Sleep-light interventions that shift melatonin rhythms earlier improve perimenopausal and postmenopausal depression: preliminary findings.

OBJECTIVE: Testing the hypothesis that a sleep-light intervention, which phase-advances melatonin rhythms, will improve perimenopausal-postmenopausal (P-M; by follicle-stimulating hormone) depression. METHODS: In at-home environments, we compared two contrasting interventions: (1) an active phase-advance intervention: one night of advanced/restricted sleep from 9 pm to 1 am , followed by 8 weeks of morning bright white light for 60 min/d within 30 minutes of awakening, and (2) a control phase-delay intervention: one night of delayed/restricted sleep (sleep from 3 to 7 am ) followed by 8 weeks of evening bright white light for 60 min/d within 90 minutes of bedtime. We tested 17 P-M participants, 9 normal controls and 8 depressed participants (DPs) (by Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria). Clinicians assessed mood by structured interviews and subjective mood ratings. Participants wore actigraphs to measure sleep and activity and collected overnight urine samples for the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), before, during, and after interventions. RESULTS: Baseline depressed mood correlated with delayed 6-SMT offset time (cessation of melatonin metabolite [6-SMT] secretion) ( r = +0.733, P = 0.038). After phase-advance intervention versus phase-delay intervention, 6-SMT offset (start of melatonin and 6-SMT decrease) was significantly advanced in DPs (mean ± SD, 2 h 15 min ± 12 min; P = 0.042); advance in 6-SMT acrophase (time of maximum melatonin and 6-SMT secretion) correlated positively with mood improvement ( r = +0.978, P = 0.001). Mood improved (+70%, P = 0.007) by both 2 and 8 weeks. CONCLUSIONS: These preliminary findings reveal significantly phase-delayed melatonin rhythms in DP versus normal control P-M women. Phase-advancing melatonin rhythms improves mood in association with melatonin advance. Thus, sleep-light interventions may potentially offer safe, rapid, nonpharmaceutical, well-tolerated, affordable home treatments for P-M depression.

Critically-timed sleep+light interventions differentially improve mood in pregnancy vs. postpartum depression by shifting melatonin rhythms.

BACKGROUND: Testing the hypothesis that combined wake + light therapy improves mood in pregnant vs. postpartum depressed participants (DP) by differentially altering melatonin and sleep timing. METHODS: Initially 89 women, 37 pregnant (21 normal controls-NC; 16 DP) and 52 postpartum (27 NCs; 25 DP), were randomized to a parallel trial of a phase-delay intervention (PDI): 1-night of early-night wake therapy (sleep 3-7 am) + 6-weeks of evening bright white light (Litebook Advantage) for 60 min starting 90 min before bedtime, vs. a Phase-advance intervention (PAI): 1-night of late-night wake therapy (sleep 9 pm-1 am) + 6-weeks of morning bright white light for 60 min within 30 min of wake time. Blinded clinicians assessed mood weekly by structured interview, and participants completed subjective ratings, a Morningness-Eveningness questionnaire, actigraphy, and collected 2 overnight urine samples for 6-sulphatoxy melatonin (6-SMT). RESULTS: In pregnant DP, mood improved more after the PDI vs. PAI (p = .016), whereas in postpartum DP, mood improved more after the PAI vs. PDI (p = .019). After wake therapy, 2 weeks of light treatment was as efficacious as 6 weeks (p > .05). In postpartum DP, PAI phase-advanced 6-SMT offset and acrophase (p < .05), which correlated positively with mood improvement magnitude (p = .003). LIMITATIONS: Small N. CONCLUSIONS: Mood improved more after 2 weeks of the PDI in pregnant DP, but more after 2 weeks of PAI in postpartum DP in which improvement magnitude correlated with 6-SMT phase-advance. Thus, critically-timed Sleep + Light Interventions provide safe, efficacious, rapid-acting, well-tolerated, at-home, non-pharmaceutical treatments for peripartum DP.

A 1-week sleep and light intervention improves mood in premenstrual dysphoric disorder in association with shifting melatonin offset time earlier.

To test the hypothesis that 1 week of combined sleep and light interventions (SALI), which phase-advance (shift earlier) melatonin circadian rhythms, improves mood significantly more than phase-delay (shift later) SALI. After a 2-month diagnostic evaluation for premenstrual dysphoric disorder (PMDD per DSM-5 criteria) in a university clinical research setting, 44 participants enrolled in baseline studies were randomized in the luteal phase at home to (A) a phase-advance intervention (PAI): 1 night of late-night wake therapy (LWT: sleep 9 pm-1 am) followed by 7 days of the morning (AM) bright white light (BWL), or (B) a phase-delay intervention (PDI): 1 night of early-night wake therapy (EWT: sleep 3-7 am) plus 7 days of the evening (PM) BWL. After a month of no intervention, participants underwent the alternate intervention. Outcome measures were mood, the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), and actigraphy (to assess protocol compliance). At baseline, atypical depression correlated positively with phase delay in 6-SMT offset time (r = .456, p = .038). PAI advanced 6-SMT offset from baseline more than PDI (p < .05), and improved raw mood scores more than PDI (p < .05). As hypothesized, percent improvement in mood correlated positively with a phase advance from baseline in 6-SMT offset time (p < .001). Treatment with 1 night of advanced/restricted sleep followed by 7 days of AM BWL (PAI) was more efficacious in reducing PMDD depression symptoms than a PDI; mood improvement occurred in association with phase advance in 6-SMT offset time. Combined SALIs offer safe, efficacious, rapid-acting, well-tolerated, non-pharmacological, non-hormonal, affordable, repeatable home interventions for PMDD. Clinical Trials.gov NCT # NCT01799733.

Bridging the bench to bedside gap: validation of a reverse-translated rodent continuous performance test using functional magnetic resonance imaging.

Vigilance, which requires attending to relevant while ignoring irrelevant stimuli, is a cognitive domain impacted by schizophrenia and bipolar disorder. Various continuous performance tests (CPT) have been used to examine neural correlates of vigilance within people with and without severe mental illness, though there are limited cross-species paradigms available. The 5-choice CPT (5C-CPT) was designed for use in rodents as a cross-species translational paradigm. Here, we evaluate construct validity of a reverse-translated human analog of the 5C-CPT in assessing the neural correlates of vigilance. Functional magnetic resonance imaging during the 5C-CPT was used to examine activation of healthy individuals during target and non-target trials separately. We found activation in brain regions implicated in sustained attention processes including premotor cortex, inferior parietal lobe, basal ganglia, and thalamus during target trials. For non-target trials, we found expected activation in inferior frontal cortex, premotor cortex, presupplementary motor area, and inferior parietal lobe. Results support the construct validity of the 5C-CPT in measuring attentional and inhibitory systems within a single task paradigm enabling the assessment of vigilance across species. This task can be used for powerful parallel human and animal investigations of the biological basis of vigilance deficits in populations with severe mental illness.

Does antidepressant treatment improve cognition in older people with schizophrenia or schizoaffective disorder and comorbid subsyndromal depression?

BACKGROUND: Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. While treatment of depression in major depressive disorder may partially ameliorate cognitive deficits, the cognitive effects of antidepressant medications in patients with schizophrenia or schizoaffective disorder and SSD are unknown. METHODS: The goal of this study was to assess the impact of SSD and their treatment on cognition in participants with schizophrenia or schizoaffective disorder aged ≥40 years. Participants were randomly assigned to a flexible dose treatment with citalopram or placebo augmentation of their current medication for 12 weeks. An ANCOVA compared improvement in the cognitive composite scores, and a linear model determined the moderation of cognition on treatment effects based on the Hamilton Depression Rating Scale and the Calgary Depression Rating Scale scores between treatment groups. RESULTS: There were no differences between the citalopram and placebo groups in changes in cognition. Baseline cognitive status did not moderate antidepressant treatment response. CONCLUSIONS: Although there are other cogent reasons why SSD in schizophrenia warrant direct intervention, treatment does not substantially affect the level of cognitive functioning. Given the effects of cognitive deficits associated with schizophrenia on functional disability, there remains an ongoing need to identify effective means of directly ameliorating them.

Cognitive profiles in persons with chronic schizophrenia.

Cognitive heterogeneity has been a key barrier to clarifying the neuropathologic underpinnings of schizophrenia. We used an idiographic method for cluster analysis of neuropsychological data from 144 middle-aged and older people with schizophrenia to characterize and group the patterns of relative (within-person) profiles of cognitive strength and weakness. Results indicated a 5-cluster solution as most appropriate, with relatively even distribution across the 5 clusters in terms of the proportion of patients in each cluster. Cognitive subtyping may be useful in imaging and genetic research on schizophrenia, as well as having practical utility in treatment planning and cognitive rehabilitation.

Emotional and cognitive health correlates of leisure activities in older Latino and Caucasian women.

This study examined differences in the frequency of leisure activity participation and relationships to depressive symptom burden and cognition in Latino and Caucasian women. Cross-sectional data were obtained from a demographically matched subsample of Latino and Caucasian (n = 113 each) postmenopausal women (age ≥60 years), interviewed in 2004-2006 for a multiethnic cohort study of successful aging in San Diego County. Frequencies of engagement in 16 leisure activities and associations between objective cognitive performance and depressive symptom burden by ethnicity were identified using bivariate and linear regression, adjusted for physical functioning and demographic covariates. Compared to Caucasian women, Latinas were significantly more likely to be caregivers and used computers less often. Engaging in organized social activity was associated with fewer depressive symptoms in both groups. Listening to the radio was positively correlated with lower depressive symptom burden for Latinas and better cognitive functioning in Caucasians. Cognitive functioning was better in Latinas who read and did puzzles. Housework was negatively associated with Latinas' emotional health and Caucasians' cognitive functioning. Latino and Caucasian women participate in different patterns of leisure activities. Additionally, ethnicity significantly affects the relationship between leisure activities and both emotional and cognitive health.

What do we know about neuropsychological aspects of schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems.

Adjudicative competence.

PURPOSE OF REVIEW: Although the basic standards of adjudicative competence were specified by the US Supreme Court in 1960, there remain a number of complex conceptual and practical issues in interpreting and applying these standards. In this report we provide a brief overview regarding the general concept of adjudicative competence and its assessment, as well as some highlights of recent empirical studies on this topic. RECENT FINDINGS: Most adjudicative competence assessments are conducted by psychiatrists or psychologists. There are no universal certification requirements, but some states are moving toward required certification of forensic expertise for those conducting such assessments. Current data indicate inconsistencies in application of the existing standards even among forensic experts, but the recent publication of consensus guidelines may foster improvements in this arena. There are also ongoing efforts to develop and validate structured instruments to aid competency evaluations. Telemedicine-based competency interviews may facilitate evaluation by those with specific expertise for assessment of complex cases. There is also interest in empirical development of educational methods to enhance adjudicative competence. SUMMARY: Adjudicative competence may be difficult to measure accurately, but the assessments and tools available are advancing. More research is needed on methods of enhancing decisional capacity among those with impaired competence.