Bonnie Aronowitz

Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders.

Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Aspergers disorder via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.

The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder

Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, we investigated whether specific neurobiological markers vary in parallel to core symptomatology. Specifically, we assessed growth hormone response to the 5-HT 1d agonist, sumatriptan, and linked this measure of serotonergic function to the severity of repetitive behaviors in adult autistic patients. Eleven adult patients with autism or Aspergers disorder were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a one-week interval. In adult autistic disorders, severity of repetitive behaviors at baseline, as measured by YBOCS-compulsion score, significantly positively correlated with both peak delta growth hormone response and area under the curve growth hormone response to sumatriptan. Thus, the severity of a specific behavioral dimension in autism (repetitive behaviors) parallels the sensitivity of the 5-HT 1d receptor, as manifest by sumatriptan elicited GH response.

Neuropsychiatric impairment in impulsive personality disorders

It has been suggested that impulsivity and aggression are associated with neuropsychiatric impairment. Neurological soft signs may be a useful marker of nonspecific brain damage, and may therefore be increased in impulsive and aggressive patients compared with normal control subjects. A structured examination was used to evaluate neurological soft signs in 28 patients with personality disorders characterized by impulsivity and 28 healthy control subjects. All of the patients met DSM-III-R criteria for borderline personality disorder, and 10 also met criteria for antisocial personality disorder. All patients were questioned about past history of physical aggression, and a subset of 18 patients underwent neuropsychological testing with a select battery. Left-sided neurological soft signs were significantly increased in patients compared with normal control subjects. Patients with a history of aggression, however, had significantly more right-sided neurological soft signs than those without a history of aggression. Increased neurological soft signs were associated with impairment on the Wisconsin Card Sort, a test of frontal lobe executive function. Specific neuropsychiatric abnormalities, such as lateralized neurological soft signs and associated impairment on select neuropsychological tests, may be present in patients with personality disorders characterized by impulsivity.

A Dimensional Approach to the Autism Spectrum

Autism is heterogeneous with respect to clinical symptoms and etiology. A significant limitation in research of the neurobiology and treatment of autism has been the lack of attention to this heterogeneity. A dimensional approach to the study of autism is valuable in linking key symptoms to the neurobiology and treatment of the disorder in a clinically meaningful way. In this article, we outline a dimensional approach to the autism spectrum, discuss the three core dimensions of autism and their neurobiology, and review the possible links of serotonin, anterior cingulate gyrus activity, and the immune marker D8/17 to the repetitive behavior/compulsivity dimensions.

m-Chlorophenylpiperazine challenge in borderline personality disorder: Relationship of neuroendocrine response, behavioral response, and clinical measures

We have previously found that a subgroup of patients with impulsive personality disorders respond to m-chlorophenylpiperazine (m-CPP) administration with a distinctive spacy/high behavioral reaction and with increased cortisol responses. In this report we analyzed the relationship between behavioral and neuroendocrine responses to m-CPP in an enlarged sample of patients with borderline personality disorder (BPD). We also assessed the association of behavioral and neuroendocrine responses with clinical symptoms and with m-CPP blood levels. We found that in BPD patients the presence of a spacy/high behavioral response was significantly associated with increased prolactin and cortisol responses to m-CPP. In BPD patients increased m-CPP levels were significantly associated with neuroendocrine hypersensitivity and with a spacy/high behavioral response, while in controls increased m-CPP levels were not significantly associated with neuroendocrine hypersensitivity but were significantly associated with dysphoric behavioral responses. Taken together with previous work on m-CPP in obsessive-compulsive disorder, these results are partially consistent with the hypothesis that compulsive and impulsive symptoms fall at opposite ends of a phenomenologic and neurobiologic spectrum.

Increased growth hormone response to sumatriptan challenge in adult autistic disorders

Serotonergic (5-HT) abnormalities have been documented in autism. To assess sensitivity of the 5-HT1d receptor, growth hormone response to the 5-HT1d receptor agonist sumatriptan was studied in adult autistic patients and matched normal controls. In this study, 11 adult patients with autism or Aspergers disorder were compared with nine matched controls. All subjects were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a 1-week interval, and growth hormone was measured before and during the challenges. The results showed a highly significant diagnosisxdrugxtime interaction on repeated measure analysis covaried for baseline. This suggests that autistic patients had significantly greater growth hormone response to sumatriptan than normal controls, independent of placebo effects. Therefore, abnormalities in 5-HT regulation in autism may be related to increased sensitivity of the 5-HT1d inhibitory receptor in autism.

The Neuropsychiatry of Autism and Asperger's Disorder: Review of the Literature and Case Reports

The literature on neuropsychiatric, neuropsychological, and neuroimaging findings in autism and Aspergers disorder is briefly reviewed. Neurological soft sign, neuropsychological, and positron-emission tomography findings in one patient with Aspergers disorder and one patient with autism are highlighted, discussed as examples of heterogeneity, and integrated with the relevant literature.

Headache responses to M-CPP in OCD and normal controls

activities in short segments of data, and during acute challenge studies to induce panic attacks. This method ensures that one does not lose important information during quick changes in cardiac sympathetic and parasympathetic activities. This method can also be used on long data segments, and the results are comparable to traditional spectral analysis or nonlinear techniques such as fractal dimensions. Using this technique, we found very high increases in sympathovagal ratios in patients during lactate and isoproterenol infusions, especially when they had panic attacks. Similar changes were also noted during human sexual activity at the time of orgasm, analyzed from the 24-hour Holter records of ECG. Complex demodulation also allows one to quantify time-dependent changes in the LF (0.04--0.15 Hz) power. This may be an important technique to analyze heart rate time series during heightened sympathetic activity, as there is a consistent peak in the time series of the LF amplitudes around 0.2 Hz, which is related to muscle sympathetic activity. Complex demodulation can be performed on heart rate time series using center frequencies of 0.09 and 0.31 Hz for the LF and HF powers with pass frequencies of 0.05 and 0.15 Hz. We use a 61 -term low-pass filter using a published algorithm for a zero-phase-shift least-square filter with convergence factors.