Schizophrenia – The “psycho” disorder?!

Schizophrenia

What is Schizophrenia?

Schizophrenia is a complex brain disorder, with its pathogenesis in neurodevelopmental anomalies. The 5 domains of schizophrenia include:

  • Positive symptoms (delusions, hallucinations).
  • Negative symptoms.
  • Ubiquitous cognitive deficits
  • Motor symptoms (dyskinesias).
  • Deficits in social cognition, or socio-occupational functioning.
Negative Symptoms: 

Negative symptoms include blunted affect, alogia, avolition, asociality, amotivation, anhedonia, ideational constriction, apathy or inertia, and abulia.

  • Blunted affect: This refers to the decreased intensity and repertoire of emotional expressions.
  • Alogia: This refers to the paucity in the speech content that is evident in patients of schizophrenia.
  • Avolition: This refers to the deficits in initiation and maintenance of goal-directed behaviors.
  • Anhedonia: This is the decreased ability to experience and anticipate pleasure, or pleasurable emotions. Recent studies have pointed out that patients with schizophrenia have the ablility to enjoy the pleasurable experience. However, they display a lack of wanting to experience these pleasurable pursuits or enjoyable experiences. Consummatory hedonia is the ability to experience an emotion. Also, anticipatory hedonia is the want to experience a pleasurable pursuit. Patients with schizophrenia display anticipatory anhedonia. However, negative symptoms have not been unique to schizophrenia alone.
Classification of Negative Symptoms:

Deficits in the brain circuitry concerning reward (nucleus accumbens), motivation and pleasure are the reason for negative symptoms.

Negative symptoms are further classified into:

  • Enduring Primary Negative Symptoms: The enduring primary negative symptoms can consistently present over long periods of time, despite fluctuations in other aspects of the disease. These enduring primary negative symptoms constitute what is called the deficit syndrome in schizophrenia.
  • Transitory Secondary Negative Symptoms: Secondary negative symptoms can occur transitory in nature, fluctuate largely over the course of the illness, and abate with reduction in the other aspects of the disease.
What Causes Secondary Negative Symptoms?
  • These are secondary to positive symptoms. That is, if a patient hears voices commanding him not to venture out of his home, lest he is attacked by his arch nemesis, such an individual is bound to stay at home for the fear of being attacked. Such an individual will also limit his social interaction, and display paucity in his speech content. People mistake this for apathy and alogia. However, in fact it is a reflection of the aftermath of auditory hallucinations, a positive symptom.
  • Secondary negative symptoms are attributable to chronic social deprivation. This is evident in patients who are chronically institutionalized in asylums. Such long bouts of social isolation serve to remove all motivation in these individuals to interact with the outside world, especially at a time when they are overwhelmed by their illness, and are unable to integrate their inner perceptual experiences. Chronic institutionalization comes across as a severely under-stimulating environment. 
  • Lastly secondary negative symptoms may be due to medications themselves. In medical terms, it is called neuroleptic-induced dysphoria. The medications which are used to treat a psychotic breakdown cause a reduction in the levels of the happy hormone serotonin, and this may produce a depression like picture. However, this is not to be confused with the post-psychotic depression that is commonly seen after a psychotic episode. Although the treatment does not differ in both these scenarios, recognition of the individual clinical scenario has important prognostic ramifications. In theory, risk of exacerbation of the psychotic symptoms exists, when the post-psychotic depression is treated with antidepressants.
Deficit Syndrome:
  • Indeed, deficit syndrome or a clustering of these negative symptoms entails a poor quality of life, and impaired socio-occupational functioning.
  • Subsequently, individuals become unproductive, and lead a life of social isolation and deprivation.
  • The motivation to go out and do something beautiful, achieve a target, strive towards betterment of oneself diminishes and stops. Also, work towards a greater good of one’s community, all day to day goals in the lives of a regular individual, cease to exist.
Degree of Future Negative Symptoms:
  • Firstly, Among the strongest predictors of the degree of future negative symptoms is Duration of Untreated Psychosis, or DUP.
  • Thus, DUP refers to the time lag between the appearance of the first psychotic symptoms, and the treatment sought for these symptoms.
  • However, greater the duration of the untreated psychosis, greater is the future occurence of negative symptoms and cognitive deficits.
  • Indeed, an individual with a substantial cognitive reserve offers some protection against the cognitive deficits in schizophrenia, and dementia.
  • Since the nature of these cognitive deficits is ubiquitous, these may be evident as early as the prodromal phase of schizophrenia.
  • Indeed, greater the volume of grey matter loss, greater is the cognitive deficit syndrome. Also, greater the duration of untreated psychosis, greater is the grey matter volume loss.

Treatment:

Factoring in all these points, it becomes imperative to seek comprehensive professional psychiatric help early in the course of the illness. The prodromal phase of schizophrenia presents with memory disturbances, vague anxiety and depressive symptoms, progressive social withdrawal, before the positive symptoms set in. This prodrome can last as long as 5 years before the onset of core psychotic symptoms, like delusions and hallucinations.

Management of Negative Symptoms:
Non-pharmacological Management:
  1. Psychosocial interventions: Indeed, this is as important as psychopharmacological interventions. Thus, forming support groups, and meeting at regular intervals of these groups is important. Nevertheless, these group meetings give voice to individual experiences and problems. So, thereapists give encouragement to client participation. Assessment is done of the progress so far. Therapists also ascertain the goals for the future.
  2. Cognitive Behavioral Therapy (CBT): Therapists aid the clients in recognizing cognitive distortions. Subsequently, they help in unlearning older maladaptive behaviors, and focusing on learning newer adaptive ones. Individualized therapy is suitable. Because, there is no one-size-fits-all treatment. Studies consistently show that individual therapy is better than group therapy in the treatment of negative symptoms.
  3. Cognitive remediation therapy for cognitive deficits: This includes pencil-paper tasks, sudoku, crossword, computer exercises. Therapists tailor some of the exercises to focus on deficits in individual domains like attention, speed of thought processing, verbal working memory, reasoning, and social cognition.
  4. Others: Thus, aerobic exercises help in neurogenesis, synaptogenesis, and modulate neuroplasticity. 
Pharmacological Management:
  1. In fact, Amisulpiride and Fluoxetine treat the negative symptoms. Amisulpride increases levels of the hormone prolactin in the long run. Hyperprolactinaemia can set the precedent for osteoporosis.
  2. However, recent studies have shown that Clozapine has the highest level of evidence in the management of negative symptoms.  With Clozapine, the improvements can be visible even after 6 months of initiation of treatment. 
  3. Moreover, Clozapine trial requires regular monitoring of the White Blood Cell counts, and causes constipation, weight gain, salivation, postural hypotension, and palpitations as common side effects.

Brain Stimulation Techniques:

  1. Transcranial Magnetic Stimulation (TMS). Firstly, TMS of the dorsolateral prefrontal cortex (DLPFC) has proven to be very effective in the treatment of negative symptoms.
  2. Electroconvulsive therapy (ECT). However, it is not as effective for negative symptoms, as it is for depression and positive symptoms.

Novel Treatment Approaches:

  • Emerging molecular targets – These include GABAergic modulation, targeting oxytocin receptors (implicated in the social cognition deficits in schizophrenia, along with mirror neurons). Also, countering neuroinflammation by using cyclo-oxygenase inhibitors like Rofecoxib. Others include – NMDA (N-Methyl-D-Aspartate) antagonists like Memantine, Glycine-reuptake inhibitors like Bitopetrin, and Metabotropic Glutamate Receptor 2/3 agonists like Pomaglumetad. Memantine, Bitopetrin and Pomaglumetad come under the purview of glutamatergic modulation.

There is definitely hope for those afflicted with the deficit syndrome, with researchers identifying a plethora of molecular targets.

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