Negative symptoms of schizophrenia: where do we go from here?
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Depression↗
Biomedical subjects
A L Miller
Publications and source records attributed to A L Miller.
Psychological stress and immunological responsiveness in normally cycling, follicular-stage women.
Nineteen women in the follicular stage of their menstrual cycles were assessed for immunological responsiveness to a 50-min series of three psychological tasks which reliably elicit cardiovascular and neuroendocrine stress responses. Ten follicular-stage women not subjected to stress served as controls. Stress decreased lymphocyte responsiveness to PHA and PWM, percent of CD4+ cells and the ratio of CD4+/CD8+ cells. Conversely, stress increased natural killer cell number and cytolytic activity, white blood cell, lymphocyte, T and B cell count. Except for natural killer cell number, none of these changes was exhibited by controls. Most of these stress responses are similar to those reported for men and form the basis for a continuing study of the effects of reproductive hormones and stress on cardiovascular and immunological function in women.
Adult↗
Effects of electrode configuration on threshold functions for electrical stimulation of the cochlea.
Psychophysical detection threshold vs frequency functions for sinusoidal electrical stimulation of the deafened cochlea were measured in 18 nonhuman primate subjects. Functions for monopolar or widely-spaced ( > 2.5 mm) bipolar stimulation were lower and usually had steeper slopes than those for more narrowly-spaced ( < 2.0 mm) bipolar stimulation. In 56% of the cases the difference between thresholds for narrowly-spaced bipolar of monopolar stimulation was greater for low frequency stimuli (63 or 100 Hz) than for high frequency stimuli (800 or 1,000 Hz) by 5 dB or more. Two cases were compared in more detail using pulsatile stimuli. For sinusoidal stimuli, one of these cases showed a moderate frequency dependent effect of electrode configuration and the other did not. The case with the frequency dependent effect of electrode configuration for sinusoids also showed a phase-duration dependent effect of electrode configuration for detection of single biphasic pulses: strength-duration curves (detection threshold in decibels vs pulse duration in ms/phase) were steeper for monopolar stimulation than for narrowly-spaced (0.7 mm) bipolar stimulation. This effect was not seen in the case that showed little or no frequency dependence in the effect of electrode configuration for sinusoidal stimuli. Slopes of threshold vs pulse rate functions where pulse duration was held constant at 2 ms/phase were not affected by electrode configuration in either subject.
Animal Welfare↗
Longitudinal analysis of communication deviance in the families of schizophrenic patients.
Considerable research on the family's contribution to the psychopathology and coping of mentally ill offspring has focused on disturbed parental communication patterns, in which parents are unable to share a common focus of attention and meaning with their children. This style of communication has been referred to as communication deviance (CD - Wynne and Singer 1963). Specifically, CD refers to instances in which speakers leave ideas incomplete, use language in an odd manner, use unclear referents, contradict previously made statements with little explanation, or make unintelligible or tangential statements.
Adult↗
Schizophrenia among Hispanics: epidemiology, phenomenology, course, and outcome.
A number of studies point to the influence of culture and ethnicity on the presentation and course of schizophrenia. In general, a relatively powerful influence of environmental factors is identified. This article reviews the literature on schizophrenia among Hispanics in the United States and uses the results of this review as a basis for identifying directions for future study. Research is divided into three major areas: epidemiology, phenomenology, and illness course and outcome. Ethnic comparisons suggest similar prevalence rates of schizophrenia. However, differences in illness phenomenology between certain subgroups of Hispanics are also observed. Moreover, culture can affect various aspects of the illness process, including illness definition, help- seeking behavior, response to treatment, and post-treatment adjustment. Proposed guidelines to direct future research ventures include (1) better delineation of the sociocultural attributes of the group under study, (2) validation of assessment instruments across ethnic groups, (3) use of innovative approaches to assess incidence and prevalence, (4) incorporation of qualitative methodology, (5) use of illness behavior models to provide a conceptual framework to guide investigations, and (6) integration of cross-cultural and biological studies.
Cross-Cultural Comparison↗
Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status.
OBJECTIVE: Interleukin-2, traditionally viewed as solely involved in immunological events, has recently been shown to exert profound effects on the development and regulation of the central nervous system. This study examined the relationships between interleukin-2 in the CSF and plasma of schizophrenic patients and clinical measures, including relapse and medication status. Plasma and CSF interleukin-1 alpha levels were also measured to ascertain the specificity of changes in cytokine levels. METHODS: Seventy-nine physically healthy male patients with schizophrenia (DSM-III-R) received diagnostic evaluation and behavioral ratings. Haloperidol treatment was withdrawn for up to 6 weeks and patients were evaluated for symptom recurrence. CSF and plasma were obtained by established procedures before haloperidol withdrawal (N = 79) and after (N = 64). RESULTS: CSF levels of interleukin-1 alpha decreased significantly after haloperidol withdrawal but showed no relation to clinical status. In contrast, levels of CSF interleukin-2 were associated with recurrence of psychotic symptoms. Relapse-prone patients, examined both while medicated and after drug withdrawal, had significantly higher levels of CSF interleukin-2 than patients who did not relapse. CSF interleukin-2 level during haloperidol treatment was a significant predictor of worsening in psychosis. CONCLUSIONS: Levels of interleukin-2, a molecule that plays both neurodevelopmental and neuroregulatory roles, may have a role in relapse in schizophrenia. Levels of CSF interleukin-2 appear to be affected by relapse mechanisms, while peripheral blood levels are not. These changes are specific to interleukin-2, since levels of interleukin-1 alpha were affected by medication withdrawal but not by change in clinical state.
Adult↗
Patterns of free calcium in multicellular stages of Dictyostelium expressing jellyfish apoaequorin.
To examine the patterns of high free cytosolic calcium or [Ca2+]i during Dictyostelium's development, we expressed apoaequorin in D. discoideum, reconstituted aequorin and observed the resultant patterns of calcium-dependent luminescence. Specific, high calcium zones are seen throughout normal multicellular development and are roughly coincident with those regions that later differentiate into stalk or stalk-like cells. A slug, for example, shows a primary high calcium zone within its front quarter and a secondary one around its tail; while a mound shows such a zone around the periphery of its base. Combined with previous evidence, our findings support the hypothesis that high [Ca2+]i feeds back to favor the stalk pathway. We also discovered several high calcium zones within the mound's base that do not coincide with any known prepatterns in D. discoideum. These include two, relatively persistent, antipodal strips along the mound's periphery. These various persistent zones of high calcium are largely made up of frequent, 10 to 30 second long, semiperiodic calcium spikes. Each of these spikes generates a correspondingly short-lived, 200 to 500 microns long, high calcium band which extends along the nearby surface. Similar, but relatively large and infrequent, spikes generate cross bands which extend across migrating slugs and just behind their advancing tips as well as across the peripheries of rotating mounds and midway between their antipodal strips. Moreover, calcium has a doubling time of about a second as various spikes rise. This last observation suggests that the calcium bands seen in Dictyostelium may be generated by so-called fast calcium waves.
Aequorin↗
Effects of electrical current configuration on stimulus detection.
Psychophysical detection of electrical stimulation of the cochlea was studied as a function of electrical-current configuration. Subjects were postlingually deaf humans with Nucleus 20 + 2, Nucleus 22, and Ineraid cochlear implants and nonhuman primates unilaterally deafened and implanted with a multielectrode array similar to the Nucleus implant. In nonhuman primate and human Ineraid subjects, which had percutaneous connectors, we compared threshold functions for sinusoids and pulse trains for quadrupolar, bipolar, monopolar, and parallel multipolar stimulation. Thresholds decreased across this set of configurations. In some cases, the effects of current configuration were dependent on sinusoidal frequency and pulse duration. Pulse duration-dependent effects were also seen when comparing bipolar, monopolar, and common-ground configurations. Bipolar and monopolar stimulation were compared in Nucleus subjects using pulse trains at 50 microseconds per phase. For bipolar stimulation, thresholds decreased as a function of electrode separation, reaching a level near that for monopolar stimulation at separations of 3.5 to 6.5 mm in most cases. These results may be interpreted in terms of effects of current configuration on the magnitude and shape of electrical-potential fields produced in the cochlea, although more central factors also play a role in determining psychophysical detection thresholds.
Animals↗
Immunological effects of acute and chronic nicotine administration in rats.
We previously demonstrated that acute nicotine administration decreased the response of rat blood leukocytes (PBL) to concanavalin A (ConA). We now extend those findings to a comparison between the effects of acute and prolonged nicotine exposure (ten daily injections), on PBL and splenocytes (SL). A single injection suppressed the PBL response to ConA and phytohemagglutinin (PHA); tolerance developed by ten injections. In contrast, acute nicotine did not affect SL response to ConA and reduced the PHA response only at the highest concentration. Ten nicotine injections enhanced SL responsiveness to PHA. The only change in PBL subsets was an increase in CD8+ cells following ten injections.
Animals↗
Imaging [Ca2+]i with aequorin using a photon imaging detector.
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Aequorin↗
Oscillations in free [Ca2+]i during early cell division cycles in Xenopus laevis embryos.
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Animals↗
Seizure following addition of erythromycin to clozapine treatment.
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Adult↗
Acute effects of neuroleptics on unmedicated schizophrenic patients and controls.
Acute administration of haloperidol (0.2 mg/kg) produced many more side effects in normal controls than in unmedicated schizophrenic patients. Prior to the neuroleptic challenge, both groups were on the peripheral monoamine oxidase inhibitor, debrisoquin, for at least 1 week, in order to enhance the relative contribution of CNS catecholamine metabolites to those measured in both plasma and urine. The patient group had higher plasma levels of methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) and higher urinary MHPG output than controls, but there were no effects of haloperidol challenge, compared to placebo challenge. In both groups there were significant declines in plasma HVA levels from 8:30 AM to 12 NOON. These declines were unaffected by the haloperidol challenge. Explanations for the marked differences in behavioral effects of haloperidol on patients and controls include the possibility that dopamine receptor numbers were increased in the brains of the schizophrenic patients.
Adult↗
Phosphorylation and subcellular location of alpha-L-fucosidase in lymphoid cells from patients with I-cell disease and pseudo-Hurler polydystrophy.
Mannose 6-phosphate is a recognition marker used by many newly made acid hydrolases for their transport to lysosomes. Previously, we investigated the incorporation of 32Pi into alpha-L-fucosidase of lymphoid cell lines from a healthy individual (control) and an I-cell disease patient [DiCioccio and Miller, Glycobiology, 1, 595-604 (1991)]. Phosphoserine was found in immunoprecipitable alpha-L-fucosidase of both control and I-cell lymphoid cells, but mannose 6-phosphate was identified only in enzyme of control cells. Extension of this investigation to lymphoid cultures of a pseudo-Hurler polydystrophy patient also identified only phosphoserine in alpha-L-fucosidase. Using [3H]mannose instead of 32Pi, the precise identification of mannose 6-phosphate in alpha-L-fucosidase of control cells, and its absence in alpha-L-fucosidase of I-cell and pseudo-Hurler cells, was established. The stoichiometry of phosphorylation of alpha-L-fucosidase in I-cell, pseudo-Hurler and control lymphoid cells was 3, 4 and 10 mol Pi/mol enzyme, respectively. alpha-L-Fucosidase was located in lysosomes isolated from control, I-cell and pseudo-Hurler lymphoid cells by subcellular fractionation on Percoll density gradients. Both I-cell and pseudo-Hurler lymphoid cells displayed normal intralysosomal activity of alpha-L-fucosidase despite lack of the mannose 6-phosphate marker. Thus, I-cell and pseudo-Hurler lymphoid cells must possess a mannose 6-phosphate-independent mechanism for directing alpha-L-fucosidase to lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Cells, Cultured↗
Metabolic inhibition enhances Ca(2+)-activated K+ current in smooth muscle cells of rabbit portal vein.
The effect of metabolic inhibition on macroscopic and single-channel K+ currents in isolated rabbit portal vein myocytes was investigated by patch-clamp technique. Depression of adenosine triphosphate synthesis was produced by 2-deoxy-D-glucose (10 mM) and either cyanide (2 mM) or dinitrophenol (50 microM). Outward quasi-steady-state current evoked by a ramp protocol and outward time-dependent current during step depolarizations were increased during metabolic inhibition. The reversal potential for quasi-steady-state current shifted negatively toward equilibrium potential of K+ during treatment consistent with a role for K+ conductance and hyperpolarization of membrane potential. The macroscopic K+ current affected was 1) voltage dependent, 2) inhibited by intracellular Ca2+ chelation and low tetraethylammonium ion (1 mM) but unaffected by 4-aminopyridine (2 mM), and 3) associated with a rise in intracellular Ca2+ assessed by indo 1. Metabolic inhibition caused an increase in voltage-dependent large-conductance K+ channel (120-130 pS) activity in cell-attached patches of myocytes bathed in physiological solution (140 mM K+ in pipette). The channels were blocked in a flickery fashion by tetraethylammonium ion (0.5 mM) and inhibited with charybdotoxin (100 nM). We conclude that metabolic inhibition increases the activity of large-conductance Ca(2+)-activated K+ channels in vascular smooth muscle.
2,4-Dinitrophenol↗
Calcium buffer injections inhibit cytokinesis in Xenopus eggs.
A slow cortical wave of high calcium accompanies the elongation of cleavage furrows in medaka fish eggs as well as in Xenopus eggs. We explored the role of such waves by injecting calcium buffers into Xenopus eggs at various times before and during first and second cleavage. Injection earlier than about 15 minutes before first cleavage normally starts delays it for hours. Injection between about 15 minutes and a few minutes before cleavage normally starts allows a (short) furrow to form on time but usually yields an eccentric one. This forms away from the injection side, often as far off-center as the egg's equator, and then regresses. Injection soon after it starts quickly arrests elongation of the furrow and eventually induces its regression; while injection a bit later likewise soon arrests elongation but allows delocalized furrow deepening to continue. The dependence of these inhibitory actions upon the dissociation constants and final cytosolic concentrations of the injected buffers indicates that they act as shuttle buffers to suppress needed zones of high calcium in the micromolar range. We conclude that the high calcium that is found within these furrows is needed to induce them, to extend them and even to maintain them. Moreover, while short, eccentric furrows often form as far off center as the equator, they somehow always form along a meridian through the animal pole. This seems difficult to explain by the orthodox, diastral model. Rather, it suggests that the cleavage furrows in Xenopus--and perhaps in animal cells quite generally--are directly induced by a diastema or telophase disc rather than by the asters.
Animals↗
Animistic thinking in psychotic versus conduct-disordered hospitalized adolescents.
25 adolescents showing a Psychotic-spectrum Disorder were compared with 24 adolescents showing Conduct Disorder on a task eliciting reasons for attributing life to an ambiguous pictorial stimulus (dough on a beach). Consistent with expectations from earlier research, the psychotic adolescents showed greater modes of animistic thinking (attributions of life to nonlife forms) than conduct-disordered youth, associated with theorized merging between self and the nonhuman environment. Implications are discussed.
Adolescent↗