D2 Receptors and Sodium Ion Channel Blockades of the Basolateral Amygdala Attenuate Lithium Chloride-Induced Conditioned Taste Aversion Applying to Cancer Chemotherapy Nausea and Vomiting.

Cancer patients regularly suffer from the behavioral symptoms of chemotherapy-induced nausea and vomiting. Particularly, it is involved in Pavlovian conditioning. Lithium chloride (LiCl) was used as the unconditioned stimulus (US) and contingent with the tastant, for example, a saccharin solution (i.e., the conditioned stimulus; CS), resulted in conditioned taste aversion (CTA) to the CS intake. The present study employed an animal model of LiCl-induced CTA to imitate chemotherapy-induced nausea and vomiting symptoms. Recently, the basolateral amygdala (BLA) was shown to mediate LiCl-induced CTA learning; however, which brain mechanisms of the BLA regulate CTA by LiCl remain unknown. The present study was designed to test this issue, and 4% lidocaine or D2 blocker haloperidol were microinjected into BLA between the 0.1% saccharin solution intake and 0.15M LiCl. The results showed lidocaine microinjections into the BLA could attenuate the LiCl-induced CTA. Microinjections of haloperidol blunted the CTA learning by LiCl. Altogether, BLA via the sodium chloride ion channel and D2 receptors control LiCl-induced conditioned saccharin solution intake suppression. The findings can provide some implications and contributions to cancer chemotherapy-induced nausea and vomiting side effects, and will help to develop novel strategies to prevent the side effects of cancer chemotherapy.

Optogenetic stimulation in the medial prefrontal cortex modulates stimulus valence from rewarding and aversive to neutral states.

Introduction: Understanding the modulations of the medial prefrontal cortex (mPFC) in the valence of the stimulus from rewarding and aversive status to neutral status is crucial for the development of novel treatments for drug addiction. This study addressed this issue and examined whether optogenetic ChR2 photostimulation in the cingulate, prelimbic, and infralimbic cortices of the mPFC regulated the valence of saccharin solution consumption from the rewarding property, the aversive property induced by morphine's conditioning, and the neutral states via saccharin extinction processes after morphine's conditioning. Methods: All rats received virus infection, buried optical fiber, optical stimulation, water deprivation, and saccharin solution consumption phases. In Experiment 1, rats were given ChR2 virus infection into the cingulate cortex (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL) to influence the rewarding saccharin solution consumption under photostimulation. In Experiment 2, rats were given ChR2 or EYFP virus infection into the Cg1, PrL, and IL to alter the saccharin solution consumption in the morphine-induced aversively conditioned taste aversion (CTA) and the saccharin solution consumption in the neutral state following the extinction process under photostimulation. Later, the immunohistochemical staining with c-Fos protein was performed for the Cg1, IL, PrL, nucleus accumbens core, nucleus accumbens shell, central amygdala, basolateral amygdala, ventral tegmental area, and dentate gyrus. Results: The results showed that optogenetic PrL stimulation decreased the rewarding valence of saccharin solution consumption and increased the morphine-induced, aversive valence of saccharin solution consumption. PrL stimulation decreased the neutral valence of saccharin solution consumption via the extinction process. Cg1 optogenetic stimulation increased the rewarding valence of saccharin solution consumption and the aversive valence of saccharin solution consumption induced by morphine in conditioning. Optogenetic IL stimulation increased the aversive valence of saccharin solution consumption induced by morphine via conditioning. Conclusion: Altogether, optogenetic stimulation in the subareas of the mPFC modulated the reward, aversion, and neutral valences of the stimulus and altered neuronal activity in the mPFC, amygdala, nucleus accumbens, and hippocampus. Notably, the change of valence was temporary alternation during light-on related to the light-off periods. However, the findings may provide insights in the development of novel treatments for addictive symptoms.

Environmental Enrichment Components Required to Reduce Methamphetamine-Induced Behavioral Sensitization in Mice: Examination of Behaviors and Neural Substrates.

Environmental enrichment (EE) involves the presentation of various sensory, physical, social, and cognitive stimuli in order to alter neural activity in specific brain areas, which can ameliorate methamphetamine (MAMPH)-induced behavioral sensitization and comorbid anxiety symptoms. No previous studies have comprehensively examined which EE components are critical for effectively reducing MAMPH-induced behavioral sensitization and anxiety. This study examined different housing conditions, including standard housing (SH, No EE), standard EE (STEE), physical EE (PEE), cognitive EE (CEE), and social EE (SEE). In the beginning, mice were randomly assigned to the different combinations of housing conditions and injections, consisting of No EE/Saline, No EE/MAMPH, STEE/MAMPH, PEE/MAMPH, CEE/MAMPH, and SEE/MAMPH groups. Then, the mice received intraperitoneal injections of 1 mg/kg MAMPH or normal saline daily for 7 days, followed by a final injection of 0.5 mg/kg MAMPH or normal saline. After behavioral tests, all mice were examined for c-Fos immunohistochemical staining. The results showed that MAMPH induced behavioral sensitization as measured by distance traveled. MAMPH appeared to induce lowered anxiety responses and severe hyperactivity. All EE conditions did not affect MAMPH-induced lowered anxiety behaviors. STEE was likely more effective for reducing MAMPH-induced behavioral sensitization than PEE, CEE, and SEE. The c-Fos expression analysis showed that the medial prefrontal cortex (i.e., cingulate cortex 1 (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL)), nucleus accumbens (NAc), basolateral amygdala (BLA), ventral tegmental area (VTA), caudate-putamen (CPu), and hippocampus (i.e., CA1, CA3, and dentate gyrus (DG)) contributed to MAMPH-induced behavioral sensitization. The Cg1, IL, NAc, BLA, VTA, CPu, CA3, and DG also mediated STEE reductions in MAMPH-induced behavioral sensitization. This study indicates that all components of EE are crucial for ameliorating MAMPH-induced behavioral sensitization, as no individual EE component was able to effectively reduce MAMPH-induced behavioral sensitization. The present findings provide insight into the development of non-pharmacological interventions for reducing MAMPH-induced behavioral sensitization.

Methamphetamine and Modulation Functionality of the Prelimbic Cortex for Developing a Possible Treatment of Alzheimer's Disease in an Animal Model.

Alzheimer's disease (AD) is a progressive neurodegenerative condition that causes cognitive impairment and other neuropsychiatric symptoms. Previously, little research has thus far investigated whether methamphetamine (MAMPH) can enhance cognitive function or ameliorate AD symptoms. This study examined whether a low dose of MAMPH can induce conditioned taste aversion (CTA) learning, or can increase plasma corticosterone levels, neural activity, and neural plasticity in the medial prefrontal cortex (mPFC) (responsible for cognitive function), the nucleus accumbens (NAc) and the amygdala (related to rewarding and aversive emotion), and the hippocampus (responsible for spatial learning). Furthermore, the excitations or lesions of the prelimbic cortex (PrL) can affect MAMPH-induced CTA learning, plasma corticosterone levels, and neural activity or plasticity in the mPFC [i.e., PrL, infralimbic cortex (IL), cingulate cortex 1 (Cg1)], the NAc, the amygdala [i.e., basolateral amygdala (BLA) and central amygdala (CeA)], and the hippocampus [i.e., CA1, CA2, CA3, and dentate gyrus (DG)]. In the experimental procedure, the rats were administered either saline or NMDA solutions, which were injected into the PrL to excite or destroy PrL neurons. Additionally, rats received 0.1% saccharin solution for 15 min, followed by intraperitoneal injections of either normal saline or 1 mg/kg MAMPH to induce CTA. A one-way ANOVA was performed to analyze the effects of saccharin intake on CTA, plasma corticosterone levels, and the expression of c-Fos and p-ERK. The results showed that the MAMPH induced CTA learning and increased plasma corticosterone levels. The mPFC, and particularly the PrL and IL and the DG of the hippocampus, appeared to show increased neural activity in c-Fos expression or neural plasticity in p-ERK expression. The excitation of the PrL neurons upregulated neural activity in c-Fos expression and neural plasticity in p-ERK expression in the PrL and IL. In summary, MAMPH may be able to improve cognitive and executive function in the brain and reduce AD symptoms. Moreover, the excitatory modulation of the PrL with MAMPH administration can facilitate MAMPH-induced neural activity and plasticity in the PrL and IL of the mPFC. The present data provide clinical implications for developing a possible treatment for AD in an animal model.

Examination of neuroinflammatory cytokine interleukin-1 beta expression in the medial prefrontal cortex, amygdala, and hippocampus for the paradoxical effects of reward and aversion induced by morphine.

A growing body of evidence has shown that abused drugs could simultaneously induce the paradoxical effect-reward and aversion. Moreover, the medial prefrontal cortex (mPFC), amygdala, and hippocampus were involved in this paradoxical effect by abused drugs. However, no research examined whether neuroinflammatory changes in the mPFC [including cingulate cortex area 1 (Cg1); prelimbic cortex (PrL); infralimbic cortex (IL)], basolateral amygdala, and hippocampus [e.g., CA1, CA2, CA3, and dentate gyrus (DG)] after morphine-induced reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA). The results showed that after morphine administration, the consumption of a 0.1% saccharin solution decreased; the mean time spent in the morphine-paired side compartment of the CPP box increased, indicating that morphine simultaneously induced the paradoxical effects of reward and aversion. The PrL and IL of the mPFC, the BLA of the amygdala, the CA1, CA2, CA3, and DG of the hippocampus but not the Cg1 presented hyperactive IL-1ß expression in response to morphine's aversion and reward. The mPFC, amygdala, and hippocampus may appear neuroinflammation activity following morphine-induced paradoxical effect-reward in CPP and aversion in CTA. The present data may provide a better understanding of the relationship between neuroinflammation and morphine addiction.

Roles of nucleus accumbens shell and core in footshock-induced stress altering behavioral sensitization by methamphetamine in acquisition and testing: Running head: stress, nucleus accumbens, and behavioral sensitization.

How the subregions of the nucleus accumbens (NAc) shell and core and stress are involved in behavioral sensitization induced by psychostimulants remains unclear. The present study manipulated methamphetamine (MAMPH) injections, lesions of the NAc shell or core, and footshock-treatment-induced stress to address this issue. The present data showed that during the acquisition phase, MAMPH injections, lesions of the NAc shell, and footshock treatments induced hyperactivity for the NAc shell. For the NAc core, MAMPH injections induced hyperactivity; however, lesions of the NAc core did not affect locomotor activity. Footshock treatments disrupted hyperactivity of behavioral sensitization. During the testing phase, MAMPH injections, lesions of the NAc shell, and footshock-treatment-induced stress facilitated hyperactivity for the NAc shell. For the NAc core, MAMPH injections and footshock-treatment-induced stress increased hyperactivity. However, the lesion of the NAc core did not affect locomotor activity. In conclusion, MAMPH injections and footshock-treatment-induced stress play an excitatory role for the NAc shell in acquisition and testing. For the NAc core, footshock-treatment-induced stress plays an inhibitory role in acquisition but an excitatory role in testing. The NAc core was not involved in MAMPH-induced behavioral sensitization in acquisition and testing. The NAc shell plays an inhibitory role in acquisition and testing phases. The present data might provide some insights for drug addiction. The results should be discussed further.

A randomised controlled trial of bright light therapy and morning activity for adolescents and young adults with Delayed Sleep-Wake Phase Disorder.

A randomised controlled trial evaluated bright light therapy and morning activity for the treatment of Delayed Sleep-Wake Phase Disorder (DSWPD) in young people. 60 adolescents and young adults (range = 13-24 years, mean = 15.9 ± 2.2 y, 63% f) diagnosed with DSWPD were randomised to receive three weeks of post-awakening Green Bright Light Therapy (∼507 nm) and Sedentary Activity (sitting, watching TV), Green Bright Light Therapy and Morning Activity (standing, playing motion-sensing videogame), Red Light Therapy (∼643 nm) and Sedentary Activity or Red Light Therapy and Morning Activity. Sleep (ie sleep onset time, wake up time, sleep onset latency, total sleep time) and daytime functioning (ie morning alertness, daytime sleepiness, fatigue, functional impairment) were measured pre-treatment, post-treatment and at one and three month follow-up. Contrary to predictions, there were no significant differences in outcomes between treatment groups; and interaction effects between treatment group and time for all outcome variables were not statistically significant. However, adolescents and young adults in morning activity conditions did not meaningfully increase their objective activity (ie movement frequency). Overall, adolescents reported significantly improved sleep timing (d = 0.30-0.46), sleep onset latency (d = 0.32) and daytime functioning (d = 0.45-0.87) post-treatment. Improvements in sleep timing (d = 0.53-0.61), sleep onset latency (d = 0.57), total sleep time (d = 0.51), and daytime functioning (d = 0.52-1.02) were maintained, or improved upon, at the three month follow-up. However, relapse of symptomology was common and 38% of adolescents and young adults requested further treatment in addition to the three weeks of light therapy. Although there is convincing evidence for the short-term efficacy of chronobiological treatments for DSWPD, long-term treatment outcomes can be improved. To address this gap in our current knowledge, avenues for future research are discussed. CLINICAL TRIAL: Australian & New Zealand Clinical Trials Registry, https://www.anzctr.org.au, ACTRN12614000308695.

Cognitive performance in adolescents with Delayed Sleep-Wake Phase Disorder: Treatment effects and a comparison with good sleepers.

The present study aimed to investigate whether Australian adolescents with Delayed Sleep-Wake Phase Disorder have impaired cognitive performance and whether chronobiological treatment for Delayed Sleep-Wake Phase Disorder improves adolescents' sleep, daytime functioning and cognitive performance. Adolescents with Delayed Sleep-Wake Phase Disorder (mean = 15.68 ±â€¯2.1 y, 62% f) reported significantly later sleep timing (d = 1.03-1.45), less total sleep time (d = 0.82) and greater daytime sleepiness (d = 2.66), fatigue (d = 0.63) and impairment (d = 2.41), compared to good sleeping adolescents (mean = 15.9 ±â€¯2.4 y, 75% f). However, there were no significant between-group differences (all p > 0.05) in performance on the Operation Span (ηp2 = 0.043), Digit Span (forwards: ηp2 = 0.002, backwards: ηp2 = 0.003), Letter Number Sequencing (ηp2 < 0.001) (working memory) and Digit-Symbol Substitution Tasks (ηp2 = 0.010) (processing speed). Adolescents with Delayed Sleep-Wake Phase Disorder went on to receive 3 weeks of light therapy. At 3 months post-treatment, adolescents with Delayed Sleep-Wake Phase Disorder reported significantly advanced sleep timing (d = 0.56-0.65), greater total sleep time (d = 0.52) and improved daytime sleepiness (d = 1.33), fatigue (d = 0.84) and impairment (d = 0.78). Performance on the Operation Span (d = 0.46), Letter Number Sequencing (d = 0.45) and Digit-Symbol Substitution tasks (d = 0.57) also significantly improved.

Citrobacter freundii as a test platform for recombinant cellulose degradation systems.

Cellulosic biomass represents a huge reservoir of renewable carbon, but converting it into useful products is challenging. Attempts to transfer cellulose degradation capability to industrially useful micro-organisms have met with limited success, possibly due to poorly understood synergy between multiple cellulases. This is best studied by co-expression of many combinations of cellulases and associated proteins. Here, we describe the development of a test platform based on Citrobacter freundii, a cellobiose-assimilating organism closely related to Escherichia coli. Standard E. coli cloning vectors worked well in Cit. freundii. Expression of cellulases CenA and Cex of Cellulomonas fimi in Cit. freundii gave recombinant strains which were able to grow at the expense of cellulosic filter paper or microcrystalline cellulose (Avicel) in a mineral medium supplemented with a small amount of yeast extract. Periodic physical agitation of the cultures was highly beneficial for growth at the expense of filter paper. This provides a test platform for the expression of combinations of genes encoding biomass-degrading enzymes to develop effective genetic cassettes for degradation of different biomass streams. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofuels have been shown to be the best sustainable and alternative source of fuel to replace fossil fuels. Of the different types of feedstocks used for producing biofuels, lignocellulosic biomass is the most abundant. Converting this biomass to useful products has met with little success. Different approaches are being used and microbial platforms are the most promising and sustainable method. This study shows that Citrobacter freundii is a better test platform than Escherichia coli for testing various combinations of cellulases for the development of microbial systems for biomass conversion.

Mutations responsible for Larsen syndrome cluster in the FLNB protein.

BACKGROUND: A gene for Larsen syndrome was recently described, and mutations were reported in five cases. OBJECTIVE: To test whether mutations in this gene, FLNB, could explain the disease in our independent collection of sporadic and dominant Larsen syndrome cases; and to test whether mutations occurred in a non-random pattern. RESULTS: Missense mutations were found in each of five cases. Four of the five were new; one was reported in a sporadic case in the original Larsen syndrome study of five cases. All mutations from the two studies were compiled. Clustered mutations were observed within three filamin B protein domains: the calponin homology 2 domain, repeat 14, and repeat 15. This suggested that as few as five (of the total of 46) coding exons of FLNB could be screened to detect Larsen syndrome mutations. Four of these exons were screened in a sixth (sporadic) case and a previously reported G1691S substitution mutation detected. CONCLUSIONS: Mutations in FLNB may be responsible for all cases of Larsen syndrome. They appear to occur in specific functional domains of the filamin B protein. This should simplify diagnostic screening of the FLNB gene. Analyses in larger patient series are warranted to quantify this. The study confirmed the extreme variability in clinical presentation and the presence of unaffected carriers. A molecular screen would be valuable for diagnosis and genetic counselling.

Associations between behavior disorders and health status among older adults with intellectual disability.

Few studies have examined the relationship of behavior and health status among aging persons with intellectual and developmental disabilities (I/DD). Behavioral disorders, which often are coincident with functional decline in older persons with I/DD, may be more related to medical morbidity than previously reported. This cross-sectional study examined the association between health status and behavior disorders with increasing age in a cohort of 60,752 adults with I/DD clustered into four adult-age groupings (21-44, 45-59, 60-74, and >74). Age grouping data suggested an association between morbidity and increased likelihood of behavior symptoms in all but the oldest age grouping. The magnitude of the association and trend varied by specific disease across age groupings compared to that found in healthy cohorts. About 25% of the adults with I/DD had psychiatric diagnoses and the frequency of such diagnoses did not decrease with age grouping. These results suggest that adverse health status may increase the likelihood of persistent behavioral disturbances in older persons with I/DD. Moreover, behavioral disorders may be sentinels for occult medical morbidity, which in turn may be responsive to intervention.

Identifying bipolar disorders in individuals with intellectual disability.

OBJECTIVE: The aim of the present study was to characterize adults with intellectual disability (ID) and concomitant clinical diagnoses of bipolar disorder (BPD), and determine whether DSM-IV criteria would distinguish individuals with BPD from patients with other psychiatric diagnoses. METHODS: A retrospective chart review was done of a convenience sample of adult patients seen over a 3-year period in a specialty clinic for adults with ID and psychiatric disorders. The DSM-IV criteria were used to differentiate individuals with clinical symptoms of BPD from groups of patients with other mood or thought disorders with behavioural symptoms which frequently overlap those of BPD. Behavioural symptoms were also catalogued and used to distinguish the diagnostic groups. RESULTS: Subjects with clinical symptoms of BPD had significantly more DSM-IV mood-related and non-mood-related symptoms, as well as functional impairments, compared to individuals with major depression, depression with psychosis or schizophrenia/psychosis NOS (not otherwise specified). Likewise, behavioural profiles of the BPD group of patients differed significantly from patients in the other three groups. CONCLUSIONS: Bipolar disorder can be readily recognized and distinguished from other behavioural and psychiatric diagnoses in individuals with ID, and DSM-IV criteria can be useful in the diagnosis of BPD.

The hospital library online--a point of service for consumers and hospital staff: a case study.

The Health Library at Stanford University is described in the context of electronic information services provided to Stanford University Medical Center, the local community, and Internet users in general. The evolution from CD-ROM-based services to Web-based services and in-library services to networked resources are described. Electronic services have expanded the mission of The Health Library to include national and international users and the provision of unique services and collections.

Characteristics of older adults with intellectual disabilities referred for crisis intervention.

The aim of the present study was to identify the age correlates of behavioural crises in adults with intellectual disability (ID) living in the community. The cohort consisted of 185 clients (IQ < 70), ranging in age from 20 to > 70 years, who were referred to a crisis intervention programme specializing in services to individuals with dual diagnosis over a 7-year period. A retrospective cross-sectional analysis of historical and contemporaneous variables was completed. Referrals for crisis intervention were not related to the age of the client Aggression and non-compliant behaviour occurred with similar frequency in all age groups. Other behaviours, including withdrawal, self-injury, stereotypy and symptoms of psychiatric disorders, occurred less often in older clients. Severity of ID affected the pattern of behavioural crises that resulted in referral. The results suggest that people with ID residing in community settings still experience behavioural crises as they grow older. Confirmation of the trends reported in the present study might signal a need for accelerating the development of comprehensive age-span community mental health and behavioural supports.

Characteristics of children and adolescents with mental retardation and frequent outwardly directed aggressive behavior.

Two interrelated cross-sectional studies were conducted to expand earlier findings about correlates of outwardly directed aggressive behavior in children with mental retardation. In Study 1 we compared children with mental retardation, 27 with and 23 without aggression. Aggression was best predicted by concurrent self-injurious behavior (SIB). In Study 2 we examined the likelihood that aggression was predicted by concurrent SIB and other nondestructive maladaptive behaviors in an archival cohort of 701 children younger than 21 with IQs below 70. Self-injurious behavior significantly predicted outwardly directed aggression for all children regardless of age. Additional predictors besides SIB showed only minimal improvements in model R2 values. Results were discussed in light of recent research proposing a common basis for aggression and SIB.

Factors predicting re-referral following crisis intervention for community-based persons with developmental disabilities and behavioral and psychiatric disorders.

Characteristics of 98 clients re-referred to receive services from a community-based crisis intervention program were compared to those of program clients who were served during the same 5.25-year period who were not referred. The majority of re-referrals occurred because of the same challenging behavior causing initial referral. Eight-eight percent of re-referral clients received the additional referral by 2 years after initial discharge. For persons under 30, nonfamily residence and initial diagnosis of self-injurious behavior were the strongest predictors. For those over 30, the most important factor was aggression. Recidivism following crisis intervention appears to be a complex function of client characteristics and community capabilities.

Is normobaric simulation of hypobaric hypoxia accurate in chronic airflow limitation?

Hypobaric hypoxemia is experienced by passengers during commercial aircraft flight. In order to assess the extent of hypoxemia and to test whether hypobaric hypoxia can be accurately estimated at sea level, the results of the normobaric hypoxia altitude simulation test (N-HAST) were compared with those of the hypobaric hypoxia altitude simulation test (H-HAST) in six normal control subjects and nine patients with chronic airflow limitation (CAL) at simulated cabin altitudes of 6,000 ft (1,829 m) and both at rest and during exercise at 8,000 ft (2,438 m). Serial arterial blood samples were drawn during the breathing of 15.1 and 16.3% inspired oxygen at sea level (N-HAST) at rest and during light exercise, and during the breathing of room air at simulated cabin altitudes (H-HAST) of 609 mm Hg (6,000 ft) and 565 mm Hg (8,000 ft) at rest and during light exercise. As measured with the H-HAST technique, the mean (+/- SD) PaO2 of the normal group fell from 96.2 +/- 6.2 mm Hg (sea level) to 70.1 +/- 6.0 mm Hg (6,000 ft), and to 61.7 +/- 1.6 mm Hg (8,000 ft at rest) and 54.8 +/- 7.1 mm Hg (8,000 ft during exercise) (p < 0.005 by analysis of variance [ANOVA]). In the CAL group, the mean (+/- SD) PaO2 fell from 75.8 +/- 8.2 mm Hg (sea level) to 57.0 +/- 6.3 mm Hg (6,000 ft), and 49.5 +/- 6.1 mm Hg (8,000 ft at rest), and 38.6 +/- 7.5 mm Hg (8,000 ft during exercise) (p < 0.005 by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Crisis intervention for community-based individuals with developmental disabilities and behavioral and psychiatric disorders.

When individuals with a developmental disability experience a behavioral or psychiatric crisis, their community placement may be threatened. A model crisis intervention program for individuals with dual diagnoses was discussed and performance and outcomes of such a service for 267 children and adults reviewed. Analysis indicated that 69% of the individuals required only one crisis intervention. Of the 31% requiring two or more, nearly all were re-referred earlier than 2 years post initial crisis intervention. The central, gulf-bridging role of a crisis intervention service in a comprehensive, coordinated, community-based mental health system for dually diagnosed individuals was discussed.

Characteristics of community-based individuals with mental retardation and aggressive behavioral disorders.

A cohort of 199 individuals with mental retardation referred for behavioral and psychiatric crisis intervention services was studied to determine attributes differentiating physically aggressive behavior from other behavioral problems. Individuals with aggressive and nonaggressive behavior had similar neurological histories and current medical status and similar levels of seizure disorders and CNS abnormalities. Aggressive individuals more often had psychiatric diagnoses of organic brain syndrome, but frequencies of this diagnosis in each group were small. Current aggression was predicted by gender, level of mental retardation, and history of previous institutional placement; the strongest predictor was history of aggression. These data suggest a complex equation to describe social inadequacy involving interactions between CNS functioning and developmental cognitive and social variables that are only partially defined at this time. Further work to characterize this interaction almost certainly must include a prospective longitudinal analysis of social and developmental functions early in life.