By: Biftu Saleh

Schizophrenia is the most common psychiatric illness, affecting 0.1-1.7% of the global population. The age of onset is typexternal image flaws_l.gifically in the late teens/ early adulthood with equal prevalence rates observed among men and women. Schizophrenia consists of a mixture of symptoms commonly divided into two major categories, positive and negative. Positive symptoms refer to symptoms that are present in excess of normal function, such as the development of psychosis that can cause people to lose touch with reality. Negative symptoms reflect the loss of normal function and affect, such as chronic apathy and reduced speech productivity. Beyond the negative and positive symptoms, schizophrenia can include three other symptom dimensions: cognitive symptoms (poor attention, impaired executive functioning), affective symptoms (mood disorders) and aggressive symptoms (verbal or physical violence). Taken together, these symptoms can result in significant real-world disabilities in everyday life.

1. Epidemiology


Prevalence

According to the World Health Organization, schizophrenia affects about 24 million people worldwide, which translates to a global prevalence rate of 0.1-1.7%[1] . However, due to demographic variation such as migration and age-specific mortality, certain populations diverge from these crude prevalence estimates. Populations in the United States, Sweden, Finland and Croatia have reported unusually high rates of Schizophrenia (2-3 times the regional or national rate)[2] . On the other hand, prevalence decreases from 2.1 to 1.4 per 1000 people have been observed for human groups in Hong Kong, Taiwan and Indonesia[2] . Although the cross-cultural prevalence rates of schizophrenia vary from the central tendency suggested by the World Health Organization, compared to other multifactorial diseases like heart disease and diabetes, the magnitude of deviation is small.

Incidence

Unlike prevalence that indicates the number of people who have schizophrenia at a given time, incidence expresses the amount of people newly diagnosed with schizophrenia during a distinct time period. Although the disorder is relatively rare, schizophrenia is found in virtually every society worldwide, with incidence rates typically ranging from 0.1 to 0.4 per 1000 people[3] . The incidence of schizophrenia is relatively the same across different geographic areas. However, substantial research has shown that the incidence of schizophrenia has prominent variations according to sex, ethnicity, migrant status and month of birth. Systematic meta-analyses have revealed that the incidence of schizophrenia is significantly higher in men than in women[4] . A recently published meta-analysis study of the incidence of schizophrenia found elevated rates in ethnic minority groups (various Caribbean, African and South Asian populations were examined) compared to a baseline British population[5] . Several studies have shown that migrants have a significantly increased risk of developing schizophrenia compared to non-migrants[6] . Further, individuals born in the winter or spring months have a significantly higher risk of developing schizophrenia in comparison to people born in other months[7] . It is important to note that these estimations depend on how accurately the time of onset can be determined. A good approximation of the onset of schizophrenia is usually provided by the first contact with medical care, where clinical symptoms become evident for the first time.

Age of Onset and Gender Differences

The symptoms of schizophrenia typically start to show in late adolescence/early adulthood, between the ages of 15 and 25. Childhood-onset schizophrenia (diagnosed before 10 years of age) and late-onset schizophrenia (diagnosed after the age of 45) are generally quite rare. Although equal prevalence rates are observed for men and women, gender differences arise when the age of onset is examined; the average age of onset is 18 for
Figure 1. Age at onset distribution of schizophrenia.
Figure 1. Age at onset distribution of schizophrenia.

men and 25 for women (figure 1)[8] . A study conducted on Chinese inpatients with schizophrenia found that the onset of the disorder occurred at a significantly earlier age in male patients compared to their female counterparts and that late-onset schizophrenia was considerably more common in female patients[9] . They suggested that the difference in onset is associated with the fact that men are generally referred for medical treatment at an earlier age than women. Notable gender differences are also observed in symptomology; males and females show different patterns of symptoms and degree of symptom severity. The paranoid subtype of schizophrenia was found to be less frequent in male patients, while female patients were more likely to have severe and persistent positive and affective symptoms, and a greater number of suicide attempts[9].

2. Positive Symptoms


Hallucinations

In simple terms, hallucinations can be defined as the experience of perceiving stimuli that are not present in the physical environment. Hallucinations can occur in any sensory modality- auditory, visual, olfactory, gustatory and tactile, but the most common and characteristic hallucination type in schizophrenia are auditory in nature.
Auditory hallucinations (perceiving speech without auditory stimuli) have received considerable attention in schizophrenia research. Many neuroimaging techniques have been used to study the patterns of neural activity and the brain areas involved in auditory hallucinations. Shergill at al. (2000) used functional magnetic resonance imaging (fMRI) to measure brain responses and found that auditory hallucinations were associated with activity in the inferior frontal gyrus/insula, the posterior parietal cortex, the anterior cingulate gyrus, the left hippocampus and the parahippocampal cortex[10] . Other studies have focused on identifying why auditory hallucinations occur. Past research suggests that patients with schizophrenia who report experiencing auditory hallucinations misidentify their own speech as coming from someone else. Mechelli et al. (2007) hypothesized that this misattribution was due to impaired functional integration within neuronal networks involved in the evaluation of speech. Their sample pool consisted of 11 schizophrenia patients with auditory hallucinations, 10 schizophrenia patients without auditory hallucinations and 10 healthy controls. They used fMRI to measure brain activity while participants judged whether stimulus words were spoken in their own voice (self) or another person’s voice (alien). Lastly, the quality of the presented stimuli were manipulated to be distorted or undistorted. Results show that the connection from the left superior temporal cortex to the anterior cingulate was greatly impaired in schizophrenia patients with auditory hallucinations compared to healthy controls and patients without auditory hallucinations[11] . In comparison with the other two groups, schizophrenia patients with auditory hallucinations made more misattribution errors when they heard their own distorted voice[11] . These findings shed some light on the underlying mechanisms involved in auditory hallucinations.
The second most common type of hallucination in schizophrenia is visual which involve seeing things that are not really there. Schizophrenic patients who experience visual hallucinations report that the images seen range from being very clear and vivid to sometimes vague or distorted[12] . Higher rates of visual hallucinations, which have been associated with greater clinical impairment and reduced overall brain functioning, are observed among patients with childhood-onset schizophrenia[13] .
Other types of hallucinations, occurring much less frequently than the previous two, involve smelling (olfactory), feeling (tactile) or even tasting (gustatory) things that have no basis in reality.

Delusions

Delusions are a set of beliefs that usually involve a misinterpretation of perceptions or experiences. They are firmly held ideas that are unaffected by reason or rational argumentation. Similarly to hallucinations, delusions can be further divided into numerous categories. Delusional subtypes include persecutory, referential, religious, somatic and grandiose.
The most common delusional theme in schizophrenia is persecutory in which patients believe that someone or something is out to get them. Past research shows that schizophrenia patients with persecutory delusions demonstrate increased attention to threat and reduced evaluation of information during decision-making in ambiguous situations[14] . Philips et al. (2000) used visual scanning measurements to locate where schizophrenic patients with and without persecutory delusions and healthy controls directed their attention in different scenarios. Participants were presented with scenes displaying neutral, ambiguous or overtly threatening activity. In comparison to the other two groups, patients with persecutory delusions showed decreased evaluation of information within all three scenes[14] . Moreover, for the ambiguous scenes, schizophrenics with persecutory delusions displayed a different viewing strategy; they paid more attention to the less threatening areas. This study showed that schizophrenia patients with persecutory delusions exhibited biased processing of contextual information in certain situations, which may contribute to them perceiving threat in inappropriate places[14] . Further, patients with schizophrenia who exhibit persecutory delusions judge the trustworthiness of unfamiliar faces in very different ways when compared to healthy controls: they tend to rely less on conventional social cues[15] .
Schizophrenia patients with referential delusions harbor the erroneous belief that random events in the world refer to them directly or have a personal significance to them[16] . For example, people who exhibit referential delusions may believe that people on a subway train are talking specifically about them or looking specifically at them. Patients who exhibit religious delusions may seriously believe that they are a prophet, or even God. Case studies have shown that religiously deluded patients have acted upon biblical statements relating to plucking out offending eyes or cutting off offending limbs[17] . Compared to other patients with schizophrenia, those with religious delusions had more severe symptoms, functioned less well and were prescribed more medication[18] . Other types of delusions observed less frequently in schizophrenia include somatic delusions (false beliefs about one’s body) and grandiose delusions (inflated beliefs pertaining to one’s worth, knowledge, wealth or power)[19] .

3. Negative Symptoms


Alogia

Among the diversity of negative symptoms found in schizophrenia, language related deficits are relatively common. Alogia refers to restrictions in fluency and productivity of thought and speech[20] . A schizophrenic patient with this dysfunction in communication may exhibit impoverished content of speech, incoherent language, increased latency when responding, and may use fewer words and nonverbal responses. A study by Sumiyoshi et al. (2005) investigated the relationship between semantic memory and alogia in Japanese patients with schizophrenia. Their results showed a greater amount of semantic structure disorganization and bizarre incoherence in schizophrenic patients with alogia compared to those without alogia[21] . Their findings indicate that semantic memory disorganization may play a substantial role in producing the symptoms of alogia.


Anhedonia

Anhedonia refers to a general reduction in the ability to experience pleasure. In schizophrenia, anhedonia in characterized by the flattening of emotions, poor eye contact, lack of reactivity to normally pleasurable stimuli and psychomotor retardation[22] . Ritsner et al. (2011) conducted a longitudinal study to examine the effects of physical and social anhedonia on health-related quality of life. They found a strong association between physical and social hedonic deficits and poor quality of life (this association remained significant even when they controlled for the adverse psychological effects and symptoms of schizophrenia)[22] . This study suggests that treatment options should also focus on improving social and physical hedonism to enhance the overall well-being of patients with schizophrenia. In terms of neurological mechanisms, studies show that dopaminergic dysfunction in the brain’s reward centres underlies the expression of anhedonia in patients with schizophrenia[23] .

Avolution

Avolition involves restrictions in initiation of goal-directed behavior such as reduced desire, motivation or persistence[20] . This is closely related to apathy which is a state of indifference or lack of interest. A recent study by Konstantakopoulos et al. (2011) explored the link between apathy, cognitive deficits and psychosocial functioning in patients with schizophrenia. It was found that apathy was strongly associated with decreased performance on executive tasks and was a strong predictor of psychosocial functioning in patients with schizophrenia[24] .

Social Deficits

Patients with schizophrenia often exhibit reduced social drive and interaction. They may display little sexual interest, little time spent with friends, or may even withdraw from social relationships completely. Mueser et al. (1991) examined the prevalence of social skill deficits in schizophrenia patients using a role playing test. After one year, a follow-up assessment was conducted and they found that most patients remained socially impaired, with common deficits arising in assertiveness and conversation initiation[25] . In terms of social cognition, patients with schizophrenia demonstrate impaired functioning in two key domains: mentalizing/theory of mind (ability to understand the mental states of others) and sense of agency (feeling responsible for causing an action). A breakdown in sense of agency causes patients to attribute their own actions to external sources, while impairments in mentalizing result in an inability to understand and predict others’ behaviour[26] .

4. Cognitive Symptoms


external image schizophrenia.gifInformation processing, attention, working verbal memory and executive control are all cognitive elements that are severely impaired or dysfunctional in schizophrenia[27] . Disorganized thought processes such as thought insertion (belief that thoughts from other people have been inserted into one's mind), thought withdrawal (belief that thoughts have been removed from one's mind by an external source) and thought broadcasting (belief that one's thoughts can be heard by others) are all common problems in schizophrenia. Further, as a group, patients with schizophrenia have lower Intelligence Quotient (IQ) scores[28] .

Impaired Attention

One of the most significant cognitive deficits observed in schizophrenia is impaired attention. Schizophrenic patients with attentional problems show high levels of distractibility, constant intruding ideas and repetitive mind wandering[28] . Even before experiencing their first psychotic episode, individuals who are genetically predisposed to develop schizophrenia display attentional deficits, such as inability to focus on tasks or maintain attention[29] .

Working Memory

Working memory is defined as the ability to maintain and manipulate information[28] . Verbal working memory allows people to remember what they hear or read so they can use that information immediately or transfer it to long-term memory. This ability is impaired in patients with schizophrenia so they perform very poorly on word list recall or digits spans tasks that test verbal working memory[28] . Spatial working memory deficits are also seen in patients with schizophrenia; they perform poorly on tasks that require people to maintain the spatial position of visual information while performing other activities[30] . Without the ability to encode and arrange information in logical and coherent ways, patients with schizophrenia experience substantial complications in situations that require paying attention to multiple types of information at once.

Executive Function

Executive function impairment embodies deficits in a wide range of cognitive processes. Schizophrenia patients experience difficulties in verbal reasoning, planning activities, solving problems, initiating and inhibiting actions, multitasking and mental flexibility[28] . One of the best predictors for functional performance in everyday life is provided by executive function tasks. Impairments in executive functioning can cause schizophrenics to show less commitment and engagement in therapy, leading to lower treatment success[31] . Furthermore, the degree of self-care, the amount of social relationships and occupational functions are all associated with the level of executive functioning[32] .

5. Other Symptoms


Affective Symptoms

Emotional response deficits occur frequently in schizophrenia. Empirical findings show that schizophrenic individuals display less emotional expression (both facially and vocally) when reacting to stimuli in the environment[33] . Although the research states that patients with schizophrenia are less emotionally expressive, no significant differences were found between schizophrenics and healthy controls in terms of reported emotional experience[34] . Tsoi et al. (2008) conducted a study to examine facial emotion recognition in schizophrenia. They found that patients with schizophrenia showed diminished sensitivity in recognizing happy faces, but not faces that displayed fear or sadness[35] . Moreover, schizophrenics were more likely to rate any facial emotion as expressing fear or sadness. These findings suggest that patients with schizophrenia have a specialized deficit involving the recognition of happy faces[35] . In terms of affective disorders, depression is significantly associated with chronic schizophrenia. Studies have shown that people with acute schizophrenia present high levels of self-depreciation, while hopelessness was the most characteristic depressive symptom in chronic schizophrenia[36] . These findings show that a longer duration of schizophrenia is a major risk factor for depression.

Aggressive Symptoms

Patients with schizophrenia may exhibit violent or aggressive actions. Such acts tend to occur in conjunction with hallucinations, delusions or disorganized thoughts and may be triggered by high stress levels and consuming inappropriate amounts of antipsychotic medication[37] . A schizophrenic patient may appear highly irritable, verbally abusive or even physically assaultive. Although no studies have directly shown that mental illness is a risk factor for violence, empirical evidence suggests that individuals of the male gender, younger age and lower socio-economic combined with severe psychotic symptoms and comorbid substance abuse have a significantly increased risk for violence and aggressive behaviour[38] .


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