Marijn Lijffijt

Baylor College of Medicine | BCM · Department of Psychiatry & Behavioral Sciences

Drug development in psychiatry has been hampered by the lack of reliable ways to determine the neurobiological effects of the assets tested, difficulties in identifying patient subsets more amenable to benefit from a given asset, and issues with executing trials in a manner that would convincingly provide answers. An emerging idea in many companies...

This study examined quality of life (QoL) in youth with misophonia compared to a general US youth sample and how misophonia-related variables (severity, number of triggers, responses), internalizing/externalizing symptoms, age and gender were associated with QoL among youth with misophonia. One-hundred and two children and adolescents (Mage = 13.7...

Background: Misophonia is characterized by intense emotional reactions to specific sounds or visual stimuli and typically onsets during childhood. An obstacle for research and clinical practice is that no comprehensively evaluated measures for pediatric misophonia exist. Methods: In a sample of 102 youth meeting the proposed diagnostic criteria of...

Ketamine is an effective intervention for treatment-resistant depression (TRD), including late-in-life (LL-TRD). The proposed mechanism of antidepressant effects of ketamine is a glutamatergic surge, which can be measured by electroencephalogram (EEG) gamma oscillations. Yet, non-linear EEG biomarkers of ketamine effects such as neural complexity a...

Background: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified. Objective: To provide cortical and deep gray matter correlates of the LPP in youth, specifically youth with PBD. Methods: Twenty-fou...

Imminent suicide is difficult to predict. Suicide usually occurs on the first attempt. Suicide may consist of suicidal crises, with fluctuating and unpredictable risk, superimposed on long-term latent susceptibility. Risk characteristics are consistent with interacting long-term (sensitization) and short-term (impulsivity) mechanisms: sensitization...

Background: There is little information on the clinical presentation, functional impact, and psychiatric characteristics of misophonia in youth, an increasingly recognized syndrome characterized by high emotional reactivity to certain sounds and associated visual stimuli. Method: One-hundred-two youth (8–17 years-old) with misophonia and their par...

Background The goal of this study was to replicate previous findings of three distinct treatment response pathways associated with repeated intravenous (IV) ketamine infusions among patients with major depressive disorder (MDD). Methods We conducted growth mixture modeling to estimate latent classes of change in depression (Quick Inventory of Depr...

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) in...

Background Posttraumatic stress disorder (PTSD) is associated with hyperarousal and stress reactivity, features consistent with behavioral sensitization. In this Phase 1b, parallel-arm, randomized, double-blind, placebo-controlled trial, we tested whether the selective low-trapping N-methyl-D-aspartate receptor (NMDAR) antagonist [Lanicemine (BHV-5...

Objective Converging evidence from structural and functional magnetic resonance imaging (MRI) studies points to amygdala alteration as crucial in the development of paediatric bipolar disorder (pBP). The high number of recent studies prompted us to comprehensively evaluate findings. We aimed to systematically review structural and functional MRI st...

Clinical trial registration: Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many non-gluta...

Background: The N-methyl-D-aspartate receptor antagonist ketamine is potentially effective in treatment resistant depression. However, its antidepressant efficacy is highly variable, and there is little information about predictors of response. Methods: We employed growth mixture modeling (GMM) analysis to examine specific response trajectories...

The kynurenine pathway (KP) is a strategic metabolic system that combines regulation of neuronal excitability via glutamate receptor function and neuroinflammation via other KP metabolites. This pathway has great promise in treatment of depression and suicidality. The KP modulator AV-101 (4-chlorokynurenine, 4-Cl-KYN), an oral prodrug of 7-chloroky...

Suicide is the leading cause of injury mortality in the United States and the second-leading cause of death in people aged 10–34 years. While many long-term risk factors are known, the short-term prediction of suicidal behavior remains elusive. Many characteristics of suicidal behavior cut across diagnoses, but suicide is increased in recurrent psy...

Background: Individuals with post-traumatic stress disorder (PTSD) have a heightened sensitivity to subsequent stressors, addictive drugs, and symptom recurrence, a form of behavioral sensitization. N-methyl-D-aspartate receptors (NMDARs) are involved in the establishment and activation of sensitized behavior. Objective: We describe a protocol of a...

Background: Suicide rate is increasing, and is higher amongst U.S. military veterans than non-veterans. Medically severe suicide attempts have been associated with changes in kynurenine pathway (KP) functioning, notably an increase in pro-inflammatory metabolite quinolinic acid (QA) and a reduction in protective metabolite kynurenic acid (KYN). KYN...

Interest in the coexistence of manic and depressive symptoms fostered hypotheses on neurobiological underpinnings of mixed states. Neurobiological properties of mixed states, however, have not been comprehensively described. The authors searched databases for articles on neurobiological markers related to mixed states. Results showed that mixed sta...

Treatment guidelines for mixed states of depression or (hypo)mania focus almost exclusively on psychopharmacologic intervention without tapping into the benefits of psychotherapy. The authors highlight the complex clinical picture and illness course of mixed states, and discuss the benefit of taking a patient-centered approach to treatment incorpor...

Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could in...

More than eleven million U.S. Veterans are at least 65 years of age, an age group of which almost 20% suffers from clinically significant depressive symptoms. Available pharmacological treatments are suboptimal for patients, including veterans, with late-life depression. Ketamine has emerged as a potentially promising rapid-acting therapy for treat...

Background: We studied emotional information processing in youth with pediatric bipolar disorder (pBD) using the late positive potential (LPP), assessing automatic allocation of attentional resources to emotionally salient stimuli, and the occipital P1, assessing early sensory processing. Methods: Participants were 20 youth with pBD and 26 healt...

Immediate and long-term mechanisms interact in the regulation of action. We will examine neurobiology and practical clinical consequences of these interactions. Long-term regulation of immediate behavioural control is based on analogous responses to highly rewarding or stressful stimuli: (i) impulsivity is a failure of the balance between activatio...

We tested whether enhanced stimulus orienting operationalized as N1 and P2 auditory evoked potentials to increasing loudness (50–90 dB clicks) could be associated with trait impulsivity (Barratt Impulsiveness Scale, BIS-11), impulsive action (commission error on the Immediate Memory Task), or impulsive choice (immediate responses on temporal discou...

Despite their apparent differences, stressful and rewarding stimuli elicit brain responses that are largely analogous. Stress and stress-related disorders have a large role in susceptibility to and development of addictions. Stressors facilitate every stage in the progression of substance use disorders. Early in the course of additions, stressors c...

Excessive alcohol drinking can lead to behavioral and health complications. Early in alcohol use, the individual is more vulnerable to psychiatric and addictive disorders, leading potentially to behavioral problems. The greatest risk is after problematic drinking episodes have occurred but before formal criteria for an alcohol use disorder are met....

This book addresses (1) candidate mechanisms across addictive behaviors, including impulsivity (Chapters 1–5); reward sensitivity (Chapter 2); behavioral sensitization and cross-sensitization to addictive, stressful, or endogenous illness-related stimuli (Chapters 1, 5–8, 13); and genetics (Chapter 11). Addictions frequently combine with other psyc...

Deficits in both empathy and cognition have been reported widely in patients with schizophrenia. However, little is known about how these deficits interact among such patients. In the present study, we used pain portraying pictures preceding a color-word Stroop task to investigate the effect of empathetic pain observation on cognition among patient...

Childhood trauma and post-childhood chronic/repeated stress could increase the risk of a substance use disorder by affecting five stages of addiction illness-course: (a) initial experimentation with substances; (b) shifting from experimental to regular use; (c) escalation from regular use to abuse or dependence; (d) motivation to quit; and (e) risk...

Objective Explore interrelationships between suicide attempt history (Objective 1) or suicide attempt severity (Objective 2) with prefrontal cortex gray matter (PFCGM) volume and illness-course in patients with bipolar disorder (BD).Method Ninety-three women with BD-I or -II diagnosis (51 with and 42 without suicide attempt history) underwent struc...

Background / Purpose: Bipolar disorder (BD) entails abnormal regulation of behavioral activation and inhibition (i.e., impulsivity), superimposed on a potentially progressive illness course resembling behavioral sensitization to stressors or stimulants, increasing risk of suicide and substance-use disorders (SUD). BD, SUD, and other disorders of...

Background / Purpose: Antisocial personality disorder (ASPD) has been related to increased impulsivity. Impulsivity refers to poor action control, potentially due to increased orientation to stimuli. We explored relationships between impulsivity, assessed by tasks capturing impulsive action and impulsive choice, and stimulus orientation, assessed...

Early responses to stimuli can be measured by sensory evoked potentials (EP) using repeated identical stimuli, S1 and S2. Response to S1 may represent efficient stimulus detection, while suppression of response to S2 may represent inhibition. Early responses to stimuli may be related to impulsivity. We compared EP reflecting stimulus detection and...

Rationale Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine. Objective We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenerg...

Background: Interactions between characteristics of bipolar and Axis II cluster B disorders are clinically and diagnostically challenging. Characteristics associated with personality disorders may be dimensional aspects of bipolar disorder. We investigated relationships among antisocial personality disorder (ASPD) or borderline personality disorde...

Bipolar disorder and antisocial personality disorder (ASPD) overlap in clinical characteristics and behavioral consequences. Impulsivity is prominent in both, but there is little information on how specific mechanisms of impulsivity differentiate, bridge, or underlie the disorders. Subjects, all males, were controls (n = 46), bipolar disorder witho...

Criminal behavior in bipolar disorder may be related to substance use disorders, personality disorders, or other comorbidities potentially related to impulsivity. We investigated relationships among impulsivity, antisocial personality disorder (ASPD) or borderline personality disorder symptoms, substance use disorder, course of illness, and history...

We investigated trait impulsivity in bipolar disorder and antisocial personality disorder (ASPD) with respect to severity and course of illness. Subjects included 78 controls, 34 ASPD, 61 bipolar disorder without Axis II disorder, and 24 bipolar disorder with ASPD, by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Dis...

Bipolar mixed states combine depressive and manic features, presenting diagnostic and treatment challenges and reflecting a severe form of the illness. DSM-IV criteria for a mixed state require combined depressive and manic syndromes, but a range of mixed states has been described clinically. A unified definition of mixed states would be valuable i...

P50, N100, and P200 auditory sensory gating could reflect mechanisms involved in protecting higher-order cognitive functions, suggesting relationships between sensory gating and cognition. This hypothesis was tested in 56 healthy adults who were administered the paired-click paradigm and two adaptations of the continuous performance test (Immediate...

The authors investigated preattentive filtering assessed by P50 gating in nine participants with antisocial personality disorder (ASPD) and seven with adult-onset antisocial behavior (AAB). Relative to 15 comparison subjects, gating was impaired in ASPD, suggesting abnormal pre-attentive filtering in pathological impulsivity.

Impulsivity as a trait characteristic is increased in bipolar disorder and may be a core factor of the illness. We have investigated relationships between trait-like impulsivity, measured by the Barratt Impulsiveness Scale (BIS-11), and demographic and illness-course characteristics of bipolar disorder. We studied 114 subjects with bipolar disorder...

Bipolar I disorder is associated with diminished gating of the auditory evoked P50 component. P50 gating may relate to early filtering of sensory information, protecting higher-order cognitive functions. Gating of the auditory evoked N100 and P200 components has not been investigated in bipolar I disorder, although N100 and P200 gating could reflec...

Impulsive behavior is a prominent characteristic of antisocial personality disorder. Impulsivity is a complex construct, however, representing distinct domains of cognition and action. Leading models refer to impulsivity as an inability to evaluate a stimulus fully before responding to it (rapid-response impulsivity), and as an inability to delay r...

P50, N100, and P200 auditory sensory gating reflect distinct mechanisms involved in protecting the integrity of higher-order functions. They have been implicated in multiple psychiatric disorders. Recent studies showed the (limited) effects of age and gender on sensory gating in control subjects, suggesting there may be other sources of variance. T...

Pathological impulsivity in bipolar disorder could be related to deficiencies in mechanisms involved in attention or response inhibition. We investigated these mechanisms in subjects with bipolar disorder and examined relationships to severity of course of illness, use of medication, affective state, age, education, and gender. We measured two comp...

Impulsivity, a component of the initiation of action, may have a central role in the clinical biology of affective disorders. Impulsivity appears clearly to be related to mania. Despite its relationship to suicidal behavior, relationships between impulsivity and depression have been studied less than those with mania. Impulsivity is a complex const...

Resumen Propósito El efecto del metilfenidato (MF) sobre el control inhibitorio evaluado por la tarea de parada ( stop task ) en niños con trastorno por déficit de atención e hiperactividad (TDAH) podría estar influido por la dificultad de la tarea y puede estar mediado por la atención. Sujetos y métodos Quince niños con TDAH realizaron la tarea...

The effect of methylphenidate (MPH) on inhibitory control as assessed by the stop task in children with attention-deficit/hyperactivity disorder (ADHD) could be influenced by task difficulty and may be mediated by attention. Fifteen children with ADHD performed the stop and the change task after placebo, 0.5 and 1.0 mg/kg MPH in a within-subject de...

The present selective review addresses attention, inhibition, and their underlying brain mechanisms, especially in relation to attention deficit/hyperactivity disorders (AD/HD), and the effects of methylphenidate. In particular, event-related potential (ERP) studies suggest a deficit in the early-filtering aspect of selective attention in children...

This review discusses whether deficient inhibitory motor control is the core deficit of attention-deficit/hyperactivity disorder (ADHD). Inhibitory motor control is commonly assessed using the stop-signal paradigm. Since the last meta-analysis that was performed, 33 new studies have appeared. The current meta-analysis revealed a significant differe...

Cognitive deficits have been reported in adults with childhood-onset growth hormone (GH) deficiency. We evaluated cognitive deficits simultaneously with parameters for neuronal integrity using (1)H magnetic resonance spectroscopy (MRS) in a cross-sectional design. We studied 11 adults (mean age 24.5 years) with childhood-onset GH deficiency, which...

The Impulsiveness–Venturesomeness–Empathy questionnaire (I7) is a frequently used questionnaire assessing aspects of impulsivity. Since a Dutch translation is lacking, comparisons and inferences regarding these traits are limited between results from studies that do use the I7. We translated the I7 and studied the psychometric properties in a Dutch...

The Impulsiveness–Venturesomeness–Empathy questionnaire (I 7) is a frequently used questionnaire assessing aspects of impulsivity. Since a Dutch translation is lacking, comparisons and inferences regarding these traits are limited between results from studies that do use the I 7. We translated the I 7 and studied the psychometric properties in a Du...

The present study investigates whether there is an association between trait impulsivity in the normal population and inhibitory motor control as assessed by the stop task. Low- and high-impulsive participants (as assessed by the I7 questionnaire; both groups n = 31) performed the stop task. Differences in performance were analyzed by an independen...

Reduced levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are associated with deteriorated cognitive performance in senescence. Little work has been done on the effect of GH and IGF-1 on a crucial aspect of cognition, selective attention. This study investigated the effect of GH/IGF-1 on performance and brain potentials (EEG) d...

This work addressed early selection based on nonspatial visual features, using event-related potentials (ERPs) with high temporal resolution and dipole-source modeling. Subjects were presented rapid sequences of gratings varying in spatial frequency and orientation, and were instructed to attend to gratings with one spatial frequency and ignore tho...

Visually evoked potentials (VEPs) are known to be sensitive to spatial frequency, especially in the time range between 50 and 100 ms post-stimulus. In two experiments we localized the cortical activity elicited by stimuli of varying spatial frequency in scalp-recorded brain potentials, using multi-electrode recordings and dipole-source analysis. Lo...