Joanne S. Carpenter

Response Rate and Reinforcement Rate in Pavlovian Conditioning

Four experiments used delay conditioning of magazine approach in rats to investigate the relationship between the rate of responding, R, to a conditioned stimulus (CS) and the rate, r, at which the CS is reinforced with the unconditioned stimulus (US). Rats were concurrently trained with four variable-duration CSs with different rs, either as a result of differences in the mean CS-US interval or in the proportion of CS presentations that ended with the US. In each case, R was systematically related to r, and the relationship was very accurately characterized by a hyperbolic function, R = Ar/(r +c). Accordingly, the reciprocal of these two variables-response interval, I (= 1/R), and CS-US interval, i (= 1/r) - were related by a simple affine (straight line) transformation, I = mi+b. This latter relationship shows that each increment in the time that the rats had to wait for food produced a linear increment in the time they waited between magazine entries. We discuss the close agreement between our findings and the Matching Law (Herrnstein, 1970) and consider their implications for both associative theories (e.g., Rescorla & Wagner, 1972) and nonassociative theories (Gallistel & Gibbon, 2000) of conditioning. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders

Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16–30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18–30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a ‘long sleep’ cluster, a ‘disrupted sleep’ cluster, and a ‘delayed and disrupted sleep’ cluster. Circadian clusters included a ‘strong circadian’ cluster, a ‘weak circadian’ cluster, and a ‘delayed circadian’ cluster. Medication use differed between clusters. The ‘long sleep’ cluster displayed significantly worse visual memory performance compared to the ‘disrupted sleep’ cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness.

Sleep–wake cycle phenotypes in young people with familial and non-familial mood disorders

Converging evidence identifies that the offspring of parents with bipolar disorder (BD), individuals at clinical high risk of BD, and young people with recent onset BD may differ from other clinical cases or healthy controls in terms of sleep–wake profiles. However, it is possible that these differences may reflect current mental state, subtype of mood disorder, or familial traits. This study aimed to determine objective and subjective sleep–wake profiles in individuals aged 15–25 years with a current major depressive episode, in relation to familial traits.

Variations in the sleep–wake cycle from childhood to adulthood: chronobiological perspectives

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php ChronoPhysiology and Therapy 2015:5 37–49 ChronoPhysiology and Therapy Dovepress

Sleep–wake profiles predict longitudinal changes in manic symptoms and memory in young people with mood disorders

Mood disorders are characterized by disabling symptoms and cognitive difficulties which may vary in intensity throughout the course of the illness. Sleep–wake cycles and circadian rhythms influence emotional regulation and cognitive functions. However, the relationships between the sleep–wake disturbances experienced commonly by people with mood disorders and the longitudinal changes in their clinical and cognitive profile are not well characterized. This study investigated associations between initial sleep–wake patterns and longitudinal changes in mood symptoms and cognitive functions in 50 young people (aged 13–33 years) with depression or bipolar disorder. Data were based on actigraphy monitoring conducted over approximately 2 weeks and clinical and neuropsychological assessment. As part of a longitudinal cohort study, these assessments were repeated after a mean follow‐up interval of 18.9 months. No significant differences in longitudinal clinical changes were found between the participants with depression and those with bipolar disorder. Lower sleep efficiency was predictive of longitudinal worsening in manic symptoms (P = 0.007). Shorter total sleep time (P = 0.043) and poorer circadian rhythmicity (P = 0.045) were predictive of worsening in verbal memory. These findings suggest that some sleep–wake and circadian disturbances in young people with mood disorders may be associated with less favourable longitudinal outcomes, notably for subsequent manic symptoms and memory difficulties.

Circadian rhythms and psychiatric profiles in young adults with unipolar depressive disorders.

Abnormalities in circadian rhythms have been reported in people with mood disorders, but these abnormalities are marked by considerable inter-individual variability. This study aimed to identify pathophysiological subgroups on the basis of circadian markers and evaluate how these subgroups relate to psychiatric profiles. Thirty-five young adults (18–31 years old) receiving clinical care for unipolar depressive disorders and 15 healthy controls took part to this study. The Hamilton Rating Scale for Depression and the Young Mania rating scale were used to evaluate the severity of mood symptoms in participants with depressive disorders. All participant underwent ambulatory sleep monitoring with actigraphy for about 12 days before attending a laboratory-based chronobiological assessment which included repeated salivary samples to determine dim light melatonin onset (DLMO) and continuous core body temperature (CBT) monitoring using an ingestible temperature sensor. Cluster analyses were conducted across all participants to identify subgroups with consistent circadian timing profiles based on DLMO and the nocturnal minima of CBT. Two clusters were identified: ‘delayed’ and ‘conventional timing’ circadian phase. Descriptive analyses showed that the delayed cluster was characterised by abnormal time relationships between circadian phase markers and the sleep–wake cycle. Importantly, individuals from the delayed cluster had worse depression severity (t(28) = −2.7, p = 0.011) and hypomanic symptoms (Z = −2.2, p = 0.041) than their peers with conventional circadian timing. These findings suggest that delayed and disorganised circadian rhythms may be linked to worse psychiatric profiles in young people with depressive disorders.

Adolescent-Onset Depressive Disorders and Inflammation

Abstract It is timely to incorporate a new perspective on the role of inflammatory, metabolic, and circadian perturbations in the onset and course of adolescent depression. The last decade of findings in the epidemiology of adolescent depression, linked with other clinical, neurobiological, and pathophysiological research, suggests that inflammatory factors may play a critical role in not only the onset of mood-related mental health problems but also the progression of illness and secondary physical health problems. Of additional relevance is the increasing recognition of the potential role of perturbed circadian systems to both risk and recurrence of depressive disorders. Together, these developments strongly suggest the need for comprehensive assessment, new therapeutic approaches, and incorporation of secondary prevention of adverse medical and psychological outcomes. Trials of new antiinflammatory approaches (as acute or secondary preventive therapies) should occur alongside the development of new therapies targeting circadian dysfunction. Future intervention research may utilize prior stratification of adolescent cohorts on the basis of relevant clinical phenotypes (e.g., “atypical” features and relevant neurological or medical comorbidity) or laboratory markers (e.g., evidence of low-grade inflammation or specific autoimmune processes). Clinically, wider use of these approaches may lead to greater personalization of treatment choices.

Profiling risk for depressive disorder by circuit, behavior and self-report measures of emotion function

BACKGROUND Major depressive disorder (MDD) is characterized by maladaptions in affective brain circuitry and in emotion regulation. It remains unknown whether these maladaptions characterize first-degree relatives of probands who are unaffected yet have a higher risk of developing MDD. METHODS Participants were 72 unaffected first-degree relatives of probands with MDD and 66 matched non-relative controls. We investigated brain circuit function and self-reported emotion regulation strategies for reappraisal and suppression. During functional magnetic resonance imaging, we probed circuitry relevant to both negative and positive valence systems using facial expressions signaling potential threat, sadness and happiness, presented under both conscious and subliminal viewing conditions. We compared groups using a statistically controlled region of interest (ROI) approach including the amygdala, insula, anterior cingulate cortex (ACC), ventromedial prefrontal cortex and dorsolateral prefrontal cortex. We also used a data-driven cluster analytic approach for characterizing the relatives by their brain function profiles. RESULTS As a group, relatives were distinguished by hyper-reactivity of the pregenual ACC during subliminal viewing of threat-related expressions but hypo-activation of the amygdala, insula and dorsal ACC during explicit viewing of the same threat-related expressions and sadness. When considered individually, this brain function profile characterized two-thirds of relatives, and these relatives were also less likely to use reappraisal to regulate negative emotion. LIMITATIONS The design was cross-sectional and therefore does not provide direct evidence as to the trait- (versus state-) like profile observed in relatives. CONCLUSIONS Familial risk for MDD may involve a disruption to the normal recruitment of neural circuits for appraising salient emotions, both implicit and explicit. Interventions targeting reappraisal strategies for regulating negative emotion may serve to buffer this risk.

Lower In vivo Myo-Inositol in the Anterior Cingulate Cortex Correlates with Delayed Melatonin Rhythms in Young Persons with Depression

Myo-inositol, a second messenger glucose isomer and glial marker, is potentiated by melatonin. In addition to common abnormalities in melatonin regulation, depressive disorders have been associated with reduced myo-inositol in frontal structures. This study examined associations between myo-inositol in the anterior cingulate cortex and the timing of evening melatonin release. Forty young persons with unipolar depression were recruited from specialized mental health services (20.3 ± 3.8 years old). Healthy controls were recruited from the community (21.7 ± 2.6 years old). The timing of dim light melatonin onset (DLMO) was estimated using salivary melatonin sampling. Myo-inositol concentrations (MI/CrPCr ratio) in the anterior cingulate cortex were obtained using proton magnetic resonance spectroscopy. After controlling for age, sex, and CrPCr concentration the depression group had significantly lower MI/CrPCr ratios than healthy controls [F(4, 75) = 11.4, p = 0.001]. In the depression group, later DLMO correlated with lower MI/CrPCr ratio (r = −0.48, p = 0.014). These findings suggest that neurochemical changes in the frontal cortex are associated with circadian disruptions in young persons with depression.