Cerebrotendinous xanthomatosis (CTX) is a rare inborn disorder of sterol storage with autosomal recessive inheritance and a variable clinical presentation. We describe two siblings with an early psychiatric presentation of CTX-associated attention-deficit/hyperactivity disorder and oppositional defiant disorder, also associated with a mild intellectual disability and major behavioral impairments. In both cases, treatment with chenodeoxycholic acid improved externalized symptoms and a partial recovery of cognitive impairments was observed. This suggests that CTX is potentially reversible, demonstrating the need for early diagnosis and treatment of this disorder before irreversible neurological lesions can occur.

Medical education often presents new material as large data dumps at a single live event (lecture or symposium), in part because it is traditional, and also because this structure can be perceived as the most time efficient for busy clinicians and their teachers. However, modern learning theory and new insights from the neurobiological basis of long-term memory formation show that the format of single-event presentation of materials is not very effective. Rather, seeing the presentation of new materials over time, in bite-sized chunks, and then seeing them again at a later time, particularly as a test, leads to more retention of information than does learning the same amount of material as a large bolus in a single setting. This notion of learning over time, also called “interval learning” or “spaced learning,” is particularly well adapted to the Internet era. Here we describe an application of this concept to the learning of psychopharmacology over time in bite-sized and repeated portions structured as an “online fellowship” called the Master Psychopharmacology Program (www.neiglobal.com/mpptour).

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids.The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

True progress in understanding how experience arises from the brain has been relatively slow when viewed from a historical perspective. Recently, several technologies to study and stimulate the brain have been applied to this field of inquiry. Such progress was made only 2,500 years after the ancient Greek philosopher Parmenides first adopted a technical procedure involving the application of formal logic instruments to explore the perception of experiences.

At the phenomenological level, consciousness has been referred to as “what vanishes every night when we fall into dreamless sleep and reappears when we wake up or when we dream. It is also all we are and all we have: lose consciousness and, as far as you are concerned, your own self, and the entire world dissolves into nothingness”. According to the integrated information theory, consciousness is integrated information.

The term “consciousness” therefore has two key senses: wakefulness and awareness. Wakefulness is a state of consciousness distinguished from coma or sleep. Having one's eyes open is generally an indication of wakefulness and we usually assume that anyone who is awake will also be aware. Awareness implies not merely being conscious but also being conscious of something. The broad definition of consciousness includes a large range of processes that we normally regard as unconscious (eg, blindsight or priming by neglected or masked stimuli).

Both sleep and anesthesia are reversible states of eyes-closed unresponsiveness to environmental stimuli in which the individual lacks both wakefulness and awareness. In contrast to sleep, where sufficient stimulation will return the individual to wakefulness, even the most vigorous exogenous stimulation cannot produce awakening in a patient under an adequate level of general anesthesia.

A 60-year-old patient with a clinical diagnosis of schizophrenia underwent a magnetic resonance imaging (MRI) scan related to the evaluation of isolated seizures that emerged while medicated with clozapine. Unexpectedly, the MRI scan revealed evidence of asymmetric and enlarged cerebral ventricles that were interpreted as congenital in origin. The presence of both congenital lateral ventricular asymmetry and ventriculomegaly may interact to increase risk of schizophrenia. The history and clinical features, including cognitive testing, of the illustrative patient are presented.

Bipolar disorder with co-occurring attention-deficit/hyperactivity disorder (ADHD) is a challenge to treat. Ten previous reports have shown potential benefit of a micronutrient treatment (consisting mainly of vitamins and minerals) for various psychiatric symptoms, including mood and ADHD. This case study aimed to investigate the longer term impact of the micronutrients on both psychiatric and neurocognitive functioning in an off-on-off-on (ABAB) design with 1 year follow-up. A 21-year-old female with bipolar II disorder, ADHD, social anxiety, and panic disorder entered an open-label trial using a nutritional treatment following a documented 8 year history of ongoing psychiatric symptoms not well managed by medications. After 8 weeks on the formula she showed significant improvements in mood, anxiety, and hyperactivity/impulsivity. Blood test results remained normal after 8 weeks on the formula. She did not report any adverse side effects associated with the treatment. She then chose to come off the formula; after 8 weeks her depression scores returned to baseline, and anxiety and ADHD symptoms worsened. The formula was reintroduced, showing gradual improvement in all psychiatric symptoms. This case represents a naturalistic ABAB design showing on-off control of symptoms. After 1 year, the patient is now in remission from all mental illness. Neurocognitive changes mirrored behavioral changes, showing improved processing speed, consistency in response speed, and verbal memory. A placebo response and expectancy effects cannot be ruled out although previous poor response to treatment and the duration of the current positive response decrease the likelihood that other factors better explain change. These consistently positive outcomes alongside an absence of side effects indicate that further research, particularly larger and more controlled trials, is warranted using this multinutrient approach.

Modern formulations of psychiatric disorders hypothesize that mother nature goes awry, causing both genetic and epigenetic disease actions. Genetic disease actions are the consequences of naturally inherited risk genes that have an altered sequence of DNA. This altered DNA sequence theoretically leads to the production of altered gene products in neurons, causing inefficient information processing in various brain circuits, and biasing those circuits towards developing symptoms of a mental illness. Epigenetic disease actions are theorized either to activate risk genes to make an altered gene product or to activate normal genes to make normal gene products but at the wrong time. Epigenetic disease mechanisms theoretically turn normal genes into risk genes by causing normal genes to be expressed in neurons when these genes should be silenced or by causing normal genes to be silenced when they should be expressed.

Objectives: To investigate the current and lifetime frequency and severity of obsessive-compulsive (OC) symptom dimensions in Tourette syndrome (TS) patients, and how these dimensions affect clinical characteristics.

Methods: Forty TS outpatients (29 males, 11 females) were interviewed with the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), the Yale Global Tic Severity Scale (YGTSS), the Shapiro Tourette Syndrome Severity Scale, and the Global Assessment of Functioning (GAF).

Results: OC symptoms were present in 80% of the total sample. The miscellaneous and the symmetry dimensions were the most frequent at the “current” and “lifetime” surveys, respectively. The aggression dimension had the smallest difference between “worst ever” and current ratings among the all OC symptom dimensions. TS patients with the aggression dimension (n=7) had significantly lower scores in the GAF scale and higher frequencies of coprolalia. There were significant correlations between the YGTSS severity scores and specific DY-BOCS dimensions.

Conclusion: OC symptoms are frequent in TS subjects and there were differences in the frequency, severity, and course of the OC symptom dimensions. These results emphasize the need for future longitudinal studies using a dimensional approach for the evaluation of OC symptoms in tic disorders.

Introduction: Internet game overuse is an emerging disorder and features diminished impulse control and poor reward-processing. In an attempt to understand the neurobiological bases of Internet game overuse, we investigated the differences in regional cerebral glucose metabolism at resting state between young individuals with Internet game overuse and those with normal use using 18F-fluorodeoxyglucose positron emission tomography study.

Methods: Twenty right-handed male participants (9 normal users: 24.7±2.4 years of age, 11 overusers: 23.5±2.9 years of age) participated. A trait measure of impulsivity was also completed after scanning.

Results: Internet game overusers showed greater impulsiveness than the normal users and there was a positive correlation between the severity of Internet game overuse and impulsiveness. Imaging data showed that the overusers had increased glucose metabolism in the right middle orbitofrontal gyrus, left caudate nucleus, and right insula, and decreased metabolism in the bilateral postcentral gyrus, left precentrai gyrus, and bilateral occipital regions compared to normal users.

Conclusion: Internet game overuse may be associated with abnormal neurobiological mechanisms in the orbitofrontal cortex, striatum, and sensory regions, which are implicated in impulse control, reward processing, and somatic representation of previous experiences. Our results support the idea that Internet game overuse shares psychological and neural mechanisms with other types of impulse control disorders and substance/non-substance-related addiction.

The issues surrounding generic drug substitution in patients with epilepsy are complex.The substitution of one formulation of an antiepileptic drug (AED) for another is controversial. Well-reasoned and defensible cases can be made both for and against such substitution. Although regulatory agencies require that generic and proprietary drugs have similar pharmacokinetic bioequivalence data, their therapeutic efficacy may not necessarily be identical. The paroxysmal nature of epilepsy, the narrow therapeutic index of some AEDs, the need to. individualize therapy to achieve seizure control, and the negative consequences of uncontrolled epilepsy distinguishes epilepsy from other clinical conditions. Epilepsy management with AEDs requires careful dose titration and consistent drug exposure at the optimal level for each patient, which can be altered if a different formulation of the AED is substituted. Unexpected variability in plasma concentrations could occur when a patient who has been receiving one formulation of an AED (generic or brand) receives an alternate formulation.Thus, no substitutions should be made for people with epilepsy without the knowledge and approval of the prescribing physician. Patients should be consulted about the substitution, with all risks and benefits carefully explained.