Langley Porter Psychiatric Hospital and Clinics

Clinical, field, and experimental studies of response to potentially stressful life events give concordant findings: there is a general human tendency to undergo episodes of intrusive thinking and periods of avoidance. A scale of current subjective distress, related to a specific event, was based on a list of items composed of commonly reported experiences of intrusion and avoidance. Responses of 66 persons admitted to an outpatient clinic for the treatment of stress response syndromes indicated that the scale had a useful degree of significance and homogeneity. Empirical clusters supported the concept of subscores for intrusions and avoidance responses.

This chapter contains sections titled: Introduction The Characteristics That Distinguish Basic Emotions Does Any One Characteristic Distinguish the Basic Emotions? The Value of the Basic Emotions Position Acknowledgements References

Abstract : Research relevant to psychotherapy regarding facial expression and body movement, has shown that the kind of information which can be gleaned from the patients words - information about affects, attitudes, interpersonal styles, psychodynamics - can also be derived from his concomitant nonverbal behavior. The study explores the interaction situation, and considers how within deception interactions differences in neuroanatomy and cultural influences combine to produce specific types of body movements and facial expressions which escape efforts to deceive and emerge as leakage or deception clues.

Observers in both literate and preliterate cultures chose the predicted emotion for photographs of the face, although agreement was higher in the literate samples. These findings suggest that the pan-cultural element in facial displays of emotion is the association between facial muscular movements and discrete primary emotions, although cultures may still differ in what evokes an emotion, in rules for controlling the display of emotion, and in behavioral consequences.

ABSTRACT Graham (1975) demonstrated that a weak prestimulus could effectively inhibit or facilitate the eyeblink component of the startle reflex in humans, depending on the temporal duration of the prestimulus. This study had three goals: 1) to replicate the findings of Graham, 2) to establish the reliability of this phenomenon by a test‐retest comparison, and 3) to compare the eyeblink reflex response of normal subjects with schizophrenic subjects. Seven prestimulus durations of continuous tone (from 0 to 2000 msec) were presented to 20 normal subjects and the results confirmed that maximal inhibition of eyeblink amplitude occurred in the 120 msec prestimulus condition. Increased amplitude occurred nonsignificantly when the prestimulus lasted for 2000 msec. On retest, 14 normal subjects showed a significant degree of reliability. When 20 normal subjects were compared to 12 schizophrenic subjects, significant differences in eyeblink response were found for blink amplitude and latency in the 60 msec prestimulus condition. This change is consistent with information processing “overload” theories of sensory overstimulation in schizophrenia. The blink reflex is a rather stable phenomenon and is probably altered in schizophrenia and/or by antipsychotic medication.

J. A. Russell (1994) misrepresents what universality means, misinterprets the evidence from past studies, and fails to consider or report findings that disagree with his position. New data are introduced that decisively answer the central question that Russell raises about the use of a forced-choice format in many of the past studies. This article also shows that his many other qualms about other aspects of the design of the studies of literate cultures have no merit. Russell's critique of the preliterate cultures is inaccurate; he does not fully disclose what those who studied preliterate subjects did or what they concluded that they had found. Taking account of all of Russell's qualms, my analysis shows that the evidence from both literate and preliterate cultures is overwhelming in support of universals in facial expressions.

The forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its complexity, cell migration in the forebrain is extremely elaborated, with widespread dispersion of cells across multiple functionally distinct areas. Two general modes of migration are distinguished in the forebrain: radial migration, which establishes the general cytoarchitectonical framework of the different forebrain subdivisions; and tangential migration, which increases the cellular complexity of forebrain circuits by allowing the dispersion of multiple neuronal types. Here, we review the cellular and molecular mechanisms underlying each of these types of migrations and discuss how emerging concepts in neuronal migration are reshaping our understanding of forebrain development in normal and pathological situations.

Conducted a cross-validational study on the Impact of Event Scale (IES), a self-report instrument assessing the essential characteristics associated with stress disorders. 35 bereaved outpatients completed the IES before entering time-limited dynamic psychotherapy and at 4 and 12 mo following termination. A further 28 Ss, not participating in therapy, completed the measure at similar intervals. Results confirm the scale's relevance, internal consistency, and sensitivity. In addition, data are interpreted as consistent with a clinically derived theoretical model of the pattern of response to serious life events. As predicted by the theory, the syndromatic group showed greater intensity of intrusive and avoidance states; the relevant salience of reported experience was similar across groups; and the syndromatic group before intervention was characterized by an absence of a movement toward completion of processing the meaning of the event. (11 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)

This study is one of a series devoted to the analysis of the relation between adult socialization patterns and adaptation. Panel data collected for an older sample are drawn upon to document further the equivocal nature of this relationship when conventional measures of social role and interaction are compared with three different types of indicators of adaptation. The comparative importance, respectively, of social privilege and social deprivation for adaptation varies in accordance with the subjectivity of adaptive measure used. It also differs for self as compared with professional appraisals of well-being. Regardless of the overall pattern of these interrelationships, deviant cells are sizeable. The introduction of a variable bearing on the quality of social relationships, in this case the presence or absence of a confidant, helps considerably to explicate both sets of findings. The presence of an intimate relationship serves as a buffer both against gradual social losses in role and interaction and against the more traumatic losses accompanying widowhood and retirement. Age and sex differences may have implications for the differential in the survival rates of men and women, as well as for the relation between socialization patterns and adaptation at earlier stages of the lifespan.

Astrocytes are no longer seen as a homogenous population of cells. In fact, recent studies indicate that astrocytes are morphologically and functionally diverse and play critical roles in neurodevelopmental diseases such as Rett syndrome and fragile X mental retardation. This review summarizes recent advances in astrocyte development, including the role of neural tube patterning in specification and developmental functions of astrocytes during synaptogenesis. We propose here that a precise understanding of astrocyte development is critical to defining heterogeneity and could lead advances in understanding and treating a variety of neuropsychiatric diseases.

Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the neural plate and neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anterior-posterior axis and the longitudinal organization of the anterior CNS. Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the neural plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx-2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic neural plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the neural plate.

The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.

OBJECTIVE: Some prolonged and turbulent grief reactions include symptoms that differ from the DSM-IV criteria for major depressive disorder. The authors investigated a new diagnosis that would include these symptoms. METHOD: They developed observer-based definitions of 30 symptoms noted clinically in previous longitudinal interviews of bereaved persons and then designed a plan to investigate whether any combination of these would serve as criteria for a possible new diagnosis of complicated grief disorder. Using a structured diagnostic interview, they assessed 70 subjects whose spouses had died. Latent class model analyses and signal detection procedures were used to calibrate the data against global clinical ratings and self-report measures of grief-specific distress. RESULTS: Complicated grief disorder was found to be characterized by a smaller set of the assessed symptoms. Subjects elected by an algorithm for these symptoms patterns did not significantly overlap with subjects who received a diagnosis of major depressive disorder. CONCLUSIONS: A new diagnosis of complicated grief disorder may be indicated. Its criteria would include the current experience (more than a year after a loss) of intense intrusive thoughts, pangs of severe emotion, distressing yearnings, feeling excessively alone and empty, excessively avoiding tasks reminiscent of the deceased, unusual sleep disturbances, and maladaptive levels of loss of interest in personal activities.

The striatum, the largest component of the basal ganglia, contains projection neurons and interneurons. Whereas there is considerable agreement that the lateral ganglionic eminence (LGE) is the origin of striatal projection neurons, less is known about the origin of striatal interneurons. Using focal injections of retrovirus into the ventral telencephalon in vitro, we demonstrate that most striatal interneurons tangentially migrate from the medial ganglionic eminence (MGE) or the adjacent preoptic/anterior entopeduncular areas (POa/AEP) and express the NKX2.1 homeodomain protein. Although the majority of striatal interneurons (cholinergic, calretinin(+), and parvalbumin(+)) maintain the expression of NKX2.1 into adulthood, most of the interneurons expressing somatostatin (SOM), neuropeptide Y (NPY), and neural nitric oxide synthase (NOS) appear to downregulate the expression of NKX2.1 as they exit the neuroepithelium. Analysis of striatal development in mice lacking Nkx2.1 suggests that this gene is required for the specification of nearly all striatal interneurons. Similar analysis of mice lacking the Mash1 basic helix-loop-helix (bHLH) or both the Dlx1 and Dlx2 homeodomain transcription factors demonstrates that these genes are required for the differentiation of striatal interneurons. Mash1 mutants primarily have a reduction in early-born striatal interneurons, whereas Dlx1/2 mutants primarily have reduced numbers of late-born striatal interneurons. We also present evidence implicating the Lhx6 and Lhx7 LIM-homeobox genes in the development of distinct interneuron subtypes. Finally, we hypothesize that, within the MGE, radially migrating cells generally become projection neurons, whereas tangentially migrating cells mainly form interneurons of the striatum and cerebral cortex.

Because of recent resurgence in its consumption, the effects and health consequences of smokeless tobacco are of considerable public health interest. We studied the extent and time course of absorption of nicotine and cardiovascular effects of smokeless tobacco (oral snuff and chewing tobacco) and compared it with smoking cigarettes and chewing nicotine gum in 10 healthy volunteers. Maximum levels of nicotine were similar but, because of prolonged absorption, overall nicotine exposure was twice as large after single exposures to smokeless tobacco compared with cigarette smoking. All tobacco use increased heart rate and blood pressure, with a tendency toward a greater overall cardiovascular effect despite evidence of development of some tolerance to effects of nicotine with use of smokeless tobacco. Relatively low levels of nicotine and lesser cardiovascular responses were observed with use of nicotine gum. Adverse health consequences of smoking that are nicotine related would be expected to present a similar hazard with the use of smokeless tobacco.

OBJECTIVE: To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease. METHOD: Systematic, retrospective, blinded chart review was performed of 252 patients with a neurodegenerative disease diagnosis seen in our specialty clinic between 1999 and 2008. Neurodegenerative disease diagnoses included behavioral-variant frontotemporal dementia (n = 69), semantic dementia (n = 41), and progressive nonfluent aphasia (n = 17) (all meeting Neary research criteria); Alzheimer's disease (n = 65) (National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association research criteria); corticobasal degeneration (n = 25) (Boxer research criteria); progressive supranuclear palsy (n = 15) (Litvan research criteria); and amyotrophic lateral sclerosis (n = 20) (El Escorial research criteria). Reviewers remained blinded to each patient's final neurodegenerative disease diagnosis while reviewing charts. Extensive caregiver interviews were conducted to ensure accurate and reliable diagnostic histories. For each patient, we recorded history of psychiatric diagnosis, family psychiatric and neurologic history, age at symptom onset, and demographic information. RESULTS: A total of 28.2% of patients with a neurodegenerative disease received a prior psychiatric diagnosis. Depression was the most common psychiatric diagnosis in all groups. Behavioral-variant frontotemporal dementia patients received a prior psychiatric diagnosis significantly more often (50.7%; P < .001) than patients with Alzheimer's disease (23.1%), semantic dementia (24.4%), or progressive nonfluent aphasia (11.8%) and were more likely to receive diagnoses of bipolar disorder or schizophrenia than were patients with other neurodegenerative diseases (P < .001). Younger age (P < .001), higher education (P < .05), and a family history of psychiatric illness (P < .05) increased the rate of prior psychiatric diagnosis in patients with behavioral-variant frontotemporal dementia. Cognitive, behavioral, and emotional characteristics did not distinguish patients who did or did not receive a prior psychiatric diagnosis. CONCLUSIONS: Neurodegenerative disease is often misclassified as psychiatric disease, with behavioral-variant frontotemporal dementia patients at highest risk. While this study cannot rule out the possibility that psychiatric disease is an independent risk factor for neurodegenerative disease, when patients with neurodegenerative disease are initially classified with psychiatric disease, the patient may receive delayed, inappropriate treatment and be subject to increased distress. Physicians should consider referring mid- to late-life patients with new-onset neuropsychiatric symptoms for neurodegenerative disease evaluation.

Astrocytes, the most abundant cell population in the central nervous system (CNS), are essential for normal neurological function. We show that astrocytes are allocated to spatial domains in mouse spinal cord and brain in accordance with their embryonic sites of origin in the ventricular zone. These domains remain stable throughout life without evidence of secondary tangential migration, even after acute CNS injury. Domain-specific depletion of astrocytes in ventral spinal cord resulted in abnormal motor neuron synaptogenesis, which was not rescued by immigration of astrocytes from adjoining regions. Our findings demonstrate that region-restricted astrocyte allocation is a general CNS phenomenon and reveal intrinsic limitations of the astroglial response to injury.

OBJECTIVE: The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans. METHOD: A selective serotonin reuptake inhibitor (SSRI), paroxetine, 20 mg/day (N = 26), or placebo (N = 25) was administered to normal volunteers in a double-blind manner for 4 weeks, and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment. RESULTS: Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation. Changes in both negative affect and affiliative behavior were significantly related to volunteers' plasma SSRI levels at the end of the experiment. CONCLUSIONS: Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology.

Daily intake of nicotine in 22 subjects was estimated from metabolic clearance data obtained after intravenous infusion of nicotine and from blood and urinary nicotine concentration data obtained over 24 hr when the subjects were smoking cigarettes. Daily intake of nicotine averaged 37.6 mg (+/- 17.7, SD) but varied widely among subjects (10.5 to 78.6 mg). Men metabolized nicotine faster than did women, but daily intake of nicotine did not differ. Intake correlated strongly with cigarettes smoked per day (r = 0.59) but not with machine-determined yield. Nicotine intake per cigarette averaged 1.04 mg (+/- 0.36) but did not correlate with machine-determined yield. Correlations between several commonly used biochemical markers of tobacco smoke and nicotine intake were examined; the afternoon (4:00 P.M.) blood level of nicotine was the best marker.

Cotinine is the major metabolite of nicotine in man. We studied cotinine disposition kinetics in 28 healthy habitual cigarette smokers. Eight subjects received cotinine fumarate, 4 micrograms base/kg/min IV for 60 min. Mean (+/- SD) metabolic clearance was 60 +/- 12 ml/min and mean renal clearance was 12 +/- 5 ml/min, averaging 17% of total clearance. Steady-state volume of distribution was slightly greater than body weight (mean 88 +/- 17 l). Terminal t 1/2 averaged 15.8 +/- 4.0 hr in these eight subjects and 19.7 +/- 6.5 hr in another 12 subjects who abstained from smoking for 3 days. The effect of urinary acidification and alkalinization on renal clearance of cotinine during cigarette smoking was studied in another group of eight subjects. Compared with baseline (mean urinary pH 5.8, renal clearance 12.3 +/- 5.9 ml/min), renal clearance was increased about 50% by urinary acidification (pH 4.4, clearance 18.6 +/- 10 ml/min), but it was not affected by alkalinization (pH 6.7, clearance 14.0 +/- 10.4 ml/min). Infusion of cotinine to blood concentrations seen in moderately heavy smokers had no effect on heart rate, blood pressure, or skin temperature, measures that are sensitive to effects of nicotine. No spontaneous subjective effects were reported. We conclude that, at levels to which cigarette smokers are generally exposed, cotinine exerts no cardiovascular activity and weak, if any, psychologic activity.