Sensory over-responsivity in adults with autism spectrum conditions.

Anecdotal reports and empirical evidence suggest that sensory processing issues are a key feature of autism spectrum conditions. This study set out to investigate whether adults with autism spectrum conditions report more sensory over-responsivity than adults without autism spectrum conditions. Another goal of the study was to identify whether autistic traits in adults with and without autism spectrum conditions were associated with sensory over-responsivity. Adults with (n = 221) and without (n = 181) autism spectrum conditions participated in an online survey. The Autism Spectrum Quotient, the Raven Matrices and the Sensory Processing Scale were used to characterize the sample. Adults with autism spectrum conditions reported more sensory over-responsivity than control participants across various sensory domains (visual, auditory, tactile, olfactory, gustatory and proprioceptive). Sensory over-responsivity correlated positively with autistic traits (Autism Spectrum Quotient) at a significant level across groups and within groups. Adults with autism spectrum conditions experience sensory over-responsivity to daily sensory stimuli to a high degree. A positive relationship exists between sensory over-responsivity and autistic traits. Understanding sensory over-responsivity and ways of measuring it in adults with autism spectrum conditions has implications for research and clinical settings.

Attention deficit hyperactivity disorder and sensory modulation disorder: a comparison of behavior and physiology.

Children with attention deficit hyperactivity disorder (ADHD) are impulsive, inattentive and hyperactive, while children with sensory modulation disorder (SMD), one subtype of Sensory Processing Disorder, have difficulty responding adaptively to daily sensory experiences. ADHD and SMD are often difficult to distinguish. To differentiate these disorders in children, clinical ADHD, SMD, and dual diagnoses were assessed. All groups had significantly more sensory, attention, activity, impulsivity, and emotional difficulties than typical children, but with distinct profiles. Inattention was greater in ADHD compared to SMD. Dual diagnoses had more sensory-related behaviors than ADHD and more attentional difficulties than SMD. SMD had more sensory issues, somatic complaints, anxiety/depression, and difficulty adapting than ADHD. SMD had greater physiological/electrodermal reactivity to sensory stimuli than ADHD and typical controls. Parent-report measures identifying sensory, attentional, hyperactive, and impulsive difficulties varied in agreement with clinician's diagnoses. Evidence suggests ADHD and SMD are distinct diagnoses.

Phenotypes within sensory modulation dysfunction.

Sensory modulation disorder (SMD) is a severe inability to regulate responses to everyday sensory stimulation to which most people easily adapt. It is estimated to affect 5% to 16% of the general population of children. Although heterogeneity is seen in the presentation clinically, previous research has not empirically investigated whether the clinical heterogeneity of SMD can be classified into subtypes. This study explores a cohort of 98 children identified with SMD at the Department of Pediatric Rehabilitation by a member of the occupational therapy team at The Children's Hospital of Denver. Two subtypes of SMD were identified through cluster analysis based on data from 4 parent-report instruments. The first subtype is characterized by sensory seeking/craving, hyperactive, impulsive, externalizing (eg, delinquent, aggressive), unsocial, inadaptive, and impaired cognitive/social behavior. The second subtype is characterized by movement sensitivity, emotionally withdrawal, and low energy/weak behavior. Findings from this study present a step toward understanding and classifying the complexities of children with SMDs.

An exploratory event-related potential study of multisensory integration in sensory over-responsive children.

Children who are over-responsive to sensation have defensive and "fight or flight" reactions to ordinary levels of sensory stimulation in the environment. Based on clinical observations, sensory over-responsivity is hypothesized to reflect atypical neural integration of sensory input. To examine a possible underlying neural mechanism of the disorder, integration of simultaneous multisensory auditory and somatosensory stimulation was studied in twenty children with sensory over-responsivity (SOR) using event-related potentials (ERPs). Three types of sensory stimuli were presented and ERPs were recorded from thirty-two scalp electrodes while participants watched a silent cartoon: bilateral auditory clicks, right somatosensory median nerve electrical pulses, or both simultaneously. The paradigm was passive; no behavioral responses were required. To examine integration, responses to simultaneous multisensory auditory-somatosensory stimulation were compared to the sum of unisensory auditory plus unisensory somatosensory responses in four time-windows: (60-80 ms, 80-110 ms, 110-150 ms, and 180-220 ms). Specific midline and lateral electrode sites were examined over scalp regions where auditory-somatosensory integration was expected based on previous studies. Midline electrode sites (Fz, Cz, and Pz) showed significant integration during two time-windows: 60-80 ms and 180-220 ms. Significant integration was also found at contralateral electrode site (C3) for the time-window between 180 and 220 ms. At ipsilateral electrode sites (C4 and CP6), no significant integration was found during any of the time-windows (i.e. the multisensory ERP was not significantly different from the summed unisensory ERP). These results demonstrate that MSI can be reliably measured in children with SOR and provide evidence that multisensory auditory-somatosensory input is integrated during both early and later stages of sensory information processing, mainly over fronto-central scalp regions.

Physiological and behavioral differences in sensory processing: a comparison of children with autism spectrum disorder and sensory modulation disorder.

A high incidence of sensory processing difficulties exists in children with Autism Spectrum Disorder (ASD) and children with Sensory Modulation Disorder (SMD). This is the first study to directly compare and contrast these clinical disorders. Sympathetic nervous system markers of arousal and reactivity were utilized in a laboratory paradigm that administered a series of sensory challenges across five sensory domains. The Short Sensory Profile, a standardized parent-report measure, provided a measure of sensory-related behaviors. Physiological arousal and sensory reactivity were lower in children with ASD whereas reactivity after each sensory stimulus was higher in SMD, particularly to the first stimulus in each sensory domain. Both clinical groups had significantly more sensory-related behaviors than typically developing children, with contrasting profiles. The ASD group had more taste/smell sensitivity and sensory under-responsivity while the SMD group had more atypical sensory seeking behavior. This study provides preliminary evidence distinguishing sympathetic nervous system functions and sensory-related behaviors in Autism Spectrum Disorder and Sensory Modulation Disorder. Differentiating the physiology and sensory symptoms in clinical groups is essential to the provision of appropriate interventions.

Perspectives on sensory processing disorder: a call for translational research.

THIS ARTICLE EXPLORES THE CONVERGENCE OF TWO FIELDS, WHICH HAVE SIMILAR THEORETICAL ORIGINS: a clinical field originally known as sensory integration and a branch of neuroscience that conducts research in an area also called sensory integration. Clinically, the term was used to identify a pattern of dysfunction in children and adults, as well as a related theory, assessment, and treatment method for children who have atypical responses to ordinary sensory stimulation. Currently the term for the disorder is sensory processing disorder (SPD). In neuroscience, the term sensory integration refers to converging information in the brain from one or more sensory domains. A recent subspecialty in neuroscience labeled multisensory integration (MSI) refers to the neural process that occurs when sensory input from two or more different sensory modalities converge. Understanding the specific meanings of the term sensory integration intended by the clinical and neuroscience fields and the term MSI in neuroscience is critical. A translational research approach would improve exploration of crucial research questions in both the basic science and clinical science. Refinement of the conceptual model of the disorder and the related treatment approach would help prioritize which specific hypotheses should be studied in both the clinical and neuroscience fields. The issue is how we can facilitate a translational approach between researchers in the two fields. Multidisciplinary, collaborative studies would increase knowledge of brain function and could make a significant contribution to alleviating the impairments of individuals with SPD and their families.

Mouse model of fragile X syndrome: behavioral and hormonal response to stressors.

Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.

Pharmacotherapy of dual substance abuse and dependence.

The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence-based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug's original indication by the FDA. Such 'off-label' prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature. The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This review finds strongest support for the use of disulfiram for treatment of alcohol and cocaine dependence (with or without concomitant methadone maintenance), baclofen for alcohol and cocaine dependence (but not opioid-dependent cocaine users), tiagabine for cocaine dependence in methadone-maintained patients, and topiramate for alcohol, nicotine and cocaine dependence. While ondansetron and olanzapine show some efficacy in treating alcohol and cocaine dependence, more research is needed to better delineate the subpopulation in which these drugs may provide their maximum effect.

Corticotropin-releasing factor type-1 receptor antagonists: the next class of antidepressants?

Corticotropin-releasing factor (CRF) is a neuropeptide that plays a primary role in the neuroendocrine, autonomic, and behavioral responses to stressors. Numerous reports suggest that alterations in CRF function contribute to the pathogenesis of depression. Recently, selective nonpeptide CRF type 1 (CRF1) receptor antagonists have been discovered and several of these CRF1 receptor antagonists have demonstrated antidepressant-like efficacy in animals. The CRF1 receptor antagonists appear to be unique, as they exhibit antidepressant-like activity principally in animal models that are hyperresponsive to stress or under experimental conditions that alter endogenous stress-hormone activity. A nonpeptide CRF1 receptor antagonist has also been shown to reduce symptoms of major depression in an open-label clinical trial. Accumulating evidence supports a role for nonpeptide CRF1 receptor antagonists among the future pharmacotherapies for the treatment of depression.

Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice.

The development of selective corticotropin-releasing factor type-1 (CRF1) receptor antagonists represents a potential novel treatment for depression. These studies evaluated CRF1 receptor antagonists for antidepressant-like activity in mice. Subchronic dosing of both R 121919 (3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidin-7-amine) and DMP 696 (4-(1,3-dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine) significantly decreased immobility time in the tail suspension test (at 30 and at 3 and 10 mg/kg, i.p., respectively). These antidepressant-like effects were observed at doses that did not impair general locomotor activity. Neither antalarmin (N-butyl-N-ethyl-[2,5,6-trimethyl-7-(2,4,6)trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) nor DMP 904 (4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine) had an effect indicative of antidepressant-like activity. These results suggest that the tail suspension assay may have utility to identify CRF1 receptor antagonists with antidepressant-like activity. Moreover, the results lend support to the theory that some nonpeptidic CRF1 receptor antagonists may possess antidepressant-like activity and therefore represent a promising novel pharmacotherapeutic strategy in the treatment of depression.

Automated analysis of foot-shock sensitivity and concurrent freezing behavior in mice.

Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to characterize different rodents, or to test various pharmacological agents for their antinociceptive or analgesic effects. All these procedures need to assess foot-shock sensitivity either to rule out possible differences (when the shock is used as a motivational stimulus) or to use the differences to compare animals or treatments. In addition, many of the procedures that utilize foot-shock as a motivational stimulus evaluate freezing as an index of anxiety or fear. In the present study, data obtained by an automated computer system was compared with data obtained by human observers to validate the automated system for examining foot-shock sensitivity in mice. The different computer measures obtained for foot-shock sensitivity exhibited high correlations with human scoring at shock levels as low as 0.2 mA. The computer controlled analysis provided a non-subjective, quantifiable measurement of the foot-shock-induced response as well as freezing behavior. Automated data collection is an improvement over the methods of human visual observation in that the data collection is more standardized, efficient and consistent.

Elevated plus maze behavior, auditory startle response, and shock sensitivity in predisease and in early stage autoimmune disease MRL/lpr mice.

Behaviors indicative of anxiety have been suggested to emerge with the onset of autoimmune disease in MRL/MpJ-Fas(lpr) (MRL/lpr) mice. This study extends the behavioral characterization of MRL/lpr and congenic MRL/MpJ+/+ (MRL/+) mice using the elevated plus maze (EPM), acoustic startle response, and foot-shock sensitivity tasks. In the elevated plus maze, predisease MRL/lpr mice exhibited less anxiety while MRL/lpr mice in the early stage of autoimmunity did not differ from age-matched control MRL/+ mice. MRL/lpr mice exhibited lower startle responses compared to MRL/+ mice. Similarly, predisease MRL/lpr mice were less reactive to various foot-shock levels than MRL/+ mice. Both the MRL/lpr and the MRL/+ strains exhibited startle habituation deficits, implicating the background MRL strain in the impairment in this process. These data do not support the hypothesis that increased anxiety is apparent with the emergence of autoimmune disease in MRL/lpr mice; however, anxiety may appear as the disease advances.

Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome.

Fragile X syndrome results from inadequate production of the fragile X mental retardation protein (FMRP). Mice with a mutation targeted to the Fmr1 gene lack FMRP and thus are a valuable animal model for studying the behavioral and neural phenotype of this human disorder. Mice of two genetic backgrounds containing the Fmr1 mutation, C57BL/6J (C57-KO) and an F1 hybrid (C57BL/6J mutant x FVB/NJ; F1-KO) did not differ from control mice in behavior in the elevated plus maze or the open field. Both the C57-KO and F1-KO mice exhibited greater startle responses than normal mice to low intensity (80 dB) white noise bursts and decreased responses to high intensity (120 dB) white noise bursts. These behavioral alterations appear to be specific to the Fmr1 mutation since they are present on both genetic backgrounds. Furthermore, the mice lacking FMRP resemble individuals with fragile X syndrome in their increased sensitivity to low intensity auditory stimuli. These findings should prove useful in determining how the absence of FMRP alters the brain and behavior, and in testing potential treatments for fragile X syndrome.