Item 9 of the Patient Health Questionnaire (PHQ) evaluates passive thoughts of death or self-injury within the last two weeks, and is often used to screen depressed patients for suicide risk. We ...aimed to validate the PHQ-9 item 9 with a brief electronic version of the Columbia Suicide Severity Rating Scale (eC-SSRS).
We analyzed data from 841 patients enrolled in the National Network of Depression Centers Clinical Care Registry. We performed a validation analysis of PHQ-9 item 9 for suicide risk and ideation, using the eC-SSRS as a gold standard (defined as positive response to suicidal ideation with intent to act or recent suicidal behavior).
Of the 841 patients, 13.4% and 41.1% were assessed as being positive for suicide risk by the eC-SSRS and PHQ-9 item 9, respectively. For the overall cohort, sensitivity was 87.6% (95%CI 80.2–92.5%), specificity was 66.1% (95%CI 62.6–69.4%), PPV was 28.6% (95%CI 24.1–33.6%), and NPV was 97.2% (95%CI 95.3–98.3%) for the PHQ-9 suicide item. These performance measures varied within subgroups defined by demographic and clinical characteristics. In addition, the validity of PHQ-9 item 9 (cutoff score of 1) with eC-SSRS-defined suicide ideation showed overall poor results.
The gold standard used in our study was a surrogate measure of suicidality based on eC-SSRS scores.
The results of our study suggest that item 9 of the PHQ-9 is an insufficient assessment tool for suicide risk and suicide ideation, with limited utility in certain demographic and clinical subgroups that requires further investigation.
•The PHQ-9 item 9 is an insufficient assessment tool for suicide risk and ideation.•The PHQ-9 item 9 has limited utility in certain subgroups.•The PHQ-9 item 9 should be used with a validated suicide risk inventory.
Using a large nationwide cohort, this study aimed to determine the risk of suicide after the use of a 5α-reductase inhibitor, an antiandrogenic medication commonly used in the treatment of lower ...urinary tract symptoms.
A retrospective population-based cohort study was performed using the Korean National Health Insurance Service database. The study consisted of 51,466 men 60 years or older who underwent health examinations between 2005 and 2006. Individuals using a 5α-reductase inhibitor were compared with nonusers based on drug exposure between 2003 and 2006. Individuals using a 5α-reductase inhibitor were additionally divided into tertiles based on cumulative 5α-reductase inhibitor exposure. The incidence of completed suicide was documented during 7 years of follow-up, starting January 1, 2007.
No significant risk of suicide was observed among 5α-reductase inhibitor users compared with 5α-reductase inhibitor nonusers (hazard ratio = 1.02, 95% confidence interval = 0.70-1.48). Cumulative 5α-reductase inhibitor exposure was also not associated with increased risk of suicide (p for trend = .543).
5α-Reductase inhibitor use was not associated with an elevated risk of suicide during a long-term follow-up period. A limitation of this study is that possible drug exposure after the index date was not accounted for. Although 5α-reductase inhibitor may increase the risk of depressive symptoms, the present data indicate that the drug is safe in terms of long-term suicide risk.
•“Aggression” in bipolar disorder is more likely to be directed to self than others.•Aggression and impulsivity reflect two pathways to suicide risk in bipolar disorder.•MRI shows distinct brain ...circuits in bipolar disorder aggression and impulsivity.
Elevated aggression and impulsivity are implicated in Bipolar Disorder (BD); however, relationships between these behavioral constructs have not been clarified, which can lead to misconceptions with negative consequences including stigma and adverse outcomes including suicide. The study aimed to clarify brain-based distinctions between the two constructs and their associations to risk factors, symptoms and suicide thoughts and behaviors.
Self-rated Brown-Goodwin Aggression (BGA) and Barratt Impulsiveness Scale (BIS) scores were compared between adults with BD (n = 38, 74% female) and healthy controls (HC, n = 29, 64% female). Relationships were examined between BGA and BIS with childhood trauma questionnaire (CTQ), mood, comorbidities, and magnetic resonance imaging gray matter volume (GMV) assessments.
In BD, BGA and BIS total scores were both elevated and associated with childhood maltreatment (CM), particularly emotional CM, depression, substance use disorders (SUDs) and suicide attempts (SAs). BGA scores were increased by items corresponding to dysregulation of emotional and social behavior and associated with elevated mood states and suicide ideation and GMV decreases in bilateral orbitofrontal cortex and left posterior insula brain regions, previously associated with these behaviors and clinical features. BIS motor impulsiveness scores were associated with GMV decreases in anterior cingulate cortex implicated in mood and behavioral dyscontrol.
modest sample size, self-reports
The findings suggest separable brain-based domains of dysfunction in BD of motor impulsiveness versus emotionally dysregulated feelings that are primarily self-directed. Both domains are associated with suicide behavior and modifiable risk factors of CM, depression and SUDs that could be targeted for prevention.
Markers to differentiate depressions of bipolar disorder (BD-Dep) from depressions of major depressive disorder (MDD-Dep), and for more targeted treatments, are critically needed to decrease current ...high rates of misdiagnosis that can lead to ineffective or potentially deleterious treatments. Distinguishing, and specifically treating the depressions, during the adolescent/young adult epoch is especially important to decrease illness progression and improve prognosis, and suicide, as it is the epoch when suicide thoughts and behaviors often emerge. With differences in functional connectivity patterns reported when BD-Dep and MDD-Dep have been studied separately, this study used a graph theory approach aimed to identify functional connectivity differences in their direct comparison.
Functional magnetic resonance imaging whole-brain functional connectivity (Intrinsic Connectivity Distribution, ICD) measures were compared across adolescents/young adults with BD-Dep (n = 28), MDD-Dep (n = 20) and HC (n = 111). Follow-up seed-based connectivity was conducted on regions of significant ICD differences. Relationships with demographic and clinical measures were assessed.
Compared to the HC group, both the BD-Dep and MDD-Dep groups exhibited left-sided frontal, insular, and medial temporal ICD increases. The BD-Dep group had additional right-sided ICD increases in frontal, basal ganglia, and fusiform areas. In seed-based analyses, the BD-Dep group exhibited increased interhemispheric functional connectivity between frontal areas not seen in the MDD-Dep group.
Modest sample size; medications not studied systematically.
This study supports bilateral and interhemispheric functional dysconnectivity as features of BD-Dep that may differentiate it from MDD-Dep in adolescents/young adults and serve as a target for early diagnosis and treatment strategies.
•Graph theory analyses distinguished depressions of bipolar and major depressive disorder in adolescents and young adults.•Both depressions showed left-sided functional dysconnectivity elevations.•Bipolar depression may be differentiated by right-sided and interhemispheric dysconnectivity.
Objectives
Identifying hubs of brain dysfunction in adolescents and young adults with Bipolar I Disorder (BDAYA) could provide targets for early detection, prevention, and treatment. Previous ...neuroimaging studies across mood states of BDAYA are scarce and often examined limited brain regions potentially prohibiting detection of other important regions. We used a data‐driven whole‐brain Intrinsic Connectivity Distribution (ICD) approach to investigate dysconnectivity hubs across mood states in BDAYA.
Methods
Functional magnetic resonance imaging whole‐brain ICD data were investigated for differences across four groups: BDAYA‐depressed (n = 22), BDAYA‐euthymic (n = 45), BDAYA‐elevated (n = 24), and healthy controls (HC, n = 111). Clusters of ICD differences were assessed for regional dysconnectivity and mood symptom relationships. Analyses were also performed for BDAYA overall (vs. HC) ICD differences persisting across mood states.
Results
ICD was higher in the BDAYA‐ depressed group than other groups in bilateral ventral/rostral/dorsal prefrontal cortex (PFC) and right lenticular nucleus (LN) (pcorrected <0.05). In BDAYA‐depressed, functional connectivity (FC) was increased between these regions with their contralateral homologues and PFC‐medial temporal FC was more negative (p < 0.005). PFC‐related findings correlated with depression scores (p < 0.05). The overall BDAYA group showed ICD increases in more ventral left PFC and right cerebellum, present across euthymia and acute mood states.
Conclusions
This ICD approach supports a PFC hub of inter‐ and intra‐hemispheric frontotemporal dysconnectivity in BDAYA with potential trait features and disturbances of higher magnitude during depression. Hubs were also revealed in LN and cerebellum, less common foci of BD research. The hubs are potential targets for early interventions to detect, prevent, and treat BD.
Older adults with bipolar disorder (BD) have received little study, although they often have severe symptoms, treatment resistance and high suicide risk. Furthermore, a subset develops cognitive ...dysfunction for unknown reasons.
Here, cortical thickness and subcortical gray matter volume were compared across individuals ages 40-79y: 103 with BD (“later-onset” at ages ≥25y, n = 21; “early-onset” < 25y, n = 82) and healthy controls (HCs, n = 98).
Overall, those with BD showed lower prefrontal, cingulate, sensorimotor, parahippocampal, insula, temporal, parietal, and occipital cortical thickness (Cohen's d: 0.4 to 0.8) and hippocampal, amygdalar, thalamic, and striatal gray matter volume (d: 0.6 to 0.8). Later-onset BD showed negative relationships between age and parahippocampal, insular, temporal, parietal, and occipital cortical thickness, and hippocampal, thalamic and striatal volume (r: −0.7 to −0.4). Suicide attempt history was associated with lower dorsolateral prefrontal cortical thickness (d = 0.5).
The study used a cross-sectional design and the sample of those with a later-onset of BD was relatively modest.
Results support widespread gray matter decreases in older adults with BD, and also suggest a separable later-onset phenotype characterized by age-related gray matter reductions in regions subserving cognitive, emotional and perceptual processes. Moreover, the results are the first to demonstrate structural brain differences associated with a history of suicide attempts in older adults with BD.
•Older adults with bipolar disorder showed lower cortical thickness.•Older adults with bipolar disorder showed lower subcortical gray matter volume.•Age-related effects in brain structure depended on bipolar disorder age of onset.•Suicide attempt history was associated with lower prefrontal cortical thickness.
Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical ...to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph-theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD.
•Women with bipolar disorder (BD) report highest levels of childhood maltreatment (CM).•In women with BD, higher CM severity was related to lower hippocampus volume.•In men with BD, higher CM was ...related to decreases in frontal surface area.•In both genders, higher CM was related to brain differences and symptom severity.
Bipolar disorder (BD) and exposure to childhood maltreatment (CM), which is present at high rates in BD, are both associated with hippocampus and prefrontal cortex structural alterations thought to contribute to clinical features. Gender-related differences are implicated in BD for CM exposure, brain structure and clinical features. However, relationships among these factors in BD are understudied. This study aimed to investigate associations among gender, CM, hippocampus and prefrontal gray matter structure and clinical features in BD. Childhood trauma questionnaire, structured clinical assessments and 3 Tesla structural magnetic resonance imaging were obtained for 236 adults (18–63 years, 32.0 ± 12.6): 119 with BD (58.8% women) and 117 healthy controls (HCs, 50.4% women). Women with BD reported higher CM severity than men with BD and HCs (B=-14.34, 95% confidence intervals (CI)-22.71,-5.97, p<.001). CM and gender showed a significant interaction for left hippocampus (B=-7.41, 95% CI-14.10,-0.71, p<.05); CM severity was negatively associated with left hippocampus only in women with BD. In women with BD, CM was associated with post-traumatic stress disorder comorbidity (B = 25.68, 95% CI15.11,36.25, p<.001). In men with BD, CM severity was associated with lower left frontal pole (B=-0.71, 95% CI-1.14,-0.28, p<.05) and right superior frontal (B=-17.78, 95% CI-30.66,-4.90, p<.05) surface area; the latter related to earlier age of first mood symptoms (B = 33.97, 95% CI7.61, 60.33, p<.05). Findings support gender-related effects of CM on frontotemporal structure and clinical features of BD. The findings bring novel perspectives for gendered pathophysiological models of effects of CM in BD.
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