Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability.

OBJECTIVES: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aß) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. PARTICIPANTS AND MEASUREMENTS: Older adults with major depression (N = 121, Ages 65-91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aß standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity. RESULTS: Greater anxiety severity was associated with lower OFC volume (ß = -68.25, t = -2.18, p = .031) and greater cognitive dysfunction (ß = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aß SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (ß = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety. CONCLUSIONS: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.

Cervical Syphilitic Lymphadenitis in a 29-Year-Old Female: A Case Report.

Cervical lymphadenopathy is a common condition characterized by the enlargement of lymph nodes. It can have various causes, including infections, inflammatory conditions, and neoplastic processes. Syphilis, a sexually transmitted disease that progresses through multiple stages, can also be a rare cause of cervical lymphadenopathy, particularly in HIV-positive individuals. In this case report, we describe a patient presenting with throat pain, systemic symptoms, and cervical lymphadenopathy, initially clinically suggestive of lymphoma but ultimately determined to be caused by syphilis of unknown duration. This case highlights the importance of considering syphilis in the differential diagnosis of cervical lymphadenitis, particularly in patients with risk factors, such as intravenous drug use and HIV infection, and the need for a thorough evaluation of the patient's social and medical histories to diagnose and treat the condition accurately.

Relapsing Polychondritis in a Patient With Auricular Chondritis and Inflammatory Bowel Disease: A Case Report With Literature Review.

Relapsing polychondritis (RP) most commonly presents as inflammation and degeneration of cartilaginous tissue in the auricles, nasal septum, and lungs (in severe instances). RP is a rare autoimmune condition associated with other autoimmune diseases in 30% of cases. The prevalence of gastrointestinal involvement with RP is tenuous; however, there is a growing collection of case studies associating auricular chondritis with concomitant inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease. We report the case of a 35-year-old patient presenting with autoimmune pancreatitis, with a past medical history of Crohn's disease, primary sclerosing cholangitis (PSC), and suspected RP. Although RP is rare, the disease's multiple clinical presentations and recurrent episodic nature can cause significant diagnostic delays and are often overlooked by physicians. Thus, low disease prevalence may be due to under-recognition and under-reporting of disease symptoms. As RP is a clinical diagnosis, increased awareness of the disease presentation and clinical characteristics may increase disease recognition and improve treatment outcomes.

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.

The Impact of Amyloid Burden and APOE on Rates of Cognitive Impairment in Late Life Depression.

BACKGROUND: Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. OBJECTIVE: To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-ß (Aß) burden. METHODS: Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aß burden. RESULTS: LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aß positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOEɛ4 genotype was associated with worse performance on Logical Memory I (p = 0.022); these relationships did not differ between LLD and ND. CONCLUSION: LLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.

Using the 2020 global pandemic as a springboard to highlight the need for amphibian conservation in eastern Asia.

Emerging infectious diseases are on the rise in many different taxa, including, among others, the amphibian batrachochytrids, the snake fungal disease and the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) virus, responsible for Coronavirus disease 2019 (COVID-19) in mammals. Following the onset of the pandemic linked to COVID-19, eastern Asia has shown strong leadership, taking actions to regulate the trade of potential vector species in several regions. These actions were taken in response to an increase in public awareness, and the need for a quick reaction to mitigate against further pandemics. However, trade restrictions rarely affect amphibians, despite the risk of pathogen transmission, directly, or indirectly through habitat destruction and the loss of vector consumption. Thus, species that help alleviate the risk of zoonoses or provide biological control are not protected. Hence, in view of the global amphibian decline and the risk of zoonoses, we support the current wildlife trade regulations and support measures to safeguard wildlife from overexploitation. The current period of regulation overhaul should be used as a springboard for amphibian conservation. To mitigate risks, we suggest the following stipulations specifically for amphibians. I) Restrictions to amphibian farming in eastern Asia, in relation to pathogen transmission and the establishment of invasive species. II) Regulation of the amphibian pet trade, with a focus on potential vector species. III) Expansion of the wildlife trade ban, to limit the wildlife-human-pet interface. The resulting actions will benefit both human and wildlife populations, as they will lead to a decrease in the risk of zoonoses and better protection of the environment. SIGNIFICANCE STATEMENT: There is an increasing number of emerging infectious diseases impacting all species, including amphibians, reptiles and mammals. The latest threat to humans is the virus responsible for COVID-19, and the resulting pandemic. Countries in eastern Asia have taken steps to regulate wildlife trade and prevent further zoonoses thereby decreasing the risk of pathogens arising from wild species. However, as amphibians are generally excluded from regulations we support specific trade restrictions: I) Restrictions to amphibian farming; II) regulation of the amphibian pet trade; III) expansion of the wildlife trade ban. These restrictions will benefit both human and wildlife populations by decreasing the risks of zoonoses and better protecting the environment.

The relationship of frailty and disability with suicidal ideation in late life depression.

OBJECTIVES: Frailty and disability are commonly found in Late Life Depression (LLD) and have been associated with increased depression severity, health comorbidities and mortality. Additionally, physical frailty has been associated with suicide in later life, independent of presence of a mood disorder. The objective of our study was to assess the associations of physical frailty and functional disability with suicidal ideation, controlling for depression severity and demographic factors, in an older depressed sample. METHODS: This study used data from community-dwelling older adults with major depression. Eligible participants were ≥ 65 years old, completed measures of depression symptom severity (Hamilton Depression Rating Scale-24 item; HDRS-24), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and physical frailty/functional capacity measures. RESULTS: Participants were 88 older adults with a mean age of 71.5 (SD = 6.0) and 66% of the sample was female. Poorer performance on frailty measures of gait speed (B = .239, p = .003) and muscle weakness (B = -.218, p = .01) were significantly associated with higher levels of suicidal ideation, independent of depression severity and demographic factors. Functional disability was also significantly related to suicide ideation, specifically impairment in financial capacity (B = -.290, p = .008), social interaction (B = .408, p < .001), and communication skills (B = .373, p = .001). CONCLUSION: Our findings show that, in LLD, frailty and functional disability are significantly associated with higher levels of suicide ideation, independent of depression symptom severity.

Late-Life Depression Is Associated With Reduced Cortical Amyloid Burden: Findings From the Alzheimer's Disease Neuroimaging Initiative Depression Project.

BACKGROUND: We evaluated the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late-life depression (LLD). METHODS: A total of 119 older adult participants with a current diagnosis of major depression (LLD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Depression Project study and 119 nondepressed (ND) cognitively unimpaired participants matched on age, sex, and APOE genotype were obtained from the ADNI database. RESULTS: Thirty-three percent of LLD participants met ADNI criteria for mild cognitive impairment. Compared with ND individuals, the LLD group exhibited less global amyloid beta (Aß) accumulation (p = .05). The proportion of amyloid positivity in the LLD group was 19.3% compared with 31.1% for the ND participants (p = .02). Among LLD participants, global Aß was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime selective serotonin reuptake inhibitor use, or lifetime length of untreated depression (p > .21 for all). Global Aß was associated with worse memory performance (p = .05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants as well as when comparing the LLD group with an ND group that included participants with mild cognitive impairment. CONCLUSIONS: Contrary to expectation, the LLD group showed less Aß deposition than the ND group and Aß deposition was not associated with depression history characteristics. Aß was associated with memory, but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of LLD are not due to greater cortical Aß accumulation.

Improvements in Functional Disability After Psychotherapy for Depression Are Associated With Reduced Suicide Ideation Among Older Adults.

OBJECTIVE: To evaluate the association between changes in functional disability and suicide ideation among older adults following psychotherapy for depression. METHODS: Sixty-five participants (65-91 years old, 72% White, and 66% female) with depression completed 12 sessions of problem solving therapy (PST) and completed measures of disability (WHO Disability Assessment Schedule 2.0) and suicide ideation (Geriatric Suicide Ideation Scale [GSIS]) at baseline and post-treatment. RESULTS: Hierarchical linear regressions found that reductions in functional disability were associated with overall reductions in suicide ideation on the GSIS (F[4,60] = 4.06, p < 0.01), particularly with the Loss of Worth GSIS subscale (F[4,60] = 7.86, p < 0.001, ΔR2 = 0.140). CONCLUSIONS: Results suggest decreased functional disability following depression treatment is associated with decreased suicide ideation, especially thoughts regarding loss of worth. These results highlight the potential for treatments that reduce functional disability (e.g., PST) to reduce risk of suicide among older adults.

A little frog leaps a long way: compounded colonizations of the Indian Subcontinent discovered in the tiny Oriental frog genus Microhyla (Amphibia: Microhylidae).

Frogs of the genus Microhyla include some of the world's smallest amphibians and represent the largest radiation of Asian microhylids, currently encompassing 50 species, distributed across the Oriental biogeographic region. The genus Microhyla remains one of the taxonomically most challenging groups of Asian frogs and was found to be paraphyletic with respect to large-sized fossorial Glyphoglossus. In this study we present a time-calibrated phylogeny for frogs in the genus Microhyla, and discuss taxonomy, historical biogeography, and morphological evolution of these frogs. Our updated phylogeny of the genus with nearly complete taxon sampling includes 48 nominal Microhyla species and several undescribed candidate species. Phylogenetic analyses of 3,207 bp of combined mtDNA and nuDNA data recovered three well-supported groups: the Glyphoglossus clade, Southeast Asian Microhyla II clade (includes M. annectens species group), and a diverse Microhyla I clade including all other species. Within the largest major clade of Microhyla are seven well-supported subclades that we identify as the M. achatina, M. fissipes, M. berdmorei, M. superciliaris, M. ornata, M. butleri, and M. palmipes species groups. The phylogenetic position of 12 poorly known Microhyla species is clarified for the first time. These phylogenetic results, along with molecular clock and ancestral area analyses, show the Microhyla-Glyphoglossus assemblage to have originated in Southeast Asia in the middle Eocene just after the first hypothesized land connections between the Indian Plate and the Asian mainland. While Glyphoglossus and Microhyla II remained within their ancestral ranges, Microhyla I expanded its distribution generally east to west, colonizing and diversifying through the Cenozoic. The Indian Subcontinent was colonized by members of five Microhyla species groups independently, starting with the end Oligocene-early Miocene that coincides with an onset of seasonally dry climates in South Asia. Body size evolution modeling suggests that four groups of Microhyla have independently achieved extreme miniaturization with adult body size below 15 mm. Three of the five smallest Microhyla species are obligate phytotelm-breeders and we argue that their peculiar reproductive biology may be a factor involved in miniaturization. Body size increases in Microhyla-Glyphoglossus seem to be associated with a burrowing adaptation to seasonally dry habitats. Species delimitation analyses suggest a vast underestimation of species richness and diversity in Microhyla and reveal 15-33 undescribed species. We revalidate M. nepenthicola, synonymize M. pulverata with M. marmorata, and provide insights on taxonomic statuses of a number of poorly known species. Further integrative studies, combining evidence from phylogeny, morphology, advertisement calls, and behavior will result in a better systematic understanding of this morphologically cryptic radiation of Asian frogs.

Determinants of Suicide-related Ideation in Late Life Depression: Associations with Perceived Stress.

Objectives: Perceived stress is emerging as a potential contributing factor in suicide-related ideation in older adults. We hypothesized higher levels of perceived stress would be associated with increased self-reported suicidal ideation independent of depressive symptom severity.Methods: This study used data from community-dwelling older adults aged ≥65 with a current diagnosis of major depression. Eligible participants completed measures of depression symptom severity (Hamilton Depression Rating Scale-17 item), current suicidal ideation (Geriatric Suicide Ideation Scale), and perceived stress (Perceived Stress Scale).Results: Participants were 225 older adults with a mean age of 71.4 (SD = 5.6). Sixty-five percent of the sample was female. Fifteen percent of the variance in suicidal ideation was accounted for by lower education (p = .03), male sex (p = .03) and higher current perceived stress (p < .001). Specifically, stress accounted for 12% of the variance.Conclusions: Perceived stress is an important avenue to increase identification of individuals with a higher risk of suicide-related ideation among older adults with a current diagnosis of major depression.Clinical Implications: Screening for perceived stress may allow for improved screening and prevention of suicidal activity in depressed older adults.

Somatic and anxiety symptoms of depression are associated with disability in late life depression.

Objectives: To assess the relationships of somatic and anxiety symptoms of depression with functional disability in a sample of older adults with late life depression.Method: Data were analyzed from 78 older adults aged 65-88 with current major depression. Somatic and anxiety symptoms from the 24-item Hamilton Depression Rating Scale (HDRS) were summed to create variables measuring severity of these symptoms. Other symptoms of depression were also assessed using the remaining items of the HDRS. Current physical health burden was assessed using the Functional Comorbidity Index (FCI). Disability was measured with the Late Life Function and Disability Instrument (LLFDI) total limitation score. A linear regression analysis was performed to assess the association of somatic and anxiety symptoms with disability independent of other factors.Results: The model accounted for 26.6% of variance in disability, (F(6,51) = 3.1, p = .01). Somatic (B = -1.9, p = .004) and anxiety (B = -3.7, p = .04) symptoms of depression were significantly associated with disability. Other depressive symptoms and physical illness burden were not associated with disability.Discussion: In older adults with major depression, somatic and anxiety symptoms of depression are associated with disability. Identification and treatment to remission of these symptoms may improve functional outcomes among older depressed adults.

Depression Severity, but Not Cognitive Impairment or Frailty, is Associated with Disability in Late-Life Depression.

OBJECTIVES: Assess the relationship of cognitive impairment to disability, accounting for depression severity and frailty, among older adults with late-life depression (LLD). METHODS: Data were analyzed from 78 community-dwelling older adults with LLD and without dementia (age M = 71.9; SD = 6.1). Cognitive functioning was assessed using a comprehensive neuropsychological battery. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HDRS; cutoff ≥15). Frailty was assessed using several motor tests. The World Health Organization Disability Assessment Schedule (WHO-DAS) measured disability status. A linear regression analysis was performed to identify relationships of cognition, frailty and depression severity with disability. RESULTS: The average number of impaired cognitive tests was 2.0 (SD = 1.9), with 28.2% of participants showing no impaired scores. On average participants reported depression severity of 17.3 (SD = 3.6), and disability total score of 15.1 (SD = 6.9). The regression model accounted for 25.1% of the variance in disability, with only depression severity significantly predicting disability status. Burden of cognitive impairment and frailty were not predictive of disability in this sample. CONCLUSIONS: In this sample, only depression severity was associated with increased disability. CLINICAL IMPLICATIONS: These findings have implications for intervention in LLD, as depression severity may represent a more modifiable risk factor for disability.

Last exit before the brink: Conservation genomics of the Cambodian population of the critically endangered southern river terrapin.

The southern river terrapin, Batagur affinis is one of the world's 25 most endangered freshwater turtle species. The major portion of the global population is currently found in peninsular Malaysia, with the only remnant Indochinese population in southern Cambodia. For more than a decade, wild nests in this remnant Cambodian population have been fenced and hatchlings reared in captivity. Here we amplified 10 microsatellite markers from all 136 captive individuals, obtained 2,658 presumably unlinked and neutral single nucleotide polymorphisms from 72 samples with ddRAD-seq, and amplified 784 bp of mtDNA from 50 samples. Our results reveal that the last Indochinese population comprised only four kinship groups as of 2012, with all offspring sired from <10 individuals in the wild. We demonstrate an obvious decrease in genetic contributions of breeders in the wild from 2006-2012 and identify high-value breeders instrumental for ex-situ management of the contemporary genetic stock of the species.

Impaired Financial Capacity in Late-Life Depression: Revisiting Associations with Cognitive Functioning.

OBJECTIVES: Impairment in financial capacity is an early sign of cognitive decline and functional impairment in late life. Cognitive impairments such as executive dysfunction are well documented in late-life major depression; however, little progress has been made in assessing associations of these impairments with financial incapacity. METHODS: Participants included 95 clinically depressed and 41 nondepressed older adults without dementia. Financial capacity (assessed with the Managing Money scale of the Independent Living Scale), cognitive functioning (comprehensive neuropsychological evaluation), and depression severity (Hamilton Depression Rating Scale - 24) were assessed. T tests were used to assess group differences. Linear regression was used to analyze data. RESULTS: Depressed participants performed significantly lower on financial capacity (t = 2.98, p < .01). Among depressed participants, executive functioning (B = .24, p < .05) was associated with reduced financial capacity, controlling for age, gender, education, depression severity, and other cognitive domains. CONCLUSIONS: Our results underscore the importance of assessing financial capacity in older depressed adults as they are likely vulnerable to financial abuse even in the absence of dementia. It will be valuable to assess whether treatment for depression is an effective intervention to improve outcomes.

Latent Classes of Cognitive Functioning Among Depressed Older Adults Without Dementia.

OBJECTIVE: Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership. METHOD: Neuropsychological assessment data from 121 participants in the Alzheimer's Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed. RESULTS: A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership. CONCLUSION: LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.

Unsupervised online neuropsychological test performance for individuals with mild cognitive impairment and dementia: Results from the Brain Health Registry.

INTRODUCTION: The purpose of this study is to compare online neuropsychological test performance of older adults across self-reported diagnoses of being cognitively normal, mild cognitive impairment, and dementia due to Alzheimer's disease and to determine the association of memory concerns and family history of dementia on cognitive performance. METHODS: Participants completed the Cogstate Brief Battery unsupervised at home. RESULTS: Data from 6463 participants over the age of 55 years were analyzed. Adults with the diagnosis of mild cognitive impairment and Alzheimer's disease were associated with poorer performance on all cognitive tests than cognitively normal adults (P < .05 for all), and online cognitive test performance significantly improved diagnostic classification (P < .001). Poorer performance on all cognitive measures was associated with memory concern (P < .001 for all) but not family history of dementia. DISCUSSION: Our results provide preliminary support for the use of cognitive tests taken online without supervision as a means to improve the efficiency of participant screening and recruitment for clinical trials.

Screening for Executive Dysfunction in Late-Life Depression: Utility of Trail Making Test and Self-Report Measures.

OBJECTIVE: Prior work suggests executive dysfunction (ED) on the Stroop Color and Word Test (SCWT) and the Mattis Dementia Rating Scale-2 Initiation/Perseveration subscale (DRS IP) predicts poor antidepressant response in late-life depression. This study examined if either patient perception of ED or the Trail Making Test Part B (TMT-B) could identify patients with impairment on the SCWT or DRS IP. METHODS: Patients were 65 or older and had a diagnosis of major depression without dementia. Cognition was assessed with the TMT-B, the SCWT, and the DRS IP. A self-reported Perceived Deficits Questionnaire (PDQ) subscale assessed patients' perceptions of ED. RESULTS: In 247 participants (mean age 71.3 years), the PDQ subscale was not associated with test performance. The sensitivity of the TMT-B in identifying impairment on the SCWT or DRS IP was low (35% and 23%, respectively). CONCLUSION: Neither the TMT-B nor self-reports are useful screening tools for ED on the SCWT or DRS IP.

Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment.

OBJECTIVES: To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI). METHODS: Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aß1-42 ), total tau (t-tau), and phosphorylated tau (p-tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group. RESULTS: As compared to the non-SSD group, the SSD group displayed lower CSF Aß1-42 levels (ß = -24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497) or p-tau levels (P = 0.392). Lower CSF Aß1-42 levels were associated with poorer performance on learning (ß = 0.041, S.E. = 0.018, P = 0.021) and memory (ß = -0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau levels were associated with poorer performance on measures of global cognition (ß = 0.022, S.E = 0.008, P = 0.007) and language (ß = -0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05). CONCLUSIONS: MCI participants with SSD displayed diminished CSF Aß1-42 levels but did not differ from non-SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.

Risk of Psychosis in Recurrent Episodes of Psychotic and Nonpsychotic Major Depressive Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: The authors conducted a systematic review and meta-analysis to determine whether the risk of psychosis is higher in past or future episodes in patients with major depression with psychotic features than in patients with nonpsychotic depression. METHOD: PubMed, Embase, and PsycINFO were searched, and studies were selected that 1) identified patients with unipolar major depression, 2) made diagnoses of psychosis based on the presence of delusions or hallucinations, 3) characterized past or subsequent episodes as psychotic or nonpsychotic, and 4) were published in English. Two meta-analyses were then conducted using data from patients having index depressive episodes with or without psychosis at study entry to determine the risk of any prior or subsequent psychotic episode and the risk of psychosis in all episodes. RESULTS: Twelve studies met the inclusion criteria, and altogether they included 546 psychotic and 1,583 nonpsychotic patients with unipolar depression. In seven of the studies, the risk ratio for a prior or subsequent psychotic episode in patients whose index depressive episode was psychotic compared with those whose index episode was nonpsychotic was 9.98 (95% CI=4.75, 20.94). In eight studies, the risk ratio for psychosis among all episodes of depression in the subgroups with psychotic and nonpsychotic index episodes was 7.24 (95% CI=5.03, 10.43). Differences in risk of psychosis between these subgroups remained robust when potential sources of heterogeneity were explored. CONCLUSIONS: The findings support the hypothesis that psychotic depression runs true to form, and they support the distinction between psychotic and nonpsychotic depression. Because patients with psychotic depression are at high risk for psychosis in future episodes, determination of effective preventive treatments is imperative.