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A sample of 473 male patients with pedophilia (assessed by the patients' sexual history and penile response in the laboratory to standardized, erotic stimuli) or other problematic sexual interests or behaviors received brief neuropsychological assessments. Neuropsychological measures included a short form of the Wechsler Adult Intelligence Scale--Revised (D. Wechsler, 1981), the Hopkins Verbal Learning Test--Revised (R. H. B. Benedict, D. Schretlen. L. Groninger. & J. Brandt, 1998), the Brief Visuospatial Memory Test--Revised (R. H. B. Benedict, 1997), and the Edinburgh Handedness Inventory (S. M. Williams, 1986). Pedophilia showed significant negative correlations with IQ and immediate and delayed recall memory. Pedophilia was also related to non-right-handedness even after covarying age and IQ. These results suggest that pedophilia is linked to early neurodevelopmental perturbations., (((c) 2004 APA, all rights reserved))

Previous research has found that pedophilic men referred for clinical assessment of their sexual behavior are more likely to report that they suffered head injuries before their 13th birthday than are nonpedophilic men referred for the same purpose. This study investigated whether pedophilic patients are also more likely to report head injuries after their 13th birthday. The 685 participants represented all patients with usable data from a consecutive series of men referred to a clinical laboratory specializing in phallometric assessment of erotic preferences. In addition to phallometric testing, participants were administered a brief neuropsychological test battery and a companion interview, which included questions on head injury, drug abuse, and childhood diagnosis of attention-deficit/hyperactivity disorder. The results showed that the pedophilic patients reported more head injuries before age 13 than did the nonpedophilic patients, but they did not report more head injuries after age 13. The association between pedophilia and childhood head injuries could mean either that subtle brain damage after birth increases a boy's risk of pedophilia, or that neurodevelopmental problems before birth increase a boy's accident-proneness along with his risk of pedophilia. Additional analyses showed that self-reported head injuries before age 13 were associated with attentional problems and with left-handedness; in contrast, head injuries after age 13 were associated with drug abuse and promiscuity. These analyses suggest that, among patients with primary presenting complaints of sexual rather than cognitive problems, childhood head injuries cluster with neuropsychological phenomena, whereas later head injuries cluster with lifestyle variables.

Deficits in cognition are a hallmark of schizophrenia. In the present study, the authors investigated the effects of schizophrenia on the neural correlates of conflict processing in a single-trial version of the Stroop task by using event-related brain potentials. Relative to matched controls, patients with schizophrenia showed increased Stroop interference in response time, but this effect was eliminated when the effect of response slowing was controlled. In controls, conflict processing was associated with a negative wave peaking between 400 and 500 ms (N450) and conflict sustained potential (SP) peaking between 600 and 800 ms after stimulus onset. In patients with schizophrenia, the amplitude of the N450 was significantly attenuated and the conflict SP was absent. These results provide evidence for the existence of altered neural processes associated with conflict processing that may be associated with dysfunction of the anterior cingulate and prefrontal cortex in patients with schizophrenia., (((c) 2003 APA, all rights reserved))

Previous studies suggest that antipsychotic medications may alter cortical inhibition (CI). The current study was designed to determine if typical or atypical antipsychotics indeed alter CI in healthy subjects using three CI paradigms as measured with transcranial magnetic stimulation (TMS): short interval intracortical inhibition (SICI), cortical silent period (CSP) and transcallosal inhibition (TCI). CI was measured before, 6 and 24 h after being randomly assigned to receive a single dose of 2 mg haloperidol (n=8), 10 mg olanzapine (n=10) or placebo (n=9). There was no significant effect on any measure of CI at 6 and 24 h after receiving olanzapine, haloperidol or placebo. Moreover, no significant change in the motor threshold was observed across the three medication groups. Therefore, single administration of an antipsychotic has no effect on CI or resting motor threshold. Whether chronic, repeated administration of antipsychotics has effects on CI requires further investigation.

Apathy is considered one of the negative symptoms of schizophrenia, but its natural history and relationship to other clinical characteristics have not been systematically studied. The purpose of this cross-sectional study was to measure the level of apathy in schizophrenia and its relation to other symptoms and functional outcome. Twenty-eight patients with schizophrenia, and receiving antipsychotic treatment, were assessed with the Apathy Evaluation Scale (AES). The mean level of apathy of patients with schizophrenia, as rated by the AES, was significantly higher than that of matched healthy control subjects. In the patients, apathy was not significantly correlated with positive symptoms or depressive symptoms. It was significantly correlated with the item "emotional withdrawal" on the negative subscale of the Positive and Negative Syndrome Scale (PANSS), but was not correlated with the overall negative subscale score. Apathy was more highly associated with functional outcome than were other symptom measures, and it was independently associated with functional outcome above and beyond other negative symptoms. It was not associated with observed interest in playing a video game or performance on a simulated clerical task.

Background: The transcranial magnetic stimulation (TMS)-induced contralateral silent period (CSP) refers to a period of interruption of voluntary muscle activity measured in tonically active muscles. The length of the CSP is generally interpreted to reflect cortical inhibition. The determination of the return of voluntary motor activity is typically accomplished via visual inspection of the electromyography (EMG) waveform and may be subject to inaccuracy on the part of the rater., Objective: To present and evaluate an automated method (AM) to determine the CSP., Methods: The CSP of 11 healthy controls was recorded using stimulus intensities 20 and 50% above the resting motor threshold (RMT). The mean CSP duration obtained by the two raters using visual inspection and our automated approach were compared., Results: The interclass correlation coefficient (ICC) between the two raters and the AM was 0.99 at 150% of RMT and was 0.97 at 120% of RMT. The level of pre-stimulus EMG amplitude and sampling rate did not affect agreement between the AM and more conventional visually guided methods., Conclusions: Our study demonstrates that this AM is a simple, objective and reliable approach for CSP determination., Significance: The CSP is an important neurophysiological measure of cortical inhibition and its determination by our AM provides a more objective and automated approach compared to visually guided methods.

The effect of catecholamine depletion, achieved by per-oral administration of 5250 mg alpha-methyl-para-tyrosine (AMPT) given in the 29 h prior to [11C]raclopride positron emission tomography (PET) was studied on measures of dopamine (DA) release, mood, and attention. Neostriatal DA levels in vivo were estimated by comparing the neostriatal DA D(2) receptor binding potential (D(2)RBP) before and after catecholamine depletion using PET and the radiotracer [11C]raclopride. Six healthy subjects completed the protocol. The AMPT treatment increased D(2)RBP significantly by 13.3+/-5.9% (average+/-standard deviation) and decreased plasma levels of the DA metabolite homovanillic acid (HVA) by 62+/-17%, and levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) by 66+/-5%. Catecholamine depletion resulted in decreased happiness, euphoria, energy, talkativeness, vigor, and attentiveness, and in increased sleepiness, fatigue, sedation, and eye blink rate (EBR). These changes were not correlated with the D(2)RBP increments. The results of this study are overall consistent with previous findings by our group using the same methodology in a different cohort of six healthy subjects.

We investigated whether the caudate nuclei volume (CNV) of 15 first episode psychosis patients increased after 5 years of treatment with either atypical antipsychotics or low doses of typical antipsychotics. Caudate volumes were measured from magnetic resonance imaging (MRI) scans in 15 patients and 10 healthy controls. Both groups demonstrated a significant 9% decline in caudate volume. We were unable to replicate previous reports of caudate enlargement in patients receiving antipsychotic treatment.

The present study investigated whetherhead injuries in childhood might increase the risk of pedophilia in males. The subjects were 1206 patients referred to a clinical sexology service for assessment of their erotic preferences. These were classified, on the basis of phallometric test results, as pedophilic (n = 413) or nonpedophilic (n = 793). Information regarding early head injuries, other signs of possible neurodevelopmental problems, and parental histories of psychiatric treatment were collected with self-administered questionnaires. The results showed that childhood accidents that resulted in unconsciousness were associated with pedophilia and with lower levels of intelligence and education. These associations were statistically significant for accidents that occurred before the age of 6, but not for accidents that occurred between the ages of 6 and 12. These results are compatible with the hypothesis that neurodevelopmental perturbations in early childhood may increase the risk of pedophilia. They are also, however, compatible with the alternative explanation that prior neurodevelopmental problems lead to accident-proneness and head injury, on the one hand, and to pedophilia, on the other, and that head injury has no causal influence on pedophilia. A secondary finding was that the pedophiles were more likely to report that their mothers had undergone psychiatric treatment. This finding suggests that pedophilia may be influenced by genetic factors, which are manifested in women as an increased risk of psychiatric problems, and in their sons, as an increased risk of erotic interest in children.

Background: It has been suggested that transiently high dopamine-2 (D(2)) receptor occupancy by antipsychotic medication may be sufficient for inducing an antipsychotic response. We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response., Method: Fourteen patients with a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were treated with quetiapine titrated to a single daily dose (mean +/- SD dose at the time of the positron emission tomography [PET] scan = 427 +/- 69 mg) for 12 weeks. Peak D(2) occupancy approximately 2 hours postdose and trough D(2) occupancy approximately 20 hours postdose were determined using PET and [(11)C]raclopride. Clinical symptoms and side effects were measured at baseline and every 2 weeks during the treatment phase., Results: Quetiapine administration led to a mean peak D(2) occupancy of 62% +/- 10% 2 hours postdose, which declined to 14% +/- 8% approximately 20 hours postdose. Ten (71%) of 14 patients responded to treatment with quetiapine, scoring "much improved" or greater on the Clinical Global Impressions-Improvement scale. Plasma drug levels and peak D(2) occupancy were highly correlated (r = 0.84; p =.003), as were prolactin and plasma drug levels when measured 2.5 hours after drug administration (r = 0.60; p <.05). Mean weight gain for the 10 subjects who completed the 12-week study was 4.2 +/- 4.6 kg (9.3 +/- 10.2 lb). No clinically relevant motor side effects occurred during the trial., Conclusion: Patients with a first episode of schizophrenia responded to treatment with a single daily dose of quetiapine despite only transiently high D(2) receptor occupancy. Our findings raise the question of whether continuously high D(2) blockade is necessary for obtaining an antipsychotic response. Future studies aimed at evaluating the relative merits of "transiently high" versus "continuously high" D(2) occupancy are warranted.

Transcranial magnetic stimulation (TMS) is a new investigational technique used to explore various neural processes and treat a variety of neuropsychiatric illnesses. The most notable advantage of TMS is its ability to directly stimulate the cortex with little effect on intervening tissue. Single-pulse stimulation techniques can measure cortical inhibition, facilitation, connectivity, reactivity, and cortical plasticity, providing valuable insights into the cortical physiology. Repetitive TMS (rTMS) is currently being used to investigate cognitive processes and as a treatment tool in disorders such as depression and schizophrenia. Both TMS and rTMS are safe and well tolerated. The most serious side effect of high-frequency rTMS is seizures. TMS represents an exciting new frontier in neuroscience research, providing insights into the pathophysiology and treatment of various neuropsychiatric disorders.

Transcranial magnetic stimulation can be used to non-invasively study inhibitory processes in the human motor cortex. Interhemispheric inhibition can be measured by applying a conditioning stimulus to the motor cortex resulting in inhibition of the contralateral motor cortex. Transcranial magnetic stimulation can also be used to demonstrate ipsilateral cortico-cortical inhibition in the motor cortex. At least two different ipsilateral cortico-cortical inhibitory processes have been identified: short interval intracortical inhibition and long interval intracortical inhibition. However, the relationship between interhemispheric inhibition and ipsilateral cortico-cortical inhibition remains unclear. This study examined the relationship between interhemispheric inhibition, short interval intracortical inhibition and long interval intracortical inhibition. First, the effect of test stimulus intensity on each inhibitory process was studied. Second, the effects of interhemispheric inhibition on short interval intracortical inhibition and long interval intracortical inhibition on interhemispheric inhibition were examined. Motor evoked potentials were recorded from the right first dorsal interosseous muscle in 11 right-handed healthy volunteers. For interhemispheric inhibition, conditioning stimuli were applied to the right motor cortex and test stimuli to the left motor cortex. For short interval intracortical inhibition and long interval intracortical inhibition, both conditioning stimuli and test stimuli were applied to the left motor cortex. With increasing test stimulus intensities, long interval intracortical inhibition and interhemispheric inhibition decreased, while short interval intracortical inhibition increased. Moreover, short interval intracortical inhibition was significantly reduced in the presence of interhemispheric inhibition. Interhemispheric inhibition was significantly reduced in the presence of long interval intracortical inhibition when matched for test motor evoked potential amplitude but the difference was not significant when matched for test pulse intensity. These findings suggest that both interhemispheric inhibition and long interval intracortical inhibition are predominately mediated by low threshold cortical neurons and may share common inhibitory mechanisms. In contrast, the mechanisms mediating short interval intracortical inhibition are probably different from those mediating long interval intracortical inhibition and interhemispheric inhibition although these systems appear to interact.

The present study was designed to investigate the time-course of neural activity underlying the disruption of response monitoring in patients with schizophrenia. Event-related brain potentials were recorded from 12 patients with schizophrenia and from 12 age-matched controls while they performed a computerized version of the Stroop color-naming task. In control participants, but not in patients with schizophrenia, intrusion errors elicited an error-related negativity (ERN) that peaked at approximately 40 ms after the response and was maximum over the central region of the scalp. Brain electrical source analysis revealed an anterior cingulate generator for the ERN. Patients also showed reduced error-related slowing of response time following intrusion errors. These findings provide neuro-physiological evidence indicating that deficits in error monitoring in schizophrenia arise from a disruption of error-detection processes, possibly attributable to anterior cingulate dysfunction.

Rationale: Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low., Objective: To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression., Methods: Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design., Results: No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition., Conclusions: Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion.

Background: Cortical inhibition (CI) deficits have been proposed as a pathophysiologic mechanism in schizophrenia. This study employed 3 transcranial magnetic stimulation (TMS) paradigms to assess CI in patients with schizophrenia. Paired-pulse TMS involves stimulating with a lower-intensity pulse a few milliseconds before a higher-intensity pulse, thereby inhibiting the size of the motor evoked potential produced by the higher-intensity pulse. In the cortical silent period paradigm, inhibition is reflected by the silent period duration (ie, the duration of electromyographic activity cessation following a TMS-induced motor evoked potential). Transcallosal inhibition involves stimulation of the contralateral motor cortex several milliseconds prior to stimulation of the ipsilateral motor cortex, inhibiting the size of the motor evoked potential produced by ipsilateral stimulation., Methods: We measured CI using these 3 paradigms in 15 unmedicated patients with schizophrenia (14 medication-naive and 1 medication-free for longer than 1 year) (13 were in the transcallosal inhibition paradigm), 15 medicated patients with schizophrenia (11 taking olanzapine, 1 risperidone, 1 quetiapine, 1 methotrimeprazine + perphenazine, 1 quetiapine + loxapine), and 15 healthy controls., Results: Unmedicated patients demonstrated significant CI deficits compared with healthy controls across all inhibitory paradigms whereas medicated patients did not (at all inhibitory intervals, paired-pulse TMS: controls = 59.9%, medicated = 44.3%, unmedicated = 28.7%; cortical silent period: controls = 55.0 milliseconds, medicated = 60.4 milliseconds, unmedicated = 39.7 milliseconds; transcallosal inhibition: controls = 33.6%, medicated = 23.7%, unmedicated = 10.4%; P<.05)., Conclusions: These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.

Previous studies suggest that there is a dopamine lowering process during major depressive episodes (MDE). To investigate this, we measured the dopamine transporter binding potential (DAT BP) in the striatum of depressed and healthy subjects using [(11)C]RTI-32 PET. The DAT, a predominantly presynaptic receptor, decreases in density after chronic dopamine depletion and the BP is proportional to receptor density. In all striatal regions, subjects with MDE had significantly lower DAT BP. Low striatal DAT BP in MDE is consistent with a downregulation of DAT in response to a dopamine lowering process. There was also a strong, highly significant, inverse correlation between striatal DAT BP and neuropsychological tests of dopamine-implicated symptoms in patients (i.e. patients with lower DAT BP performed better). Lower DAT BP itself reduces extracellular clearance of dopamine. Patients who did not decrease their striatal DAT BP failed to compensate for low dopamine and showed greater impairment on dopamine related tests.

Objective: To investigate the effects of the home environment, socioeconomic status (SES), and health status on cognitive functioning in a sample of children with HIV-1 infection in a cross-sectional study., Methods: Forty-three caregivers and their children (2.5 to 12 years) participated. Caregivers completed two self-report measures of the home environment that included questions regarding the organization of the environment, play materials, parental involvement, variety of stimulation, and parental attitudes toward the provision of a cognitively stimulating environment. Cognitive functioning was assessed using a standardized intelligence (IQ) test. Children's medical charts were reviewed for HIV-1 classification status (CDC, 1994), CD4 cell counts, and current medication., Results: This study revealed two primary findings. First, measures of the home environment mediated the association between SES and child IQ. Second, measures of the home environment had a stronger association with child IQ during the advanced stages of disease than earlier stages of disease., Conclusions: The home environment is associated with cognitive functioning among children with HIV-1 infection. Moreover, interventions aimed at enhancing the quality of the home environment may have a positive impact on these children's cognitive development.

Objective: The authors investigated the relationship between anxiety--a facet of the Revised NEO Personality Inventory dimension of neuroticism--and serotonin 5-HT(1A) receptor binding potential., Method: Positron emission tomography with [(11)C]WAY-100635 was used to estimate regional 5-HT(1A) binding potential in 19 healthy volunteers who completed the Revised NEO Personality Inventory. Correlation coefficients were calculated to determine the degree of association between 5-HT(1A) binding potential and personality inventory measures., Results: There was a significant negative correlation between 5-HT(1A) binding potential and anxiety in four regions: the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and occipital cortex., Conclusions: The inverse relationship between 5-HT(1A) receptor binding potential and anxiety is consistent with 1) animal models that have shown higher anxiety in mice lacking 5-HT(1A) receptors and 2) clinical trial data that have demonstrated antianxiety properties of partial 5-HT(1A) agonists.

Positron emission tomography (PET) and [11C]WAY-100635 were used to examine the effect of age on serotonin-1A (5-HT1A) receptor binding potential (BP) in 19 healthy subjects. Regions of interest (ROI) were drawn on the co-registered magnetic resonance imaging (MRI) in orbitofrontal (OFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), lateral (LTC), and mediotemporal (MTC), parietal, occipital and cerebellar cortex, and the raphe nuclei. BP values were calculated using a simplified reference tissue method. In addition, a voxelwise analysis was performed using SPM99. Voxelwise analysis revealed a significant global decrease of 5-HT(1A) BP with age (set level <.001). ROI analysis revealed significant age-related 5-HT(1A) BP decreases in DLPFC (r = -0.56), ACC (r = -0.44), OFC (r = -0.42), LTC (r = -0.40), parietal (r = -0.65), and occipital cortex (r = -0.43), but not in MTC or raphe nuclei. Overall, cortical 5-HT(1A) BP declined by approximately 10% per decade, except for the MTC, where we did not find a significant age effect. Hence, careful age matching may be recommended for future studies using PET and [11C]WAY-100635 to examine 5-HT1A receptors.

Rationale: Dopamine D2 receptor upregulation in the striatum is regularly seen in response to the administration of traditional antipsychotics in animal experiments. This is associated with hyperactivity and, for this reason, D2 receptor upregulation has long been postulated as central to tardive dyskinesia (TD)., Objective: Using positron emission tomography (PET), the present study attempted to determine whether antipsychotic-induced D2 receptor up-regulation also occurs in humans., Methods: The long-term effects of traditional and novel antipsychotics on dopamine D2 receptors were investigated in nine subjects meeting DSM-IV criteria for schizophrenia who were deemed eligible for temporary treatment washout. Subjects had been treated with traditional antipsychotics (haloperidol n=3, perphenazine n=1) and novel antipsychotics (risperidone n=3, olanzapine n=2) in the moderate to high dosage range. Fourteen days after treatment withdrawal, the binding potentials (BPs) of dopamine D2 receptors were measured using 11[C] raclopride. The obtained BPs were compared to the BPs from antipsychotic-naive control subjects with schizophrenia., Results: There was a significant increase in the D2 BP in both groups combined that reached 34%. The increases in the D2 BPs in the groups treated with conventional and novel antipsychotics were 37% and 31%, respectively. Significantly, the patients showing the highest degree of D2 receptor upregulation (98%) developed severe and persistent TD shortly after being started on a new antipsychotic with low affinity for D2 receptors., Conclusion: This study demonstrates for the first time, using in vivo neuroreceptor imaging, that dopamine D2 receptor binding is increased after long-term treatment with antipsychotics in humans. The data suggest that both traditional and novel antipsychotics with high affinity for dopamine D2 receptors are associated with a substantial increase in D2 receptor binding. The present data in humans agree well with animal data that implicate D2 receptor-mediated mechanisms in motor hyperactivity.

Objective: To introduce and discuss an evolutionary model of frontal lobe functioning (the dual cytoarchitectonic trends theory [DTT]) and its application to understanding the neurobiology of schizophrenia and anxiety disorders., Method: An introduction to the DTT with respect to neural architecture, connectivity, and function is presented. In addition, neurobiologic, neuropathologic, clinical, and cognitive research supporting the application of this model to schizophrenia and anxiety disorders is reviewed., Results: Traditional neuropsychologic models of acquired brain damage have been limited in their ability to explain frontal lobe dysfunction and its consequences in relation to psychopathology. The DTT offers an appropriately general neural-systems framework that may be better able to account for the diversity of symptoms, widespread neuropathology, and developmental abnormalities that are associated with most forms of psychopathology., Conclusions: Research investigating the neurobiology of psychopathology would benefit from adopting models of brain dysfunction that are consistent with neurodevelopmental pathology and evolution. Such efforts would likely lead to a greater understanding of neurobiologic mechanisms and, ultimately, better treatment strategies.

Objective: Review the existing literature on the incidence, neurobiological and psychosocial correlates, and methods of assessment and treatment of depression following traumatic brain injury (TBI)., Data Sources: Computerized database searches of the English-language literature from Index Medicus, Psychological Abstracts, Excerpta Medica, and Cumulative Index of Nursing and Allied Health Literature., Study Selection: Given the relatively small number of publications specifically related to TBI and depression, all studies appearing in the peer-reviewed literature were included in the review. In addition, studies examining depression and other neurologic diseases (eg, stroke) were also reviewed as to the potential applicability of the theoretical model or methodology used., Conclusions: Depression occurs with sufficient frequency to be considered a significant consequence after TBI. Depression can impede the achievement of optimal functional outcome, whether in the acute or chronic stages of recovery. It appears that a combination of neuroanatomic, neurochemical, and psychosocial factors is responsible for the onset and maintenance of depression. Its treatment is typically psychopharmacologic, with best results obtained from nontricyclic antidepressants. These results have not been confirmed in double-blind clinical trials, however. Future research should use comprehensive, integrative models of depression that include demographic, biologic, and psychosocial factors; enhanced functional neuroimaging techniques; controlled studies of psychopharmacologic and other interventions; and prospective designs with long-term follow-up.

Although biologic and environmental risk factors show an age-dependent effect on children's cognitive development, outcome studies have yet to consider the role such factors play in the development of children born to HIV-1-infected women. This study explored the age-dependent differential impact of such risk factors on the cognitive functioning of children exposed in utero to HIV-1. Eighty-two children were administered a standardized measure of cognitive functioning and divided into two groups depending on their age when tested. Group 1 included children age 2 to 29 months (n = 46); Group 2 included children age 30 to 101 months (n = 36). Correlations between cognitive test scores and specific risk factors revealed an age-related double-dissociation. Serostatus and percent of CD4 cells correlated moderately with cognitive test scores in Group 1; however, these correlations were attenuated and nonsignificant in Group 2. Conversely, caregiver status and cognitive test scores were uncorrelated in Group 1, but were correlated in Group 2. These findings support a risk and resilience model of development. That is, in the context of biologic risk factors, aspects of the child's environment may either facilitate or hinder cognitive development.

Sexually active male rats received five 30-min copulation tests with sexually receptive females, one every 4 days. One group of rats received alcohol (1 g/kg, IP) 45 min before, and an equivalent volume of saline 45 min after, each test; a second group received saline before and alcohol after each test; and a third, control group received saline both before and after. Four days after the last of the five tolerance-development trials, each rat received an injection of alcohol (1 g/kg, IP) 45 min before a copulation test so that the development of tolerance in the three groups could be compared. Tolerance to the disruptive effects of alcohol on mount, intromission, and ejaculation latencies, and on the duration of the postejaculatory interval was found to be significantly greater in the rats injected with alcohol before each copulation test than it was in the rats in the other two groups. These results constitute the first experimental evidence that tolerance develops to the disruptive effects of alcohol on male sexual behavior, and they support the theory that tolerance is an adaptive response to the disruptive effects of drugs on concurrent patterns of neural activity, rather than to drug exposure per se.

Rats (Rattus norvegicus) deprived of the opportunity to interact with particulate matter until they were young adults engaged in defensive burying after they were shocked by a wire-wrapped dowel in a test chamber that held bedding material. Interacting with a particulate substrate during development is not necessary for the expression of defensive burying in adulthood. However, interacting with a particulate substrate early in the rats' lives did have a substantial effect on the emergence and maintenance of burying behavior. Defensive burying developed at a later age and declined at an earlier age in rats maintained on wire mesh from birth until testing than it did in rats raised until weaning on bedding and housed on mesh thereafter. Because defensive burying is a complex, flexible, yet reliable response sequence that cannot be performed without the appropriate substrate, it has considerable potential as a model for the study of the development of species-specific defense responses.