Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response

Koirala, Parashar; Hu, Bo; Altinay, Murat; Li, Manshi; DiVita, Amy L.; Bryant, Kelly A.; Karne, Harish; Fiedorowicz, Jess G.; Anand, Amit

doi:10.1016/j.jpsychires.2018.12.006

Cited by 13 publications

(10 citation statements)

References 38 publications

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“…This so called subthreshold bipolar subgroup of MDD patients differs from MDD patients without subthreshold hypomanic manifestations in several ways. For instance, a wide array of studies demonstrated that subthreshold bipolarity is associated with increased levels of suicidality [20,21,22,23].…”

Section: Epidemiology Of Suicidal Behaviour In Bipolar Disordermentioning

confidence: 99%

Suicide Risk in Bipolar Disorder: A Brief Review

2019

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Bipolar disorders (BDs) are prevalent mental health illnesses that affect about 1–5% of the total population, have a chronic course and are associated with a markedly elevated premature mortality. One of the contributors for the decreased life expectancy in BD is suicide. Accordingly, the rate of suicide among BD patients is approximately 10–30 times higher than the corresponding rate in the general population. Extant research found that up to 20% of (mostly untreated) BD subjects end their life by suicide, and 20–60% of them attempt suicide at least one in their lifetime. In our paper we briefly recapitulate the current knowledge on the epidemiological aspects of suicide in BD as well as factors associated with suicidal risk in BD. Furthermore, we also discuss concisely the possible means of suicide prevention in BD.

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Section: Epidemiology Of Suicidal Behaviour In Bipolar Disordermentioning

confidence: 99%

Suicide Risk in Bipolar Disorder: A Brief Review

2019

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“…In the United States, 14% of adults currently meet the criteria for AUD, 29% met AUD criteria once during their lifetime 1 ; in addition, the prevalence of AUD is increasing 2 . Because of high prevalence and lack of efficient treatment modalities as well as due to association with multiple medical and psychiatric illnesses 3,4 , AUD causes a significant socioeconomic burden. The annual cost of AUD and alcohol-related disorders is~$250 billion 5 .…”

Section: Introductionmentioning

confidence: 99%

Alcohol use disorder causes global changes in splicing in the human brain

Booven

Rao

et al. 2021

Transl Psychiatry

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Alcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs.

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“…Depression subgroup ascertainment using best practices: Three psychiatrists independently reviewed all information available for each subject and classified all MDD subjects as MDD+ or MDD-at the conclusion of the study (Koirala, Hu et al 2019). Based on review of previous studies (Angst, Gamma et al 2003, Zimmermann, Brückl et al 2009, Fiedorowicz, Endicott et al 2011, Merikangas, Jin et al 2011, Koirala, Hu et al 2019, which have used varying definitions for subthreshold mania symptoms, we formulated conservative criteria and defined MDD+ as: euphoric mood with at least 2 mania symptoms or increased irritability with 3 mania symptoms if only the latter was present, as well as if full mania symptoms were present then duration to be for less than 4 days. All Other MDD subjects who did not have subthreshold symptoms, no family history of BD, and no history of psychosis (Angst, Gamma et al 2003, Zimmermann, Brückl et al 2009, Fiedorowicz, Endicott et al 2011, Merikangas, Jin et al 2011, Koirala, Hu et al 2019, were ascertained to be MDD-.…”

Section: Subjectsmentioning

confidence: 99%

“…Naturalistic follow-up for change in diagnosis: as an exploratory aim of the study, MDD subjects who wanted to be treated were started on a selective serotonin reuptake inhibitor (SSRI) and followed up for up to 2 years. The course of the larger sample, which was clinically followed up has been reported previously (Koirala, Hu et al 2019). Any change in diagnosis to BD was recorded.…”

Section: Subjectsmentioning

confidence: 99%

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Neuroimaging Correlates of Emotional Response-Inhibition Discriminate Between Young Depressed Adults With and Without Sub-threshold Bipolar Symptoms

Cha

Speaker

et al. 2020

Preprint

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Background: A significant number of subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neurobiology of MDD+ subjects is more akin to bipolar disorder depression (BDD) or to MDD subjects without any subthreshold bipolar symptoms (MDD-). Method: This study included 118 medication-free young adult subjects (16 -30 yrs.): 20 BDD, 28 MDD+, 41 MDD-, and 29 HC subjects. Participants underwent fMRI during emotional and non-emotional Go/No-go tasks during which they responded for Go stimuli and inhibited response for happy, fear, emotional (happy + fear) and non-emotional (gender) faces No-go stimuli. Linear mixed effects (LME) analysis for group effects and Gaussian Process Classifier (GPC) analyses was conducted. RESULTS: MDD-group compared to both the BDD and MDD+ groups, exhibited significantly lower activation in parietal, temporal and frontal regions (cluster-wise corrected p <0.05) for emotional inhibition conditions vs. non-emotional condition. No significant differences were found between BDD and MDD+ groups. GPC classification of emotional vs non-emotionalresponse-inhibition activation pattern showed good discrimination between BDD and MDDsubjects (AUC: 0.70; balanced accuracy: 70% (p = 0.006)) as well as MDD+ and MDDsubjects (AUC: 0.72; balanced accuracy: 67% (p = 0.015)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (p = 0.091)). Notably, classification of the MDD-group was weighted for left amygdala activation pattern.

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Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response

Cited by 13 publications

References 38 publications

Suicide Risk in Bipolar Disorder: A Brief Review

Suicide Risk in Bipolar Disorder: A Brief Review

Alcohol use disorder causes global changes in splicing in the human brain

Neuroimaging Correlates of Emotional Response-Inhibition Discriminate Between Young Depressed Adults With and Without Sub-threshold Bipolar Symptoms

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