BIOLOGY :MANAGEMENT OF MENTAL DISORDERS






Mechanism of normal personality

Each human behaves differently ,has a unique personality. However it is wrong to consider animals as without unique behaviour. This is so because though animals lack speech and abstract thinking ,behaviour is determined in the brain by very ancient neural networks present in all higher animals.

   The Amygdala is an ancient network present in all mammals. It along with a few other centres in striatum determine all emotion and motivation behaviour.Emotions consist of detection neurons which detect contexts and associate them with favourable or unfavourable actions which are programmed.. Thus fear producing contexts need to be conditioned to painfull stimuli and must be aligned with withdrawal action. This conditioning circuit exists in amygdala at birth but the contexts are gradually built up by perception action cycles. Apart from fear animals have emotions of rage/ anger,frustration,exploration where appropriate contexts need to be aligned with an emotional action. 

   The hippocampus creates memory of events and later transfers them to DLPFC. Amygdala emotions condition memory of events to particular emotions. Thus a car accident leads to pain . The car is linked to memory of the painfull event thereafter leading to fear of travelling by a car.

   The memory ,coloured by emotions are sent to DLPFC which is the working memory. It is alo sent to medial PFC which is a default network. Both these networks can alter the sequence of events and create new plans . However the medial PFC unique to humans can do counter factual thinking mentally / offline. The thinking in medial PFC allows development of theory of mind,self concept,meta cognition,understanding social rules.It can use language and symbolic thinking in addition to visual thinking.Thinking involves similarity detection ,comparison, goal achievement ,all present in working memory.Since events sent to working memory is already coloured by emotions ,thinking gets influenced and follows the leads sent by amygdala. However stored memory,episodic or semantic can alter events sent by amygdala. Then the amygdala is inhibited and alternative action to the emotional reaction is taken.

Types of normal personality

In humans individual differences can occur in various networks which cooperate in forming personality.

Extroversion/ introversion:This is a function of amygdala,and higher control centre. It is responsible for the emotion of assertiveness/ submission.Neuroticism: Again it is a function of amygdala and stress system of HPA axis. It is responsible for the emotions of irritability/ anger ,anxiety/ depressionConscientiousness: This is an executive function controlled by DLPFC . It leads to self regulation or impulsivity.The basis is inhibitory control by DLPFCAgreeableness: This is a function of medial PFC network responsible for social control of behaviour.It leads to social adjustments.Openness/ intellect: Intelligence is a function of working memory along with attention network

Individuals differ in the bias or responsiveness of individual networks .This results in varied performance in agreeableness ,intellect, neuroticism and so on. Personality is usually determined at birth and is called temperament . The temperament is the result of individual bias in networks concerned with amygdala, medial PFC, Hippocampus. Neuronal network development is unique as there are numerous types of them and each type requires a different cellular protein architecture. The neurons are unique in the types of neurotransmitters and their synaptic receptors. These neurotransmitter and proteins production are regulated by GTP Control protiens which assemble synthetic and secretory pathways within the neurons. Alteration in Gprotiens lead to insufficient or over secretion of neurotransmitters.

   Abnormal G protien and neurotransmitter synthesis  is in turn under gene control. Neuronal DNA synthesise  RNA which undergoes post transcription epigenetic modification by RNA splicing. This leads to production of multiple proteins from a single RNA molecule and allows wide variation in protien specificity in different neuronal types. The DNA mutations may thus lead to wide difference in protien production in different neuronal types.

Abnormal personality and Mental disorders

Alterations in Gprotiens in neutrotransmitters and receptors numbers can lead to abnormal personality and mental illness if more severe.If receptors are less in number the the network is hypo responsive. However alterations in inhibitory neurotransmitter may lead to hyperactivity. 

Dependant personality:Here amygdala has hypersensitivity to abandonment. This influences hippocampus events. The medial PFC  has altered self perception and altered reward centre of compulsive seeking of approval.Narcissistic personality: Amygdala is hyper vigilant to negative criticism,Medial PFC has altered self perception with viewing self as grandiose.In insula there is altered empathy and social awareness. Antisocial personality disorder:Amydala has altered perception of empathy ,medial PFChas altered self conception with self as always correct. Borderline personality disorder: Amygdala hyper reactive to fear  and medial PFC has altered self conception of emotions.Autism: There is failure of face recognition in amygdala and fusiform face area. Medial PFC has altered self awareness leading to abnormal theory of mind. Anxiety - depression: Amygdala is over reactive to fear ,depressive or anxiety cues. Medial PFC has altered self with loss of pain or pleasure response,solitary living,apathy. Schizophrenia: There is a failure to detect self thoughts from external strategies. Internal thoughts are externalised as delusions or hallucinations.There may be abnormalities in insula leading to failure of corollary discharge required to cancel self actions and thought.Mania: Hyperreactive hippocampus leads to selection of memories which may be pleasurable or depressive. The selection of fearfull events can lead to a stress response of increased adrenaline or dopamine. It causes altered thoughts and aggression acutely.

  Obsessive compulsive disorder: Cingulate gyros detects error in actions and thought. If it is altered theorbitofrontal  cortex initiated reward actions continue without inhibition by medial PFC..ADHD: Here again failure of cingulate gyrus  to detect error magnitude leads to preference for immediate rewards . This loss of impulse control affects medial PFC and DLPFC leading to impulsive thinking

Management of personality and mental disorders

The pharmacological treatment of mental disorders and severe personality disorders is based on altering the neurotransmitter availability or their inhibition. This occurs at the level of PFC striatum loops. Whenever there is a mismatch in Perception  action cycle the reward error is detected by midbrain neurons which secrete dopamine to change the association of event and action. However the altered neuronal networks though causing errors in emotion,social actions are not detected due to change in bias in the networks, If dopamine is supplied externally the error is detected in altered reward to emotions or social actions . Similarly serotonin alters the magnitude of rewards in corticostriatal basal loops. The drug’s do not act by neurotransmitter receptor inhibition but by changing receptor numbers in neurons.

   In schizophrenia to treat acute delusions dopamine inhibitors are used to inhibit defective thought at striatal level. In chronic apathetic stage with altered thought serotonin uptake inhibitors are used to increase serotonin related reward to the striatum.In depression  again serotonin uptake inhibitors are effective in increasing reward quantity at striatum level . In anxiety disorders GABA nergic receptors responsible for inhibitory activity.These are specifically activated by benzodiazepines.

Ack: Dorsolateral prefrontal cortex; Cognitive biases in health and psychiatric disorders;Handbook of personality development; The psychology of thinking; The construction of the self;Disorders of personality; Disordered mind and brain; The neurobiology of mental illness

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