Revisiting the monoamine hypothesis of depression: a new perspective.

As the incidence of depression increases, depression continues to inflict additional suffering to individuals and societies and better therapies are needed. Based on magnetic resonance spectroscopy and laboratory findings, gamma aminobutyric acid (GABA) may be intimately involved in the pathophysiology of depression. The isoelectric point of GABA (pI = 7.3) closely approximates the pH of cerebral spinal fluid (CSF). This may not be a trivial observation as it may explain preliminary spectrophotometric, enzymatic, and HPLC data that monoamine oxidase (MAO) deaminates GABA. Although MAO is known to deaminate substrates such as catecholamines, indoleamines, and long chain aliphatic amines all of which contain a lipophilic moiety, there is very good evidence to predict that a low concentration of a very lipophilic microspecies of GABA is present when GABA pI = pH as in the CSF. Inhibiting deamination of this microspecies of GABA could explain the well-established successful treatment of refractory depression with MAO inhibitors (MAOI) when other antidepressants that target exclusively levels of monoamines fail. If further experimental work can confirm these preliminary findings, physicians may consider revisiting the use of MAOI for the treatment of non-intractable depression because the potential benefits of increasing GABA as well as the monoamines may outweigh the risks associated with MAOI therapy.

Challenges in the diagnosis and treatment of depression in autism spectrum disorders across the lifespan.

Diagnosis and treatment of comorbid neuropsychiatric illness is often a secondary focus of treatment in individuals with autism spectrum disorder (ASD), given that substantial impairment may be caused by core symptoms of ASD itself. However, psychiatric comorbidities, including depressive disorders, are common and frequently result in additional functional impairment, treatment costs, and burden on caregivers. Clinicians may struggle to appropriately diagnose depression in ASD due to communication deficits, atypical presentation of depression in ASD, and lack of standardized diagnostic tools. Specific risk and resilience factors for depression in ASD across the lifespan, including level of functioning, age, family history, and coping style, have been suggested, but require further study. Treatment with medications or psychotherapy may be beneficial, though more research is required to establish guidelines for management of symptoms. This review will describe typical presentations of depression in individuals with ASD, review current information on the prevalence, assessment, and treatment of comorbid depression in individuals with ASD, and identify important research gaps.

The effect of prenatal or early postnatal irradiation on the production of anti-arsonate antibodies and Cross-reactive idiotypes

Preliminary studies on the long-term effects of prenatal and early postnatal irradiation on the immune response to arsonate were performed using A/J mice. Pregnant mice were irradiated (0·5 Gy, X-rays) or sham-irradiated on a single occasion during gestation (between day 5 and 18 post-conception). Alternatively, newborn mice received the same treatment between day 2 and 7 after birth. Mice were immunized with keyhole limpet haemocyanin-arsonate (KLH-Ars) in adjuvant from 2 months after birth. The levels of specific antibodies to arsonate (anti-Ars) were measured by radioimmunoassay. In addition, the Ars-related cross-reactive idiotype (CRIA) was measured by the haemagglutination technique. In the primary response the titre of anti-Ars was reduced in animals that had been irradiated between day 12 and 15 of gestation. In the second response, in contrast, they had increased levels of anti-Ars. After immunization with KLH-Ars, high levels of CRIA were observed in all groups. However, in mice irradiated 18-20 days after conception the level of CRIA was often much higher than the level of anti-Ars, indicating that a large proportion of the CRIA-positive molecules were not specific for Ars. Thus, in this particular case, some specificity of the immune response was lost after irradiation. The expression of recurrent idiotypes may be a sensitive indicator of immunological perturbations after irradiation. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Neurodevelopmental and respiratory follow-up results at 7 years for children from the United Kingdom and Ireland enrolled in a randomized trial of early and late postnatal corticosteroid treatment, systemic and inhaled (the Open Study of Early Corticosteroid Treatment)

The goals were to compare early school-age neurodevelopmental and respiratory outcomes for children who were treated with either early (15 days) postnatal corticosteroid therapy and to compare systemic dexamethasone treatment with inhaled budesonide treatment.

Mothers' antenatal depression and their children's antisocial outcomes

Interviews of 120 British adolescents and their parents (80% of a random sample of antenatal patients drawn from a representative urban population and followed longitudinally) revealed that 40 (33%) had been arrested and/or had a diagnosis of DSM-IV conduct disorder by 16 years of age; of those, 18 (45%) had committed violent acts. Depression in pregnancy significantly predicted violence in adolescence, even after controlling for the family environment, the child's later exposure to maternal depression, the mother's smoking and drinking during pregnancy, and parents' antisocial behavior. Mothers with a history of conduct problems were at elevated risk to become depressed in pregnancy, and the offspring of depressed women had a greater chance of becoming violent by age 16.