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Biomedical subjects

B Kirkpatrick

Publications and source records attributed to B Kirkpatrick.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neurological signs and the heterogeneity of schizophrenia.

OBJECTIVE: More than 20 studies of schizophrenia have found a three-factor model of symptom complexes or syndromes consisting of hallucinations/delusions, disorganization of thought and behavior, and negative symptoms. Several lines of evidence suggest that these syndromes relate to neurobiological differences. We examined the relationship of these three syndromes to neurological signs. METHOD: The relationships among the subscales of the Neurological Evaluation Scale and hallucinations/delusions, disorganization, and the deficit syndrome were examined in 83 clinically stable outpatients with schizophrenia. Patients with the deficit syndrome have enduring, idiopathic (or primary) negative symptoms. RESULTS: Each of the three syndromes had a distinctive pattern of relationships to neurological signs. Disorganization was significantly related to the total score on the Neurological Evaluation Scale, to sensory integration, and to the sequencing of complex motor acts. The deficit syndrome was significantly related to sensory integration only. Neither hallucinations/delusions nor a continuous measure of negative symptoms derived from the Brief Psychiatric Rating Scale (that measured both primary and secondary negative symptoms, as well as enduring and transient symptoms) was related to any of the Neurological Evaluation Scale subscales or total score. Drug treatment was not related to neurological impairment. CONCLUSIONS: The results further support the neurobiological significance of the three clinical syndromes of schizophrenia. Ratings on a scale measuring negative symptoms appear to be less sensitive to neurobiological correlates than is the categorization of the presence or absence of the deficit syndrome.

Adult↗
PubMed2000

Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families.

OBJECTIVE: The deficit syndrome is a subtype of schizophrenia characterized by primary and enduring negative features of psychopathology. It appears to reflect a distinct subtype within the syndrome of schizophrenia. Little is known about the familial or genetic aspects of the deficit syndrome. The purpose of this study was to determine whether deficit versus nondeficit subtypes are correlated in sibling pairs affected with schizophrenia. METHOD: The present study was based on the Irish Study of High-Density Schizophrenia Families. From the earlier study the authors selected a subset of patients who were members of sibling pairs in which both siblings had been diagnosed with "core" schizophrenia, which included schizophrenia, simple schizophrenia, and schizoaffective disorder with poor outcome. The Schedule for the Deficit Syndrome was used to make deficit versus nondeficit diagnoses, which were based on chart examinations by reviewers blind to sibling status. This method resulted in 65 patients being diagnosed with the deficit syndrome and 401 patients diagnosed as nondeficit (prevalence=13.9%). This group included 347 full sibling pairs, which were analyzed for resemblance with respect to deficit versus nondeficit subtype by means of logistic regression. RESULTS: Deficit versus nondeficit subtypes were significantly correlated in sibling pairs concordant for core schizophrenia. CONCLUSIONS: Familial factors contribute significantly to whether a person has the deficit subtype of schizophrenia. This familial contribution could be genetic or environmental.

Adult↗
PubMed1999

Deficit psychopathology and a paradigm shift in schizophrenia research.

Despite recognition that schizophrenia must have syndrome status in the absence of proof of a single etiopathophysiologic process, a century of work has been based on designs that conceptualize schizophrenia as a single disease entity. Reducing heterogeneity at several levels of functioning is desirable. In this article we summarize progress using deficit syndrome psychopathology to address heterogeneity. The deficit syndrome has proven to be reliable, with construct validity, as well as predictive validity with biological, treatment, and course variables. We propose a shift in schizophrenia research away from the syndrome level toward study designs that identify more homogeneous entities. Doing so will increase the statistical power of study designs by reducing false positive cases.

Affect↗
PubMed1999

Interstitial cells of the white matter in the inferior parietal cortex in schizophrenia: An unbiased cell-counting study.

Previous studies have found an increased density of the interstitial cells of the white matter (ICWMs) in the frontal and temporal cortex in schizophrenia. Some data suggested this abnormality was restricted to a subgroup of patients, whose clinical features were consistent with the presence of the deficit syndrome. Clinical studies suggest deficit features are due to an abnormality in a cortical-subcortical circuit that includes dorsolateral prefrontal and inferior parietal cortex. We compared the density of ICWMs labeled for MAP2 immunoreactivity in Brodmann area 39 (inferior parietal cortex) from nine schizophrenia subjects (three deficit and six nondeficit) and nine matched controls using an unbiased cell-counting technique. The density of ICWMs was significantly greater in the deficit syndrome subjects compared to the nondeficit schizophrenia group (respective means +/- SEM, 0.22 +/- 0.04, and 0. 13 +/- 0.02; P < 0.05). The density of ICWMs in the deficit group was also significantly greater (P < 0.05) than that of the control group (0.09 +/- 0.02), but the nondeficit and control groups were not significantly different. These findings 1) confirm that an abnormal placement of neurons in the white matter is found in schizophrenia, 2) provide evidence for a microscopic anatomical abnormality in the inferior parietal cortex, and 3) suggest the ICWM abnormality may be confined to deficit patients.

Adult↗
PubMed1999

Forebrain connections of medial agranular cortex in the prairie vole, Microtus ochrogaster.

Fluorescent axonal tracers were used to investigate the connections of medial agranular cortex (frontal area 2, Fr2) in male prairie voles. The rostral and caudal portions of Fr2 (rFr2 and cFr2) have distinct but partially overlapping patterns of connections. Thalamic labeling after cFr2 injections was present in anteromedial nucleus (AM), ventrolateral nucleus (VL), lateral segment, mediodorsal nucleus (MDl), centrolateral nucleus (CL), ventromedial nucleus (VM), posterior nucleus (Po) and lateral posterior nucleus (LP). A band of labeled cells involving CL, central medial nucleus (CM) and rhomboid nucleus (Rh) formed a halo around the periphery of submedial (gelatinosus) nucleus (Sm). Within cFr2 there is a rostrocaudal gradient whereby projections from VL and MDl become progressively sparser caudally, whereas those from LP and Po become denser. Rostral Fr2 receives afferents from a similar group of thalamic nuclei, but has denser innervation from VL and MDl, lacks afferents from LP, and receives less input from nuclei around the periphery of Sm. Caudal Fr2 has extensive cortical connections including orbital cortex, rostral Fr2, Fr1, caudal parietal area 1 (Par1), parietal area 2 (Par2), and posterior parietal, retrosplenial and visual areas. Rostral Fr2 has similar connections with areas Fr1, Par1 and Par2; orbital connections focused in ventrolateral orbital cortex (VLO); connections with caudal Fr2; greatly reduced connections with posterior parietal cortex and the visual areas; and no connections with retrosplenial cortex. The axons linking rFr2 and cFr2 with each other and with other cortical areas travel predominately in the deep gray matter of layers VI and VII rather than in the white matter. Projections to the dorsal striatum from rFr2 are widespread in the head of the caudate, become progressively restricted to a dorsocentral focus more caudally, and disappear by the level of the anterior commissure. The projections from cFr2 are largely restricted to a focal dorsocentral region of the striatum and to the dorsolateral margin of the caudatoputamen. In comparison to area Fr2, the laterally adjacent area Fr1 has thalamic and cortical connections which are markedly restricted. Area Fr1 receives thalamic input from nuclei VL, anteroventral nucleus (AV), CL and Po, but none from mediodorsal nucleus (MD) or LP, and its input from VM is reduced. Cortical afferents to Fr1 originate from areas Fr2, caudal Par1 and Par2. Medial agranular cortex of prairie voles has a pattern of connections largely similar to that seen in rats, suggesting that area Fr2 in prairie voles is part of a cortical network that may mediate complex behaviors involving spatial orientation.

Animals↗
PubMed1999

Diazepam treatment of early signs of exacerbation in schizophrenia.

OBJECTIVE: Therapeutic intervention at the earliest phase of symptom exacerbation in schizophrenia is an important clinical need, but specific pharmacotherapeutic interventions for this phase of illness have not been established. This study examined diazepam efficacy for this phase of treatment. METHOD: A double-blind, randomized clinical trial with 53 schizophrenic patients compared diazepam with placebo (with fluphenazine treatment for a comparison group). Treatment was initiated at the earliest signs of exacerbation, and symptom progression was the dependent measure used to evaluate efficacy. RESULTS: Diazepam was statistically superior to placebo in preventing symptom progression and was comparable to fluphenazine. CONCLUSIONS: Efficacy data support the use of diazepam in treating prodromal and early warning signs of symptom exacerbation in schizophrenia. This therapeutic strategy may be especially important for patients who refuse antipsychotic drugs or as a supplemental approach in a treatment plan that emphasizes low-dose antipsychotic therapy.

Acute Disease↗
PubMed1999

Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.

OBJECTIVE: Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. METHOD: Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. RESULTS: The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. CONCLUSIONS: The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.

Adult↗
PubMed1999

Stability of the diagnosis of deficit syndrome in schizophrenia.

OBJECTIVE: Primary, enduring negative symptoms have been distinguished from negative symptoms more generally and are used to define the deficit syndrome of schizophrenia. Although the validity of the deficit syndrome has been demonstrated by using brain imaging, neuropsychological, illness outcome, and developmental history data, the stability of this diagnostic category has not been tested prospectively by using direct patient assessments. METHOD: Forty-three outpatients with schizophrenia and schizoaffective disorder were categorized into deficit and nondeficit groups an average of 3.8 years after having been previously categorized. RESULTS: There was 83% agreement between initial and blind follow-up designations of deficit status and 88% agreement on the nondeficit categorization. CONCLUSIONS: These results provide evidence for the long-term stability of the deficit syndrome in patients with schizophrenia and the reliability of the deficit/nondeficit categorization when diagnosed by those with appropriate training. Furthermore, they validate the method of categorizing deficit patients by using cross-sectional and retrospective data.

Adult↗
PubMed1998

Identification of a mutation in the low density lipoprotein receptor gene associated with recessive familial hypercholesterolemia in swine.

Elevated blood plasma cholesterol (hypercholesterolemia) is a major risk factor for coronary artery disease (CAD) in humans. Genetic dissection of polygenic lipid and lipoprotein disorders in swine, a key animal model for the study of familial hypercholesterolemia (FH) and CAD, led to the isolation of a monogenic subphenotype (FH-r), that is inherited in the recessive (r) manner. A genome scan mapped the FH-r locus close to the centromere of chromosome 2. Comparative mapping showed that this region shares homology with a part of human chromosome 19 that harbors the low density lipoprotein receptor (LDLR) locus, and therefore suggested LDLR as the prime candidate gene for FH-r. Cloning and sequencing of hepatic LDLR cDNA from two FH-r/r and one normal (N/N) animals disclosed a single missense mutation (R84C) in a region that corresponds to human exon 4. The C84 mutation cosegregates invariantly with hypercholesterolemia, which strongly suggests that this mutation is responsible for the observed hyperlipidemia.

Amino Acid Sequence↗
PubMed1998

Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome.

OBJECTIVE: In a preliminary report, the authors observed that clozapine was superior to haloperidol in the treatment of positive and negative symptoms in stable outpatients with schizophrenia. In this final report, they examine the effects of clozapine on positive and negative symptoms in patients with and without the deficit syndrome to determine which patients receive the positive symptom advantage of clozapine and the extent of clozapine's therapeutic effects on negative symptoms. In addition, they examine the long-term effects of clozapine on positive, negative, and affective symptoms, social and occupational functioning, and quality of life. METHOD: Seventy-five outpatients with schizophrenia, who met retrospective and prospective criteria for residual positive or negative symptoms, were entered into a 10-week double-blind, parallel-groups comparison of clozapine and haloperidol. Patients who completed the double-blind study were then entered into a 1-year open-label clozapine study. RESULTS: For patients who completed the 10-week double-blind study, clozapine was superior to haloperidol in treating positive symptoms. This effect was not observed in the intent-to-treat analyses. There was no evidence of any superior efficacy or long-term effect of clozapine on primary or secondary negative symptoms. Long-term clozapine treatment was associated with significant improvements in social and occupational functioning but not in overall quality of life. CONCLUSIONS: For schizophrenic patients who are able to tolerate clozapine therapy, clozapine has superior efficacy for positive symptoms but not negative symptoms and is associated with long-term improvements in social and occupational functioning for patients with and without the deficit syndrome.

Adult↗
PubMed1998

Summer birth and the deficit syndrome of schizophrenia.

OBJECTIVE: Patients with the deficit syndrome differ from other patients with schizophrenia relative to physiological correlates, course of illness, and response to treatment. Because of the abnormal seasonality of birth among persons with schizophrenia, the authors examined the relation between this risk factor and the deficit syndrome. METHOD: Findings in two clinical groups suggested an increase in summer births among deficit syndrome patients. The association between summer birth and the deficit syndrome was then examined in a catchment area study of first-admission patients with psychosis. RESULTS: In the catchment area sample, summer birth was also significantly associated with the deficit syndrome; negative symptoms broadly defined were not. CONCLUSIONS: These findings add to the increasing evidence that 1) patients with the deficit syndrome have a disease with an etiopathophysiology separate from that of other patients with what is now called schizophrenia and 2) the correlates of broadly defined negative symptoms are different from those for the deficit syndrome. The previously reported association between winter birth and schizophrenia appears to apply to nondeficit schizophrenia only.

Adult↗
PubMed1998

Recurrent pregnancy loss. An update.

OBJECTIVE: To comprehensively review causes of recurrent pregnancy loss and the currently applied methodologies for their diagnosis and management. STUDY DESIGN: A review article addressing pertinent issues on the subject of recurrent pregnancy loss, which, by definition, is three consecutive pregnancy losses prior to the 20th week of gestation. RESULTS AND CONCLUSION: Diagnostic workup and treatment of recurrent abortion often poses a special challenge as numerous conclusive and nonconclusive causes have been described with varied and often controversial approaches for their management. While a definitive cause may not be discovered in a significant number of cases, among those with an identifiable cause, anatomic disorders are by far the most conclusively diagnosable and effectively treatable conditions, making their exclusion or inclusion an essential part of the evaluation. That up to 60% of these cases may achieve successful pregnancy without any intervention should receive serious consideration when analyzing results of studies that claim therapeutic benefits from treatment modalities.

Abortion, Spontaneous↗
PubMed1997

Eye tracking disorder in schizophrenia is characterized by specific ocular motor defects and is associated with the deficit syndrome.

The objective was to determine the relationships between eye tracking disorder (ETD) in schizophrenia, specific ocular motor measures, and the deficit syndrome. Twenty-five normal comparison subjects and 53 schizophrenic patients had eye movements tested with infrared oculography using a sinusoidal target. Patients were assessed with the Schedule for the Deficit Syndrome. For the patients, the distribution of position root mean square error (a global measure of pursuit) was best fit by a mixture of two normal distributions. This information was used to divide the patients into two subgroups, those with and those without ETD. ETD was almost completely accounted for by several specific ocular motor measures and was significantly associated with the deficit syndrome. The finding that ETD was almost completely accounted for by specific measures bridges a gap of interpretation in this field. ETD and the deficit syndrome of schizophrenia may share a common pathophysiology of cerebral cortical-subcortical circuits.

Adult↗
PubMed1997

Borna disease virus antibodies and the deficit syndrome of schizophrenia.

We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p < 0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia.

Adult↗
PubMed1997

The integrative neurobiology of affiliation. Introduction.

The research presented at this conference, including a series of excellent posters from junior investigators, documents the pervasive importance of affiliation and other social behaviors. Affiliative behaviors interact with, but are distinct from reproductive and aggressive behaviors. Patterns of social behaviors tend to be more species-typical than the behaviors associated with reproduction or aggression. However, neural circuits necessary for approach or avoidance also are necessary for the expression of various types of affiliative behavior such as maternal behavior or pair-bond formation. Furthermore, candidate neurochemical systems have been identified that contribute to various types of affiliative behavior. For example, studies revealing new behavioral functions for steroid hormones of the adrenal axis, such as corticosterone, and neuropeptides, including the endorphins, oxytocin and vasopressin, extend our general knowledge of neurobiology; they may also lead to studies that expand our understanding of social behavior and the connections to systems that regulate emotions. The work represented in this volume also has important implications for the study of serious neuropsychiatric disorders. For example, episodes of certain of these disorders can be induced by social stressors; in other disorders, a marked decrease in affiliative behaviors is a prominent feature of the patients' difficulties. Furthermore, abnormalities in animal systems implicated in the neurobiology of affiliation (oxytocin, vasopressin, and the hypothalamic-pituitary-adrenal system) have also been documented for major depression in humans. Animal models, such as those described at this conference, offer evolutionary perspectives, from which it is possible to extract general principles. At the same time, our understanding of the mechanistic and neurobiological substrates of both constructive and destructive social behaviors is increasing. At the conference, the evolutionary and mechanistic perspectives converged on the theme that studies of affiliative behaviors cannot be fully interpreted in isolation from other social behaviors; neither can they effectively be isolated from the biological and social contexts that shape their expression. Advances in this research area seem dependent on integrating experimental research across levels of analysis. Although this task is challenging, we are confident that an awareness of integrative principles can lead to new and important research opportunities.

Aggression↗