Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder

Pu, Shenghong; Nakagome, Kazuyuki; Yamada, Takeshi; Yokoyama, Katsutoshi; Matsumura, Hiroshi; Yamada, Sayaka; Sugie, Takuya; Miura, Akihiko; Mitani, Hiroaki; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

doi:10.1016/j.jad.2015.04.010

Cited by 96 publications

(50 citation statements)

References 75 publications

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“…There is less extensive literature on using WM tasks with fNIRS, but, again, bilateral activation has been found. 92,113 Consistent with extensive literature, [94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][112][113][114] we found significantly decreased, and possibly delayed, prefrontal haemodynamic responses in depressed patients in the VF task and, less certainly, in the n-back task. For the VF task we found a significant negative correlation between MADRS score and the haemodynamic response in the LVF cortex in patients.…”

Section: Near-infrared Spectroscopy Studysupporting

confidence: 91%

“…NIHR Journals Library www.journalslibrary.nihr.ac.uk reliably demonstrate decreased lateral prefrontal cortex-anterior temporal cortex haemodynamic responses compared with control subjects during a VF task, [94][95][96][97][98][99][100][101][102][103][104][105][106] including in bipolar depression. [107][108][109] There is some uncertainty over whether this is a state or trait abnormality, as some studies have found restored activation to a VF task following treatment 110 and increased activation has been seen in hypomanic patients, 108 whereas blunted responses have been found in remitted depressed patients 111 and euthymic bipolar patients 109 or failure to normalise after antidepressant treatment in depressed patients.…”

Section: Background and Objectivesmentioning

confidence: 91%

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Randomised controlled trial of ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT study)

et al. 2017

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BackgroundElectroconvulsive therapy (ECT) is the most effective acute treatment for severe depression, but there are concerns about its adverse cognitive effects. ECT may impair cognition through stimulation of glutamate receptors, and preliminary evidence has suggested that ketamine, a glutamate antagonist, may alleviate these effects. Ketamine has been shown to have a rapid, but temporary, antidepressant effect after a single infusion.ObjectiveTo determine the efficacy and safety of adjunctive low-dose ketamine to reduce cognitive impairments caused by ECT and, secondarily, to improve symptomatic outcome.DesignMulticentre, two-arm, parallel-group, patient-randomised, placebo-controlled superiority trial.SettingEleven ECT suites based in seven NHS trusts in the north of England.ParticipantsSeverely depressed hospitalised patients or outpatients who received ECT as part of their usual clinical care.InterventionsPatients were randomised to ketamine (0.5 mg/kg) or saline as an adjunct to their anaesthetic for their ECT course in a 1 : 1 ratio.Main outcome measuresThe primary outcome was delayed verbal recall on the Hopkins Verbal Learning Task – Revised (HVLT-R) after four ECT treatments (mid-ECT), analysed using a Gaussian repeated measures model. Secondary outcomes included autobiographical, working and visual memory and verbal fluency, symptoms and quality of life; assessments occurred at mid-ECT, end of treatment and 1 and 4 months after the last ECT. Neuropsychological function was compared with that of healthy control subjects and a functional near-infrared spectroscopy (fNIRS) substudy investigated prefrontal cortex function. A patient survey of study participation was carried out.ResultsSeventy-nine severely depressed patients were randomised to ketamine (0.5 mg/kg) or saline as an adjunct to their anaesthetic for their ECT course; the modified intention-to-treat sample included 70 patients. Compared with saline, adjunctive ketamine had no significant effect on HVLT-R delayed recall [treatment effect difference –0.43, 95% confidence interval (CI) –1.73 to 0.87], other neuropsychological outcomes, improvement in depression [difference in Montgomery–Åsberg Depression Rating Scale (MADRS) score of 0.44, 95% CI –1.03 to 1.91], the number of ECT treatments to remission (MADRS score of ≤ 10: 0.83, 95% CI –3.2 to 4.9), anxiety symptoms or quality of life. By the end of ECT treatment, 37% (saline 35%, ketamine 39%) of patients had remitted. Tolerability was similar in the two treatment arms; two patients had isolated transient psychological effects attributable to ketamine. Preliminary fNIRS analysis found that patients had blunted prefrontal cortical haemodynamic responses compared with control subjects during a verbal fluency task at baseline; this was further diminished at mid-ECT without modulation by ketamine. Greater haemodynamic responsivity to ECT appeared to be associated with a better clinical response. The majority of patients surveyed reported a positive experience of study participation.ConclusionsThe results of the study do not support the use of adjunctive ketamine in routine ECT treatment in the NHS. Although no evidence of benefit was found for ketamine, moderate benefits or harms cannot be excluded, as recruitment was < 50% of that planned, limiting the power of the clinical trial. Low numbers also meant that in the fNIRS substudy the effect of ketamine could not be assessed and the other findings must be viewed as preliminary. Included patients were younger than those not included and had only limited cognitive impairment with ECT, limiting generalisation to more cognitively compromised patients. fNIRS appeared to be a potentially feasible portable brain imaging technology in severely ill patients and further research is warranted to investigate its clinical utility.Trial registrationCurrent Controlled Trials ISRCTN14689382.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

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Section: Near-infrared Spectroscopy Studysupporting

confidence: 91%

Section: Background and Objectivesmentioning

confidence: 91%

Randomised controlled trial of ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT study)

et al. 2017

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“…This region includes the dorsolateral prefrontal area, which also plays a critical role in the development of suicidal behavior [16, 17]. A previous investigation using NIRS for MDD also reported that the severity of suicidal ideation was associated with hemodynamic responses in dorsolateral prefrontal region [23]. In our study, SAs showed significant correlation between the severity of suicide ideation and hemodynamic responses in the right dorsolateral prefrontal region (ch45; r = −0.39, p = 0.037; uncorrected), but NAs did not show such correlation.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is a neuroimaging tool that can be applied clinically for assessing potential biomarkers in patients with psychiatric disorders. Many studies using NIRS have demonstrated that changes in mean oxy-Hb levels in frontotemporal regions induced by a verbal fluency task (VFT) are significantly lower in patients with MDD than in control subjects [19–23]. However, it is still unclear whether these NIRS signal changes are associated with a history of suicide attempts and a diathesis for suicidal behavior in MDD.…”

Section: Introductionmentioning

confidence: 99%

Reduced left precentral regional responses in patients with major depressive disorder and history of suicide attempts

Tsujii¹,

Mikawa²,

Tsujimoto³

et al. 2017

PLoS ONE

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Previous neuroimaging studies have revealed frontal and temporal functional abnormalities in patients with major depressive disorder (MDD) and a history of suicidal behavior. However, it is unknown whether multi-channel near-infrared spectroscopy (NIRS) signal changes among individuals with MDD are associated with a history of suicide attempts and a diathesis for suicidal behavior (impulsivity, hopelessness, and aggression). Therefore, we aimed to explore frontotemporal hemodynamic responses in depressed patients with a history of suicide attempts using 52-channel NIRS. We recruited 30 patients with MDD and a history of suicidal behavior (suicide attempters; SAs), 38 patient controls without suicidal behavior (non-attempters; NAs), and 40 healthy controls (HCs) matched by age, gender ratio, and estimated IQ. Regional hemodynamic responses during a verbal fluency task (VFT) were monitored using NIRS. Our results showed that severities of depression, impulsivity, aggression, and hopelessness were similar between SAs and NAs. Both patient groups had significantly reduced activation compared with HCs in the bilateral frontotemporal regions. Post hoc analyses revealed that SAs exhibited a smaller hemodynamic response in the left precentral gyrus than NAs and HCs. Furthermore, the reduced response in the left inferior frontal gyrus was negatively correlated with impulsivity level and hemodynamic responses in the right middle frontal gyrus were negatively associated with hopelessness and aggression in SAs but not in NAs and HCs. Our findings suggest that MDD patients with a history of suicide attempts demonstrate patterns of VFT-induced NIRS signal changes different from those demonstrated by individuals without a history of suicidal behaviors, even in cases where clinical symptoms are similar. NIRS has a relatively high time resolution, which may help visually differentiate SAs from NAs.

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“…Evidence regarding the relationship between depression severity and blood flow measurements scaled by Near-Infrared Spectroscopy (NIRS) is accumulating [30, 36, 41]. NIRS comprises a non-invasive imaging device that uses multiple channels to visualize brain activity.…”

Section: Introductionmentioning

confidence: 99%

Clinical application of DEX/CRH test and multi-channel NIRS in patients with depression

et al. 2016

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BackgroundTo reduce the number of patients with depression, biomarkers for clarifying psychiatric disorders are warranted. Numerous candidates have been proposed; however, near-infrared spectroscopy (NIRS) with multi-channel probes and a dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are still surviving for practical demand. Thirty-one outpatients with depressed moods were analyzed using both biological tests.ResultsThe non-suppressors, as indicated by the DEX/CRH test, exhibited a high severity on the Hamilton Depression Scale and severe anxiety on the State Trait Anxiety Scale. In addition, a unique response was identified via NIRS in the same group suggested by the DEX/CRH assessment.ConclusionsThe results obtained from these biological tests did not fit well with the category defined by operative diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders or The International Classification of Diseases. Thus, it is critical that the utility evaluations of candidate biomarkers not be assessed by comparisons with the categorized criteria for a specific psychiatric disorder.Trial registration UMIN000013214, Registered 21 February 2014

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Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder

Cited by 96 publications

References 75 publications

Randomised controlled trial of ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT study)

Randomised controlled trial of ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT study)

Reduced left precentral regional responses in patients with major depressive disorder and history of suicide attempts

Clinical application of DEX/CRH test and multi-channel NIRS in patients with depression

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