Deepak Jayarajan

Visual Image-induced Craving for Ethanol (VICE): Development, validation, and a pilot fmri study

Background: Craving induction in a controlled environment is helpful in the research of craving mechanism and its role in development of alcohol dependence (AD). We describe a novel tool Visual Image-induced Craving for Ethanol (VICE) and its effects on brain activation with pilot functional magnetic resonance imaging (fMRI). Materials and Methods: Alcohol-related visual cues (ARCs) in 5 scenarios were photographed, which included pictures of bars, alcoholic beverage bottles, pouring of alcohol into glasses, glasses filled with alcohol, and scenes of people sipping alcohol, counterbalanced with neutral pictures (involving water, milk etc.,). Craving scores were obtained from 15 hospitalized patients with AD to validate this tool. In the pilot fMRI (3-Tesla) study, 5 patients were examined using VICE in a symptom provocation model. Group level-fixed effect analysis of brain activation differences was done using SPM8. Results: VICE showed a high internal consistency with Cronbachs α coefficient of 0.86, which confirmed its reliability. Concurrent validity of VICE was demonstrated via its convergence with the Penn Alcohol Craving Scale. ARCs had significantly greater mean craving scores than neutral cues in all the 5 scenarios (intentional validity). In the pilot fMRI, patients were found to have greater activation while viewing ARCs compared to the neutral cues in right insular cortex and deficient activation in right orbitofrontal cortex. Conclusions: The VICE is a reliable and valid measure of alcohol craving with promising clinical and translational research implications. Preliminary fMRI findings indicate it can be used as a symptom provocation tool for fMRI experiments.

Technology Enhanced Learning in Addiction Mental Health: Developing a Virtual Knowledge Network: NIMHANS ECHO

Addiction or Substance Use Disorders (SUD) is a growing public health problem in India. There are very few trained health professionals to provide evidence based care for these conditions. We initiated a weekly tele-ECHO clinic to train health professionals in the recognition and management of Alcohol and tobacco use disorders. The preliminary results points towards the feasibility as well as acceptability of the ECHO model of training in addiction mental health. There is a need for more involvement of the health care providers in future NIMHANS ECHO Programs.

Brain Functional Magnetic Resonance Imaging Cue-reactivity Can Predict Baclofen Response in Alcohol Use Disorders

Objective Baclofen is a promising treatment for alcohol use disorders (AUD), although its clinical response in humans is mixed. The present study aimed at investigating the impact of baclofen treatment on cue-induced brain activation pattern and its relationship with relapse outcomes. Methods Twenty-three inpatients with AUD underwent a functional magnetic resonance imaging cue-reactivity task before beginning medication with baclofen and 2 weeks later. Twelve additional inpatients with AUD, who did not receive any anticraving medications, formed the control group. All subjects were prospectively followed up for 90 days post-discharge or until lapse to first alcohol use. Results Whole-brain linear mixed effects analysis revealed a significant group-by-time interaction with greater activation of the bilateral dorsolateral pre-frontal cortex and right anterior cingulate cortex (ACC) following baclofen treatment in comparison with the control group. Further, cox regression analysis revealed that increased activation of ACC and deactivation of insular cortex (IC) was associated with longer time to first alcohol use only in the baclofen treatment group but not in the control group. Conclusion This study provides preliminary evidence for the neural predictors of baclofen treatment response in AUD. Baclofen treatment in AUD was associated with changes in cue-reactivity at critical brain regions within the incentive-salience network. Importantly, baclofen treatment-related specific activation of regions involved in cognitive control (ACC) and deactivation of regions involved in reward anticipation (IC) prolonged the time to first alcohol drink.

Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science

BackgroundThere is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer’s dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository.MethodsThe identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo whole exome sequencing.DiscussionWe hope to identify unique and overlapping brain endophenotypes for major psychiatric syndromes. In a proportion of subjects, we expect these neuro-endophenotypes to progress over time and to predict treatment outcome. Similarly, cellular assays could differentiate cell lines derived from such groups. The repository of biomaterials as well as digital datasets of clinical parameters, will serve as a valuable resource for the broader scientific community who wish to address research questions in the area.

From Nihilism to Hope: Reframing the Concept of Addiction

The treatment of substance use disorders (SUDs) has been characterised by a focus on the goal of abstinence, fostering a sense of therapeutic nihilism when relapse occurs. This chapter will focus on an overview of the factors that determine individuals’ vulnerability to SUDs, and how it differs between those at high risk and those at lower risk for an SUD. It will also discuss how this conceptual understanding can be used by clinicians to reframe the focus from an abstinence only model (focused solely on halting drug use) to a more nuanced interventional model that combines harm reduction along with interventions that target the underlying risk factors for addictive disorders, with a longer term focus on recovery.

Lamotrigine-induced manic switch: a report of 2 cases.

To the Editor: Lamotrigine is currently used for treatment of bipolar depression alone or as an adjunct to other drugs. The exact mechanism of the antidepressant action of lamotrigine is not known. Lamotrigine used as an adjuvant mood stabilizer has been reported to induce mania1 and hypomania2 in case reports. Here we present 2 cases of lamotrigine-induced switch, 1 in which lamotrigine was used as a single agent and another in which it was added in a very small dose as an adjuvant. Case 1. Mr A, a 24-year-old single male university graduate, had a family history of bipolar affective disorder in a grandfather and unspecified psychosis in a maternal uncle. He presented in 2008 with a 2-year history of episodic illness characterized by an episode of mania (DSM-IV criteria) lasting for 6 months treated with olanzapine (10 mg/d) and risperidone (2 mg/d) and an episode of moderate depression with somatic symptoms lasting for 11.5 months characterized by pervasive low mood, anhedonia, loss of interest in pleasurable activities, hopelessness, wish to die, somatic symptoms, and disturbed biofunctions. Results of routine investigations and workup for organicity were within normal limits. He was started on lamotrigine 25 mg at bedtime, and the dose was gradually increased to 200 mg. Two weeks after initiation of the drug, he developed irritability and anger outbursts on a dose of 150 mg. When the dose was increased to 200 mg/d, he developed mania along with mood-congruent psychotic symptoms (his Young Mania Rating Scale3 [YMRS] score was 20). As a result, lamotrigine was tapered and stopped over 2 weeks and lithium was added (300–1,200 mg/d) along with risperidone (2–3 mg/d). His symptoms improved over 2 weeks. He has remained well after discharge from the hospital. Case 2. Mr B, a 23-year-old single man, had a family history of alcohol dependence syndrome in his father and past history of childhood oppositional defiant disorder, cannabis dependence syndrome (currently abstinent), and harmful alcohol use. He presented with an episodic illness since 19 years of age characterized by 1 manic episode (DSM-IV criteria) without psychotic symptoms lasting 3 months treated with risperidone 4 mg/d and clonazepam 1.5 mg/d. He discontinued these medications after 1 year. He had another episode of mania (DSM-IV criteria) lasting for 3 months at 21 years of age and was treated with lithium carbonate 1,600 mg/d, risperidone 8 mg/d, and trihexyphenidyl 4 mg/d. He continued taking lithium, and risperidone was tapered off. He most recently presented in 2008 with pervasive low mood, loss of interest in pleasurable activities, hopelessness, somatic symptoms, and disturbed biofunctions of 3 weeks’ duration. He was diagnosed with bipolar affective disorder, current episode moderate depression with somatic symptoms. Lamotrigine 25 mg/d was added to lithium. A week later, he started to exhibit elated mood, overactivity (goal directed), overfamiliarity with people, grandiose plans of starting a business, increased cigarette smoking, and decreased need for sleep. He was admitted and diagnosed with bipolar affective disorder, current episode mania (lamotrigine induced). Urine cannabis screen was negative. He rated 13 on the YMRS and was started on sodium valproate 1,000 mg/d and tablet clonazepam 3 mg/d along with the lithium carbonate he was receiving. His symptoms improved over a duration of 3 weeks, and he was discharged. He has remained well after discharge on regular medications. In the first case, manic symptoms developed when lamotrigine was gradually hiked to 200 mg/d. The patient was not on any other medications during this time, and lamotrigine was the sole agent that might have induced a manic switch. This is possibly the first such case reported. In the second case, the patient developed a manic switch on the addition of a very small dose of lamotrigine. Lamotrigine may induce a switch through its ability to decrease glutamate release, thereby reducing binding to the N-methyl-D-aspartate receptor complex.4