Objective: Better methods for detecting preclinical neuropathological change are required for prevention of dementia. Mild behavioral impairment (MBI) and subjective cognitive decline (SCD) can represent neurobehavioral and neurocognitive axes of early stage neurodegenerative processes, which are represented in Stage 2 of the NIA-AA Alzheimers disease research framework. Both MBI and SCD may offer an opportunity for premorbid detection. We test the hypothesis that MBI and SCD confer additive risk for incident cognitive decline. Methods: Participants were cognitively normal older adults followed up approximately annually at Alzheimers Disease Centers. Logistic regression was used to determine the relationship between baseline classification (MBI+, SCD+, neither (MBI-SCD-), or both (MBI+SCD+)) and cognitive decline, defined by Clinical Dementia Rating (CDR) total score, at 3 years. Results: Of 2769 participants (mean age=76; 63% females), 1536 were MBI-SCD-, 254 MBI-SCD+, 743 MBI+SCD-, and 236 MBI+SCD+. At 3-years, 349 individuals (12.6%) developed cognitive decline to CDR>0. Compared to SCD-MBI-, we observed an ordinal progression in risk, with ORs [95% CI] as follows: 3.61 [2.42-5.38] for MBI-SCD+ (16.5% progression), 4.76 [3.57-6.34] for MBI+SCD-, (20.7% progression) and 8.15 [5.71-11.64] for MBI+SCD+ (30.9% progression). Conclusion: MBI in older adults alone or in combination with SCD is associated with a higher risk of incident cognitive decline at 3 years. The highest rate of progression to MCI is observed in those with both MBI and SCD. Used in conjunction, MBI and SCD could be simple and scalable methods to identify patients at high risk for cognitive decline for prevention studies.

Objective: To clarify whether certain Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), borderline personality disorder (BPD) symptoms are more prevalent among people who die by suicide, and thereby better predict suicide risk. Method:A psychological autopsy method with best informants was used to investigate DSM-IV BPD symptoms and suicide risk among people who died by suicide and met criteria for BPD (n = 62), and BPD control subjects (n = 35).Results: BPD symptoms in people who died by suicide were less likely to include affective instability and paranoid ideation-dissociative symptoms. The negative association between paranoid ideation-dissociative symptoms and suicide was independent of all other BPD symptoms, Cluster B comorbidity, and alcohol dependence. Conclusions:We found that discrete DSM-IV BPD symptoms differentiate people with BPD who die by suicide and those who do not. People with BPD who go on to die by suicide appear to constitute a specific subgroup of those who meet criteria for BPD, characterized by different general clinical presentation, but also by different characteristics within BPD.Can J Psychiatry. 2009;54(2):87-92.Clinical Implications · Suicide attempts appear to be predicted by different factors than suicide deaths in people with BPD. · Affective instability and paranoid ideation-dissociative symptoms are not strongly associated with death by suicide in BPD. · DSM-IV BPD symptoms can improve suicide risk assessment in addition to comorbid conditions. Limitations· Information was obtained retrospectively. · Subjects could not be interviewed directly, and therefore we were limited to proxy-based interviews. · Males were overrepresented in this sample, compared with people with BPD encountered in clinical practice, yet this sex distribution is characteristic of those who die by suicide.

In our sample, same-sex sexual orientation and gender identity issues do not appear to be more prevalent among youth who die by suicide, compared with youth recruited from the general population, nor for same-sex sexual-related intimidation. While exhibiting comparable levels of general psychopathological diagnoses associated with suicide, suicide victims with same-sex sexual orientation were more likely to meet criteria for anxiety disorders and to have consulted mental health professionals before their deaths.

Background Mild behavioral impairment (MBI) is a syndrome that uses later‐life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting‐state functional magnetic resonance imaging (rs‐fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI–). Methods From two harmonized dementia‐free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI– individuals were identified (mean age: 71.7 years; 54.7% female). Seed‐based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p ‐value of .05 considered significant. Results For the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI–. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula. Conclusion MBI in dementia‐free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers. Highlights Resting‐state functional magnetic resonance imaging was completed in 95 dementia‐free persons from FAVR and COMPASS‐ND studies. Participants were stratified by informant‐rated Mild Behavioral Impairment Checklist (MBI‐C) score, ≥6 for MBI+. MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network. These FC changes are consistent with those seen in early‐stage Alzheimer's disease. MBI may help identify persons with early‐stage neurodegenerative disease.

ImportanceThe antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to be N-methyl-D-aspartate (NMDA)–receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD.ObjectiveTo test whether low doses of the NMDA-receptor partial-agonist, D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD.Design, Setting, and ParticipantsThis was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work (including complete blood cell count, electrolytes, liver function tests, and creatinine level).InterventionsParticipants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plus D-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4.Main Outcomes and MeasuresThe primary outcome was change in depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores.ResultsA total of 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]) were randomly assigned to treatment groups: iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plus D-cycloserine (mean [SD] baseline score, 30.4 [4.5]). The iTBS plus D-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group (mean difference, −6.15; 95% CI, −2.43 to −9.88; Hedges g = 0.99; 95% CI, 0.34-1.62). Rates of clinical response were higher in the iTBS plus D-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%). This was reflected in lower CGI-severity ratings and greater CGI-improvement ratings. No serious adverse events occurred.Conclusions and RelevanceFindings from this clinical trial indicate that adjunctive D-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment outcomes in MDD using iTBS requiring further investigation.Trial RegistrationClinicalTrials.gov Identifier: NCT03937596

Objective: Eating disorders (ED) may be associated with an increased prevalence of non-suicidal self-injury (NSSI) and suicidal thoughts and behaviors (STBs) relative to healthy (HC) and psychiatric (PC) controls. However, precise estimates of differences in prevalence between individuals with EDs and controls are unclear. We compared the prevalence of NSSI, suicidal ideation (SI), suicide attempts (SA), and deaths by suicide in controls and individuals with EDs.Method: We searched MEDLINE, PsycINFO, EMBASE, and CINAHL for peerreviewed publications reporting the prevalence of NSSI and/or STBs in EDs and HC or PC group (PROSPERO: CRD42021286754). A series of random-effects metaanalyses were conducted to estimate pooled odds ratios (ORs) for NSSI, SI, SA, and death by suicide in EDs.Results: Across 32 studies, individuals with an ED had a significantly increased preva-

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INTRODUCTION: Dementia assessment includes cognitive and behavioral testing with informant validation. Conventional testing is resource intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. We interrogated the relationship between informant-rated behavioral changes and neuropsychological test performance in older adults in the Brain Health Registry. METHODS: Participants completed online unsupervised cognitive tests, and informants completed the Mild Behavioral Impairment Checklist via a Study Partner portal. Cognitive performance was evaluated in MBI+/- individuals, as was the association between cognitive scores and MBI symptom severity. RESULTS: Mean age of the 499 participants was 67, 61% of which were female. MBI+ participants had lower working memory and executive function test scores. Lower cognitive test scores associated with greater MBI burden. DISCUSSION: Our findings support the feasibility of remote, informant-reported behavioral assessment and support its validity by demonstrating a relationship to cognitive test performance using online unsupervised assessments for dementia risk assessment.