Tetrahydrobiopterin as a novel therapeutic intervention for autism

Tetrahydrobiopterin (BH₄) is an essential cofactor for several critical metabolic pathways that have been reported to be abnormal in autism spectrum disorder (ASD). In addition, the cerebrospinal fluid concentration of BH₄ is reported to be depressed in children with ASD. Over the past 25 years, several clinical trials have suggested that treatment with BH₄ improves ASD symptomatology in some individuals. Two ongoing clinical protocols may help further define the efficacy of BH₄ treatment in children with ASD. First, children with ASD who had low concentrations of cerebrospinal fluid or urine pterins were treated in an open-label manner with 20 mg/kg per day of BH₄. The majority of children (63%) responded positively to treatment, with minimal adverse events (AEs). Second, a double-blind placebo-controlled study examining the efficacy of 20 mg/kg per day of BH₄ treatment in children with ASD is currently underway. Safety studies from the commercially available forms of BH₄ document the low incidence of AEs, particularly serious AEs. Studies have also documented the ability of BH₄ to cross the blood-brain barrier. Based on the importance of BH₄ in neurodevelopmental metabolic pathways, the safety of BH₄ treatment, and the evidence for a therapeutic benefit of BH₄ treatment in children with ASD, we conclude that BH₄ represents a novel therapy for ASD, one that may gain wider use after further clinical studies have established efficacy and treatment guidelines.     

Dawn simulation light: a potential cardiac events protector

Objective/BackgroundMajor cardiovascular events frequently increase in the morning due to abrupt changes in the sympatho-vagal cardiac control during the transition from sleep to wakefulness. These neural changes are translated into stepwise increases in cardiac functions, resulting in a potential cardiovascular stress. Here, we explored whether light can “optimize” heart rate and its neural control, by actively promoting a less steep transition from sleep to wakefulness, thus minimizing morning cardiovascular vulnerability.MethodsSeventeen healthy young men were awakened 2-hours before their habitual wake-time. In a counterbalanced within-subject design, we applied a control condition (darkness during sleep and dim light during wakefulness) or dawn-simulation-light (DSL) starting 30-minutes before and ending 30-minutes after scheduled wake-up time.ResultsOur data reveal a significantly gradient reduction in heart rate during the transition from sleep to wakefulness, when applying DSL as compared to a control condition. Likewise, cardiac sympatho-vagal control smoothly increased throughout the 30-min sleep episode preceding scheduled wake-up under DSL and remained stable for the first 30-min of wakefulness. Interestingly, these effects were mostly driven by changes in the parasympathetic cardiac control.ConclusionsOur data demonstrate for the first time that a non-invasive strategy, as light exposure surrounding the wake-up process, can significantly reduce the deleterious sleep-to-wake evoked cardiac modulation in healthy young men awakened under conditions of increased sleep pressure. A translational approach of this light exposure, which closely resembles natural lighting conditions in the morning, may therefore act as a potential protector for cardiac vulnerability in the critical morning hours.     

The use of in vivo desensitization as part of a total therapeutic intervention

The use of in vivo and imaginal desensitization procedures for treatment of a fear of flying in airplanes is described. The direct benefits of the program, along with the positive effects it had upon progress on a series of other, equally troublesome presenting problems is discussed.     

Dawn simulation vs. lightbox treatment in winter depression: a comparative study

Dawn simulation, with gradually increasing bedside light in the morning, has shown promising results as an alternative to bright light treatment for winter depression. To compare these treatments, 61 out-patients with winter depression (20–70 years of age, 80% women) were randomized to receive either lightbox treatment with 1500–2500 lux white light for 2 h in the morning for 6 days on an out-patient basis (n=34), or dawn simulation treatment in their homes, with 60 or 90 min of light augmentation time to 100–300 lux, for 2 weeks (n=27). Patients’ ratings of improvement on a visual analogue scale (correlating strongly with percentage reduction in an extended Montgomery-Åsberg Depression Rating Scale (MADRS) score) at the end of treatment showed a mean of 40.0% (SD 27.7%) in the dawn simulation group and 57.4% (SD 29.9%) in the lightbox group (p =0.02). The majority of the patients in both groups maintained their improvement during a 9-week follow-up. Age, sex, current major depression or current use of antidepressants did not predict outcome in either group. No serious side-effects were observed.     

Dawn simulation and bright light in the treatment of SAD: a controlled study.

BACKGROUND: Some small controlled studies have found that dawn simulation is effective in treating seasonal affective disorder (SAD). With a larger sample size and a longer duration of treatment, we compared dawn simulation with bright light therapy and a placebo condition in patients with SAD. METHOD: Medication-free patients with SAD were randomly assigned to one of three conditions: bright light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo condition, a dim red light (1.5 hour dawn signal from 4:30 am to 6:00 AM peaking at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of the remissions (SIGH-SAD < or = 8) and response (> or =50% decrease in SIGH-SAD) to treatment over time using Cox proportional hazards models. RESULTS: The sample consisted of 95 subjects who were randomized to the three conditions: bright light (n = 33), dawn simulation (n = 31) and placebo (n = 31). Dawn simulation was associated with greater remission (p <.05) and response (p <.001) rates compared to the placebo. Bright light did not differ significantly from the placebo. Dawn simulation was associated with greater remission (p <.01) and response (p <.001) rates compared to the bright light therapy. The mean daily hours of sunshine during the week before each visit were associated with a significant increase in likelihood of both remission (p <.001) and response (p <.001). CONCLUSIONS: Dawn simulation was associated with greater remission and response rates compared to the placebo and compared to bright light therapy. The hours of sunshine during the week before each assessment were associated with a positive clinical response.     

Drawings as a therapeutic medium

This paper describes a 4-year-old boy whose presenting problem was anxiety. The treatment used is of particular interest because of the graphic exposition of the development of the therapeutic alliance, the immediacy of the Oedipal issues, and the usefulness of the child's drawings as a therapeutic medium. The phases of therapy are reflected in the drawings, as is identification with the therapist and the integration of loss when patient and therapist terminate.     

Psychiatry as a therapeutic discipline

European Archives of Psychiatry and Clinical Neuroscience -     

Autocatharsis as a therapeutic measure

Psychiatric Quarterly -     

Alpha-methyltryptophan as a therapeutic agent

1. Alpha-methyltryptophan, on administration to experimental animals gives rise to cerebral alpha-methylserotonin, which substitutes for serotonin in certain behavioral and functional tests.

2. Such results are consistent wich the similarity of the properties of the two indoleamlnes with respect to storage, uptake and release, as well as with the 5HT₂receptor agonist activity of alpha-methylserotonin.

3. It is proposed that alpha-methyltryptophan be regarded as a candidate drug for the provision of alpha-methylserotonin as a substitute for serotonin in disorders where the latter amine is thought Co be deficient.     

Guardianship as a therapeutic option

The HIV/AIDS epidemic has posed a significant challenge to our legal system, demanding that it evolve to provide more flexible ways for parents to transfer guardianship of their children to other caring adults in a timely and minimally traumatic manner. Although a number of states have responded to the challenge, adopting new guardianship options such as delegations of parental authority for limited purposes, standby guardianship, co-guardianships, and subsidized guardianships, the majority of states still do not provide this continuum of options. Moreover, few states have established multidisciplinary programs that help parents take full advantage of the new guardianship options. Few have even begun to address the complex needs of the "second" families. Few have developed plans to meet the needs of the older AIDS-affected youth. How well we ensure the quality and continuity of parental care for children whose parents are living with HIV and AIDS, or who later die of it, is one of the tests of our generation. If we fail to meet this challenge, we are knowingly placing thousands of children and youth at enormous, predictable, and potentially fatal risk.