Search PubMed⌕ Search

Biomedical subjects

K L Davis

Publications and source records attributed to K L Davis.

At least 73 records · Page 4Linked to original sources
PubMed1999

Identifying families with likely genetic protective factors against Alzheimer disease.

Elderly individuals who lived beyond the age of 90 years without dementia were hypothesized to have increased concentrations of genetic protective factors against Alzheimer disease (AD), conferring a reduced liability for this disease relative to less-aged nondemented elderly. However, testing this hypothesis is complicated by having to distinguish such a group from those who may lack genetic risk factors for AD, have had protective environmental exposures, or have escaped dementia for other reasons. Probands carrying genetic protective factors, however, should have relatives with lower illness rates not only for earlier-onset disease, when genetic risk factors are a strong contributing factor to the incidence of AD, but also for later-onset disease, when the role of these factors appears to be markedly diminished. AD dementia was assessed through family informants in 6,660 first-degree relatives of 1,049 nondemented probands aged 60-102 years. The probands were grouped by age (60-74, 75-89, and 90-102 years), and the cumulative survival from AD and 10-year-age-interval hazard rates of AD were calculated in their first-degree relatives. Cumulative survival from AD was significantly greater in the relatives of the oldest proband group (aged 90-102 years) than it was in the two younger groups. In addition, the reduction in the rate of illness for this group was relatively constant across the entire late life span. The results suggest that genetic factors conferring a lifelong reduced liability of AD may be more highly concentrated among nondemented probands aged >/=90 years and their relatives. Efforts to identify protective allele-bearing genes that are associated with very late-onset AD should target the families of nonagenarians and centenarians.

Aged↗
PubMed1999

Contamination of lymph from the major prenodal cardiac lymphatic in dogs.

Cannulation of the canine major prenodal cardiac lymphatic (MPCL) is the most common approach for the investigation of myocardial lymphatic function. However, the assumption that the MPCL drains pure cardiac lymph has been questioned. We studied variations of MPCL anatomy and investigated whether noncardiac lymph is drained by this lymphatic. After dye was injected into the lungs and left ventricular myocardium in 21 dogs, dissection of the cardiac lymphatic system yielded 3 anatomic variations. In variations 1 and 2 (81% of dogs), a mixture of cardiac and pulmonary lymph was drained via the MPCL. In variation 3 (19% of dogs) no connection was found between MPCL and pulmonary lymphatics. In variations 1 and 2, alteration of tidal volume resulted in significant changes of lymph flow rate. The pulmonary contribution to MPCL lymph flow was estimated as 34% in variation 2. We conclude that MPCL lymph may contain not only cardiac lymph but also significant pulmonary contamination. This finding should be considered in the interpretation of lymph data from cannulation of the canine MPCL.

Animals↗
PubMed1999

Test-retest reliability of psychological and neurobehavioral tests self-administered by computer.

A series of 12 psychological and 7 neurobehavioral performance tests were administered twice to a nonclinical normative sample with 1 week between administrations. The tests were presented in a self-administered computerized format. One week test-retest reliabilities were comparable to conventional administration formats. The results suggest that individual test reliability is not affected when tests are administered as part of an extensive multi-measure battery. Computer administered test reliability coefficients also were compared to a Mixed Format (computer-conventional) administration with mixed format reliabilities generally similar to the reliabilities of published conventional tests but also generally lower than same format testing. Compared to psychological test reliability, neurobehavioral test reliability appeared more vulnerable to decreases with mixed format testing. These conclusions should not be generalized to all computer implemented tests as the qualities of the test implementation will affect the outcome.

Adult↗
PubMed1999

CSF beta-amyloid, cognition, and APOE genotype in Alzheimer's disease.

OBJECTIVES: We examined the relationship between CSF amyloid beta peptide (A beta) concentration and AD severity in 31 probable AD patients and explored whether APOE genotype modifies this relationship. BACKGROUND: A beta deposition in AD brains has been correlated with disease severity and with APOE-epsilon4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF A beta and disease severity in an antemortem sample. METHODS: Patients carried the clinical diagnosis of probable AD and did not have serious medical illness, current or past diagnosis of mood disorder, schizophrenia or alcoholism, or current psychotic features. The Mini-Mental State Examination (MMSE) was administered to the patient within 3 months of CSF collection. CSF was analyzed for A beta1-40 and A beta1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run from blood. Correlations were performed between MMSE score and A beta1-40 and A beta1-42 concentrations while controlling for potential confounding variables. RESULTS: CSF measures of A beta1-40 and A beta1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01). CSF A beta1-40 and A beta1-42 concentrations were positively correlated with MMSE score. The negative association between CSF A beta measures and disease severity remained significant after controlling for age (A beta1-40 and MMSE score: r = 0.46, df = 28, p = 0.01; A beta1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-epsilon3/3 homozygotes there was a significant positive correlation only between A beta1-42 and MMSE score (A beta1-42, r = 0.94, p = 0.02; A beta1-40, r = 0.79, p = 0.11). CONCLUSIONS: We hypothesize that an increased deposition of A beta in plaques results in decreased CSF A beta concentration. The stronger relationship between MMSE score and CSF A beta, specifically in APOE-epsilon3/3 homozygotes, suggests that patients with APOE-epsilon3/3 genotype may have different pathogenic mechanisms than the other genotypes for A beta deposition or clearance.

Aged↗
PubMed1999

Alzheimer's disease: seeking new ways to preserve brain function. Interview by Alice V. Luddington.

Alzheimer's disease (AD) is characterized in the brain by the deposition of amyloid protein outside the neuron, resulting in the formation of plaques, and inside the neuron with neurofibrillary tangles. It is not yet known what causes these pathologic changes, although age and genetics are major risk factors. The cholinesterase inhibitors tacrine and donepezil block acetylcholinesterase and therefore preserve the neurotransmitter acetylcholine. Three other investigational cholinesterase inhibitors are rivastigmine, metrifonate, and galanthamine. Existing therapies being studied for use in AD include vitamin E, estrogen preparations, and anti-inflammatory agents. The physician's role is to care for both the AD patient and the family, which are profoundly affected by this disease.

Alzheimer Disease↗
PubMed1998

Ventricular enlargement in poor-outcome schizophrenia.

BACKGROUND: A subset of patients with schizophrenia, defined on the basis of longitudinal deficits in self-care, may show a classic ("Kraepelinian") degenerative course. An independent validator of the phenomenologically defined Kraepelinian subtype might be provided by a structural indicator of possible brain degeneration: ventricular size as measured by computed tomography (CT). METHODS: To examine whether Kraepelinian patients would show a differential increase in ventricular size over time, two CT scans were conducted at intervals separated by > 4 years, an average of 5 years. Fifty-three male patients with DSM-III-R diagnoses of chronic schizophrenia were subdivided into Kraepelinian (n = 22; mean age = 42 +/- 6 years) and non-Kraepelinian (n = 31; mean age = 38 +/- 12.2 years) subgroups. Kraepelinian patients were defined on the basis of longitudinal criteria: > 5 years of complete dependence on others for life necessities and care, lack of employment, and sustained symptomatology. Thirteen normal elderly volunteers (mean age = 60 +/- 17.8) were also scanned at 4-year intervals. CT measurements were made by raters without knowledge of subgroup membership. A semiautomated computer program was used to trace the anterior horn, lateral ventricles, and temporal horns for each slice level on which they were clearly seen. RESULTS: The ventricles showed a bilateral increase in size over the 4-year interval in the Kraepelinian subgroup, more marked in the left hemisphere than the right. By contrast, neither the non-Kraepelinian subgroup nor the normal volunteers showed significant CT changes from scan 1 to scan 2. CONCLUSIONS: Thus, the longitudinal dysfunctions in self-care that characterize the Kraepelinian patients were associated with an independent indicator of brain abnormality.

Adult↗
PubMed1998

Human erythropoietin dimers with markedly enhanced in vivo activity.

Human erythropoietin, a widely used and important therapeutic glycoprotein, has a relatively short plasma half-life due to clearance by glomerular filtration as well as by other mechanisms. We hypothesized that an erythropoietin species with a larger molecular size would exhibit an increased plasma half-life and, potentially, an enhanced biological activity. We now report the production of biologically active erythropoietin dimers and trimers by chemical crosslinking of the conventional monomeric form. We imparted free sulfhydryl residues to a pool of erythropoietin monomer by chemical modification. A second pool was reacted with another modifying reagent to yield monomer with maleimido groups. Upon mixing these two pools, covalently linked dimers and trimers were formed that were biologically active in vitro. The plasma half-life of erythropoietin dimers in rabbits was >24 h compared with 4 h for the monomers. Importantly, erythropoietin dimers were biologically active in vivo as shown by their ability to increase the hematocrits of mice when injected subcutaneously. In addition, the dimers exhibited >26-fold higher activity in vivo than did the monomers and were very effective after only one dose. Dimeric and other oligomeric forms of Epo may have an important role in therapy.

Animals↗
PubMed1998

Lateral ventricular enlargement in schizophrenic probands and their siblings with schizophrenia-related disorders.

BACKGROUND: To investigate possible genetic determinants of ventricular enlargement in schizophrenia, we compared lateral ventricle/brain ratios (VBRs) in schizophrenic patients with their own siblings, some with and some without other schizophrenia-related disorders [e.g., schizotypal personality disorder (SPD)], as well as with a group of unrelated normal controls. METHODS: VBRs, measured by computed tomography, were compared in both groupwise and within-sibship analyses, the latter method providing a measure of control over familial/genetic factors related to VBR, but unrelated to schizophrenia. RESULTS: The VBRs were significantly different across the groups, but the only significant pairwise group comparison was between the schizophrenia and no-SRD family member groups. In the within-sibship analyses, however, the VBRs of those with SPD and schizophrenia were similar, and both groups had significantly larger VBRs than their own siblings without SRD. In addition, siblings with a negative family history for SRD had larger VBRs than family history positive siblings. CONCLUSIONS: The results suggest that specific schizophrenia-related genetic factors may help determine ventricular enlargement in familial schizophrenia. The larger VBRs in family history negative siblings might be attributable to genetic factors not specifically associated with schizophrenia, but which nevertheless increase its susceptibility.

Adult↗
PubMed1998

Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease.

BACKGROUND: Identification of the neuropathological lesions that are most closely associated with the earliest symptoms of Alzheimer disease (AD) is crucial to the understanding of the disease process and the development of treatment strategies to affect its progress. Do the classical neuropathological lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? DESIGN AND OUTCOME MEASURES: We examined the extent of neuritic plaque (NP) formation in 5 neocortical regions and the hippocampus, entorhinal cortex, and amygdala in 66 elderly subjects with no dementia, questionable dementia, or mild dementia as assessed using the Clinical Dementia Rating Scale (CDR). SETTING AND PATIENTS: Postmortem study of nursing home residents. RESULTS: Even questionable dementia (CDR, 0.5) was associated with a significant (P = .04) increase in neocortical NP density. The density of NPs increased further with increasing dementia severity in all brain regions examined. However, subjects with questionable dementia or definite but mild dementia did not differ significantly from each other. Density of NPs was nearly maximal in subjects with moderate dementia (CDR = 2.0), suggesting that other neuropathological changes may be responsible for cognitive deficits beyond this level. Dementia severity correlated significantly with the density of NPs in all brain regions examined (r range, 0.47-0.56; P < .001), even when subjects with a CDR of 0 were excluded. CONCLUSIONS: These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia.

Aged↗
PubMed1998

Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases.

BACKGROUND: Clinical studies suggest that severe cognitive impairment is common among elderly patients with schizophrenia who reside in long-stay psychiatric institutions; however, previous autopsy-based neuropathologic investigations have provided conflicting results about the occurrence of Alzheimer disease (AD) in elderly patients with schizophrenia. We report the results of a comprehensive neuropathologic study performed to identify AD and other dementing neurodegenerative diseases in elderly patients with schizophrenia. METHODS: A neuropathologic examination was performed on 100 consecutive autopsy brain specimens of patients aged 52 to 101 years (mean, 76.5 years). A cognitive assessment of these cases was also done by employing the Clinical Dementia Rating Scale. For comparison, we included 47 patients with nonschizophrenic psychiatric disorders from the same psychiatric hospital and 50 age-matched control subjects. RESULTS: Although 72% of the patients with schizophrenia showed cognitive impairment, AD was diagnosed in only 9% of the patients and other dementing diseases were diagnosed in only 4% of the patients. The degree of senile plaques or neurofibrillary tangles was not different in the group with schizophrenia compared with the age-matched controls or the group with nonschizophrenic psychiatric disorders. The higher Clinical Dementia Rating Scale scores lacked correlation with neuropathologic evidence of dementing disorders. In the 87 cases lacking a neuropathologic diagnosis of AD or other dementing disorders, the mean (+/-SD) Clinical Dementia Rating Scale score was 2.21 (+/-1.14), with 43 of the cases scoring 3 or higher (indicating severe, profound, or terminal cognitive impairment). CONCLUSIONS: This study provides evidence that elderly patients with schizophrenia are not inordinately prone to the development of AD or to increased senile plaques or neurofibrillary tangle formation in the brain. Other dementing neurodegenerative disorders are also uncommon. The cognitive impairment in elderly patients with schizophrenia must, therefore, be related to some alternative mechanisms.

Age Distribution↗
PubMed1998

Tardive dyskinesia in a chronically institutionalized population of elderly schizophrenic patients: prevalence and association with cognitive impairment.

BACKGROUND: Chronically hospitalized geriatric inpatients with schizophrenia are at particular risk for both tardive dyskinesia (TD) and cognitive impairment but have been insufficiently studied in this regard. Similarly, the relationship between TD and cognitive impairment has not be adequately addressed in this population. OBJECTIVES: (1) To determine the prevalence of TD in a cohort of chronically institutionalized schizophrenic geriatric inpatients. (2) To examine the relationship between the manifestations of TD in various body regions and several potentially related variables including current pharmacological regimen, age, age at first hospitalization and cognitive status. METHOD: TD was assessed by the Modified Simpson Dyskinesia Scale and cognitive status by the Mini-Mental State Examination (MMSE). The relationship between manifestations of TD and other variables was examined by t-tests, ANOVA, MANOVA and correlational analysis. RESULTS: The prevalence of TD was 60%. Prevalence increased with age but was not related to current antipsychotic or anticholinergic regimen. Mean MMSE score did not differ between groups of patients with and without TD as defined by the criteria of Schooler and Kane (1982); however, the mean MMSE score was significantly (p < 0.0004) lower in subjects with orofacial TD as defined by Waddington and Youssef (1996), and the difference was not entirely accounted for by the older age of the latter group. CONCLUSIONS: TD and cognitive impairment both increase with age. However, TD alone does not account for the severity of cognitive impairment in this population. The present study provides further support for the hypothesis that the correlation between TD and cognitive impairment holds primarily for the orofacial manifestations of TD.

Age Factors↗
PubMed1998

Beta-blockade as an alternative to cardioplegic arrest during cardiopulmonary bypass.

BACKGROUND: As an alternative to cardioplegic arrest, cardiac surgical conditions have been produced using beta-blocker-induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to produce cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest with MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function. METHODS: Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined using microgravimetry and preload recruitable stroke work was determined using sonomicrometry and micromanometry. RESULTS: Significant lactate washout was demonstrated after cardioplegic arrest but not after MMC. Myocardial water content was significantly less during and after MMC compared with cardioplegic arrest (p < 0.05). Preload recruitable stroke work was decreased compared with baseline values in both groups (p < 0.05). CONCLUSIONS: In contrast to a previous study that involved 1 hour of MMC, in this study, ventricular function was decreased to the same extent as with cardioplegic arrest after 2 hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol, which possesses beta-antagonist properties. Although postbypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema formation.

Adrenergic beta-Antagonists↗
PubMed1998

The relationship between apolipoprotein E, dementia, and vascular illness.

The purpose of this study was to concurrently assess the relationship of Apolipoprotein E (APOE) with both dementias and vascular illnesses in the very old. Nine hundred and fifty nine subjects (mean age 85 years) in a long-term care facility were genotyped and cognitively tested with the Mini Mental State Exam. All subjects were studied for the relationship of APOE with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. Four hundred fifty individuals met criteria for inclusion into one of the following groups: Alzheimer's disease (n = 318), vascular dementia (n = 49), or not demented controls (n = 83) and were investigated for the relationship between APOE and these diagnostic categories. APOE epsilon4 was not associated with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. The APOE epsilon3 allele was more common in men with atherosclerotic heart disease. In contrast, the APOE epsilon4 allele was more common in patients with Alzheimer's disease (22%) and vascular dementia (26%) than in not demented controls (7%). APOE epsilon4 is associated with dementias in the very old, whereas its relationship with either peripheral or central nervous system vascular disease without dementia is not as robust.

Aged↗
PubMed1998

AMPA receptor binding and subunit mRNA expression in prefrontal cortex and striatum of elderly schizophrenics.

The dopamine hypothesis of schizophrenia has recently evolved into a model of dysfunctional integration between cortical and subcortical dopaminergic activity. Anatomical data suggest that regional alterations in dopaminergic activity may be linked by means of the rich glutamatergic innervation of the striatum by corticostriatal projections, suggesting a potential role for glutamatergic dysfunction in schizophrenia. Although pharmacological data have implicated the NMDA subtype of glutamate receptor in this illness, disturbance in AMPA receptor expression could potentially lead to the NMDA receptor hypoactivity hypothesized in schizophrenia. To address this possibility, we examined AMPA receptor binding and subunit mRNA levels in prefrontal cortex and striatum of schizophrenics and matched controls. There were no significant differences in AMPA receptor binding or subunit mRNA levels in either prefrontal cortical or striatal regions of schizophrenics. Furthermore, AMPA receptor expression did not seem to be regulated by chronic antipsychotic drug exposure, when neuroleptic treated and drug-free schizophrenics were analyzed separately. These data do not support a role for altered AMPA receptor expression in cortex and striatum in schizophrenia.

Aged↗
PubMed1998

Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction.

UNLABELLED: Our recent work demonstrated that normothermic continuous antegrade blood cardioplegia results in cardiac dysfunction related to myocardial oedema. This oedema was partially due to increased myocardial microvascular fluid filtration induced by crystalloid hemodilution. We hypothesized that increasing the colloid osmotic pressure of blood cardioplegia would stop fluid filtration into the cardiac interstitium, thus preventing myocardial oedema and cardiac dysfunction. METHODS: We determined myocardial water content in six dogs by microgravimetry and myocardial lymph flow from the major prenodal cardiac lymphatic. Preload recruitable stroke work was derived from sonomicrometry and micromanometry. The dogs were subjected to normothermic cardiopulmonary bypass primed with 6% hetastarch and 1 h of normothermic continuous antegrade blood cardioplegia (4:1 blood:6% hetastarch colloid osmotic pressure 21 +/- 2 mmHg) delivered at 50 mmHg perfusion pressure. RESULTS: We found that despite increased colloid osmotic pressure, a small but significant increase in myocardial water content still occurred during blood cardioplegia. As myocardial lymph flow virtually ceased during cardioplegia, myocardial microvascular filtration must have been present. However, increased myocardial lymph flow following cardioplegia resulted in complete oedema resolution associated with normal left ventricular performance post-cardiopulmonary bypass. CONCLUSIONS: Our data show that the plegic myocardium is prone to oedema formation because of both relatively enhanced fluid filtration and lymph flow cessation. We conclude that increasing the colloid osmotic pressure of normothermic blood cardioplegia minimizes myocardial oedema, thus preventing post-cardiopulmonary bypass cardiac dysfunction.

Animals↗
PubMed1998

Mild traumatic brain injury does not modify the cerebral blood flow profile of secondary forebrain ischemia in Wistar rats.

The rat hippocampus is hypersensitive to secondary cerebral ischemia after mild traumatic brain injury (TBI). An unconfirmed assumption in previous studies of mild TBI followed by forebrain ischemia has been that antecedent TBI did not alter cerebral blood flow (CBF) dynamics in response to secondary ischemia. Using laser Doppler flowmetry (LDF), relative changes in regional hippocampal CA1 blood flow (hCBF) were recorded continuously to quantitatively characterize hCBF before, during, and after 6 min of forebrain ischemia in either normal or mildly traumatized rats. Two experimental groups of fasted male Wistar rats were compared. Group 1 (n = 6) rats were given 6 minutes of transient forebrain ischemia using bilateral carotid clamping and hemorrhagic hypotension. Group 2 (n = 6) rats were subjected to mild (0.8 atm) fluid percussion TBI followed 1 h after trauma by 6 min of transient forebrain ischemia. The laser Doppler flow probe was inserted stereotactically to measure CA1 blood flow. The electroencephalogram (EEG) was continuously recorded. During the forebrain ischemic insult there were no intergroup differences in the magnitude or duration of the decrease in CBF in CA1. In both groups, CBF returned to preischemic values within one minute of reperfusion but traumatized rats had no initial hyperemia. There were no intergroup differences in the CBF threshold when the EEG became isoelectric. These data suggest that the ischemic insult was comparable either with or without antecedent TBI in this model. This confirms that this model of TBI followed by forebrain ischemia is well suited for evaluating changes in the sensitivity of CA1 neurons to cerebral ischemia rather than assessing differences in relative ischemia.

Animals↗
PubMed1998

Postmortem studies in schizophrenia.

The past decade has seen renewed interest in the neuropathology of schizophrenia. The advent of new postmortem techniques and functional imaging, along with a greater understanding of the neuropsychology of schizophrenia, have provided many new clues to the nature of the underlying brain dysfunction in this disorder. There has also been a greater understanding of the presence of severe cognitive dysfunction among many elderly persons with schizophrenia. In this article, a series of investigations are described that seek to answer basic questions about the neuropathology of schizophrenia, in particular as it pertains to cognitive impairment. The first study describes neuropathological findings in 100 consecutively autopsied persons with schizophrenia, the majority of whom had had detailed antemortem assessments. Results from this first study prompted the conclusion that schizophrenia is not characterized by classical, histologically identifiable neuropathology. Moreover, most cases of dementia in schizophrenia are probably not the result of neuropathologically identifiable dementing illnesses. The next four studies examined chemical markers that are altered in Alzheimer's disease and some other dementing conditions and have also been suggested to be abnormal in schizophrenia: choline acetyltransferase, catecholamines and indolamines, neuropeptides, and synaptic proteins. Schizophrenia cases as a group did not show a cholinergic deficit; nor did they differ from elderly comparison cases with respect to cortical catecholamines and indolamines. Among the schizophrenia cases, however, cognitive impairment was negatively correlated with choline acetyltransferase activity. Those with cognitive impairment showed evidence of cortical noradrenergic and serotonergic deficits. Neuropeptide deficits were also present in schizophrenia, but their pattern differed from that seen in Alzheimer's disease. Increased synaptic protein activity was found in the cingulate cortex of persons with schizophrenia, and this activity was correlated with schizophrenia symptoms. From this second series of studies, it was concluded that some biological measures in schizophrenia may be related to cognitive impairment (e.g., cortical amines), whereas others may be related to diagnosis (e.g., neuropeptide deficits). In addition, synaptic organization may correlate with schizophrenia symptoms.

Aged↗