Linda E. Nee

Hippocampal lesions in dominantly inherited Alzheimer's disease.

We compared hippocampal lesions in three pedigrees of Familial Alzheimers Disease (FAD). In these pedigrees, the disease is inherited as an autosomal dominant disorder and has been linked to DNA markers on chromosome 21. In eight cases of FAD (four from one pedigree and two each from two others) we quantified neurofibrillary tangles (NFT) and senile plaques (SP) in hippocampal subdivisions CA1-4, subiculum, presubiculum, and dentate gyms. We observed consistent patterns of the distribution of lesions: The highest density of NFT and SP was present in CA1-2; virtually no SP or NFT were present in presubiculum; SP diameter was consistently greatest in CA4. We found no overall differences among pedigrees in total densities of NFT and SP, but statistical analyses disclosed that an uncommon type of SP was disproportionately present in two pedigrees. This type of SP was usually restricted to CA4, had a marked amyloid core devoid of argyrophilic neurites. These studies also disclosed inter- and intrafamilial heterogeneity of lesion distribution (including congophilic angiopathy and cerebellar plaques) in these three pedigrees.

Pilot Trial of Mianserin Hydrochloride for Childhood Hyperactivity

Stimulant drug treatment of children with attention deficit disorder with hyperactivity (ADDH) is often dramatically successful in controlling impulsive, distractible, and even antisocial behaviors. Although this increased vigilance and decreased motor restlessness has been shown to be a nonspecific effect of stimulants (Rapoport et al., 1978), the mechanism of action of stimulants may still be of considerable importance in understanding the biological basis of restless and inattentive behavior in children. Recent reports suggest a link between alteration in central nervous system norepinephrine (NE) metabolism and the therapeutic action of stimulants in hyperactive children. Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) is decreased with amphetamine treatment in hyperactive children (Shekim et al., 1977, 1979; Brown et al., 1979), and this decrease may correlate with clinical response to the drug.

Clinical research in neuropsychiatry

This paper presents the thesis that rapidly developing areas of knowledge in neuroscience will rekindle interest in neuropsychiatry, and increase scientific and clinical interaction between psychiatrists and neurologists in teaching hospitals. A neuropsychiatric clinical research unit at the National Institute of Mental Health is described. Examples of research conducted on the unit illustrate areas of biological science that are likely to increase the interface between psychiatry and neurology. Hopefully, the explosion of knowledge in the basic neurosciences in the last decade will be followed in this decade by clinical research of increasing specificity and sophistication of central nervous system disorders.