Human Behavioral Disorders Research Articles

The human genome: chromosome 22q11 deletion syndrome.

Deletion of chromosome 22q11.2 is the most frequent known interstitial deletion found in humans. The deletion has been associated with a highly variable phenotype that occurs in many combinations and with widely differing severities. This composite microdeletion syndrome encompasses DiGeorge syndrome, velocardiofacial (or Shprintzen) syndrome, conotruncal anomaly face, and isolated conotruncal anomalies as the most common disorders. The full disorder is referred to as 22q11 deletion syndrome. In addition to the numerous structural malformations associated with gene deletions at the 22q11 chromosome, developmental delay, learning disability, and neuropsychiatric disturbances are common. Many studies have reported a greater incidence of psychotic illness (schizophrenia or bipolar disorder) in adults with 22q11 deletion syndrome, and deletions in the 22q11.2 chromosome have also been found in 2%–3% of individuals with schizophrenia, predominantly in patients with childhood-onset schizophrenia. Most patients with velocardiofacial syndrome or DiGeorge syndrome have overlapping deletions on one chromosome 22q11, which suggests that a lower copy number of the same genes may be responsible for the etiology of these diseases. Fluorescent in situ hybridization is the technique in widespread use to detect these deletions in individual chromosomal preparations. A fluorescently labeled DNA or RNA probe is hybridized to immobilized metaphase chromosomes prepared from a blood sample. These types of molecular cytogenetic techniques are routinely used to diagnose human behavioral disorders due to chromosomal rearrangements (deletions, translocations, and insertions) and will be increasingly applied in the future as additional genetic illnesses are established.

Human monoamine oxidase: from genetic variation to complex human phenotypes

Monoamine oxidases A and B (MAOA and MAOB) have been suggested to be involved in human behavior and neuropsychiatric disorders. These observations were supported by several lines of evidence provided by pharmacological studies as well as enzyme deficiency investigations in humans and model animals. Numerous allelic association studies have attempted to detect a link between different alleles of the genes encoding monoamine oxidases and certain complex human traits. Many of these studies have reported contradictory findings, probably due to population stratification and limitations of the experimental and statistical designs used in the studies. Here, we review all the genetic variants described for the MAO genes, we summarize the allelic associations found with different traits, and we discuss these results in the context of the factors that affect detection of allelic association. Finally, we discuss the advantages of the use of haplotypes for studying associations with human traits.

Circadian rhythm genetics: from flies to mice to humans.

A successful genetic dissection of the circadian regulation of behaviour has been achieved through phenotype-driven mutagenesis screens in flies and mice. Cloning and biochemical analysis of these evolutionarily conserved proteins has led to detailed molecular insight into the clock mechanism. Few behaviours enjoy the degree of understanding that exists for circadian rhythms at the genetic, cellular and anatomical levels. The circadian clock has so eagerly spilled her secrets that we may soon know the unbroken chain of events from gene to behaviour. It will likely be fruitful to wield this uncommon degree of knowledge to attack one of the most challenging problems in genetics: the basis of complex human behavioural disorders. We review here the genetic screens that provided the entreé into the heart of the circadian clock, the model of the clock mechanism that has resulted, and the prospects for using the homologues as candidate genes in studies of human circadian dysrhythmias.

Human dopamine D4 receptor allele genotyping by ultrathin agarose gel electrophoresis with To-Pro-3 complexation.

Growing evidence shows the correlation between the allelic type of the dopamine D4 receptor and the human novelty-seeking personality trait. A sensitive, ultrathin agarose gel electrophoresis-based, high-throughput screening method was developed for genotyping the dopamine D4 receptor (D4DR) exon III 48 base pair repeat polymorphism. The efficiency of the method was increased by reamplification nested polymerase chain reaction (PCR) - of the 48 base pair repeat containing the PCR product with internal primers. The nested PCR fragments were analyzed by ultrathin layer agarose gel electrophoresis with an automated real-time laser-induced fluorescent detection system. Noncovalent affinity complexation was accomplished during the separation process by the addition of a very low concentration of intercalation dye, To-Pro-3 (2 nM) to the gel buffer system. This resulted in instant fluorescent labeling of the migrating PCR fragments. This method can readily facilitate genetic association studies between dopamine receptor genotypes and some human behavioral and neuropsychiatric disorders.

Human behavioural genetics of cognitive abilities and disabilities.

Although neither the genome nor the environment can be manipulated in research on human behaviour, some of the new tools of molecular genetics can be brought to bear on human behavioural disorders (e.g. cognitive disabilities) and quantitative traits (e.g. cognitive abilities). The inability to manipulate the human genome experimentally has had the positive effect of focusing attention on naturally occurring genetic variation responsible for behavioural differences among individuals in all their complex multifactorial splendour. Genes in such complex multiple-gene systems are called quantitative trait loci (QTLs), which merge the two worlds of genetic research, quantitative genetics and molecular genetics. Although most genetic research on complex human behaviour has focused on severe mental disorders, cognitive abilities and disabilities may be even more immediately relevant to neuroscience. For example, verbal ability and spatial ability are two of the most heritable cognitive abilities, and reading disability is the first behavioural disability for which replicated QTL linkage has been found. The purpose of this essay is to provide an overview of the genetics of cognitive abilities and disabilities as an example of the impending merger of quantitative genetics and molecular genetics in QTL analysis of complex traits.

Genetic analyses of complex behavioral disorders.

Many behavioral disorders are likely to be “complex,” influenced by several genetic and environmental factors. Although a single gene’s variants might thus account for only a portion of the vulnerability to the disorder, the high population frequencies of many of these problems makes understanding such gene variants important for public health. Insights into identifying single gene influences in human complex behavioral disorders have come from family, twin, and adoption studies, mathematical models for complex genetics, identification of candidate genes, elucidation of functional variants in some of the perhaps 40,000 genes expressed in the human brain, and studies in transgenic mice with experimental manipulations of single genes. Modeling studies now suggest that the magnitude of gene effects on a disease is a primary determinant of our ability to identify a disease-associated gene variant (1). Heritability reflects the proportion of the total interindividual variation due to a gene variant, reflecting both the gene variant’s frequency in the population and the size of the effects that the gene variant causes. Sibling relative risk assesses the increased disease risk to siblings that share one-half of the genes with affected probands. Values for heritability, sibling relative risk, environmental contributions, and the power of genetic approaches can be estimated from studies of disease frequencies and patterns in monozygotic and dizygotic twins and in biologically related …

The relations between neuroscience and human behavioral science.

Neuroscience seeks to understand how the human brain, perhaps the most complex electrochemical machine in the universe, works, in terms of molecules, membranes, cells and cell assemblies, development, plasticity, learning, memory, cognition, and behavior. The human behavioral sciences, in particular psychiatry and clinical psychology, deal with disorders of human behavior and mentation. The gap between neuroscience and the human behavioral sciences is still large. However, some major advances in neuroscience over the last two decades have diminished the span. This article reviews the major advances of neuroscience in six areas with relevance to the behavioral sciences: (a) evolution of the nervous system; (b) visualizing activity in the human brain; (c) plasticity of the cerebral cortex; (d) receptors, ion channels, and second/third messengers; (e) molecular genetic approaches; and (f) understanding integrative systems with networks and circadian clocks as examples.

Topography of pyramidal neuron intrinsic connections in macaque monkey prefrontal cortex (areas 9 and 46).

An understanding of the normal organization of prefrontal cortex is essential to the recognition of pathology underlying human behavioral disorders believed to depend on this region. We have therefore studied the pattern of intrinsic intra- and interlaminar pyramidal neuron connectivity in prefrontal areas 9 and 46 (of Walker) in macaque monkey cerebral cortex (anterior to the arcuate sulcus between the principal sulcus and midline). We made focal (200-400 microns) injections of biocytin and mapped the pattern of orthogradely transported label. Injections made into the superficial layers label wide-ranging lateral projections within the same areas of prefrontal cortex. Projections local to such small injections form a narrow band of terminals in layers 1-3 (200-400 microns wide, 2-4 mm long) centered on the injection site. Collateral fibers spread orthogonal to this terminal band, making frequent bifurcations, to establish a series of parallel bands of terminals with uninnervated bands between, spaced regularly across the cortex (center to center 500-600 microns). The entire pattern of terminal label is stripe-like, with occasional narrower interbands and crosslinks between the bands, and can extend over 7-8 mm across the cortex. These projections arise from pyramidal neurons in layers 2, 3, and 5 and terminate in layers 1-3. The stripe-like pattern contrasts with patch-like patterns in other cortical regions (V1, V2, V4, motor, somatosensory) and is smaller in scale than stripe-like zones of corticocortical afferent terminals to this region, reported to be 300-750 microns wide and spaced 1.0-1.5 mm center to center.

Human tryptophan oxygenase localized to 4q31: Possible implications for alcoholism and other behavioral disorders

A human tryptophan oxygenase clone was isolated by screening a liver cDNA library with a rat tryptophan oxygenase cDNA clone. Analysis showed extensive homology between the rat and the human DNA and protein sequences. The combined use of cell hybrids and in situ hydridization indicated that human tryptophan oxygenase was localized to chromosome band 4q31. The tryptophan oxygenase gene may be important in some human behavior disorders, especially those associated with abnormalities of serotonin metabolism.

Behavioral correlates of presynaptic events in the cholinergic neurotransmitter system.

A quarter century ago in the Epilogue to his critical review of information about “Drug and Chemical Stimulation of the Brain” Myers (215a) stated: “Most impressive is the singular fact that ACh is the only substance that can influence every physiological or behavioral response thus far examined.” The present quarter century has seen our knowledge about the cholinergic neurotransmitter system develop by quantal steps arising from imaginative new concepts and from innovative techniques for testing hypotheses generated by them. The new knowledge is upgrading our basic understanding of the roles of the cholinergic system in functions, both centrally and peripherally, within the organism. It is contributing very significantly to our understanding of ways in which the system may malfunction and enter into abnormal states of the organism. Such information is essential to uncovering the etiology of human behavioral disorders and the invention of treatments for them. These are disorders that affect human health and happiness and may, through illness, incapacitation and demand for health services, have an important impact on a society’s economy. The paragraphs that follow are viewed within this broad context. They focus on how presynaptic events in the cholinergic system are involved as living organisms cope with their physical and psychosocial environments.

The effects of neurotoxicants on kindling and kindled seizures

The application of a constant-amplitude electrical stimulation to many parts of the brain leads to the expression of progressively more severe epileptiform responses. The process of acquisition is termed kindling, and the acquired response is termed the kindled seizure. This state has been used in a number of important ways including the modeling of human epilepsy and behavioral disorders, the testing of drugs for anticonvulsant effects, and, more recently, the examination of hyperexcitability states induced by pesticides and other environmental chemicals. This report discusses attributes of kindling and kindled seizures, examines possible mechanisms responsible for them, and summarizes drug and chemical effects on them. Kindling is powerfully accelerated by exposures to only a few substances, among the most effective of which are the chlorinated hydrocarbon insecticides, lindane and dieldrin. An analysis of the acceleration of kindling produced by lindane suggests that the threshold concentration in the nervous system for kindling enhancement is approximately 0.4 μg/g (1.4 × 10 −9 mol/g).

Extraordinary Disorders of Human Behavior

Extraordinary Disorders of Human Behavior

Extraordinary Disorders of Human Behavior—edited by Claude T. H. Friedmann, M.D., and Robert A. Faguet, M.D.; Plenum, New York City, 1982, 314 pages, $35

Back to table of contents Previous article Next article ArticleNo AccessExtraordinary Disorders of Human Behavior—edited by Claude T. H. Friedmann, M.D., and Robert A. Faguet, M.D.; Plenum, New York City, 1982, 314 pages, $35Michael H. SacksMichael H. SacksSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ps.34.8.746-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Extraordinary Disorders of Human Behavior—edited by Claude T. H. Friedmann, M.D., and Robert A. Faguet, M.D.; Plenum, New York City, 1982, 314 pages, $35." Psychiatric Services, 34(8), pp. 746-a–747 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - Psychiatric Services $35.00 Add to cart PPV Articles - Psychiatric Services Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byNone Volume 34Issue 8 August 1983Pages 746-a-747 Metrics PDF download History Published online 1 April 2006 Published in print 1 August 1983

The apparatus of mind: Brain structure and function in mental disorder

In this overview, the author contemplates the complexity of the psychiatrist's task, which he defines as the attempted understanding and rectification of disorders of human behavior and subjective experience. He reviews recent studies of brain structure, as examined through computerized tomography (CT) scans, and brain function, as examined through neuropsychological approaches, with an emphasis on schizophrenic patients, and attempts to delineate current directions in our understanding of brain structure and mental function.

Schizophrenia. By J. S. Strauss and W. T. CarpenterJr. (Pp. 220; $22.50.) Plenum Medical Books: New York. 1981. - Extraordinary Disorders of Human Behavior. Edited by C. T. H. Friedmann and R. A. Faguet. (Pp. 310; illustrated; $35.00.) Plenum Medical Books: New York. 1982.

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Extraordinary Disorders of Human Behavior

The editors of this collection, Extraordinary Disorders of Human Behavior , set out to collate material on rare and unusual disorders that is scattered throughout the psychiatric literature and to contemporize and update [the material] in one clinically relevant volume. Rationalizing that although the average clinical may see only one or two of these disorders in a lifetime, they justifiably contend that partial or fragmentary expressions of these disorders may be frequently observed in dream material, fantasies, and behaviors and, as such, should be of interest and fascination to all clinicians. The reader, then, is newly introduced to or refamiliarized with, as the case may be, the gamut of situationspecific and idiopathic syndromes such as folie a deux, Ganser's syndrome, Gilles de la Tourette's, and Capgras' syndromes; the culturebound phenomena such as amok, latak, and wihtigo; paraphilias such as necrophilia, vampirism, and zoophilia; and a number of other syndromes that are

Book ReviewExtraordinary Disorders of Human Behavior

Book ReviewExtraordinary Disorders of Human Behavior

"Learned helplessness," "learned hopefulness," and "learned obsessiveness": effects of varying contingencies on escape responding.

Two types of outcome appearing in most research on learned helplessness were studied. Subjects performing under an extinction, i.e., non-occurring, programmed outcome evidenced “learned helplessness.” Contrary to learned helplessness theory, however, most subjects given response-independent outcomes developed superstitious behavior and reported perceived control of events. Subjects in a third group whose responses were reinforced during a 50-trial “training” phase showed response “excesses” during 10 subsequent “test” trials. These results have important implications for the theory of learned helplessness and the relevance of laboratory phenomena to human behavioral disorders.

Relevance of Animal Learning Models to Behavioral Psychotherapy

Pavlov's words presaged a twentieth century development for study of human behavioural disorders: Animal learning models. In essence, animal modeling involves induction of disorders analogous to naturally occurring human psychopathologies in animal subjects. The goal, of course, is illumination of cause, cure, and prevention of human disorders. Historically, although Pavlov's (1941, 1966) discovery of “experimental neurosis” in dogs generated initial enthusiasm for animal modeling, the approach later fell into disrepute probably because the early animal experimentation was rather poor (McKinney, 1974). The experimental analyses of the apparently maladaptive animal behaviours were reasonably thorough, but the claim that they represented and/or analyzed some form of naturally occurring disorder was usually unconvincing. Currently, however, a resurgence of interest in the method of animal modeling coupled with increased concern by investigators to set down ground rules for evaluation of animal models is apparent in the recent compilation of several books on the subject (two still in press): Experimental psychopathology: Recent research and theory, Psychopathology: Experimental models, and Relevance of the Psychopathological animal model to the human.

Genetics, Interaction, and Mental Illness: Setting the Problem

Probably no other approach to the understanding of behavior has met more enduring opposition than that which includes the possibility of hereditary contributions underlying man's intellectual or emotional development, normal or abnormal. Nearly everyone has found it easy to acknowledge the coexistence of inherited and environmental factors in the instinctive behavioral patterns of insects, birds, and other animals, and not too difficult, either, to concede a possible role played by heredity in some higher-order behaviors of animals other than man. In a few specific disorders of human behavior, such as Huntington's chorea or phenylketonuria, also, a genetic basis has long been recognized. But, on the whole, the idea that genes could have much to do with the complex activities of human mental life has gained only slow acceptance in most of the behavioral sciences and mental health professions. To many workers in these fields, the idea is still remote, despite a growing tendency in the literature to give at least a nod to the concept of gene-environment interaction .