Robert B. Innis

Bio: Robert B. Innis is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Radioligand & Dopamine. The author has an hindex of 90, co-authored 455 publications receiving 32492 citations. Previous affiliations of Robert B. Innis include Yale University & Veterans Health Administration.

Consensus nomenclature for in vivo imaging of reversibly binding radioligands

Abstract: An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.

MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.

Abstract: Patients with combat-related posttraumatic stress disorder (PTSD) clinically demonstrate alterations in memory, including nightmares, flashbacks, intrusive memories, and amnesia for war experiences. In addition, descriptions from all wars of this century document alterations in memory occurring in combat veterans during or after the stress of battle. These include forgetting one's name or identity and forgetting events that had just taken place during the previous battle (1, 2), as well as gaps in memory that continue to recur for many years after the war (3). Servicemen who had been prisoners of war during the Korean conflict were found to have an impairment in short-term verbal memory, as measured by the logical memory component of the Wechsler Memory Scale, in comparison with veterans of the Korean war who did not have a history of imprisonment (4). We also found deficits in short-term verbal memory, as measured by the logical memory component of the Wechsler Memory Scale, in Vietnam combat veterans with combat-related PTSD in comparison with healthy subjects who were matched for age, years of education, and alcohol abuse (5). Several lines of evidence suggest a relation between stress and damage to the hippocampus (6). The hippocampus and the adjacent perirhinal, parahippocampal, and entorhinal cortex play an important role in short-term memory (7). Studies in humans have shown that reductions in hippocampal volume secondary to either neurosurgery (8) or the pathophysiological effects of epilepsy (9) are associated with deficits in short-term memory as measured by the Wechsler Memory Scale. Monkeys exposed to the extreme stress of improper caging have shown increased glucocorticoid release as well as damage to the CA2 and CA3 subfields of the hippocampus (10). Studies in a variety of animal species suggest that direct glucocorticoid exposure results in a loss of neurons and a decrease in dendritic branching in the hippocampus (11, 12) with associated deficits in memory function (13). The mechanism of action of glucocorticoid toxicity is probably through an increase in the vulnerability of neurons to the toxicity of excitatory amino acids (14–16). Studies using computed tomography in human subjects who are exposed to high levels of glucocorticoids secondary to glucocorticoid steroid therapy (17, 18) or who have affective disorders (also felt to be related to stress) (19) have shown changes in brain structure, including ventricular enlargement and widening of the cortical sulci. Magnetic resonance imaging (MRI) studies in patients with affective disorders have shown a smaller right hippocampal volume (20) and temporal lobe volume (21) in bipolar disorder and abnormalities of the hippocampus, including alterations in T1 (22), but no change in hippocampal volume (23) in major depression. One MRI study (24) found a relation between deficits in short-term memory and smaller hippocampal volume, as well as higher plasma cortisol levels and smaller hippocampal volume, in patients with Cushing's disease. Stress in both healthy human subjects (25) and soldiers undergoing random artillery bombardment (26) results in an increase in urinary cortisol, suggesting the possibility that exposure to the extreme stress of combat may be associated with damage to the hippocampus. The purpose of this study was to use MRI to measure the volume of the hippocampus and comparison brain structures in patients with PTSD and in matched comparison subjects. We hypothesized that PTSD would be associated with smaller hippocampal volume in relation to that of the comparison subjects. We also hypothesized that smaller hippocampal volume would be associated with deficits in short-term verbal memory in patients with PTSD.

Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects

Abstract: The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive. We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls. Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D2 receptor availability, measured as the binding potential of the specific D2 receptor radiotracer [123I] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]benzamide ([123I]IBZM). The amphetamine-induced decrease in [123I]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1%) compared with the control group (-7.6 +/- 2.1%). In the schizophrenic group, elevated amphetamine effect on [123I]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms. This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia.

Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.

Abstract: OBJECTIVE: The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects. METHOD: Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D2 receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D2 receptor availability was measured with single photon emission computed tomography and the D2 receptor radiotracer [123I]IBZM. RESULTS: No differences were observed ...

Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene

Abstract: In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.

Parkinson’s disease: clinical features and diagnosis

Abstract: Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

Neuroinflammation in Alzheimer's disease

Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.