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Scientists suggest new approach unravelling aetiology and possible reversal of complex psychiatric disorders

New Delhi: Aetiology of the complex psychiatric disorders remains elusive owing to unapproachability of intricate neural circuits in living human. Indian scientists have published a study in the journal ‘Neurology, Psychiatry and Brain Research’ proposing the possible use of an emerging advanced neuroscience research technique optogenetics in transgenic zebrafish model for understanding genesis, progression and possible reversal of various psychiatric disorders.

Inducing psychiatric disorders in transgenic zebrafish by optogenetic inactivation of descending habenular pathways. (Image source: Neurology, Psychiatry and Brain Research)
Inducing psychiatric disorders in transgenic zebrafish by optogenetic inactivation of descending habenular pathways. (Image source: Neurology, Psychiatry and Brain Research)

The collaborative research work, titled ‘Induction-reversal modelling of psychiatric disorders by functional manipulation of habenular pathways in zebrafish’, is authored by scientists from apex Indian medical research institutions such as All India Institute of Medical Sciences (AIIMS), New Delhi; the National Brain Research Centre (NBRC), Manesar; and Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry.

Optogenetics, an advance neuroscience research technique propagated by Karl Disseroth’s lab at Stanford University combines knowledge of optics and genetics to explore the function of specific neural circuits which may be functionally manipulated based on activation or inactivation of the specific ion channels in the targeted group of neurons by illumination of light.

The proposed model will lead to finding the basic solution regarding the complexity of psychiatric disorders, said Dr Ashutosh Kumar, Assistant Professor in Department of Anatomy, JIPMER (Karaikal), Pondicherry.

Further adding to the research outcomes, Dr Ashutosh Kumar explained that the optogenetics mediated inactivation of lateral subnucleus of dorsal habenular nuclei in transgenic zebrafish leads to freezing rather than flight response in fearful stimuli similar to indecisiveness shown by Post Traumatic Stress Disorder (PTSD) subjects facing acute stress.

Dysregulation of the emotional behaviour forms the base of psychiatric disorders like anxiety, depression, and PTSD hence functional manipulation of habenular nuclei and gradual increase and decrease in levels of stress may prove to be a basic model for induction and reversal of such psychiatric disorders.

Dr Muneeb Faiq, Dr Khursheed Raza and Dr Subramnyam Dantham from AIIMS Optogenetics Study Group said that this is the first of its kind study where a basic psychiatric disorder model using transgenic zebrafish and optogenetics has been proposed to unravel aetiology and possible reversal of complex psychiatric disorders with functional manipulation of specific neural circuits.

Vikas Pareek, Registered Pharmacist and PhD Scholar from NBRC, and Dr Khursheed Raza and Dr Pavan Kumar from AIIMS asserted that close anatomical and functional resemblance of the fish and human habenular neural circuits has led to the feasibility of a fish brain model for the complex human psychiatric disorders.

Habenula is an evolutionarily conserved bilateral brain structure having a major role in adaptive behaviour under aversive and fruitful conditions via regulation of brainstem aminergic neurotransmitters and neuromodulators. Optogenetic inactivation with the graded amount of stress in the lateral habenular descending pathway and medial habenular pathway may lead to two opposing character psychiatric disorders as mania and major depression, said the authors.

The conceptual basis of the hypothesis, as stated by the authors, has been that the psychiatric disorders aetiologically may be the stress adaptation response of the psychologically traumatized brain, and disease process may be reversed within unspecified limits with specialized interventional techniques and rehabilitation approaches.

The proposed theory may prove to be beneficial for translational research aimed to develop efficient therapeutic modules for complex psychiatric disorders.

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