Childhood maltreatment, pituitary volume and adolescent hypothalamic-pituitary-adrenal axis - Evidence for a maltreatment-related attenuation.

BACKGROUND: Alterations of the development of the hypothalamic-pituitary-adrenal axis (HPAA) have been suggested to be related to experiences of early maltreatment. It has been postulated that early stress (i.e., maltreatment) leads to initial hyperactivation of the HPAA, which subsequently may progress to hypoactivation during the course of adolescence, however empirical studies on this hypothesis are rare. In the current study, we aimed to examine the longitudinal relationships between childhood maltreatment, early adolescent pituitary gland volume (PGV) and mid-adolescent cortisol output in an existing data set to explore the utility of PGV as a measure of HPAA function, and as an indirect test of the attenuation hypothesis. METHODS: The sample comprised 69 adolescents (30 females), subsampled from a larger longitudinal, community-based study on adolescent development. PGV, as an estimate of chronic childhood HPAA activity, was measured by magnetic resonance imaging during early adolescence (mean age 12.62 ± 0.45 years). Cortisol output was assessed via multiple salivary cortisol measures in mid-adolescence (mean age 15.52 ± 0.39 years). The cortisol awakening response (CAR) was calculated as a measure of HPAA functioning. Retrospective assessment of childhood maltreatment was performed using the Childhood Trauma Questionnaire (CTQ). Regression analyses were conducted to examine whether childhood maltreatment, PGV, and their interaction, predicted mid-adolescent CAR. RESULTS: No main effect of PGV or maltreatment was found on adolescent CAR. PGV did however significantly interact with childhood maltreatment in predicting the CAR (t = -2.26; p = 0.024). Larger PGV positively predicted lower CAR in the context of relatively high childhood maltreatment (t = 2.032; p = 0.046), but showed no relationship in the context of relatively low maltreatment (t = 0.723; p = 0.472). Maltreatment also interacted with sex, such that (only) in females, higher levels of maltreatment predicted a lower CAR (t = -2.04, p = 0.042). CONCLUSIONS: In the presence of childhood maltreatment, larger PGV was associated with lower CAR in adolescence, providing support for the application of PGV in studies of HPA axis function. Our finding is consistent with a maltreatment-related attenuation of HPAA functioning that may derive from a stress induced chronic hyperactivation during childhood. Prospective longitudinal studies are now required to further explicate these findings and relationships with psychopathology.

Recurrence of major depressive disorder is predicted by inhibited startle magnitude while recovered.

BACKGROUND: Major depressive disorder, for some, follows a chronic relapsing course. However, no reliable marker has been established that allows the identification of this sub-group of patients. Preliminary findings suggest that baseline startle magnitude may be such a marker. This study evaluated whether differences in baseline startle magnitude during remission could prospectively predict depressive symptomatology and recurrence. METHODS: A group of previously depressed individuals (n=25), who were in full remission at the time of testing, had their startle reflex measured via surface EMG electrodes on the left orbicularis oculi muscle. These people were then followed-up 2 years later and their depressive symptomatology during the intervening period was assessed using the psychiatric ratings scale of the Longitudinal Interval Follow-up Evaluation (LIFE; [Keller, M.B., Lavori, P.W., Friedman, B., Nielsen, E., Endicott, J., McDonald-Scott, P., et al. (1987). The Longitudinal Interval Follow-up Evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies. Arch. Gen. Psychiatry, 44(6), 540-548]) and incidents of recurrence assessed using the Structured Clinical Interview for DSM-IV (SCID-I/P; [First, M.B., Spitzer, R.L., Gibbon, M., & Williams, J.B.W. (2001). Structured clinical interview for axis 1 DSM-IV disorders. New York: New York State Psychiatric Institute]). RESULTS: It was found that a relatively attenuated startle response at initial assessment was strongly predictive of both depressive symptomatology and those who would experience relapse. LIMITATIONS: This study has a relatively small sample size that limits the degree to which a thorough co-variant analysis can be conducted and also makes the analysis of gender-based difference impracticable. Additionally, as no healthy control group is included, we report a relative rather than absolute attenuation of startle to be indicative of symptom severity and recurrence proclivity. CONCLUSIONS: These preliminary findings suggest that an attenuated startle response may have utility as an endophenotypic marker of risk for recurrence of Major Depression and residual sub-syndromal symptomatology. Such a marker may facilitate the early identification and treatment of those most at risk of recurrent Major Depression.

Impaired theory of mind in first-episode schizophrenia: comparison with community, university and depressed controls.

First order theory of mind, as measured by the 'Reading the Mind in the Eyes Test' Revised, is impaired in schizophrenia. However, no study has investigated whether this occurs in first-episode schizophrenia. Also, it is unclear whether such a deficit is specific to schizophrenia, and whether convenience control samples, particularly undergraduate university students, represent valid comparison groups. This study investigated theory of mind ability, measured by the 'Reading the Mind in the Eyes Test' Revised, in a group of first-episode schizophrenia outpatients (n=13) and three control groups: outpatients with non-psychotic major depression (n=14), individuals from the general community (n=16) and from an undergraduate university course (n=27). The schizophrenia group exhibited significant theory of mind impairments compared to both non-psychiatric control groups but not the depression group. Unexpectedly, the depression group was not significantly impaired compared to the community control group, and the university control group exhibited superior theory of mind ability relative to all three groups. The findings indicate theory of mind deficits in first episode schizophrenia and support the implementation of theory of mind interventions in first-episode schizophrenia treatment programs. Results also indicate that community rather than university control groups represent more valid comparison groups in first-episode schizophrenia research.