Adith Mohan

Deep Brain Stimulation of the Antero-Medial Globus Pallidus Interna for Tourette Syndrome

Background We have previously reported the results of Deep Brain Stimulation (DBS) of the antero-medial globus pallidus interna (GPi) for severe Tourette Syndrome (TS) in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. Methods 17 patients (14 male; mean age 29.1 years, range 17–51 years) with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS). Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8–46 months) following surgery. Results Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6%) patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1), transient anxiety (2), dizziness (1), poor balance (1) and worsening of stuttering (1). Conclusions This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.

Basic treatment principles for psychotic disorders in patients with epilepsy.

In patients with epilepsy, coexisting psychoses, either interictal (IIP) or postictal (PIP), are associated with serious disturbance in psychosocial function and well‐being, and often require the care of a specialist. Unfortunately, evidence‐based treatment systems for psychosis in patients with epilepsy have not yet been established. This article aims to propose concise and practical treatment procedures for IIP and PIP based on currently available data and international consensus statements, and primarily targeting nonpsychiatrist epileptologists who are often the first to be involved in the management of these complex patients. Accurate and early diagnosis of IIP and PIP and their staging in terms of acuity and severity form the essential first step in management. It is important to suspect the presence of psychosis whenever patients manifest unusual behavior. Knowledge of psychopathology and both individual and epilepsy‐related vulnerabilities relevant to IIP and PIP facilitate early diagnosis. Treatment for IIP involves (1) obtaining consent to psychiatric treatment from the patient, whenever possible, (2) optimization of antiepileptic drugs, and (3) initiation of antipsychotic pharmacotherapy in line with symptom severity and severity of behavioral and functional disturbance. Basic psychosocial interventions will help reinforce adherence to treatment and should be made available. Due consideration must be given to patients’ ability to provide informed consent to treatment in the short term, with the issue being revisited regularly over time. Given the often prolonged and recurrent nature of IIP, treatment frequently needs to be long‐term. Treatment of PIP consists of two aspects, that is, acute protective measures and preventive procedures in repetitive episodes. Protective measures prioritize the management of risk in the early stages, and may involve sedation with or without the use of antipsychotic drugs, and the judicious application of local mental health legislation if appropriate. As for preventative procedures, optimizing seizure control by adjusting antiepileptic drugs or by surgical treatment is necessary.

DSM-5 and Mental Disorders in Older Individuals: An Overview.

Learning ObjectivesAfter participating in this activity, learners should be better able to:• Assess the changes in DSM-5 relative to earlier versions.• Evaluate the implications of the DSM-5 for practicing geriatric psychiatrists. AbstractAbout every 20 years, the American Psychiatric Association revises its official classification of mental disorders. The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, prompting considerable commentary, debate, and criticism. This article briefly describes the process leading up to DSM-5 and the main changes from the previous version (DSM-IV) that would be of interest to a geriatric psychiatrist. The changes in the areas of schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders have been many, but the majority of them are minor and unlikely to have major treatment implications. The classification of neurocognitive disorders, however, has seen a major revision and elaboration in comparison to DSM-IV; of special note is the introduction of “mild and major neurocognitive disorders,” the latter equated with dementia. A common language has also been introduced for the criteria for the various etiological subtypes of neurocognitive disorders. All physicians treating patients with neurocognitive disorders should familiarize themselves with these criteria. Their use in research has the potential to harmonize the field.

Gene expression in the aging human brain: an overview

Purpose of review The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Recent findings Profiling differentially expressed genes or ‘transcripts’ in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Summary Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

Neuropsychiatry: Where are we and where do we go from here?

Introduction: Neuropsychiatry has generally been regarded as a hybrid discipline that lies in the borderland between the disciplines of psychiatry and neurology. There is much debate on its current and future identity and status as a discipline. Materials and Methods: Taking a historical perspective, the future of neuropsychiatry is placed within the context of recent developments in clinical neuroscience. Results: The authors argue that with the maturation of the discipline, it must define its own identity that is not dependent entirely upon the parent disciplines. The requirements for this are the claiming of neuropsychiatric territory, a strong training agenda, an emphasis on treatments that are uniquely neuropsychiatric, and a bold embrace of new developments in clinical neuroscience. Conclusion: The exponential growth in neuroscientific knowledge places neuropsychiatry in an excellent position to carve out a strong identity. It is imperative that the leaders of the discipline seize the moment.

Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex

Altered inhibition-excitation balance is implicated in brain aging. We hypothesized that expression of 14 genes encoding proteins localized to synapses or interneurons would show age-related changes relative to 1 another in postmortem tissue from the prefrontal cortex of 37 individuals (18-78 years) and that synaptic or interneuron markers would be differentially correlated with human brain volumes across aging. The majority of genes examined were differentially expressed with age, most being downregulated. Expression of 3 interneuron-related genes was significantly negatively associated with age (calbindin, somatostatin, cholecystokinin), whereas 3 synapse-related genes showed significant age-related expression change (PSD95, GAP43, VGLUT1). On covarying for 2 glial markers (GFAP, IBA1), all 3 interneuron genes and 1 synaptic gene (Growth-associated protein 43) remained significant. Two genes were significantly associated with total brain volume (calbindin, complexin 2) and a marker of synaptic density (synaptophysin) was significantly associated with cortical gray matter volume. Age-related change in expression of genes involved in maintenance of inhibition-excitation balance and regulation of prefrontocortical network dynamics suggests these pathways may contribute to brain aging.

Anti-N-methyl-D-aspartate encephalitis – a case study of symptomatic progression

Objective: To present the diagnosis course and sequelae of a case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, drawing attention to early psychiatric symptoms. Method: The literature on anti-NMDA encephalitis is reviewed and possible psychopathological mechanisms discussed. Result: New onset psychoses, presenting with the combination of hallucinations, dyskinesias and seizures and progressing to catatonia should be referred to neurology for consideration of anti-NMDA receptor encephalitis. Conclusion: Early diagnosis is important for a favourable prognosis.

Surviving acute cyanide poisoning: a longitudinal neuropsychological investigation with interval MRI

We report the case of a 22-year-old woman who presented with self-poisoning by cyanide ingestion. We have elected to pay particular attention to describing the neuropsychological sequelae of cyanide poisoning, and the evolution of these deficits over a 6-month period. Prominent deficits in episodic memory were noted from an early stage, which were consistent with the findings noted on structural neuroimaging. These deficits remained persistent, although improving in severity over the follow-up period. No focal neurological deficits or abnormal involuntary movements emerged, and the patients overall functional status remained satisfactory. The patients psychiatric presentation and background history are briefly discussed.

Pre-treatment attentional processing speed and antidepressant response to transcranial direct current stimulation: Results from an international randomized controlled trial

BACKGROUND Transcranial direct current stimulation (tDCS) has promising antidepressant effects, however, clinical trials have shown variable efficacy. Pre-treatment neurocognitive functioning has previously been identified as an inter-individual predictor of tDCS antidepressant efficacy. OBJECTIVE In this international multicentre, sham-controlled study, we investigated this relationship while also assessing the influence of clinical and genotype (BDNF Val66Met and COMT Val158Met polymorphisms) factors as predictors of response to active tDCS. METHODS The study was a triple-masked, parallel, randomized, controlled design across 6 international academic medical centers. Participants were randomized to active (2.5 mA) or sham (34 μA) tDCS for 30 min each session for 20 sessions. The anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over the lateral right frontal area at F8. RESULTS Better pre-treatment attentional processing speed on the Ruff 2 & 7 Selective Attention Test (Total Speed: β = 0.25, p < .05) and concurrent antidepressant medication use (β = 0.31, p < .05) predicted antidepressant efficacy with active tDCS. Genotype differences in the BDNF Val66Metand COMT Val158Met polymorphisms were not associated with antidepressant effects. Secondary analyses revealed that only participants in the highest performing Ruff 2 & 7 Total Speed group at pre-treatment in both active and sham tDCS conditions showed significantly greater antidepressant response compared to those with lower performance at both the 2 and 4 week treatment time points (p < .05). CONCLUSIONS These results suggest that high pre-treatment attentional processing speed may be relevant for identifying participants more likely to show better tDCS antidepressant response to both high (2.5 mA) and very low (34 μA) current intensity stimulation. CLINICAL TRIALS REGISTRATION www.clinicaltrials.gov, NCT01562184.

DIFFERENTIAL EXPRESSION OF SYNAPTIC AND INTERNEURON GENES IN THE AGING HUMAN PREFRONTAL CORTEX

O5-04-06 DIFFERENTIAL EXPRESSION OF SYNAPTIC AND INTERNEURON GENES IN THE AGING HUMAN PREFRONTAL CORTEX Adith Mohan, Anbupalam Thalamuthu, Karen Mather, Yiru Zhang, Vibeke S. Catts, Cynthia S. Weickert, Perminder S. Sachdev, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New SouthWales, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia; School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, Australia; University of New South Wales, Sydney, Australia. Contact e-mail: a.mohan@unsw.edu.au