Multiple-dose arecoline infusions in Alzheimer's disease.

Twelve patients with dementia of the Alzheimer type received two-hour infusions of placebo and the muscarinic cholinergic agonist arecoline hydrobromide at rates of 1, 2, and 4 mg/h in a double-blind, randomized fashion. These infusions resulted in dose-dependent physiologic and neuroendocrine effects consistent with central cholinergic stimulation. Infusions were generally well tolerated. No statistically significant improvement in performance on most cognitive tasks assessing knowledge memory and episodic learning and memory was observed at any dose, although marginal improvement in picture recognition ability and in ratings of word-finding were observed at the lower doses. Psychomotor activation and slightly improved affect were reliably observed at the lower doses, whereas increasing psychomotor retardation was observed at the highest dose. The data support a role for central cholinergic modulation of some aspects of cognition, behavior, and affect in this population. The apparent greater behavioral sensitivity of patients with Alzheimer's disease in comparison with subject populations previously studied, as well as the altered dose responsiveness, merit further study in relationship to normal aging.

Clinical predictors of response to antidepressants in elderly patients.

A group of 42 patients, ages 55 and above, suffering from major depression were examined in an attempt to isolate clinical variables that would predict response to antidepressants. These patients were part of a placebo-controlled, double-blind study and were given either nortriptyline or phenelzine for 5-7 weeks. There was no significant difference in response rates between patients subclassified as endogenous or nonendogenous by either RDC or Newcastle criteria. No difference in response rates was found between the DSM-III melancholic and nonmelancholic subtypes. Neither drug preferentially treated a subtype. None of the 21 variables representing symptoms, demographic traits, or characteristics of the depressive illness were found to be significant predictors of antidepressant response.

Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly.

This comprehensive study investigated both the role of antidepressant drugs in the treatment of affective disorders of later life and their safety with careful clinical and pharmacological monitoring. A 7-week double-blind comparison was made of the efficacy and safety of nortriptyline (a tricyclic), phenelzine (a monoamine oxidase inhibitor), and placebo. The results indicated a response rate of approximately 60% for both nortriptyline and phenelzine versus a 13% response rate for placebo. Anticholinergic side effects were more frequently reported in the nortriptyline group. Orthostatic symptoms were reported with similar frequency in both drug groups. Overall, both drugs were well tolerated.

Lateralization for the expression and perception of facial emotion as a function of age.

In order to test the hypothesis of right hemisphere changes with age, this study examined lateralization for facial emotion in young, middle-aged, and older women (N = 90). For expression, subjects were photographed while posing positive and negative emotions. Composite photographs were created and rated for intensity. For perception, subjects were required to make intensity judgements about emotional chimeric faces. Overall, subjects demonstrated significant left-sided facial asymmetry for expression and significant left hemispace biases for perception. The findings for facial expression were not influenced by emotional valence or resting face asymmetries. There were no changes in lateralization as a function of age for either expression or perception. Taken together, these findings lend support to the notion that the right hemisphere mediates emotional processing across the adult life span.

Right hemisphere specialization for the identification of emotional words and sentences: evidence from stroke patients.

This study examines the contribution of the lexical/verbal channel to emotional processing in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD) and 16 normal control (NC) right-handed adults. Emotional lexical perception tasks were developed; analogous nonemotional tasks were created to control for cognitive and linguistic factors. The three subject groups were matched for gender, age and education. The brain-damaged groups were similar with respect to cerebrovascular etiology, months post-onset, sensory-motor status and lesion location. Parallel emotional and nonemotional tasks included word identification, sentence identification and word discrimination. For both word tasks, RBDs were significantly more impaired than LBDs and NCs in the emotional condition. For all three tasks, RBDs showed a significantly greater performance discrepancy between emotional and nonemotional conditions than did LBDs or NCs. Results were not affected by the valence (i.e. positive/negative) of the stimuli. These findings suggest a dominant role for the right hemisphere in the perception of lexically-based emotional stimuli.

Hemispheric specialization for discourse reports of emotional experiences: relationships to demographic, neurological, and perceptual variables.

This study examined hemispheric specialization for discourse reports of emotional and nonemotional experience in 16 right-brain-damaged (RBD), 16 left-brain-damaged (LBD), and 16 demographically-matched normal control (NC) right-handed adults. Patient groups did not differ on etiology, months post-CVA onset, and intrahemispheric lesion location. Subjects were requested to produce monologues about positive and negative emotional and nonemotional experiences. The lexical content of written transcriptions of these monologues was later rated for "emotionality" by naive judges. Overall, RBDs described experiences with less emotional intensity than did NCs and LBDs, providing support for right hemisphere involvement in lexical emotion. Although the RBDs in the current study demonstrated similar patterns of deficits in a prior study [9] on tasks involving lexical emotional perception, there were no significant relationships between the current measures of emotional expression and the previous measures of emotional perception. Finally, the expression and the perception data were examined with respect to intrahemispheric factors. Among the brain-damaged subjects, subcortical structures were more involved in reports of emotional experience, and cortical structures were more involved in the perception of emotion.

Cognitive effects of L-deprenyl in Alzheimer's disease.

Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor which may selectively inhibit MAO-B at low doses, while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT. Two doses of L-deprenyl (10 mg/day and 40 mg/day) and placebo were compared in a double-blind, serial treatment design. Episodic learning and memory, knowledge memory, attention, recognition, and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions. Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with L-deprenyl 10 mg/day. Knowledge memory, intrusions, and other cognitive functions relevant to DAT were not altered by L-deprenyl at either dose.

Design and interpretation of opiate antagonist trials in dementia.

In view of the reports of possible beneficial effects of naloxone in dementia, rationales and strategies for studying endogenous opiate systems are reviewed. Important considerations in the design and interpretation of clinical investigations using naloxone are also reviewed. The nature and distribution of endogenous opiate systems are summarized from an historical perspective. Endogenous opiate systems are distributed throughout the central nervous system and play important roles in a variety of brain functions, including memory and learning. In view of this, several rationales are evident for studying endogenous opiate systems in dementia, since it is a syndrome in which structures known to contain opiate systems are disturbed, functions modulated by opiate systems are disturbed, and other neurotransmitter systems (functionally linked to endogenous opiate systems) are disturbed. Different strategies for studying endogenous opiate systems are reviewed, including examination of body fluids and pharmacologic challenge studies. Naloxone hydrochloride, a competitive opiate receptor antagonist, is a commonly used pharmacologic agent. The design of a multidose naloxone study of 12 dementia patients is discussed, with reference to the pharmacokinetics, pharmacodynamics, and specificity of naloxone as well as to the nature of the dependent measures selected for this study. No cognitive benefit was observed in this study. Behavioral arousal was observed at naloxone doses, with more evident psychomotor retardation at higher doses. These findings are contrasted with the results of naloxone challenges in other studies. The varying effects of naloxone within and across populations can be conceptualized in terms of the basic and clinical considerations previously discussed. The importance of dose-finding studies is stressed for this and other drug trials.

Right hemisphere emotional perception: evidence across multiple channels.

Emotional perception was examined in stroke patients across 3 communication channels: facial, prosodic, and lexical. Hemispheric specialization for emotion was tested via right-hemisphere (RH) and valence hypotheses, and relationships among channels were determined. Participants were 11 right-brain-damaged (RBD), 10 left-brain-damaged (LBD), and 15 demographically matched normal control (NC) adults. Experimental measures, with analogous psychometric properties, were identification and discrimination tasks, including a range of positive and negative emotions. Nonemotional control tasks were used for each channel. For identification, RBDs were significantly impaired relative to LBDs and NCs across channels and valences, supporting the RH hypothesis. No group differences emerged for discrimination. Findings were not influenced by demographic, clinical, or control variables. Correlations among the channels were more prominent for normal than for brain-damaged groups.

Verbal pragmatics following unilateral stroke: emotional content and valence.

Verbal pragmatic aspects of discourse production were examined in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD), and 16 normal control right-handed adults. The facilitation effect of emotional content, valence hypothesis, and relationship between pragmatics and emotion were evaluated. Participants produced monologues while recollecting emotional and nonemotional experiences. Transcribed monologues were rated for appropriateness on 6 pragmatic features: conciseness, lexical selection, quantity, relevancy, specificity, and topic maintenance. Overall, brain-damaged groups were rated as significantly less appropriate than normals. Consistent with the facilitation effect, emotional content enhanced pragmatic performance of LBD aphasic participants yet suppressed performance of RBD participants. Contrary to the valence hypothesis, RBD participants were more impaired for positive emotions and LBD participants for negative emotions. Pragmatic appropriateness was not strongly correlated with a measure of emotional intensity.

The usefulness of DST in predicting response to antidepressants: a placebo-controlled study.

Seventy-two out-patients, 55 years or older, suffering from major depression were treated with either nortriptyline or phenelzine for seven weeks under placebo-controlled double-blind conditions. The dexamethasone suppression test (DST) was administered at baseline and at weeks 3 and 7 of treatment, and its usefulness in predicting and/or paralleling clinical response was examined. No correlation was found between baseline DST results and treatment response with antidepressants. Of 13 patients whose abnormal baseline DSTs normalized during treatment, six were responders and seven were nonresponders (P = 0.24). However, all (seven) patients whose DSTs persisted to be abnormal throughout the seven weeks did not respond. The authors conclude that the DST has not been shown to have practical value as an indicator of impending recovery from major depression in the elderly, but its failure to normalize may have ominous prognostic significance.

Mapping schizophrenic negative symptoms onto measures of the patient's speech: set correlational analysis.

We describe a system designed to assess the speech behaviors that inform clinicians about their patients' negative symptoms. Measures are formed into scales to reflect the patient's Pausing, Speech Rate, and Dyadic Interaction with the interviewer. Using set correlation, we examined the associations between the acoustic scales and the clinician's ratings of Flat Affect, Alogia, and Asociality. Over half of the multivariance in the clinical scales was accounted for by the acoustic scales. Unique isomorphisms between the acoustic and rating scales were found for: Dyadic Interaction with Flat Affect; Pause Production with Alogia; and Rate with Asociality.

A new pictorial instrument for child and adolescent psychiatry: a pilot study.

A pictorial instrument was developed to assess psychopathology in children aged 6 to 16 years. Symptom pictures (n = 137) representing DSM-III-R criteria were organized into seven diagnostic subscales. Clarity of the pictures was assessed in 31 normal children. Fifty-one psychiatric inpatient children completed the instrument using a 6-point visual analogue scale. Sensitivity to change was assessed in 15 children. The subscales' internal consistencies (Cronbach's alpha) ranged from 0.54 to 0.86. A canonical discriminant analysis among four diagnostic groups achieved a Wilks' lambda of 0.67 (p = 0.02). This instrument may be a valuable adjunct to psychiatric interviews in children.

Psychometric aspects of verbal pragmatic ratings.

This study examined the psychometric aspects of a verbal pragmatic rating scale. The scale contained six pragmatic features (i.e., Conciseness, Lexical Selection, Quantity, Relevancy, Specificity, and Topic Maintenance) based on Grice's cooperative principles. Fifteen right brain-damaged (RBD), 15 left brain-damaged (LBD), and 16 healthy normal control (NC) right-handed adult participants produced narratives while recollecting emotional and nonemotional experiences. Naive raters evaluated each pragmatic feature for appropriateness on a 5-point Likert scale. When reliability was examined, the overall internal consistency of the pragmatic scale was extremely high (alpha =.96). Factor analysis was conducted to examine the theoretical relations among the six pragmatic features. Three meaningful factors involving discourse content, conceptual unity, and parsimony were identified. Findings are discussed in light of Grice's model and the construct validity of the scale.

Obsessive-compulsive disorder and comorbid anxiety problems in a national anxiety screening sample.

Questionnaire data were obtained from 5867 participants attending a national anxiety screening program. These participants were selected from more than 15,000 respondents on the basis of never having received treatment for a mental health problem. A screening instrument was designed to assess five anxiety disorders (obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, generalized anxiety disorder, and panic disorder). The present study focused on those participants meeting full or partial screening criteria for obsessive-compulsive disorder (n = 3212), with those not meeting criteria for obsessive-compulsive disorder (n = 2655) serving as a comparison group. Significant relationships were found between questionnaire scores on both interference with daily living, readiness for treatment, and the number of comorbid anxiety problems. These findings shed light on the extent to which undiagnosed and untreated persons with obsessional or compulsive symptoms, or both, are experiencing, as well as the factors that may lead them to seek formal psychiatric or psychological treatment.

Attribution of psychological characteristics from masked and unmasked conversations.

A specific contribution of this study was the development of a procedure for separating the semantic and physical parameters of conversation. This procedure permits testing of the hypothesis that coverbal dimensions of conversation, that is, patterns of sounds and silence, convey information to independent listeners about the psychological states of speakers engaged in conversation. The masking procedure destroyed intelligibility of the conversation, but not the sequences of sounds and silences. Listeners rated speakers on three dimensions--warmth, anxiety, and dominance--under two conditions--masked and unmasked. Significant correlations were found between the ratings under both masked and unmasked conditions and between the ratings and a number of physical parameters of speech.

Interpersonal communication in the context of dementia.

The assessment of dementia draws, primarily, on measures of memory and language. However, dementia also affects interpersonal and social functioning. Therefore, objective assessment of interpersonal interaction may provide relevant and sensitive measures of the severity and type of dementia. We examined the vocal acoustics and interpersonal interactions of a group of patients with Parkinson's disease and mild to moderate dementia. Objective measures of performance during a semistructured interview correlated with clinical ratings made independently by a neurologist. Our findings indicate that dementia affects interpersonal abilities in specific ways that can be objectively measured using computer analyses of speech patterns.

An automated system for the analyses of temporal speech patterns: description of the hardware and software.

A system (WELMAR II) is described for analyzing time patterns of speech on small computers. Temporal speech patterning refers to the pacing of the sounds and silences that make up a stream of speech. The system is particularly useful for research involving clinical populations since it has been shown that speech rhythms are sensitive to interpersonal influence, to dimensions of personality, and to psychological pathology.

Parameters of emotional processing in neuropsychiatric disorders: conceptual issues and a battery of tests.

Components of emotional processing were examined in psychiatric and neurological populations: communication channel (face/voice), processing mode (expression/perception), and emotional valence (positive/negative). These were assessed with an experimental affect battery which was administered to schizophrenic, unipolar depressive, right-brain-damaged, Parkinson's disease, and normal control right-handed adults. For expression, subjects were taped while producing facial and vocal emotional expressions. Judges rated the expressions for accuracy and intensity. For perception, subjects were asked to identify and discriminate facial and vocal emotions. Using correlational techniques, relationships between facial and vocal channels and between expressive and perceptual modes were explored. The test battery has good psychometric properties and discriminates among diagnostic groups.

Spontaneous expression of facial emotion in schizophrenic and right-brain-damaged patients.

The primary neuropsychological theories of schizophrenia have emphasized disturbed dominant hemisphere functioning, although schizophrenics (SZs), particularly those with flat affect, may have deficits resembling those of patients with damage to their right hemisphere. SZs, right-brain-damaged patients (RBDs), and normal controls (NCs) were videotaped while talking about a pleasant and an unpleasant experience. Raters viewed the video recordings of facial activity with the audio portion turned off and assessed the intensity of emotion, the amount of positive emotion, and the amount of negative emotion. Compared to controls, both patient groups were judged as less expressive and as displaying more negative than positive emotion. In particular, the patients seemed to have difficulty with the expression of positive feelings. For the SZ group, these findings may be related to anhedonia or to poor social functioning, which are often features of the illness. The findings for the RBD group are contrary to previous studies which have suggested that the right hemisphere is specialized for negative emotion.