidepressant agents and antidepressant potentiating modalities. This suggests that effective treatments provide both trophic and neurochemical support, which serves to enhance and maintainnormal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning.

Defining clinical phenotypes of juvenile mania.

Objective: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children, differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria.

Method: Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought.

Results: Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis.

Childhood trauma associated with smaller hippocampal volume in women with major depression.

Objective: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma.

Frontotemporal neural systems in bipolar disorder.

Relatively less research has been performed in the delineation of the neural system abnormalities underlying bipolar disorder (BD) than in their correlates in unipolar depression. However, neuroimaging research has recently provided in vivo evidence to support the involvement of regional brain abnormalities in BD implicated by the localization of lesions associated with secondary mood symptoms. This article reviews (1) neural systems implicated in BD by brain lesions associated with secondary mood changes and impaired neuropsychologic paradigm performance; (2) structural and functional neuroimaging evidence to support the involvement of these neural systems in BD; and (3) potential functional neuroanatomic models of BD symptoms.