Auditory P50 Sensory Gating Alterations in Major Depressive Disorder and their Relationship to Clinical Symptoms.

Cognitive deficits in depression are pervasive and include impairments in attention and higher-order functions but the degree to which low-level sensory processes are affected is unclear. The present work examined event-related potential (P50 and N100) features of auditory sensory gating (i.e., the ability to inhibit P50/N100 responses to redundant stimuli) and their relationship to depressive symptoms, including ruminations and dysfunctional attitudes. In 18 patients with major depressive disorder (MDD) and 18 healthy volunteers, auditory sensory gating was measured using a paired-stimulus paradigm yielding ratio (rP50, rN100) and difference (dP50, dN100) gating indices, which reflected amplitude reductions from first (S1) to second (S2) stimulus. Patients with MDD exhibited diminished rP50 and dP50 gating scores and delayed S1-N100 latencies compared to healthy volunteers. These measures were positively associated with ruminative thoughts, negative attitudes and degree of depression. Study findings implicate aberrant sensory processing in depressed patients that is related to severity of maladaptive thinking.

Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial.

(Reprinted with permission from The American Journal of Psychiatry 2019; 176:401-409).

Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression.

Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P < 0.001, Cohen's d = 0.83). Participants had cumulative reductions in MADRS-SI scores with repeated infusions (P < 0.001), and no further change with maintenance infusions (P = 0.94). QIDS-SI results were consistent with MADRS-SI. Overall, 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions. This study adds to the growing body of research suggesting ketamine as a possible novel treatment strategy for SI in mood disorders.

Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial.

OBJECTIVE: Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions. METHODS: Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control). After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered thrice weekly over 2 weeks. Responders, classified as those participants who had a ≥50% decrease in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), received four additional infusions administered once weekly (maintenance phase). RESULTS: Compared with midazolam, a single ketamine infusion elicited a significantly greater reduction in depressive symptoms at the primary efficacy endpoint (24 hours postinfusion). Linear mixed models revealed cumulative antidepressant effects with repeated infusions and doubling of the antidepressant response rate. Fifty-nine percent of participants met response criteria after repeated infusions, with a median of three infusions required before achieving response. Participants had no further change in MADRS scores during weekly maintenance infusions. CONCLUSIONS: Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings.

Weight Status and DSM-5 Diagnoses of Eating Disorders in Adolescents From the Community.

OBJECTIVE: To estimate jointly the point prevalence of weight and eating disorders in a community sample of adolescents; to investigate psychosocial correlates of thinness, overweight, and obesity, and of full- and subthreshold eating disorders (EDs); and to examine the relationships between weight status and prevalence of EDs. METHOD: A total of 3,043 Canadian adolescents (1,254 males and 1,789 females; mean age = 14.19 years, SD = 1.61 years) completed self-report questionnaires, including the Eating Disorder Diagnostic Scale, and measures of psychosocial functioning. Objective weight and height were collected, and weight status was defined according to the International Obesity Task Force body mass index growth curve centiles. RESULTS: In all, 29.5% (95% CI = 26.7, 32.5) of males and 22.8% (95% CI = 20.5, 25.2) of females were overweight or obese. A total of 2.2% (95% CI = 1.5, 3.2) of males and 4.5% (95% CI = 4.4, 4.5) of females met DSM-5 criteria for an ED; in addition, 1.1% (95% CI = 0.7, 1.9) of males and 5.1% (95% CI = 4.0, 6.5) of females were identified with a subthreshold ED. Both full- and subthreshold EDs were significantly associated with markedly impaired psychosocial functioning. There was a significant relationship between prevalence of EDs and weight status, with an increased risk for a bulimic disorder in obese relative to normal-weight males (odds ratio [OR] = 7.86) and females (OR = 3.27). CONCLUSION: This study provides estimates for the prevalence of DSM-5 EDs in adolescents, further support for their impact on mental health, and new evidence for an association between bulimic disorders and obesity. Results call for an integrated approach in research and prevention regarding the whole spectrum of eating- and weight-related disorders.