Understanding the link between low self-esteem and depression

Although it is well documented that low self-esteem and depression are related, the precise nature of the relation has been a topic of ongoing debate. We describe several theoretical models concerning the link between self-esteem and depression, and review recent research evaluating the validity of these competing models. Overall, the available evidence provides strong support for the vulnerability model (low self-esteem contributes to depression), weaker support for the scar model (depression erodes self-esteem), and little support for alternative accounts such as the diathesis-stress model. Moreover, the vulnerability model is robust and holds across gender, age, affective-cognitive versus somatic symptoms of depression, European background versus Mexican-origin participants, and clinical versus nonclinical samples. Research on further specifications of the vulnerability model suggests that the effect is (a) partially mediated by rumination, (b) not influenced by other characteristics of self-esteem (i.e., stability and contingency), and (c) driven predominantly by global rather than domain-specific self-esteem. The research has important theoretical implications because it counters the commonly repeated claim that self-esteem has no long-term impact. Moreover, the research has important practical implications, suggesting that depression can be prevented, or reduced, by interventions that improve self-esteem.

Moderate concentrations of 4-O-methylhonokiol potentiate GABAA receptor currents stronger than honokiol

BACKGROUND Magnolia bark preparations from Magnolia officinalis of Asian medicinal systems are known for their muscle relaxant effect and anticonvulsant activity. These CNS related effects are ascribed to the presence of the biphenyl-type neolignans honokiol and magnolol that exert a potentiating effect on GABAA receptors. 4-O-methylhonokiol isolated from seeds of the North-American M. grandiflora was compared to honokiol for its activity to potentiate GABAA receptors and its GABAA receptor subtype-specificity was established. METHODS Different recombinant GABAA receptors were functionally expressed in Xenopus oocytes and electrophysiological techniques were used determine to their modulation by 4-O-methylhonokiol. RESULTS 3μM 4-O-methylhonokiol is shown here to potentiate responses of the α₁β₂γ₂ GABAA receptor about 20-fold stronger than the same concentration of honokiol. In the present study potentiation by 4-O-methylhonokiol is also detailed for 12 GABAA receptor subtypes to assess GABAA receptor subunits that are responsible for the potentiating effect. CONCLUSION The much higher potentiation of GABAA receptors at identical concentrations of 4-O-methylhonokiol as compared to honokiol parallels previous observations made in other systems of potentiated pharmacological activity of 4-O-methylhonokiol over honokiol. GENERAL SIGNIFICANCE The results point to the use of 4-O-methylhonokiol as a lead for GABAA receptor potentiation and corroborate the use of M. grandiflora seeds against convulsions in Mexican folk medicine.

A mutation in hairless dogs implicates FOXI3 in ectodermal development

Mexican and Peruvian hairless dogs and Chinese crested dogs are characterized by missing hair and teeth, a phenotype termed canine ectodermal dysplasia (CED). CED is inherited as a monogenic autosomal semidominant trait. With genomewide association analysis we mapped the CED mutation to a 102-kilo-base pair interval on chromosome 17. The associated interval contains a previously uncharacterized member of the forkhead box transcription factor family (FOXI3), which is specifically expressed in developing hair and teeth. Mutation analysis revealed a frameshift mutation within the FOXI3 coding sequence in hairless dogs. Thus, we have identified FOXI3 as a regulator of ectodermal development.