Mefloquine Use, Psychosis, and Violence: A Retinoid Toxicity Hypothesis.

Mefloquine use, psychosis, and violence: A retinoid toxicity hypothesis.

Med Sci Monit. 2013; 19: 579-83
Mawson A

Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects. HubMed – depression

A Model of Stimulus-Specific Adaptation in Neuromorphic Analog VLSI.

IEEE Trans Biomed Circuits Syst. 2011 Oct; 5(5): 413-9
Mill R, Sheik S, Indiveri G, Denham SL

Stimulus-specific adaptation (SSA) is a phenomenon observed in neural systems which occurs when the spike count elicited in a single neuron decreases with repetitions of the same stimulus, and recovers when a different stimulus is presented. SSA therefore effectively highlights rare events in stimulus sequences, and suppresses responses to repetitive ones. In this paper we present a model of SSA based on synaptic depression and describe its implementation in neuromorphic analog very-large-scale integration (VLSI). The hardware system is evaluated using biologically realistic spike trains with parameters chosen to reflect those of the stimuli used in physiological experiments. We examine the effect of input parameters and stimulus history upon SSA and show that the trends apparent in the results obtained in silico compare favorably with those observed in biological neurons. HubMed – depression

The ethics of providing hope in psychotherapy.

J Psychiatr Pract. 2013 Jul; 19(4): 316-22
Dembo JS, Clemens NA

The instillation of hope is a common factor in most psychotherapies. A considerable literature exists on the ethics of providing false or positively biased hope in non-psychiatric medical settings, and ethicists have generally concluded that this practice is unethical. However, the literature on the ethics of encouraging hope in psychotherapy, especially in the case of treatment-resistant mental illness, is sparse. The author explores two clinical cases with the intention of examining the nature of hope, false hope, positive illusions, and denial, as they relate to our definitions of mental health and psychotherapy. The cases highlight the ethics of balancing an acknowledgment of likely treatment futility with a desire to hope. Clinical psychological studies on depressive realism and optimistic bias indicate that some degree of positive bias, referred to by some authors as “the optimal margin of illusion,” is in fact necessary to promote what we define as “good mental health;” conversely, stark realism is correlated with mild to moderate depression. An examination of the existential literature, including Ernest Becker’s work, The Denial of Death, indicates that without the defense mechanism of denial, human beings tend to experience paralytic despair as a result of being fallible, mortal creatures in a frightening world. The combination of these diverse bodies of literature, along with the surprising outcomes of our case examples, leads to an unexpected conclusion: it may occasionally be ethical to encourage some degree of optimistic bias, and perhaps even positive illusion, when treating patients in psychotherapy. (Journal of Psychiatric Practice 2013;19:316-322). HubMed – depression