Cristina Cusin

Massachusetts General Hospital | MGH · Department of Psychiatry

Recent observations suggest a role of the choroid plexus (CP) and cerebral ventricle volume (CV), to identify treatment resistance of major depressive disorder (MDD). We tested the hypothesis that these markers are associated with clinical improvement in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study characteri...

Objective: Ketamine is a novel and rapidly acting treatment for major depressive disorder (MDD). Benzodiazepines are commonly coprescribed with antidepressants in MDD. This study sought to examine data from a randomized clinical trial that compared a single infusion of intravenous (IV) ketamine to midazolam placebo in treatment-resistant depression...

Objective: This study compared the impact of 3 eicosapentaenoic acid (EPA) doses versus placebo on inflammatory biomarkers and depressive symptoms. Methods: Sixty-one unmedicated adults (75% female; 45.5 ± 13.8 years) with DSM-5 major depressive disorder (MDD), body mass index > 25 kg/m2, and plasma high-sensitivity C-reactive protein (hs-CRP) ≥ 3...

Background: Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD. Methods: A 2...

Introduction: Family caregivers of patients with dementia suffer a high burden of depression and reduced positive emotions. Mentalizing imagery therapy (MIT) provides mindfulness and guided imagery skills training to improve balanced mentalizing and emotion regulation. Objective: Our aims were to test the hypotheses that MIT for family caregiver...

Background: Some staging models for treatment-resistant depression (TRD) have been developed in the attempt to predict treatment outcome, in particular with electroconvulsive therapy. However, these models have not been tested in predicting clinical outcome of ketamine treatment. We assessed the relationship between patients' classification with d...

Option generation is a critical process in decision making, but previous studies have largely focused on choices between options given by a researcher. Consequently, how we self-generate options for behaviour remain poorly understood. Here, we investigated option generation in major depressive disorder and how dopamine might modulate this process,...

Background Predicting future states of psychopathology such as depressive episodes has been a hallmark initiative in mental health research. Dynamical systems theory has proposed that rises in certain ‘early warning signals’ (EWSs) in time-series data (e.g. auto-correlation, temporal variance, network connectivity) may precede impending changes in...

Novel interventions are needed to manage treatment-resistant depression (TRD), defined as patients who do not respond to two or more antidepressant trials of adequate dose and duration. We report on a 28-year-old female with TRD with nonresponse to several adequate trials of antidepressants who experienced full symptomatic remission after participa...

Objective Both cognitive behavioral therapy for depression (CBT-D) combined with brief motivational interviewing (CBT-D+BMI) and alone are associated with symptom improvement among college students with co-occurring depression and heavy episodic drinking (HED). However, little is known about change processes underlying these different treatments.Th...

Background: While preliminary evidence suggests that sensors may be employed to detect presence of low mood it is still unclear whether they can be leveraged for measuring depression symptom severity. This study evaluates the feasibility and performance of assessing depressive symptom severity by using behavioral and physiological features obtained...

Ketamine is increasingly being used as a therapeutic for treatment-resistant depression (TRD), yet the effects of ketamine on the human brain remain largely unknown. This pilot study employed diffusion magnetic resonance imaging (dMRI) to examine relationships between ketamine treatment and white matter (WM) microstructure, with the aim of increasi...

Background Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific ma...

Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC struc...

Objective: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function...

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active plac...

Supplementary Figure 1 and Supplementary Tables 1–4 have been re-uploaded so as to reflect the versions supplied during proofs stage. The publisher apologizes for the error in versioning. The HTML version of the paper has been updated.

Receptor ligand-based dynamic Positron Emission Tomography (PET) permits the measurement of neurotransmitter release in the human brain. For single-scan paradigms, the conventional method of estimating changes in neurotransmitter levels relies on fitting a pharmacokinetic model to activity concentration histories extracted after PET image reconstru...

Background Little is known about the long-term outcomes of repeated ketamine infusions for depression. We conducted a retrospective chart review to investigate outcomes of maintenance intravenous ketamine treatment at Massachusetts General Hospital. Methods Eighty-five patients with treatment-resistant depression (TRD) who started intravenous keta...

Objective: The neuroactive steroid metabolite of progesterone, allopregnanolone, is a positive allosteric modulator of γ-aminobutyric acid-A (GABAA) receptors and a putative treatment for mood disorders. This pilot study was performed to determine whether an oral allopregnanolone analog (ganaxolone) may be effective adjunctive therapy for persiste...

Major depressive disorder is a common mental health condition that affects an estimated 16.2 million adults and 3.1 million adolescents in the United States. Yet, a lack of uniformity remains in measurements and monitoring for depression both in clinical practice and in research settings. This project aimed to develop a minimum set of standardized...

Objective: Nonresponse to selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor treatment is common in patients with major depressive disorder (MDD), particularly in women, occurring in about 70% of patients despite adequate dosing. Well-tolerated augmentation strategies are needed, particularly ones that do not cau...

Purpose/background: Major depressive disorder (MDD) and obesity commonly co-occur. We sought to assess the impact of body mass index (BMI) on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. Methods/procedures: Post hoc analyses were conducted from a multisite, randomized, double-blind, placebo-contro...

Background This report tests the association of self-reported symptoms of irritability with overt behavior of anger attacks (uncharacteristic sudden bouts of anger that are disproportionate to situation and associated with autonomic activation). Methods Participants of the Establishing Moderators and Biosignatures of Antidepressant Response in Cli...

The neuroactive steroid 3α-5α-tetrahydroprogesterone (allopregnanolone), a metabolite of progesterone, is a positive allosteric modulator of GABAA receptors, and low levels have been implicated in the etiology of mood disorders. However, it is not known whether metabolism of progesterone to allopregnanolone varies across the menstrual cycle or is l...

Background: The optimal dose of S-adenosyl methionine (SAMe) for major depressive disorder (MDD) remains unclear. The objective of this analysis was to address whether a dose increase provided further improvement in cases of insufficient response using data from an existing randomized clinical trial. Methods: Sixty-five patients with MDD who fai...

Objective: To examine the rate and time to relapse for remitters and responders to ketamine in treatment-resistant depression (TRD). Methods: Subjects with TRD were randomized to a single infusion of one of several doses of intravenous ketamine, or midazolam. Using Kaplan-Meier survival function, the current report examines the rate and time to rel...

Background: While riluzole has been investigated for the treatment of depression, little is known about its longer-term efficacy and optimal treatment duration in treatment-resistant depression (TRD). The objective of this study is to characterize the longer-term outcome of adjunctive riluzole therapy for TRD in an open-label extension of an 8-wee...

Background: Neuroactive steroids such as 3α-5α-tetrahydroprogesterone (allopregnanolone) and 5α-androstane-3α,17β-diol (3α-androstanediol) are modulators of traditional neurotransmitter receptors and have been implicated in the etiopathology of psychiatric disorders, including depression, but levels have not been assessed in women with treatment-re...

Objective To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment‐resistant depression (TRD). Methods In a multisite, double‐blind, placebo‐controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or mida...

Background: While ketamine has been increasingly studied for treatment resistant depression (TRD), the impact of sex differences on treatment outcomes has not been well studied. The objective was to ascertain whether there were differences in response to a single administration of ketamine for TRD between men and women, and between pre- and post-m...

In this chapter, we will present an overview of the current status of research on ketamine as a rapid-acting antidepressant agent. We will introduce a brief case vignette, exemplary of the patients presenting at our center for ketamine treatment. At the time of publication of this book ketamine is not yet FDA-approved for depression. We will review...

Major depression is one of the most common psychiatric disorders, and it often presents in combination with other medical and psychiatric illnesses. In almost one third of cases, it manifests as “difficult-to-treat depression” or “treatment-resistant depression” (TRD). In this chapter we will present an overview of this complex clinical problem, in...

This book present the most cutting edge treatment options for patients struggling with depression. Written by experts in this area, the book begins by establishing the general themes that are most critical to accurately diagnosing and effectively treating depression. The text then covers new medication options, new psychotherapy, non-pharmacologica...

DBS has shown initial promise for treating Obsessive-Compulsive Disorder (OCD), but lacks reliable clinical response and biomarkers for stimulation guidance (Bilge, Gosai, & Widge, 2018). We’ve recently begun simultaneously stimulating and recording from the Ventral Capsule/ Ventral Striatum (VC/VS) DBS target and the Supplementary Motor Area (SMA)...

Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplast...

Background: Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown. Methods: Twenty-...

Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapi...

Background: Low-Field Magnetic Stimulation (LFMS) is a novel, non-invasive, sub-threshold neuromodulation technique, shown in preliminary studies to have immediate mood elevating effects in both unipolar and bipolar depressed patients. Objective: We aimed to assess the antidepressant augmentation effects at 48 h of LFMS administered on two conse...

Objective: To examine the efficacy of adjunctive ziprasidone for cognitive symptoms in adult patients with major depressive disorder (MDD) experiencing persistent symptoms after 8 weeks of open-label escitalopram. Methods: This post hoc analysis was conducted on a database derived from a previously published study. The parent study was a multice...

Background: Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods: 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stim...

Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-...

Electroconvulsive therapy (ECT) was the first device-based treatment to become available for psychiatric disorders, and it consists of the application of an electric stimulus to the surface of the head, with the aim of inducing a seizure. To date, ECT is considered the gold standard device-based treatment for treatment-resistant depression (TRD), t...

Background: Neuromuscular blockade is required to control excessive muscle contractions during electroconvulsive therapy (ECT). In a crossover, assessor-blinded, prospective randomized study, we studied the minimum effective dose (MED) of succinylcholine and rocuronium for ECT. The MED was the lowest dose to provide a predefined qualitative measur...

Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. The...

Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone's safety and efficacy as an augmentation agent in outpati...

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a novel therapy for neuropsychiatric disorders. Hypomania is a known complication of VC/VS DBS, but who is at risk is less understood. Factors such as family history, combined with details of DBS programming, might quantify that risk. The authors performed an iterative...

We compared treatment response (≥50 decrease in Nine-Item Patient Health Questionnaire total score) among 24 Latinos with major depressive disorder, presenting with and without specific psychosislike symptoms: A, hearing noises or house sounds, B, hearing voices calling one's name, C, seeing fleeting visions such as shadows, and D, symptoms more li...

Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR ve...

We examined efficacy and safety of one specific cranial electrical stimulator (CES) device at a fixed setting in subjects with treatment-resistant major depressive disorder (MDD). Thirty subjects (57% female, mean age 48.1 ± 12.3 years) with MDD and inadequate response to standard antidepressants were randomized to 3 weeks of treatment with CES (15...

In the last decade, many studies have used automated processes to analyze magnetic resonance imaging (MRI) data such as cortical thickness, which is one indicator of neuronal health. Due to the convenience of image processing software (e.g., FreeSurfer), standard practice is to rely on automated results without performing visual inspection of inter...

OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conduc...

Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flan...

Suicide is the third leading cause of death in college students, but there is limited consensual evidence to guide clinicians' assessment and management of suicide. The aim of the current study was to assess the capability of a simple and practical measure, the Beck Depression Inventory (BDI) suicide item, to identify college students at high risk...

We tested the hypothesis that etomidate and ketamine produce residual effects that modify functional mobility (measured by the balance beam test) and adrenal function (adrenocorticotropic hormone (ACTH) stimulation) immediately following recovery from loss of righting reflex in rats. Intravenous etomidate or ketamine was administered in a randomize...

Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published. Thirty patients with TRD participated in a sham-controlled tri...

Background / Purpose: We analyzed the test-retest reliability of automated cortical thickness (CT) and cortical volume (CV) measures acquired from different sites. Main conclusion: Cortical thickness and cortical volume measures should be used carefully.

Depression is a prevalent psychiatric disorder associated with significant personal and societal burden. There is accumulating evidence for the presence of a subtype of depression characterized by the presence of irritability that is associated with increased morbidity, risk for suicidal ideation, and functional impairments in adults. Little is kno...

CME Educational Objectives 1. Provide an overview of the history and origins of deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD). 2. Describe the various neuroanatomic targets of DBS implant for OCD as well as the neurocircuitry involved. 3. Explain the effects of DBS for OCD, both intended and unintended, a...

Multiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application. This study investigat...