Measurement properties of the 6-min walk test in individuals with exercise-induced pulmonary arterial hypertension.

BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPAH) is associated with reduced peak exercise cardiac output (CO) and aerobic capacity (peak ). We investigated the validity of the encouraged 6-min walk test (6MWT) to identify exercise limitation and estimate aerobic capacity in subjects with EIPAH. METHODS: Seventeen subjects with EIPAH (56 ± 14 years, 15 women) and 20 healthy controls (57 ± 13 years, 19 women) underwent two encouraged 6MWTs and a symptom-limited cardiopulmonary exercise test (CPET). To measure central haemodynamics, subjects with EIPAH performed the CPET with a pulmonary artery catheter in situ. RESULTS: Compared with controls, subjects with EIPAH had reduced peak (1.2 ± 0.4 vs 1.7 ± 0.5, L/min, P < 0.01), 6-min walk distance (6MWD) (575 ± 86 vs 669 ± 76 m, P < 0.001) and 6-min walk work (6MWW) (39 ± 11 vs 45 ± 7 km.kg, P < 0.01). In subjects with EIPAH, there was a moderate correlation between 6MWD and peak (r= 0.72, P < 0.01) and a strong correlation between 6MWW and peak (r= 0.86, P < 0.001). There were significant correlations between 6MWD and peak CO (r= 0.59, P < 0.05), and between peak and peak CO (r= 0.55, P < 0.05). Peak heart rate was similar in the CPET and 6MWT in subjects with EIPAH (133 ± 15 vs 133 ± 19 beats/min, P= 0.8). CONCLUSIONS: The encouraged 6MWT identifies reduced exercise capacity and provides a valid estimate of aerobic capacity in EIPAH.

Successful treatment of ventricular assist device associated ventricular thrombus with systemic tenecteplase.

We report a case of intracardiac thrombus in a patient supported by the Jarvik 2000 Flowmaker successfully treated with a single dose of peripherally administered TNK-tissue plasminogen activator (Tenecteplase, Metalyse, Boehringer Ingelheim). This strategy may be considered in the case of life-threatening VAD associated thrombosis to avoid the need for intracardiac drug delivery or VAD replacement. We also discuss the apparent increased thrombotic risk in patients receiving a VAD for chemotherapy induced cardiomyopathy and the implications this may have for the choice of VAD.

Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.

We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.

Strategy of aggressive steroid weaning and routine alendronate therapy to reduce bone loss after cardiac transplantation.

OBJECTIVE: Osteoporosis is common after cardiac transplantation. The routine use of prednisolone posttransplantation is a major contributor to bone mineral loss. We sought to study the effectiveness of a strategy combining aggressive steroid weaning and routine prophylaxis with alendronate to reduce bone loss without adversely affecting posttransplantation survival. PATIENTS AND METHODS: This retrospective clinical study compared 2 cohorts of patients. Group A included 28 patients who had undergone transplantation since June 1999, all of whom were prescribed alendronate (10 mg daily or 70 mg weekly). All were aggressively weaned off prednisolone with the aim of being steroid-free by 9 months posttransplantation. Only 10 of the 28 patients were on prednisolone at the time of the study. Group B was an historical control cohort of 28 posttransplant patients reviewed in a cross-sectional study in 1995. Only 2 patients were on osteoporosis prophylaxis with estrogen or vitamin D; 26 patients were on prednisolone at the time of the study. The groups were compared by dual-energy X-ray absorptiometry (DEXA) bone mineral densitometry at the femoral neck and lumbar spine at a mean of 3 years after transplantation. We compared the cumulative survival of the 2 groups. RESULTS: Cumulative survival posttransplantation was similar in both groups. Compared with group B, group A showed a significantly higher mean femoral Z-score (+0.3 vs -0.5, P=.01) and lumbar spine Z-score (0.0 vs -0.9, P<.02). The incidence of osteoporosis (defined by WHO criteria as T-score

Late humoral rejection in a cardiac transplant recipient treated with the anti-CD20 monoclonal antibody rituximab.

Humoral or vascular rejection results from a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ, producing immune complex deposition on the vascular endothelium, activation of the complement cascade, generation of endothelial dysfunction, and regional ischemic injury. Antibody-mediated rejection, which may be accompanied by hemodynamic compromise, is associated with reduced long-term graft survival. Patients believed to be at an increased risk of developing humoral rejection include women, particularly those with high levels of panel reactive antibodies, cytomegalovirus seropositivity, and positive cross matches, and subjects with prior sensitization to OKT3. Treatment options for humoral rejection include plasmapheresis to lower the circulating immunoglobulin levels followed by high-dose cyclophosphamide to reduce the B-cell population. Other modalities include total lymphoid irradiation, photophoresis, splenectomy, and, for treatment failures, retransplantation. Rituximab is a chimeric humanized monoclonal antibody directed against the pan B-cell surface molecule, CD20. It is approved for the treatment of low-grade B-cell non-Hodgkin's lymphoma. It has also been used successfully for the treatment of posttransplant B-cell lymphoproliferative disease. We report a case of late humoral rejection successfully treated with rituximab.

Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.

OBJECTIVES: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. BACKGROUND: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.

OBJECTIVES: The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function. METHODS: The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography. RESULTS: Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed. CONCLUSIONS: Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.

The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes.

OBJECTIVES: The purpose of this study was to examine whether exercise training stimulates a generalized improvement in vascular function in patients with type 2 diabetes mellitus. BACKGROUND: Exercise is often recommended for patients with type 2 diabetes to improve physical conditioning and glycemic control. This study examined the effect of eight weeks of exercise training on conduit and resistance vessel function in patients with type 2 diabetes, using a randomized crossover design. METHODS: Both resistance vessel endothelium-dependent and -independent functions were determined by forearm plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16 patients with type 2 diabetes. Conduit vessel endothelial function was assessed in 15 of these patients using high-resolution ultrasound and flow-mediated dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an endothelium-independent dilator. RESULTS: Flow-mediated dilation increased from 1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood flow ratio to ACh was significantly improved (analysis of variance, p < 0.05). Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was enhanced in both conduit and resistance vessels. CONCLUSIONS: If endothelial dysfunction is an integral component of the pathogenesis of vascular disease, as currently believed, this study supports the value of an exercise program in the management of type 2 diabetes.

Antisaccades and smooth pursuit eye tracking and schizotypy.

BACKGROUND: Eye tracking deficits are one of a few widely validated behavioral markers of risk for schizophrenia. Recently, it has been proposed that antisaccade performance may also constitute a marker of schizophrenia risk. This study investigated whether eye tracking and antisaccade deficits could be found in another population with putative liability to schizophrenia-nonclinical subjects with elevated scores on a psychometric index of perceptual aberrations. METHODS: Subjects were 55 university students who received either high or normal scores on the Perceptual Aberration Scale, a measure of schizotypy indexing body image and perceptual distortions. Subjects completed a smooth pursuit eye tracking task and an antisaccade task. Eye movements were monitored using an infrared limbus tracker. RESULTS: Subjects with high Perceptual Aberration Scale scores (putative "schizotypes") had lower pursuit quality and a lower percentage correct on the antisaccade task than the controls. The 2 groups did not differ in antisaccade or error latencies. The increase in antisaccade errors in the schizotypes was accounted for almost entirely by an increase in perseverative errors, but virtually no difference between groups on random errors. Antisaccade performance was significantly related to pursuit quality. CONCLUSIONS: Subjects with elevated Perceptual Aberration Scale scores have performance deficits on oculomotor tasks that have been linked to latent liability to schizophrenia, namely, smooth pursuit and antisaccade performance. The antisaccade errors in the schizotype group were primarily perseverations, a behavioral pattern often associated with frontal lobe dysfunction and observed in the performance of schizophrenic patients.

Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients: a positron emission tomography study.

BACKGROUND: Schizophrenia is thought to arise from the interaction of genetically mediated and environmentally triggered abnormalities in brain function. Reduced frontal activation, reported in schizophrenic patients, may be one expression of genetic risk. The present study investigated whether frontal activation in relatives of schizophrenic patients would be related to eye tracking deficits (ETD), which are considered a behavioral marker of risk for schizophrenia. METHODS: Subjects were first-degree relatives of schizophrenic patients (n = 17) and controls (n = 11). Relatives were divided into those with normal and abnormal pursuit based on qualitative ratings. Subjects were scanned using positron emission tomography and the H(2)15O bolus subtraction technique while performing smooth pursuit and fixation. Brain areas more active in pursuit than fixation were identified in the 3 groups. Correlations were used to investigate the relationship between activation of pursuit regions and pursuit gain in the relatives. RESULTS: Controls significantly activated frontal eye fields (FEFs) and posterior areas, including the motion processing area, V5, and cuneus. The 2 groups of relatives activated the same posterior regions as controls, but differed from each other in activation of FEFs. Relatives with normal tracking activated right dorsal FEFs while relatives with ETD did not. Individual subtractions revealed that 90% of controls and 100% of the relatives with normal tracking activated FEFs during pursuit compared with 42% of relatives with ETD (P = .009). Pursuit gain was significantly and selectively associated with percent activation of right dorsal FEFs (r = 0.74). CONCLUSIONS: Subtle frontal dysfunction seems to be a pathophysiological substrate of ETD in relatives of schizophrenic patients, and may be one aspect of genetically mediated differences in brain function relevant to schizophrenia.

Differences in cerebral activation during smooth pursuit and saccadic eye movements using positron-emission tomography.

BACKGROUND: Abnormalities of smooth pursuit eye movements occur commonly in schizophrenia, but the pathophysiological significance of these abnormalities is unknown. To address this, the authors conducted a pilot study in which we examined differences in regional cerebral activation using positron-emission tomography (PET) in normal volunteers as they performed two types of eye movements. METHODS: Cerebral activation in 10 normal volunteers was studied using C15O2 PET while subjects tracked a visual target using smooth pursuit and saccadic eye movements. A left-hand movement comparison task provided a physiologic landmark for verification of the location of the frontal eye fields (FEFs). RESULTS: Subjects exhibited FEF activation during both smooth pursuit and saccadic eye movements, which was greater in the latter. During smooth pursuit, subjects also exhibited increased cerebral activation in the left temporal-occipital border and left superior frontal cortex and decreased activation in medial superior parietal and insular regions relative to saccades. Other cortical visual and eye-movement brain regions also demonstrated differences in activation between the two visual tasks. CONCLUSIONS: Significant fEF activation appears to underlie both smooth pursuit and saccadic eye movements but may be more critical in the former. Dysfunction of the frontal lobe, and possibly of other areas in the pursuit pathway such as the temporo-occipital motion area, may contribute to observed eye-movement abnormalities in patients with schizophrenia.

A prospective follow-up study of so-called borderline children.

OBJECTIVE: The purpose of this study was to ascertain the current diagnosis in late adolescence or early adulthood of children who had previously been diagnosed as "borderline." METHOD: This was a prospective follow-up study of 19 of a group of 32 children (ages 6-10) who had been diagnosed as "borderline" during their treatment at the Massachusetts Mental Health Center approximately 10-20 years earlier. Life history information was collected, and axis I and axis II diagnoses were assigned by use of the Structured Clinical Interview for DSM-III-R and unstructured clinical interviews. RESULTS: The most significant finding was that, contrary to expectations, there were no axis I diagnoses of affective disorders or schizophrenia. On the other hand, axis II diagnoses were prevalent, and the overall outcome for the subjects was poor. Family stability was the only significant predictor of the relatively good outcome of five of the subjects. CONCLUSIONS: The childhood borderline diagnosis appears to be an antecedent of an array of adult personality disorders, but it is not associated with the adult borderline personality disorder per se, nor with axis I diagnoses.

Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study.

BACKGROUND: Considerable evidence indicates that the lipophilic beta-blocker propranolol is useful in treating organically based aggression. This study looked at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression in chronic psychiatric inpatients. METHOD: Forty-one chronic psychiatric inpatients with an average of one aggressive outburst per week (defined by the Overt Aggression Scale [OAS]) were entered into a double-blind, placebo-controlled study lasting 17 weeks. The OAS was used to track aggression on a per-incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions scale (CGI) were used to track clinical status. RESULTS: Nadolol subjects showed a significant decline in frequency of aggression compared with controls (p = .026) and a significant decline in the BPRS total score (p = .007) and in the subfactors "hostility and suspicion," "negative symptoms," and "signs of hyperarousal/tension." There was no significant change in CGI "severity of illness" ratings between groups, although the nadolol group was significantly improved from baseline at every subsequent time period while the placebo group was unchanged throughout the study. CONCLUSION: Nadolol is of significant benefit in the treatment of aggression in chronic psychiatric inpatients. This drug does penetrate the brain over time, but the success of a drug whose primary locus of action is peripheral may implicate a bimodal mechanism of action, i.e., a role for the CNS and the soma in the maintenance of aggression.

Functional neuroanatomy of smooth pursuit and predictive saccades.

We used PET to study differences in cerebral blood flow (CBF) in smooth pursuit, predictive saccades and fixation. Eye movements were monitored in the scanner. Compared with fixation, pursuit and predictive saccades activated a network of highly similar areas, including frontal eye fields, supplementary eye fields, V5 and medial cuneus. Our findings are consistent with non-human primate studies that suggest that pursuit and saccades are controlled by similar and adjacent neural areas. Pursuit was associated with greater activation of caudate than saccades, suggesting a role for basal ganglia in pursuit that is consistent with studies of neurological populations. Saccades were associated with greater activation of cerebellum and frontal eye fields. A frontal-cerebellar loop may be important in coordinating the preparation and timing of saccades in predictive tracking.

Combined aerobic and resistance exercise training improves functional capacity and strength in CHF.

This study examined the effect of a novel circuit weight training (CWT) program on cardiorespiratory fitness, muscular strength, and body composition in 13 patients with chronic heart failure (CHF), using a prospective randomized crossover protocol. Peak exercise oxygen uptake (VO(2 peak)) increased after the 8-wk CWT program (19. 5 +/- 1.2 vs. 22.0 +/- 1.5 ml. kg(-1). min(-1), P < 0.01), as did exercise test duration (15.2 +/- 0.9 vs. 18.0 +/- 1.1 min, P < 0. 001). Submaximal exercise heart rate was lower after training at 60 and 80 W (121 +/- 3 vs. 134 +/- 5 beats/min, P < 0.01) as was rate pressure product, whereas ventilatory threshold increased, from 52 +/- 3 to 58 +/- 3% of VO(2 peak) (P < 0.05). CWT also increased maximal isotonic voluntary contractile strength for seven different muscle groups, from 392 to 462 kg (P = 0.001). CWT, an exercise prescription specifically targeting peripheral abnormalities in CHF, improves functional capacity and muscular strength in these patients.

Control of skeletal muscle blood flow during dynamic exercise: contribution of endothelium-derived nitric oxide.

Traditional explanations for the hyperaemia which accompanies exercise have invoked the 'metabolic theory' of vasodilation, whereby contractile activity in the active muscle gives rise to metabolic by-products which dilate vessels bathed in interstitial fluid. Whilst metabolites with vasodilator properties have been identified, this theory does not adequately explain the magnitude of hyperaemia observed in active skeletal muscle, principally because large increases in flow are dependent on dilation of 'feed' arteries which lie outside the tissue parenchyma and are not subjected to changes in the interstitial milieu. Coordinated resistance vessel dilation during exercise is therefore dependent on a signal which 'ascends' from the microvessels to the feed arteries located upstream. Recent studies of ascending vasodilation have concentrated on the possible contribution of the endothelium, a monolayer of flattened squamous cells which lie at the interface between the circulating blood and vascular wall. These cells are uniquely positioned to respond to changes in rheological and humoral conditions within the cardiovascular system, and to transduce these changes into vasoactive signals which regulate blood flow, vascular tone and arterial pressure. Endothelial cells produce nitric oxide (NO), a rapidly diffusing labile substance which relaxes adjacent vascular smooth muscle. NO is released basally and contributes to the regulation of vascular tone by acting as a functional antagonist to sympathetic neural constriction. In addition, NO is spontaneously released in response to deformation of the endothelial cell membrane, indicating that changes in pulsatile flow and wall shear stress are likely physiological stimuli. Since the dilation of microvessels in response to exercise increases blood flow through the upstream feed arteries, which subsequently dilate, one explanation for ascending vasodilation is that NO release is stimulated by flow-induced shear stress. Evidence that NO contributes to ascending vasodilation is reviewed, along with studies which indicate that NO mediates exercise hyperaemia, that physical conditioning upregulates NO production and that NO controls blood flow by modifying other physiological mechanisms.

Fat necrosis in surveillance biopsies of heart transplants.

Fat necrosis was observed in surveillance biopsies of five patients following heart transplant. This reaction is poorly documented in the literature, but in personal communication, some pathologists working in the field have had experience with it. Four of the cases developed two to six days after transplantation, but in the fifth case, fat necrosis developed ten months after transplantation. Autopsy study of one case showed extensive severe fat necrosis involving both donor and recipient tissues. The cause is not known, and the changes are independent of rejection. However, the fat necrosis can be found within the interstitial tissues of the myocardium and subendocardium and may be mistaken for rejection if lymphocytes and polymorphs are part of the inflammatory response. The only clinical finding thought to be related to the fat necrosis was the development of transient complete heart block in a patient in whom the International Society for Heart and Lung Transplantation (ISHLT) standardised rejection grading was never greater than IA.

Exercise training, vascular function, and functional capacity in middle-aged subjects.

PURPOSE: The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. METHODS: After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. RESULTS: Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). CONCLUSION: These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

Open trial effects of beta-blockers on speech and social behaviors in 8 autistic adults.

We began open trials of beta-blockers, as adjunctive medication, in eight consecutive autistic adults. The immediate result across all patients was a rapid diminution in aggressivity (Ratey et al., 1987). As time on the drug increased, subtler changes in speech and socialization emerged. While results of open trials must be interpreted with caution, these changes were significant and lasting. We speculate that these effects may be the result of a lessening of the autistic individual's state of hyperarousal. As the individual becomes less anxious, defensive and dearousing behaviors are relinquished and more social and adaptive behaviors appear. There is a concomitant improvement in language, though it is unclear whether lost skills are recouped or new ones developed. Further research is indicated.

Amygdala-hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients.

Verbal memory deficits have been related to reduced volume of medial temporal structures in several neurological and psychiatric populations, including schizophrenic patients. Impairments in verbal memory have been proposed to be a marker of risk for schizophrenia. Recently, relatives of schizophrenic patients have been reported to have reduced volume of the amygdala-hippocampal complex. In this study, we evaluate the possibility that amygdala-hippocampal volume reductions may constitute one neural substrate of verbal memory deficits in first-degree relatives. Subjects were 20 healthy first-degree relatives of schizophrenic patients and 14 demographically similar controls. Verbal memory was assessed with the Logical Memory Test. Subjects were scanned with high-resolution MRI and the images were transformed into Talairach space. Volumes of interest were amygdala-anterior hippocampus and posterior hippocampus. Relatives of schizophrenic patients had intact immediate verbal memory but significantly poorer delayed verbal memory than controls. Relatives also had significantly reduced amygdala-anterior hippocampus volumes. Across all subjects, delayed verbal memory was significantly correlated with amygdala-anterior hippocampus volume. The magnitude of the correlation did not differ between the groups. These data provide an empirical link between memory performance and volumetric abnormalities in the amygdala-hippocampal complex in the relatives of schizophrenic patients.