Jessica Bick Law
Abnormal Psych
10/7/18

Schizophrenia: Causes and Prognosis

The cause and origin of schizophrenia are not yet known. Scientists speculate that schizophrenia may have already been present in the population of homo sapiens who lived in Africa before they spread across the globe, but there may have been changes in our brains much earlier. There are thought to be two relevant stages of our cognitive evolution that may be relevant to the development of schizophrenia. The first occurred 2-16 million years ago when we developed specialized neural processing and complex connections adapted for social living. At this point our brain changed to allow it to mature for an extended length of time rather than solely in utero. This extended growth of the brain over the course of many years, while advantageous in terms of neuroplasticity, also opens the window for more genetic interactions and accidents. Schizophrenia may be one of the side effects of evolving complex cognitive and social abilities that are also learn during this time of growth.
The second turning point was 100,000 to 150,000 years ago when we left Africa. One theory is that schizophrenia lends people artistic and creative talent, making them unique thinkers and progressive leaders. Perhaps these people also contributed to the decision to move out of Africa. But the question remains: why wasn’t this disorder weeded out by natural selection? It is peculiar, given that schizophrenia seems to have to reproductive advantage. Some researchers suspect that our ancestors showed compassion towards those who were physically ill or suffering, because they have examined remains of warped, aged, and malformed bones in burial sites and this might mean that they would show the same compassion towards those who were mentally ill, to whom they were already emotionally attached when the disorder manifested itself. Today we know that the disorder appears in a recognizable manner across time and space, which suggests that schizophrenia is likely an ancient genetic malformation that spread with the spreading of humanity.
Schizophrenia is "a debilitating psychotic disorder in which individuals may hear voices or see images not seen by others, believe that others wish to harm or control them, believe that others wish to harm or control them, and bizarre thoughts" (Ray, 2015). It belongs to a class of disorders called "psychotic disorders that involve a loss of being in touch with reality and are characterized by abnormal thinking and sensory processes" (Ray, 2015). These symptoms tend to appear in adolescence or early adulthood. One theory suggests that because the human brain takes so long to mature, the process that results in schizophrenia is actually begun before birth. Moreover, there seems to be a link to poor treatment, stress, or trauma to the mother while pregnant and the development of schizophrenia later in life. This is the neurodevelopmental hypothesis. Weinberger (1987) suggested that problems during the second trimester lead to an incomplete development of the frontal lobes during adolescence, a time of great brain reorganization (Ray, 2015). Greater amounts of stress during childhood and early adolescence have also been noted as influential in the appearance of schizophrenia later in life.
	The genetic component of schizophrenia is as yet unclear. We have not discovered a specific gene or chromosome to blame, unlike Down syndrome. In fact, there is a wide variety of possible genetic variants and combinations thereof that might be at play. In an attempt to chase the genetic cause of this disorder, research has been done on monozygotic twins in both childhood and adulthood. There have been many instances in which one twin develops schizophrenia while the other twin remains healthy. One theory is that as genes are being produced there may be a slight variation in genes, called copy number variations, between twins. Next, differences in twins may be epigenetic, which suggests that internal and environmental factors both play a role in the appearance of schizophrenia (Ray, 2015). Finally, environmental factors may play a role that does not involve genetic changes. Evidence suggests, however, that the development of schizophrenia is by and large a result of nature over nurture. This is further supported by the fact that first-degree relatives of people with schizophrenia often show schizotypal traits, behaving similarly to their schizophrenic relatives on cognitive testing.
	The onset of schizophrenia can be dramatic. The positive symptoms of the disorder, those that appear as a detriment to the individual, include delusions, hallucinations, disordered thinking, and disorganized behavior. Delusions present as "beliefs without support for their occurrence and which are at odds with the individual's current environment" (Ray, 2015). Delusions are separated into three categories: persecution (believing someone is out to get you); grandeur (believing you are famous); and control (which can manifest as someone or some entity putting thoughts into one's mind, or that others can hear your thoughts) (Ray, 2015). Hallucinations are "sensory experiences that can involve any of the senses and that are at odds with the individual's current environment" (Ray, 2015). Both of these symptoms are usually severe at the onset of the disease and are what the public typically associates with this disorder.
	The negative symptoms, normal abilities lacking in an individual with the disorder, include "lack of affect in situations that call for it, poor motivation, and social withdrawal" (Ray, 2015). Some schizophrenics speak in word salad, which means that they use all random words in a recognizable cadence but they are unaware. Many suffer from depression and become suicidal or self harm. In some instances a schizophrenic person may become catatonic, unable to speak or move. They may exhibit avolition, alogia, or anhedonia. The more negative symptoms there are, the poorer the prognosis. However, with modern medicines and other treatments, many schizophrenics are able to lead relatively normal and healthy lives.
	Onset of schizophrenia occurs in late adolescence or young adulthood. In the premorbid phase there are only "subtle or nonspecific problems with cognition, motor, or social functioning; poor academic achievement and social functioning" (Ray, 2015). Then the individual moves into the prodromal phase, in which the initial symptoms appear alongside declining functioning. This is followed by the psychotic phase in which positive psychotic symptoms appear, and finally the stable phase in which there are fewer positive symptoms and an increase in negative ones; as well as stable cognitive and social deficits. Schizophrenics also experience earlier mortality than the general population. Many with this disorder become paranoid and believe they are in danger when they are not. Schizophrenics who exhibit symptoms of catatonia often appear "mannequin-like" with "waxy flexibility" (Ray, 2015). The disorder's onset in early adulthood shows "chronic and deteriorating progression and results in pervasive impairments in mental functions over the lifespan" (Ray, 2015).
	The term "dementia praecox" predated schizophrenia as the name for this set of signs and symptoms. There are four types of dementia praecox. First is the simple type which shows a slow decline along with social withdrawal and apathy. Second, a paranoid type, characterized by a fear of persecution. Third is hebephrenic, which has a mania-like presentation. And finally catatonia which refers to a lack of motion by the individual and a somewhat "waxy flexibility" (Ray, 2015). In 1911, Eugene Bleuler coined the name schizophrenia from the Greek "to split the mind" (Ray, 2015). He suggested that the disorder was not singular but rather a conglomerate of similar disorders. He focused on his "four A’s": affect, associations, ambivalence, and autism, meaning social aloofness and an inability to remain in contact with the external world (Ray, 2015). Since then schizophrenia has become accepted as its own distinct disorder.
	Currently there are several types of schizophrenia. The first is the paranoid subtype: "delusions whose themes generally center on ideas of grandiosity or persecution" (Ray, 2015). They might have disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect. The next subtype is called disorganized or hebephrenic schizophrenia, which is characterized by "disorganized speech patterns like word salad; little affect in serious situations; random silly responses; and no theme to delusions" (Ray, 2015). The catatonic subtype is characterized by non-normal activity of the motor system. In catatonia the individual will remain in a fixed position, even an unnatural one as when placed by another person. Some people in this subtype exhibit echolalia, or the repetition of another's speech, and echopraxia, a repetition of another's movements. The undifferentiated subtype is schizophrenia NOS, as it doesn't fit easily into one of the subtypical roles. Finally, there is the residual subtype, in which individuals have had episodic experiences with schizophrenia but no longer show positive symptoms like hallucinations and delusions.
	Researchers are now searching for endophenotypes. They look for minor physical abnormalities, including differences in head or body size or motor movements (Ray, 2015). These include neuro-motor abnormalities, like smooth pursuit eye movement. Schizophrenics display different eye patterns when following a finger back and forth across the field of vision. Instead of smooth eye movement a schizophrenic’s eye stutters and lags behind the finger. In the search for an explanation, researchers posited the membrane theory, which suggests that the normal metabolism in a healthy brain is disrupted in the brain of someone with schizophrenia, which we will return to. One advantage modern scientists have is access to advanced neuroimaging abilities. This has given us the ability to compare schizophrenic brains and the brains of healthy controls. What researchers discovered was that people with schizophrenia showed larger ventricles and greater gray matter loss in the parietal and frontal areas in children who developed schizophrenia before puberty than those who develop it in adulthood (Ray, 2015). There are four ventricles in the brain and they create cerebrospinal fluid. Because the ventricles appear larger in schizophrenics, one assumes that there is a decrease in the volume of the rest of the brain. This is the case and we find that schizophrenics have smaller frontotemporal cortices, ACC, and a smaller right insular cortex.
	There are five levels of analysis from the neuroscience perspective. The first is the anatomical changes such as loss of brain volume. The second are functional processes like the manner in which cortical areas and networks process information. The third are neural oscillations that underlie the cortical networks. And the fourth are the changes in neurotransmitters like dopamine, GABA, glycine and glutamate (Ray, 2015). Studies of schizophrenics show different activity in the dorsolateral pre-frontal cortex, the ACC, and the thalamus. Over time, schizophrenic brains show a reduction in white matter. One theory is that the neurons in schizophrenics are more densely packed than in the brains of healthy people. This suggests that neuropil, the filler between neurons, is reduced in those with schizophrenia. Another aspect of brain function that researchers studied was the role of the default mode network, which is the network we use when we daydream, for instance, when we let our mind wander. In healthy people greater suppression of the default mode network is associated with better task performance. Both people with schizophrenia and their first-degree relatives scored poorly in task related testing.
	The brain imaging also revealed that the sensory cortices plus prefrontal premotor, cingulate, subcortical, and cerebellar regions all contribute to hallucinations. Persons with schizophrenia also show less connectivity between frontal and temporal lobes. Neurotransmitters are also suspected to play a role in the progression of schizophrenia. The dopamine imbalance hypothesis suggests that dopamine neurons are overactive in schizophrenia in midbrain areas and underactive in higher cortical areas (Ray, 2015). There seems to be a direct connection between meds and dopamine receptors. Stress can exacerbate symptoms and increase activation of the hippocampus and an increase in dopamine activity. Creative ability, for which many schizophrenics are known, has been associated with dopamine functioning, especially in the thalamus. Others suggest that the neurotransmitters that regulate dopamine are to blame. This theory is supported by the fact that schizophrenics don’t have noticeably elevated levels of dopamine. Instead glutamate, an excitatory neurotransmitter, and GABA are involved in nearly all neuronal processes that engage the glutamate system. Blocked glutamate receptors are linked with psychosis. There are also disturbances in working memory, as seen in the WCST. Most interesting, is the schizophrenic’s response to the Charlie Chaplin mask test. From behind schizophrenics saw it as hollow while the average person saw the mask as convex. From this, scientists assume that schizophrenics showed more top-down processing, experiencing sensory stimuli as they are without any expectation of what they should be. People with schizophrenia also have a hard time connecting the emotions of others with the context of the situation.
	Today, schizophrenia can be treated if not cured. The first generation of antipsychotics were literal life savers, allowing people trapped in mental institutions and homes to exist in the world for the first time. The second generation of antipsychotics are generally not considered as effective as the first, and many of the first-generation antipsychotics are used frequently today. The prognosis for schizophrenia varies from person to person and depends on independent internal and external factors. Many people with schizophrenia live practically normal lives, as long as they have proper treatment and medication. The typical problem that doctors encounter is that people do not like to take their medication because of problematic side effects like weight gain or dulled thinking and lethargy. Unmedicated, this disorder can have devastating effects on one’s life. Unfortunately, until researchers find the source of schizophrenia precisely, we will have to rely on palliative treatment of the disorder.