Joseph E. O. Newton

Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans

We measured event-related brain potential (ERP) component amplitudes and heart rate (HR) to four intensities of randomly presented tones in two matched groups of drug-free male Vietnam veterans: 12 patients diagnosed with posttraumatic stress disorder (PTSD) and 6 normal combat veterans. Subjects were evaluated with structured diagnostic interviews and anxiety and depression rating scales. We found a significant group X intensity interaction for P2 peak amplitude at CZ. Subjects were classified as augmenters or reducers: positive P2 slopes as a function of stimulus intensity implying augmentation and negative slopes implying reduction. Nine of 12 PTSD subjects were reducers (sensitivity of 75%) and 5 of 6 normals were augmenters (specificity of 83.3%). By the third and fourth second following tone onset, the mean HR of PTSD subjects increased more than twice that of the normals. HR change scores were significantly responsive to the manipulation of stimulus intensity and to the difference between our two groups. P2 reduction differentiates Vietnam veterans with combat-related PTSD from combat veteran controls, and PTSD subjects are more autonomically arousable than their combat veteran peers.

Internalizing and externalizing characteristics of sexually and/or physically abused children

This study evaluates the behavioral consequences of childhood abuse (sexual, physical, or both), with particular focus on prevalence of posttraumatic stress disorder (PTSD). Three abuse type groups and nonabused controls were contrasted on behavioral rating scales and on structured psychiatric interview data. The participants (109 abused children and 16 normal control children) were recruited from Arkansas Children’s Hospital and local agencies for abused children. As expected, proportionately more females than males were sexually abused. Overall, males were rated as more disturbed than females. Type of abuse did not consistently influence behavioral ratings. Externalizing scores were significantly higher than internalizing scores in all abused groups. PTSD was diagnosed in 50% of the abused children, with a higher rate for boys who had been sexually abused as opposed to physically abused only (58% versus 13%). The most frequent comorbid condition with PTSD was Separation Anxiety. Sexually abused boys were hospitalized for psychiatric treatment at a higher rate than were other abused children.

Fluoxetine and trifluoperazine in human brain: A 19F-nuclear magnetic resonance spectroscopy study

Fluorine-19 (19F) is a nonradioactive isotope that is well-suited to nuclear magnetic resonance spectroscopy (NMRS) and is a constituent of several medications used to treat psychiatric illnesses. Fluoxetine, a trifluorinated agent, generated a signal from brain that was readily measured by 19F-NMRS. Estimated brain concentrations ranged from 1.3-5.7 micrograms/ml in six subjects at a steady state dose of 40 mg/day. Enhanced sensitivity of 19F has been obtained by conforming the surface coil to the shape of the forehead. Hence, at the current state of development, 19F-NMRS can be applied to clinical questions relevant to concentrations of fluoxetine in brain. We also report observation of NMRS signals from fluorinated neuroleptics in a number of patients at steady state. These signals continue to be difficult to obtain, although a correlation between dose and estimated brain concentrations is suggested.

Posttraumatic stress disorder: A sensitization reaction

This article discusses past research bearing on the question of the etiology of Posttraumatic Stress Disorder (PTSD). It argues that PTSD can be adequately accounted for by a process of emotional sensitization and that this is a more parsimonious explanation than the two-factor learning theory of Mowrer, now postulated by several writers. In brief, the etiology and subsequent development of PTSD is viewed as the result of the sensitization of fear/anxiety which is linked to a variety of to be conditional stimuli by both backward and forward association: these become conditional stimuli (CSi) once paired with the instigating circumstances. It is furthermore assumed that PTSD will not occur in the absence of a genetic susceptibility that may vary from zero to absolute certainty. Thus far, our evidence is limited to a sensitivity to loud sounds, but it is highly probable that touch and other sensory systems are involved (not necessarily in parallel). The fact that abuse often leads to behavioral disorders, including sexually seductive behaviors in children sexually abused, requires a recognition that emotional reactions other than fear may be sensitized. Fear in combination with pleasure or pleasure alone coupled with a loss of self-esteem may explain these acting-out behaviors.

In vivo 7Li nuclear magnetic resonance study of lithium pharmacokinetics and chemical shift imaging in psychiatric patients

New data are presented on the application of 7Li in vivo nuclear magnetic resonance (NMR) spectroscopy to human studies. The technique was used to monitor the between-dose pharmacokinetics of lithium (Li) in brain for three patients on Li therapy. Brain Li concentrations were at their highest from 0 to 2 hours after the peak occurred in serum concentration. Elimination from brain tissue took longer than elimination from muscle, and no signal could be detected from brain at 10 days after termination of therapy. A birdcage radiofrequency coil for 7Li was constructed and used to measure the 7Li spin-lattice relaxation time of 4.6 seconds in vivo in human head, and to acquire preliminary spectroscopic images of a phantom and human brain.

Induced immobility in nervous and normal Pointer dogs.

Pointer dogs learn complex hunting tasks such as vigorous aim-directed activity in tracking specific birds and sudden rigid immobility “on point” at appropriate distance from the prey. In the presence of a human, dogs of the Arkansas Line of Nervous Pointers show markedly reduced activity. In close quarters, where they cannot flee, they usually react to humans by freezing. These responses do not extinguish. The breed demonstrates a strong capacity to inhibit motion. In our nervous dogs, this trait is greatly exaggerated. In the search for an objective and rapidly modifiable target motor sign to correlate with biochemical and pharmacological events, we discovered that 10 of 10 nervous dogs, in contrast to kennel mates of a normal line, developed tonic immobility (TI) which was induced by manual inversion into a sling and stroking. This is the first systematic demonstration of TI in mature dogs. The TI was accompanied by reduced telemetered heart rate (HR) compared to baseline. Release from the inverted position was accompanied by marked HR increase. In the absence of humans, both before and after the inversion, all nervous dogs showed little or no movement about the testing area. This was in contrast to the nine normal line dogs, which were comparable in age and sex. These normal dogs were very active before and after inversion into the sling. Five of the normals remained in the sling but did not show head and neck immobility and were generally relaxed. Their HRs increased slightly while in the inverted position, thereafter returning to baseline. The four normals which righted themselves soon after the inversion showed reduced HR with the resumed activity. We discuss possible mechanisms and review some of the implications for psychiatry and behavioral biology.

The prediction of abnormal behavior from autonomic indices in dogs.

This report describes autonomic and behavioral measures that reliably discriminate two strains of pointer dogs. These two strains, one abnormal and the other normal in behavior, have been produced by a combination of inbreeding and selection. In this context, abnormal behavior means marked timidity, excessive startle, and catatonic-like immobility. The prepotent stimulus eliciting such “phobic” behavior is man. Discriminant analyses were done on 20 pathological and 19 normal dogs using behavioral measures alone, autonomic measures alone, and combined behavioral and autonomic measures. Resting heart rate (HR) as well as HR and electrocardiographic changes due to an intravenously administered parasympathetic blocker (atropine) and a sympathetic stimulant (isoproterenol) were studied. The combined battery of behavioral and autonomic variables separated the two strains of pointers with 100 per cent accuracy; behavioral measures alone and autonomic measures alone were 95 per cent accurate. To test the validity of the discriminant coefficients derived from the autonomic analysis, 10 additional animals were studied. The previously computed discriminant coefficients were blindly applied to this new sample. Of the 10 dogs, 9 were correctly identified as abnormal or normal (one misclassification). It would appear that in these animals, abnormal behavior has specific autonomic correlates. The results of this study along with hematological and CNS biochemical data from our laboratory are discussed in terms of brain mechanisms that might underlie the behavior of the pathological strain.

Visual slow brain potentials in children with attention deficit disorder.

Using a two-stimulus reaction time paradigm, with two separate reward conditions (contingent and noncontingent), we compared slow wave brain potentials (ERPs) in 144 children with attention deficit disorder (ADD) and 30 normal control children. This article reviews the findings during the 900 msec visual warning stimulus.As we had expected, based on ERP work of Forth and Hare (1989) and Raine, Venables and Williams (1990), and on previous work from our own laboratory, the group differences were found in the negative slow wave portions of the ERP complex during the contingent reward condition but not during the noncontingent condition. Aggressive hyperactive subjects with attention deficit disorder (ADDHA) were discriminated from nonaggressive subjects (including control subjects) during the contingent reward condition in the following ways: (1) greater fronto-central negativity (640–900 msec slow wave) and (2) greater right parietal than left parietal negativity (430–750 msec slow wave).All ADD subgroups, when compared to control (CONTR) subjects, showed greater slow wave negativity (700–900 msec) at the midline occipital electrode site during the contingent reward condition. This could be explained in part as an IQ effect on ERPs reflecting the IQ difference between the ADD subgroups and the controls.These slow wave findings seem to relate to attentional problems of these children. They are discussed in terms of a psychobiological model of inhibition/disinhibition and appetitive activation.

Immobility reactions: a modified classification.

This theoretical paper sets the stage for subsequent experimental reports on mobility and immobility in the Arkansas Line of Nervous Pointer dogs as contrasted with kennel mates of the normal line. Exactly opposite to the normal animals, the nervous dogs show marked inhibition of heart rate and musculoskeletal responses to man, including reduced ambulation and durable immobility following inversion and brief manual restraint in an open sling. The sling immobility of the nervous dogs (which may not differ basically from their freezing in upright position) might be designated as “tonic immobility” (TI). We hypothesize that such immobility, common in laboratory and natural conditions in many species, should be divided into two classes: hypotonic (cataleptic) and hypertonic (catatonic). We provide examples of such behaviors, particularly in man and dog, and cursorily review TI studies of other species. Neurophysiologic and neurochemical studies which bear on possible immobility mechanisms are briefly noted. We suggest that inconsistencies in reported concommitants of TI might result from failure to discriminate between types of behavioral responses.

A multivariate discriminate analysis of behavioral measures in genetically nervous dogs.

For some years we have studied a strain of genetically nervous dogs in the Neuropsychiatric Research Laboratory, Veterans Administration Hospital, North Little Rock, Arkansas. In the manner of Pavlov and Gantt and later Scott and Fuller we have characterized these dogs in such descriptive terms as timid, human aversive, and catatonic-like. Behavioral tests have been administered on nearly all dogs in this longitudinal study, and we are using these data to try to develop statistical procedures to maximize the discriminatory power of the behavioral assay and to more accurately characterize the behavioral deficit. A multivariate discriminate analysis of 13 variables on 91 healthy and 63 nervous dogs assayed at 3 months of age shows: (1) that much of our present behavioral testing procedures is redundant, and (2) that simple“friendliness to humans” in the dog is as effective for discriminating between the two groups as any of the 13 measures, taken either singly or collectively.