Ch.13, Schizophrenic Disorders Flashcards
Psychosis
the hallmark of schizophrenia is a significant loss of contact with reality,
John Haslam and schizophrenia/ démence précoce
The first detailed clinical description of what we now recognize to be schizophrenia was offered in 1810 by John Haslam, the apothecary at the Bethlem Hospital in London, England. Haslam described the case of a patient who appears to have suffered from a variety of symptoms—including delusions—that are typical of schizophrenia
=(mental deterioration at an early age) to describe the condition and to distinguish it from the dementing disorders associated with old age.
Emil Kraepelin and schizophrenia
Emil Kraepelin (1856–1926) who is best known for his careful description of what we now regard as schizophrenia. Kraepelin used the Latin version of Morel’s term (dementia praecox) to refer to a group of conditions that all seemed to feature mental deterioration beginning early in life
-Kraepelin also noted that the disorder was characterized by hallucinations, apathy and indifference, withdrawn behavior, and an incapacity for regular work.
Eugen Bleuler and schizophrenic diagnostics
Bleuler used schizophrenia (from the Greek roots of schizo, meaning “to split or crack,” and phren, meaning “mind”) because he believed the condition was characterized primarily by disorganization of thought processes, a lack of coherence between thought and emotion, and an inward orientation away (split off) from reality. Although the term is often thought to reflect a “Jekyll and Hyde” split personality, this is a major misconception. The splitting does not refer to multiple personalities (an entirely different form of disorder, now called dissociative identity disorder). Instead, in schizophrenia there is a split within the intellect, between the intellect and emotion, and between the intellect and external reality.
men vs women and age onset schizophrenia
The characteristic age of onset of schizophrenia differs in men and women. In men, there is a peak in new cases of schizophrenia between ages 20 and 24. The incidence of schizophrenia in women peaks during the same age period, but the peak is less marked than it is for men (see Figure 13.1). After about age 35, the number of men developing schizophrenia falls markedly, whereas the number of women developing schizophrenia does not. Instead, there is a second rise in new cases that begins around age 40, as well as a third spike in onset that occurs when women are in their early sixties
-males also tend to have a more severe form of schizophrenia (Leung & Chue, 2000). Brain-imaging studies show that schizophrenia-related anomalies of brain structure (discussed later) are more severe in male patients than they are in female patients. Gender-related differences in illness severity may also explain why schizophrenia is more common in males than it is in females. The male-to-female ratio is 1.4:1. So for every three men who develop the disorder, only two women do so
=f women have a less severe form of schizophrenia, and if they also have more symptoms of depression (see Leung & Chue, 2000), they may either not be diagnosed at all or else be diagnosed with other disorders, thus giving rise to the sex ratio imbalance.
What might explain the better clinical outcome of women with schizophrenia?
t female sex hormones play some protective role. When estrogen levels are low (as is true premenstrually) or are falling, psychotic symptoms in women with schizophrenia often get worse (Bergemann et al., 2007). The protective effect of estrogen may therefore help explain both the delayed onset of schizophrenia and the more favorable clinical course of the disorder in females. Declining levels of estrogen around menopause might also explain why late-onset schizophrenia is much more likely to strike women than men. There is some evidence that this late-onset pattern in women is associated with a more severe clinical presentation
Delusions
A delusion is essentially an erroneous belief that is fixed and firmly held despite clear contradictory evidence. The word delusion comes from the Latin verb ludere, which means “to play.” In essence, tricks are played on the mind. People with delusions believe things that others who share their social, religious, and cultural backgrounds do not believe. A delusion therefore involves a disturbance in the content of thought. Not all people who have delusions suffer from schizophrenia. However, delusions are common in schizophrenia, occurring in more than 90 percent of patients at some time during their illness
Prominent themes in delusions (made impulses, thought broadcasting, thought insertion, thought withdrawal, delusions of reference, delusions of bodily changes)
certain types of delusions or false beliefs are quite characteristic. Prominent among these are beliefs that one’s thoughts, feelings, or actions are being controlled by external agents (made feelings or impulses), that one’s private thoughts are being broadcast indiscriminately to others (thought broadcasting), that thoughts are being inserted into one’s brain by some external agency (thought insertion), or that some external agency has robbed one of one’s thoughts (thought withdrawal).
delusions of reference, where some neutral environmental event (such as a television program or a song on the radio) is believed to have special and personal meaning intended only for the person. Other strange propositions, including delusions of bodily changes (e.g., bowels do not work) or removal of organs, are also not uncommon.
delusions of reference, where some neutral environmental event (such as a television program or a song on the radio) is believed to have special and personal meaning intended only for the person. Other strange propositions, including delusions of bodily changes (e.g., bowels do not work) or removal of organs, are also not uncommon.
. However, delusions are common in schizophrenia, occurring in more than 90 percent of patients at some time during their illness (Cutting, 1995). In schizophrenia, certain types of delusions or false beliefs are quite characteristic. Prominent among these are beliefs that one’s thoughts, feelings, or actions are being controlled by external agents (made feelings or impulses), that one’s private thoughts are being broadcast indiscriminately to others (thought broadcasting), that thoughts are being inserted into one’s brain by some external agency (thought insertion), or that some external agency has robbed one of one’s thoughts (thought withdrawal). Also common are delusions of reference, where some neutral environmental event (such as a television program or a song on the radio) is believed to have special and personal meaning intended only for the person. Other strange propositions, including delusions of bodily changes (e.g., bowels do not work) or removal of organs, are also not uncommon.
hallucination i
sensory experience that seems real to the person having it, but occurs in the absence of any external perceptual stimulus. This is quite different from an illusion, which is a misperception of a stimulus that actually exists. The word comes from the Latin verb hallucinate or allucinere, meaning to “wander in mind” or “idle talk.”
-Hallucinations can occur in any sensory modality (auditory, visual, olfactory, tactile, or gustatory). However, auditory hallucinations (e.g., hearing voices) are by far the most common.
Caffeine consumption/stress and elicitin g hallucinations
s, the combination of high caffeine consumption and high stress can render normal people vulnerable to auditory hallucinations. Caffeine is known to increase how much cortisol is produced in response to a stressor. Caffeine consumption has also been found to correlate with hallucination proneness in other studies of healthy people (Jones & Fernyhough, 2009). It is also important to note that patients with schizophrenia typically drink a great deal of coffee. During times of high stress, this might perhaps increase their risk of having an exacerbation in hallucinatory symptoms.
neuroimaging data/ Are patients who are hallucinating really hearing voices?
Neuroimaging studies that compare hallucinating patients with nonhallucinating patients suggest that patients with speech hallucinations have a reduction in brain (gray matter) volume in the left hemisphere auditory and speech perception areas (Allen et al., 2008). Reduced brain volume in these areas could lead to a failure to correctly identify internally generated speech, erroneously tagging it as coming from an external source. PET and fMRI studies that have looked at activity in the brains of patients when they are actually experiencing auditory hallucinations provide further support for this idea. Rather than showing an increase of activity in areas of the brain involved in speech comprehension (e.g., Wernicke’s area in the temporal lobe), neuroimaging studies reveal that hallucinating patients show increased activity in Broca’s area—an area of the frontal lobe that is involved in speec
pattern of brain activation that occurs when patients experience auditory hallucinations
auditory hallucinations is very similar to that seen when healthy volunteers are asked to imagine that there is another person talking to them
=Auditory hallucinations are really a form of misperceived subvocal speech
tms and reducinng hallucinations
if transcranial magnetic stimulation (in which a magnetic field passing through the skull temporarily disrupts activity in underlying brain areas) is used to reduce activity in speech production areas, hallucinating patients actually show a reduction in their auditory hallucinations (Hoffman et al., 2005). Such an approach could possibly have promise for the future as a novel form of treatment (Slotema et al., 2014). Overall, however, the research findings suggest that auditory hallucinations occur when patients misinterpret their own self-generated and verbally mediated thoughts (inner speech or self-talk) as coming from another source.
Disorganized speech and schizophrenia/ “cognitive slippage”
Disorganized speech, on the other hand, is the external manifestation of a disorder in thought form. Basically, an affected person fails to make sense, despite seeming to use language in a conventional way and following the semantic and syntactic rules governing verbal communication. The failure is not attributable to low intelligence, poor education, or cultural deprivation. Years ago, Meehl (1962) aptly referred to the process as one of “cognitive slippage”; others have referred to it as “derailment” or “loosening” of associations or, in its most extreme form, as “incoherence.”
types of disorganized speech
n some cases, completely new, made-up words known as neologisms (literally, “new words”) appear in the patient’s speech. An example might be the word detone, which looks and sounds like a meaningful word but is a neologism. Formal thought disorder (a term clinicians use to refer to problems in the way that disorganized thought is expressed in disorganized speech) is well illustrated in the following example.
Disorganized Behavior and why it occurs
Goal-directed activity is almost universally disrupted in schizophrenia. The impairment occurs in areas of routine daily functioning, such as work, social relations, and self-care, to the extent that observers note that the person is not himself or herself anymore. For example, the person may no longer maintain minimal standards of personal hygiene or may exhibit a profound disregard of personal safety and health. In other cases, grossly disorganized behavior appears as silliness or unusual dress (e.g., wearing an overcoat, scarf, and gloves on a hot summer day). These disruptions of “executive” behavior may stem from impairment in the functioning of the prefrontal region of the cerebral cortex
catatonia
Catatonia is an even more striking behavioral disturbance. The patient with catatonia may show a virtual absence of all movement and speech and be in what is called a catatonic stupor. At other times, the patient may hold an unusual posture for an extended period of time without any seeming discomfort.
two types of symptoms in schizophrenia (negative vs positive)O
Positive symptoms are those that reflect an excess or distortion in a normal repertoire of behavior and experience, such as delusions and hallucinations. Disorganized thinking (as revealed by disorganized speech) is also thought of in this way. Negative symptoms, by contrast, reflect an absence or deficit of behaviors that are normally present.
**Positive, negative, and disorganized symptoms can co-occur in the same patient.
two categories of negative symptoms
One domain involves reduced expressive behavior—either in voice, facial expression, gestures, or speech. This may show itself in the form of blunted affect or flat affect or in alogia, which means very little speech.
- The other domain concerns reductions in motivation or in the experience of pleasure. The inability to initiate or persist in goal-directed activity is called avolition. For example, the patient may sit for long periods of time staring into space or watching TV with little interest in any outside work or social activities. Diminished ability to experience pleasure is called anhedonia.
internal state vs external symptoms in negative symptoms
Measures of autonomic arousal also showed that when they were watching the films, the patients exhibited more physiological reactivity than the controls did. Although the original research used only male patients, a recent study that includes women with schizophrenia has replicated the results about diminished emotional expression (Mote et al., 2014). What the findings suggest, therefore, is that even though patients with schizophrenia may sometimes appear emotionally unexpressive, they are nonetheless experiencing plenty of emotion.
Schizoaffective Disorder
This diagnosis is conceptually something of a hybrid, in that it is used to describe people who have features of schizophrenia and severe mood disorder. In other words, the person not only has psychotic symptoms that meet criteria for schizophrenia but also has marked changes in mood for a substantial amount of time. Because mood disorders can be unipolar or bipolar in type, these are recognized as subtypes of schizoaffective disorder.
diagnosis of schizoaffective disorder/ outcomes compared to schizophrenia
The reliability of schizoaffective disorder has tended to be quite poor, and clinicians often do not agree about who meets the criteria for the diagnosis (Maj et al., 2000; Vollmer-Larsen et al., 2006). In an effort to improve this, DSM-5 specifies that mood symptoms have to meet criteria for a full major mood episode and also have to be present for more than 50 percent of the total duration of the illness. This clarification should help improve the reliability of this diagnosis and possibly also decrease the number of people who receive it.
Research suggests that the long-term (10-year) outcome is much better for patients with schizoaffective disorder than it is for patients with schizophrenia
Schizophreniform Disorder
category reserved for schizophrenia-like psychoses that last at least a month but do not last for 6 months and so do not warrant a diagnosis of schizophrenia (see the DSM-5 box for diagnostic criteria). It may include any of the symptoms described in the preceding sections. Because of the possibility of an early and lasting remission after a first psychotic breakdown, the prognosis for schizophreniform disorder is better than that for established forms of schizophrenia.
Delusional Disorder
-vhold beliefs that are considered false and absurd by those around them. Unlike individuals with schizophrenia, however, people given the diagnosis of delusional disorder may otherwise behave quite normally. Their behavior does not show the gross disorganization and performance deficiencies characteristic of schizophrenia, and general behavioral deterioration is rarely observed in this disorder, even when it proves chronic
erotomania
One interesting subtype of delusional disorder is erotomania. Here, the theme of the delusion involves great love for a person, usually of higher status. Some evidence suggests that a significant proportion of female stalkers are diagnosed with erotomania
Brief Psychotic Disorder
It involves the sudden onset of psychotic symptoms or disorganized speech or catatonic behavior. Even though there is often great emotional turmoil, the episode usually lasts only a matter of days (too short to warrant a diagnosis of schizophreniform disorder). After this, the person returns to his or her former level of functioning and may never have another episode again (see the DSM-5 box for criteria for brief psychotic disorder). Cases of brief psychotic disorder are infrequently seen in clinical settings, perhaps because they remit so quickly. Brief psychotic disorder is often triggered by stress, as illustrated in the following case.
genetic influence and schizophrenia
here is a strong association between the closeness of the blood relationship (i.e., level of gene sharing or consanguinity) and the risk for developing the disorder. For example, the prevalence of schizophrenia in the first-degree relatives (parents, siblings, and offspring) of a proband with schizophrenia is about 10 percent. For second-degree relatives who share only 25 percent of their genes with the proband (e.g., half-siblings, aunts, uncles, nieces, nephews, and grandchildren), the lifetime prevalence of schizophrenia is closer to 3 percent.
Genain quadruplets
The Genain quadruplets, born sometime in the early 1930s, were rare MZ quadruplets who each developed schizophrenia, an outcome that would be expected to occur by chance only once in approximately 1.5 billion births. The genetically identical girls, given the pseudonym Genain (from the Greek for “dreadful gene”), were hospitalized at the National Institute of Mental Health in the mid-1950s and studied intensively by lead researcher David Rosenthal (see Rosenthal, 1963; see also Mirsky & Quinn, 1988). Rosenthal also selected first names for the girls using the initials of the institution, NIMH. Accordingly, the women are known to us as Nora (the firstborn), Iris, Myra, and Hester. They were all concordant for schizophrenia. However, they were discordant with regard to the severity of their illnesses: WERE NOT ALL IDENTICAL IN MANIFESTATION OF IT
CONCORDANCE rate schizophrenia
The overall pairwise concordance rate is 28 percent in MZ twins and 6 percent in DZ twins. This suggests that a reduction in shared genes from 100 percent to 50 percent reduces the risk of schizophrenia by nearly 80 percent.
=First, genes undoubtedly play a role in causing schizophrenia. Second, genes themselves are not the whole story. Twin studies provide some of the most solid evidence that the environment plays an important role in the development of schizophrenia. But why one MZ twin should develop schizophrenia when his or her co-twin does not is a fascinating question.
age-corrected incidence rate
Incidence is the number of new cases that develop. An age-corrected incidence rate takes into account predicted breakdowns for subjects who are not yet beyond the age of risk for developing the disorder.
Dutch adoption studies and schizophrenia
The first study of this kind was conducted many years ago by Heston in 1966. Heston followed up 47 children who had been born to mothers who were in a state mental hospital suffering from schizophrenia. The children had been placed with relatives or into foster homes within 72 hours of their birth. In his follow-up study, Heston found that 16.6 percent of these children were later diagnosed with schizophrenia. In contrast, none of the 50 control children (selected from among residents of the same foster homes whose biological mothers did not have schizophrenia) developed schizophrenia. In addition to the greater probability of being diagnosed with schizophrenia, the offspring whose mothers had schizophrenia were also more likely to be diagnosed as intellectually impaired, neurotic, or psychopathic (i.e., antisocial). They also had been involved more frequently in criminal activities and had spent more time in penal institutions. These findings are often taken to suggest that any genetic liability conveyed by the mothers is not specific to schizophrenia but also includes a liability for other forms of psychopathology. But we must be careful about drawing such a conclusion. Heston’s study provided no information about psychopathology in the fathers of the children. We therefore cannot know to what extent some of the problems the children had were due to genetic liability conveyed by their fathers.
Communication deviance and schizophrenia
Communication deviance is a measure of how understandable and “easy to follow” the speech of a family member is. Vague, confusing, and unclear communication reflects high communication deviance. What Wahlberg and colleagues found was that it was the combination of genetic risk and high communication deviance in the adopted families that was problematic. Children who were at genetic risk and who lived in families where there was high communication deviance showed high levels of thought disorder at the time of the follow-up. In contrast, the control adoptees who had no genetic risk for schizophrenia showed no thought disorder, regardless of whether they were raised in a high- or a low-communication-deviance family
schizophrenia, children, and disorganized families
, these findings indicate a strong interaction between genetic vulnerability and an unfavorable family environment in the causal pathway leading to schizophrenia. Of course, it could be argued that the children who went on to develop problems caused the disorganization of their adoptive families. However, there is little support for this alternative interpretation (see Tienari et al., 2004; Wahlberg et al., 1997). Some independent work reported by Kinney and colleagues (1997) also fails to show diminished mental health in adoptive parents raising children who later developed schizophrenia. Everything considered, the Finnish Adoptive Family Study has provided strong confirmation of the diathesis–stress model as it applies to the origins of schizophrenia.
COMT (catechol-O-methyltransferase) gene and schizophrenia
Candidate genes are genes that are involved in processes that are believed to be aberrant in schizophrenia. An example is the COMT (catechol-O-methyltransferase) gene. This gene is located on chromosome 22 and is involved in dopamine metabolism. As you will soon learn, dopamine is a neurotransmitter that has long been implicated in psychosis (impaired reality testing).
velocardiofacial syndrome and schizophrenia vulnerability
children who have a genetic syndrome (called velocardiofacial syndrome) that involves a deletion of genetic material on chromosome 22 are at high risk for developing schizophrenia as they move through adolescence (Gothelf et al., 2007). Prior to the onset of any disorder, they often report transient psychotic symptoms (such as auditory hallucinations) and have poor social functioning and reduced IQ
COMT and cannibis use
Furthermore, as we shall see later, people with a particular variant of the COMT gene are much more likely to become psychotic as adults if they use cannabis during adolescence. For obvious reasons, schizophrenia researchers have been very interested in chromosome 22 and in the COMT gene in their search to understand the origins of the disorder.
3 other candidate genes for schizophrenia
neuregulin 1 gene (located on chromosome 8), the dysbindin gene (on chromosome 6), the DISC1 (which stands for “disrupted in schizophrenia”) gene on chromosome 1, as well as several dopamine receptor genes
genome-wide association study (GWAS)
in a GWAS the entire genome is investigated. Typically two groups of participants are tested: one group that has the disease or disorder of interest (for example, schizophrenia) and another group that does not (the control or comparison group). Study participants provide a sample of DNA and then millions of genetic variants are explored and compared across the two groups. By using such an approach, researchers can identify single nucleotide polymorphisms (SNPs—pronounced “snips”), which are sequences of DNA, or other types of genetic variants, that are more frequently found in people with the disorder than without it.
=One advantage of the GWAS method, therefore, is that this approach may help us detect genes that have very small effects but that might contribute to susceptibility for schizophrenia.
GSWAS study results and schizophrenia
d 108 loci that are associated with the presence of schizophrenia, 83 of which are newly discovered genetic regions. No one believes that this number of genetic loci will be sufficient to fully explain the genetics of schizophrenia = they provide further evidence that a large number of alleles (an allele is an alternative form of a gene) are involved in creating genetic susceptibility for schizophrenia. Second, many of the genes that are implicated are involved in processes that have long been thought to be important for understanding schizophrenia. For example, some dopamine-related genes (such as DRD2) discriminated between people who had schizophrenia and people who did not. Other genetic regions that were identified in the analysis involved glutamate, another neurotransmitter that, as we shall see soon, has been implicated in schizophrenia. Perhaps the biggest surprise, however, was that the strongest finding to emerge concerned a region on chromosome 6 that contains genes involved in immune functioning.
schizophrenia liaaability and bipolar
oking beyond schizophrenia itself, GWAS approaches are also telling us that some of the risk alleles that are being implicated in schizophrenia are implicated in bipolar disorder (Smoller, 2013). What this means is that, far from being distinct disorders (which is the impression one gets from reading the DSM), schizophrenia and bipolar disorder (at least at the genetic level) have a lot of overlap. Third, even though lots of common alleles likely work in combination to increase a person’s risk for schizophrenia, rare alleles also probably play an important role
copy number variations and schizophrenia
y. Recent research has shown links between deletions and duplications of DNA (these are called copy number variations or CNVs) and schizophrenia. CNVs have also been implicated in autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (see Doherty et al., 2012). All of these conditions are characterized by mental challenges in various ways. Viewed in this regard, schizophrenia may be one form of neurodevelopmental disorder with genetic links to autism, ADHD, and intellectual disability. Although much more remains to be learned, it is fast becoming clear that we can no longer consider schizophrenia to be a discrete disorder that (at least from a genetic perspective) is in a category of its own. What is also becoming apparent is that the genetics of schizophrenia can be considered, at least in part, to be the genetics of brain development.
multifactoriaal etiology of schizophrenia
The multifactorial etiology of schizophrenia includes (1) rare genes that have a large effect, (2) common genes that have a small effect, and (3) the environmental factors and gene–environmental interactions that confer risk for schizophrenia.
endophenotypes
discrete, stable, and measurable traits that are thought to be under genetic control. By studying different endophenotypes, researchers hope to get closer to specific genes that might be important in schizophrenia
prenatal exposure to viral infection anbd schizophrenia
-You have just learned that new genetic research is linking schizophrenia to the presence of genes involved with immune function. Although we are still far from understanding what this might mean, the idea that schizophrenia might result from some kind of virus is not new.
he researchers were thus able to establish definitively which mothers had had influenza during their pregnancies. The results showed that influenza exposure during the first trimester of pregnancy was associated with a sevenfold increased risk of schizophrenia or schizophrenia spectrum disorders in the offspring. More generally, influenza exposure during the first half of pregnancy was associated with a threefold increase in risk. Because of the small sample size, neither of these results was statistically significant
= Other maternal infections such as rubella (German measles) and toxoplasmosis (a very common parasitic infection) that occur during pregnancy have also been linked to increased risk for the later development of schizophrenia
But how can maternal influenza or other infections set the stage for schizophrenia in a child two or three decades later?
Most infections do not cross the blood–brain barrier. However, infections in the mother trigger an immune response, resulting in an increase in proinflammatory cytokines (you read about these in Chapter 5). We also know from animal studies that cytokines play a role in shaping brain development and that fetal exposure to proinflammatory cytokines can lead to abnormalities in brain structure and functioning—many of which are highly relevant to schizophrenia
c reactive protein and schizophrenia
What Canetta and colleagues found was that when maternal levels of C-reactive protein were high, the offspring had a nearly 60 percent higher risk of developing schizophrenia decades later.
schizophrenia and autoimmune disorders
people with schizophrenia have a 53 percent increased risk of developing autoimmune diseases such as psoriasis, Crohn’s disease, and multiple sclerosis (Benros et al., 2014). And people with autoimmune diseases are at increased risk of developing schizophrenia (Eaton et al., 2010). So there is now an established link between schizophrenia and autoimmune disorders.
anti-inflammatory cytokines and reduced schizophrenia
Other research suggests that higher levels of anti-inflammatory cytokines in mothers are associated with a reduced risk of schizophrenia in their offspring in adulthood (Allswede et al., 2016). So it is possible that, whereas higher levels of proinflammatory cytokines are problematic, high levels of anti-inflammatory cytokines are beneficial and perhaps neuroprotective.
Rhesus (Rh) incompatibility and schizophrenia
Rhesus (Rh) incompatibility occurs when an Rh-negative mother carries an Rh-positive fetus. (Rhesus-positive or -negative is a way of typing a person’s blood.) Incompatibility between the mother and the fetus is a major cause of blood disease in newborns. Interestingly, Rh incompatibility also seems to be associated with increased risk for schizophrenia.
=One possibility is that the mechanism involves oxygen deprivation, or hypoxia. This suggestion is supported by studies that have linked the risk for schizophrenia to birth complications. Recent research also suggests that incompatibility between the blood of the mother and the blood of the fetus may increase the risk of brain abnormalities of the type known to be associated with schizophrenia
Early Nutritional Deficiency and schizophrenia
children were born during this time. Those who were conceived at the height of the famine had a twofold increase in their risk of later developing schizophrenia (Brown, 2011). Early prenatal nutritional deficiency appears to have been the cause. Whether the problem was general malnutrition or the lack of a specific nutrient such as folate or iron is not clear.
maternal stress and schizophrenia
If a mother experiences an extremely stressful event late in her first trimester of pregnancy or early in the second trimester, the risk of schizophrenia in her child is increased (King et al., 2010). For example, in a large population study conducted in Denmark, the death of a close relative during the first trimester was associated with a 67 percent increase in the risk of schizophrenia in the child (Khashan et al., 2008). Currently, it is thought that the increase in stress hormones that pass to the fetus via the placenta might have negative effects on the developing brain, although the mechanisms through which maternal stress increases risk for schizophrenia are not yet well understood.
overestimated heritability of schizophrenia and concordance rates
It is also possible that the focus on MZ concordance rates has caused us to overestimate the heritability of schizophrenia. This is because some MZ, and all DZ, twins do not have equally similar prenatal environments. Around two-thirds of MZ embryos are monochorionic, which means they share a placenta and blood supply. The remaining MZ twins and all DZ twins are dichorionic; they have separate placentas and separate fetal circulations. This is shown in Figure 13.5. The higher concordance rate for schizophrenia in MZ than in DZ twins might therefore be a consequence, at least in part, of the greater potential for monochorionic MZ twins to share infections.
major histocompatibility complex (MHC
. This region (which is called the major histocompatibility complex (MHC)) also plays an important role in brain development and neuronal function. Although very speculative at this time, it is possible that genetic vulnerability to schizophrenia could be explained by greater genetic vulnerability to infection. It is also possible that infection could affect gene expression (which genes are turned on or off) and lead to changes in brain development that “prime” the brain for the later onset of schizophrenia
childhood deviancy and schizophrenia
One of the most consistent findings from high-risk research is that children with a genetic risk for schizophrenia are more deviant than control children on research tasks that measure attention (Erlenmeyer-Kimling & Cornblatt, 1992). Adolescents at risk for schizophrenia are also rated lower in social competence than adolescents at risk for affective illness (Dworkin et al., 1994; Hooley, 2010). Some of the social problems that these high-risk children have may result from underlying attentional problems
=Moreover, these movement abnormalities became more marked with time and also became more strongly correlated with psychotic symptoms as the children got older. Although we might have suspected that schizophrenia would first begin to show itself via hallucinations or delusions, it may be that the first signs of the illness can instead be found in the way that children move. This could be because movement abnormalities and psychotic symptoms share some of the same neural circuitry in the brain. Problems in this neural circuitry might show themselves first via movement abnormalities. Then, as the brain matures, problems in the same neural circuits manifest themselves in psychotic symptoms
prodromal
very early, signs of schizophrenia, researchers are hoping to improve their ability to detect, and also perhaps intervene with, people who appear to be on a pathway to developing the disorde
Attenuated Psychosis Syndrome
Attenuated psychosis syndrome is characterized by mild psychotic symptoms that are not severe enough to meet clinical criteria for another full-blown psychotic disorder. People with this syndrome are thought to be at risk for later psychosis. They are also experiencing some distress or disability and are seeking help for their problems. Proponents of including the syndrome in DSM-5 argued that it would help clinicians identify these people and provide them with treatment at an early stage. This could, in theory, reduce distress in the short term and prevent the onset of a full-blown psychotic disorder in the long term. This is important because, once schizophrenia has developed, most patients are likely to experience recurring positive and negative symptoms, as well as persistent impairments in their work or social functioning for a large part of their lives
controversy of attenuated psychosis syndrom as a diagnosis
The potential for stigma is one problem (Yang et al., 2013). Another concern is that the majority of people who are identified as being at high risk are not on their way to developing a psychotic disorder. Addington and colleagues (2011) followed 303 young adults who were showing prodromal symptoms of schizophrenia. At the end of the follow-up period the majority of these young people (71 percent) had not made the transition into psychosis. Although the follow-up period was relatively short it seems that the false-positive rate here is very high
Cognitive impairments and schizophrenia
appear early. Even before they have a diagnosable illness, young people at clinical high risk for developing psychosis perform less well than healthy controls on certain neurocognitive tests (Corigliano et al., 2014). Because cognitive difficulties can be seen right from the start of the illness (or even well before), it is unlikely that they are due to the effects of extended hospitalizations or medications
IQ and schizophrenia
recent research suggests that having a lower IQ may itself be an independent risk factor for developing schizophrenia at a later point and that having a higher IQ may be protective in some way
stages of cognitive decline and schizophrenia
the cognitive impairments we see in patients experiencing their first episodes of illness are more severe and more wide ranging than the cognitive impairments found in people in the early (premorbid or prodromal) phases. It is also noteworthy that patients who have only recently become ill perform about the same on neuropsychological tests as patients who have been ill for many years (McCleery et al., 2014; Mesholam-Gately et al., 2009). For this reason researchers think that a sharp decline in cognitive ability (and IQ) occurs during the period of transition from the premorbid period into full-blown illness (Meier et al., 2014). After the first psychotic episode, the cognitive decline seems to stabilize
cognitive problems schizophrenia
stimulus inhibition, working memory, eye-tracking dysfunction (see Figure 13.6) and are deficient in their ability to track a moving target such as a pendulum (mooth-pursuit eye movement), = Especially interesting is that around 50 percent of the first-degree relatives of patients with schizophrenia also show eye-tracking problems even though they do not have schizophrenia themselves
sensory gating and schizophrenia/ p50 surpression
people with schizophrenia show problems with a process called sensory gating (Heinrichs, 2001; Potter et al., 2006). When two clicks are heard in close succession, the brain (receiving the auditory signal) produces a positive electrical response to each click. This response is called P50 because it occurs 50 milliseconds after the click. In normal subjects, the response to the second click is less marked than the response to the first click because the normal brain dampens, or “gates,” responses to repeated sensory events. If this didn’t happen, habituation to a stimulus would never occur. Many patients with schizophrenia, in contrast, respond almost as strongly to the second click as to the first. This is referred to as “poor P50 suppression.” First-degree family members of patients with schizophrenia are also more likely than controls to have problems with P50 suppression
Social Cognition and schizophrenia
- people with schizophrenia show significant impairments in social cognition (Pinkham, 2014). For example, they fail to spot the kinds of subtle (or not so subtle) social hints that most of us (as in the example about the dessert) can detect without difficulty. They also have difficulties recognizing emotion in faces (Kohler et al., 2010) and emotion being conveyed in speech/ they are less able to recognize when someone has made a social error (a faux pas) such as forgetting that a party is supposed to be a surprise
difference between neurocognition and social cognition
Of course, intact cognitive functions are required for a person to perform well on tests of social cognition. Nonetheless, although social cognition and nonsocial (neurocognition) are related, they are largely distinct constructs (Lee et al., 2013). Both help explain how well patients are able to function in the real world. However, when it comes to predicting social skills or quality of life, social cognitive abilities (such as social perception, emotion recognition, ability to detect irony and the like) seem to play a greater role than neurocognitive skills such as attention or memory
ventricles and schizophrenia
-, patients with schizophrenia have enlarged brain ventricles, with males possibly being more affected than females (Haijma et al., 2013; Lawrie & Abukmeil, 1998; Shenton et al., 2001). However, enlarged brain ventricles are not seen in all patients and are not specific to schizophrenia. They are also characteristic of patients with Alzheimer’s disease, Huntington’s disease, and chronic alcohol problems.
-Enlarged brain ventricles are important because they are an indicator of a reduction in the amount of brain tissue. The brain normally occupies fully the rigid enclosure of the skull. Enlarged ventricles therefore imply that the brain areas that border the ventricles have somehow shrunk or decreased in volume, the ventricular space becoming larger as a result. In fact, MRI studies of patients with schizophrenia show about a 3 percent reduction in whole brain volume relative to that in controls
-This decrease in brain volume is present very early in the illness. Even patients with a recent onset of schizophrenia have lower overall brain volumes than controls
grey matter and schizophrenia
adolescents who became psychotic showed steep declines in the gray matter in their prefrontal cortex. The loss of gray matter (which is made up of nerve cells) also seemed to be occurring exactly as psychosis was developing. In addition, the researchers were able to determine that this was not due to any influences of medications. Especially interesting was that the adolescents who showed the steepest declines in brain gray matter (more cortical thinning) also had the highest levels of inflammatory markers in their blood. Unclear at the moment is whether inflammation causes gray matter loss or whether loss of gray matter leads to inflammation. What we do know, though, is that psychosis and cortical thinning go hand in hand. The brain changes that occur during the transition to psychosis may explain why we see declines in cognitive functioning as the illness gains momentum
shcizophrenia as a neuroprogressive disorder
Overall, the research findings support the idea that in addition to being a neurodevelopmental disorder, schizophrenia is also a neuroprogressive disorder characterized by a loss of brain tissue over time.
temporal lobes and schizophrenia
reduction in the volume of such medial temporal areas as the amygdala, which is involved in emotion; the hippocampus, which plays a key role in memory; and the thalamus, which is a relay center that receives almost all sensory input
white matter and schizophrenia
Nerve fibers are covered in a myelin sheath (which looks white in color in a chemically preserved brain). Myelin acts as an insulator and increases the speed and efficiency of conduction between nerve cells. White matter is therefore crucially important for the connectivity of the brain. If there are disruptions in the integrity of white matter, there will be problems in how well the cells of the nervous system can function.
=Studies of patients with schizophrenia show that they have reductions in white matter volume as well as structural abnormalities in the white matter itself (Haijma et al., 2013). Interestingly, these abnormalities can be found in first-episode patients and also in people at genetic high risk for the disorder. This suggests that they are not a result of the disease itself or the effects of treatment. The fundamental problem seems to be one of dysconnectivity—abnormal integration between distinct brain regions, particularly those involving the frontal lobes
corpus collosum and schizophrenia
Another interesting finding is that children of people with schizophrenia, even though they are not psychotic themselves, have a reduction in the volume of the corpus callosum—a massive tract of white matter fibers that connects the two hemispheres of the brain
“hypofrontality”) and schizophrenia
some patients show abnormally low frontal lobe activation (known as “hypofrontality”) when they are involved in mentally challenging tasks such as the Wisconsin Card Sorting Test (WCST) or in other tests generally thought to require substantial frontal lobe involvement. Essentially, this brain area does not seem to be able to kick into action when patients perform complex tasks (see Figure 13.8). In other patients, hyperactivation in frontal brain areas is found, suggesting that they are having to work harder to be successful on the task. In both sets of circumstances, however, the brain is not functioning in an optimal and efficient way.
“default mode network. and schizophrenia
Whereas healthy people find it easy to suppress activity in the default mode network (tuning their brains into the “correct station” so to speak), people with schizophrenia may not be able to do this as efficiently (Guerrero-Pedrazza et al., 2011; Ren et al., 2013; Whitfield-Gabrieli et al., 2009). This lack of ability to disengage the default mode network may help us understand why people with schizophrenia have so many difficulties with a wide range of tasks across a broad array of areas
cytoarchitecture and schizophrenia
As we have seen, one hypothesis about schizophrenia is that genetic vulnerabilities, perhaps combined with prenatal insults, can lead to disruption of the migration of neurons in the brain. If this is true, some cells will fail to arrive at their final destinations, and the overall organization of cells in the brain (the brain’s cytoarchitecture) will be compromised.
researchers have reported an increase in neuronal density in some areas of the brains of patients with schizophrenia (see Selemon, 2004). There are also abnormalities in the distribution of cells in different layers of the cortex and hippocampus (Arnold, 2000; Kalus et al., 1997; Selemon et al., 1995). Of particular importance is the finding that patients with schizophrenia are missing particular types of neurons known as “inhibitory interneurons” (Benes & Berretta, 2001). These are called GABA interneurons and they are responsible for regulating the excitability of other neurons.
synaptic pruning and schizophrenia
, normal processes that occur during adolescence prune (or reduce) these synapses, so decreasing “neuronal redundancy.” There is also a normal reduction in gray matter volume that occurs in adolescence, as well as an increase both in white matter and in the volume of the hippocampus and the amygdala. In addition, the number of excitatory synapses decreases and the number of inhibitory synapses increases. All of these processes are thought to occur to enhance brain function overall and to make the brain more “adult”
tbi and schizophrenia
People who have had a hospital contact for a head injury have a 65 percent increase in later risk for schizophrenia (Orlovska et al., 2014). This increased risk appears to be independent of having a family history of psychiatric illness. Furthermore, if the head injury occurs between the ages of 11 and 15, the risk of schizophrenia is increased even more (85 percent increase).
dopamine hypothesis/. drugs and schizophrenia
dopamine hypothesis dates back to the 1960s and was derived from three important observations. The first was the pharmacological action of the drug chlorpromazine (Thorazine). Chlorpromazine was first used in the treatment of schizophrenia in 1952. It rapidly became clear that this drug was helpful to patients. Eventually, it was learned that the therapeutic benefits of chlorpromazine were linked to its ability to block dopamine receptors.
The second piece of evidence implicating dopamine in schizophrenia came from an entirely different direction. Amphetamines are drugs that produce a functional excess of dopamine (i.e., the brain acts as if there is too much dopamine in the system). In the late 1950s and early 1960s, researchers began to see that abuse of amphetamines led, in some cases, to a form of psychosis that involved paranoia and auditory hallucinations (Connell, 1958; Kalant, 1966; Tatetsu, 1964). There was thus clinical evidence that a drug that gave rise to a functional excess of dopamine also gave rise to a psychotic state that looked a lot like schizophrenia.
How could dopamine induce psychosis?/ aberrant salience
Activity in the dopamine system may play a role in determining how much salience we give to internal and external stimuli. Dysregulated dopamine transmission may actually make us pay more attention to and give more significance to stimuli that are not especially relevant or important. This is called “aberrant salience”
-If this is the case, it is quite easy to see why patients might develop delusions or experience hallucinations and why psychotic experiences might be so shaped by the patient’s culture and history. In the early stages of their illnesses, patients often report heightened sensory awareness
How does too much dopamine happen in the brain?
But how might a functional excess of dopamine in the system come about? One way is through too much dopamine being available in the synapse (the gap between nerve cells that has to be “bridged” by a neurotransmitter for a nerve impulse to be carried from one neuron to another). This could come about by increasing the synthesis or production of dopamine, by releasing more of it into the synapse, by slowing down the rate at which dopamine is metabolized or broken down once it is in the synapse, or by blocking neuronal reuptake (the “recycling” of dopamine back into the neuron). Any or all of these could increase the overall availability of dopamine.
homovanillic acid, or HVA.
The major metabolite of dopamine is homovanillic acid, or HVA. However, HVA is best collected in cerebrospinal fluid (CSF).
types of dopamine receptors relevant to schizophrenia
There are five subtypes of dopamine receptors (D1–D5). Of these, the D2 receptor is the most relevant clinically, and most of the research has focused on this. So what do we know? The most current findings tell us that the biggest abnormality in dopamine functioning occurs presynaptically. In other words, too much dopamine (about 14 percent more) is being synthesized and released into the synapse
There is also some evidence that patients with schizophrenia have an increased number of D2 or D3 receptors. However, the difference is small and is not found in patients who have not taken antipsychotic medications. This suggests that elevations in dopamine receptor density are more likely linked to treatment effects rather than being integral to schizophrenia itself.
Glutamate and schizophrenia / PCP
is an excitatory neurotransmitter that is widespread in the brain. As was the case for dopamine, there are a number of reasons why researchers suspect that a dysfunction in glutamate transmission might be involved in schizophrenia. First, PCP, or angel dust, is known to block glutamate receptors. PCP also induces symptoms (both positive and negative) that are very similar to those of schizophrenia. Moreover, when people with schizophrenia take PCP, it exacerbates their symptoms.
psychosis and ketamine
Second, physicians had to stop using ketamine, which is an anesthetic, because when it is given intravenously to healthy volunteers, it produces schizophrenia-like positive and negative symptoms (see Krystal et al., 2005). When given to patients whose schizophrenia is stable and well controlled, ketamine exacerbates hallucinations, delusions, and thought disorder. But what is all the more remarkable about ketamine is that it does not cause any of these problems when it is administered to animals or to children, for whom it continues to be used as an anesthetic. This suggests that age (and brain maturity) determines whether ketamine causes psychosis.
NMDA receptors and schizophrenia/ glutamte hypothesis
glutamate receptors (known as “NMDA” receptors) may not only trigger schizophrenia-like symptoms but may also cause the degeneration of neurons in key brain areas. In other words, if the NMDA receptors are not normally active (perhaps because glutamate levels are low), subtle brain damage may result. NMDA receptor activity is also important for learning and memory—cognitive processes that are compromised in schizophrenia.
=Finally, does the importance of glutamate challenge the importance of dopamine in the neurochemistry of schizophrenia? No. One action of dopamine receptors is to modulate the excitability of glutamate neurons and inhibit the release of glutamate (pressing the brake pedal on glutamate neurotransmission, as it were). An overactive dopaminergic system could result in excessive suppression (too much heavy braking) of glutamate, leading to the underactivity (hypofunction) of the NMDA receptors. The dopamine hypothesis of schizophrenia is actually made all the more credible by discoveries about glutamate.
“schizophrenogenic mother,”
The idea of the “schizophrenogenic mother,” whose cold and aloof behavior was the root cause of schizophrenia, was very influential in many clinical circles (Fromm-Reichman, 1948). Understandably, this was very distressing for families. Not only were they faced with the difficulties of coping with a son or daughter who had a devastating illness, but they suffered all the more because of the blame that was directed toward them by mental health professionals.
double-bind hypothesis schizophrenia
A double bind occurs when the parent presents the child with ideas, feelings, and demands that are mutually incompatible (e.g., a mother may complain about her son’s lack of affection but freeze up or punish him when he approaches her affectionately). According to Bateson’s etiologic hypothesis, such a son is continually placed in situations where he cannot win, and he becomes increasingly anxious. Presumably, over time, such disorganized and contradictory communications in the family come to be reflected in his own thinking. However, no solid support for these ideas has ever been reported.
expressed emotion and relapse
Expressed emotion is a measure of the family environment that is based on how a family member speaks about the patient during a private interview with a researcher (Hooley, 2007). It has three main elements: criticism, hostility, and emotional overinvolvement (EOI). The most important of these is criticism, which reflects dislike or disapproval of the patient. Hostility is a more extreme form of criticism that indicates a dislike or rejection of the patient as a person. Finally, EOI reflects a dramatic or overconcerned attitude on the part of the family member toward the patient’s illness.
Expressed emotion is important because it has been repeatedly shown to predict relapse in patients with schizophrenia. In a meta-analysis of 27 studies, Butzlaff and Hooley (1998) demonstrated that living in a high-EE home environment more than doubled the baseline level of relapse risk for patients with schizophrenia in the 9 to 12 months after hospitalization. Moreover, even though EE predicts relapse regardless of whether the patients studied have been ill for a short, medium, or long time, EE seems to be an especially strong predictor of relapse for patients who are chronically ill.
schizophrenia and stressssssss sensitivty
But how might EE trigger relapse? There is a great deal of evidence that patients with schizophrenia are highly sensitive to stress. Consistent with the diathesis–stress model, environmental stress is thought to interact with preexisting biological vulnerabilities to increase the probability of relapse (Nuechterlein et al., 1992). We know, for example, that independent stressful life events occur more frequently just prior to psychotic relapse than at other times (Ventura et al., 1989, 1992) and may exert their effects over longer periods of time too. Furthermore, one of the primary manifestations of the stress response in humans is the release of cortisol (a glucocorticoid) from the adrenal cortex. Animal and human studies show that cortisol release triggers dopamine activity (McMurray et al., 1991; Rothschild et al., 1985). Glucocorticoid secretion also affects glutamate release (Walker & Diforio, 1997). In other words, two of the major neurotransmitters implicated in schizophrenia (dopamine and glutamate) are affected by cortisol, which is released when we are stressed.
Urban Living and schizophrenia
. Other methodologically sound studies also confirm this association (Sundquist et al., 2004). It has been estimated that if this risk factor could be removed (that is, if we all lived in relatively rural settings) the number of cases of schizophrenia could decrease by about 30 percent
Immigration and schizophrenia
The findings showing that urban living raises a person’s risk for developing schizophrenia suggest that stress or social adversity might be important factors to consider with respect to this disorder. Supporting this idea, research is also showing that recent immigrants have much higher risks of developing schizophrenia than do people who are native to the country of immigration. -One possibility is that immigrants are more likely to receive this diagnosis because of cultural misunderstandings (Sashidharan, 1993). However, there is no convincing evidence that this is the case (Harrison et al., 1999; Takei et al., 1998). Another hypothesis is that people who are genetically predisposed to develop schizophrenia are more likely to move to live in another country. However, some of the impairments associated with the early stages of schizophrenia seem incompatible with this idea because negative symptoms and frontal lobe dysfunctions may make it harder to be organized enough to emigrate
-Perhaps the strongest clue comes from the finding that immigrants with darker skin have a much higher risk of developing schizophrenia than do immigrants with lighter skin (Cantor-Graae & Selten, 2005). This raises the possibility that experiences of being discriminated against could lead some immigrants to develop a paranoid and suspicious outlook on the world, which could set the stage for the development of schizophrenia. In support of this idea, the results of a prospective study show that healthy people who felt discriminated against were more likely to develop psychotic symptoms over time than were healthy people who did not perceive any discrimination
cannabis use during adolescence
Other studies have now replicated this link and have highlighted early cannabis use as being particularly problematic (see van Winkel & Kuepper, 2014, for a review). For example, Arsenault and colleagues (2002) report that 10.3 percent of those who used cannabis by age 15 were diagnosed with signs of schizophrenia by age 26, compared with only 3 percent of the controls who did not use cannabis. Taken together, the research findings suggest that using cannabis during adolescence more than doubles a person’s risk of developing schizophrenia at a later stage of life.
=A major methodological concern in studies of this kind is whether people who are in the early stages of developing psychosis are more likely to use cannabis. If this were the case, cannabis use would simply be a correlate of schizophrenia and not a cause. However, even after childhood psychotic symptoms are considered and accounted for statistically, cannabis use has still been found to be a predictor of later schizophrenia vvvvvvvvvv
A Diathesis–Stress Model of Schizophrenia
schizophrenia is a genetically influenced, not a genetically determined, disorder
Genetic factors and acquired constitutional factors (such as prenatal events and birth complications) combine to result in brain vulnerability. Normal maturational processes, combined with stress factors (family stress, cannabis use, urban living, immigration, etc.), may push the vulnerable person across the threshold and into schizophrenia.
nongenetic causal faccccctors: Older father
Virus exposure
Obstetric complications
Urban upbringing
Head injury
Cannabis use
Migrant status
Clinical Outcomes of schizophrenia
Rather, it means that with the help of therapy and medications, patients can function quite well. For a minority of patients (around 12 percent), long-term institutionalization is necessary. And around a third of patients show continued signs of illness, usually with prominent negative symptoms.
When more stringent criteria are used to define recovery (i.e., remission of symptoms and good general social functioning with improvements in at least one of these areas lasting 2 years or more), rates of recovery are even more modest. Recent estimates suggest that they are around 14 percent (Jääskeläinen et al., 2013). What this means is that, despite many advances in treatment during the past 50 to 60 years, a “cure” for schizophrenia has not materialized.
=Interestingly, patients who live in less industrialized countries tend to do better overall than patients who live in more industrialized nations (Jablensky et al., 1992). This may be because levels of EE are much lower in countries such as India than in the United States and Europe. For example, in highly industrialized cultures, more than 50 percent of families are high in EE. In contrast, studies with Mexican American and Hindi-speaking Indian samples show that only 24 and 41 percent of families, respectively, are high in EE (see Karno et al., 1987; Leff et al., 1987). These differences may help explain why the clinical outcome of patients is different in different parts of the world.
life expectancy and schizophrenia
The health risks of having schizophrenia cannot be understated. This is a disorder that reduces life expectancy. Recent data from the United Kingdom show that men with schizophrenia die 14.6 years earlier than would be expected based on national norms. For women with schizoaffective disorder the reduction in life span is 17.5 years (Chang et al., 2011). Suicide is a major factor in increased mortality, especially for patients in the early stages of the illness. Compared to the general population, about 12 percent of patients end their lives in this way (Dutta et al., 2010). Some of the other factors implicated in the premature deaths of patients with schizophrenia and schizophrenia-related illnesses are long-term use of antipsychotic medications, obesity, smoking, poor diet, use of illicit drugs, and lack of physical activity. Many of these factors lead to cardiovascular disease. In general, overall mortality is lower in patients who are treated with antipsychotic medications compared to untreated patients (Tiihonen et al., 2011). This no doubt reflects the extent to which people who are actively psychotic are a risk to themselves.
First-Generation Antipsychotics
chlorpromazine (Thorazine) and haloperidol (Haldol), which were among the first to be used to treat psychotic disorders. Sometimes referred to as neuroleptics (literally, “seizing the neuron”), these medications revolutionized the treatment of schizophrenia when they were introduced in the 1950s and can be regarded as one of the major medical advances of the twentieth century (Sharif et al., 2007). They are called first-generation antipsychotics (or typical antipsychotics) to distinguish them from another class of antipsychotics that was developed more recently. These are referred to as second-generation (or atypical) antipsychotics.
Some clinical change can be seen within the first 24 hours of treatment (Kapur et al., 2005). This supports the idea that these medications work by interfering with dopamine transmission at the D2 receptors because dopamine blockade begins within hours after a patient is given the medication. However, it may take several weeks or even months for maximal clinical benefit to be achieved, although how a patient does on a particular medication in the first 2 to 4 weeks of treatment is a good predictor of how much he or she will benefit overall
first gen antipsycs and symptoms it treats best and side effects
First-generation antipsychotics work best for the positive symptoms of schizophrenia. In quieting the voices and diminishing delusional beliefs, these medications provide patients with significant clinical improvement (Tandon et al., 2010). This comes at a cost, however. Common side effects of these medications include drowsiness, dry mouth, and weight gain. Many patients on these antipsychotics also experience what are known as extrapyramidal side effects (EPS). These are involuntary movement abnormalities (muscle spasms, rigidity, shaking) that resemble Parkinson’s disease.
tardive dyskinesia/ neuroleptic malignant syndrome and neuroleptics
This involves marked involuntary movements of the lips and tongue (and sometimes the hands and neck). Rates of tardive dyskinesia are about 56 percent when patients have taken neuroleptics for 10 years or more, with females being especially susceptible (Bezchlibnyk-Butler & Jeffries, 2003). Finally, in very rare cases there is a toxic reaction to the medication that is called neuroleptic malignant syndrome (Strawn et al., 2007). This condition is characterized by high fever and extreme muscle rigidity, and if left untreated it can be fatal.
Second-Generation Antipsychotics
-Although initially reserved for use with treatment-refractory patients (those who were not helped by other medications), clozapine is now used widely.
-“second-generation antipsychotics” is that they cause fewer extrapyramidal symptoms than the earlier antipsychotic medications such as Thorazine and Haldol. Although it was initially believed that second-generation antipsychotics were more effective at treating the symptoms of schizophrenia, there is little support for this view (Lieberman & Stroup, 2011; Tandon et al., 2010). The exception here concerns clozapine, which does seem to be more valuable than other medications for treatment-refractory patients. Nonetheless, most patients are now treated with these newer (and more expensive) medications.
side effects of second generation antipsycotics
Drowsiness and considerable weight gain are very common. Diabetes is also a very serious concern (Sernyak et al., 2002). In rare cases, clozapine also causes a life-threatening drop in white blood cells known as agranulocytosis.
estroigen and schizophrenia
e women who had worn the genuine (estrogen-containing) patches reported significantly fewer overall symptoms at the end of the 1-month study compared to the placebo group, with the difference for positive symptoms (shown in Figure 13.12) being most striking. Overall, the results suggest that estrogen has antipsychotic effects and that providing supplemental estrogen to women with schizophrenia may give them additional clinical benefits.
blockade of D2 dopamine receptors and pet scans
Research using PET also shows that increased blockade of D2 dopamine receptors is associated with patients reporting more negative subjective experiences such as feeling tired and depressed even when other side effects (such as movement problems) are absent (Mizrahi et al., 2007). This highlights the need for better medications and for using lower dosages wherever this is clinically feasible. We also need to remember that some patients may try to avoid taking medications because, to them, needing to take medications confirms that they are mentally ill. The following comes from the mother of a daughter who suffers from schizophrenia:
Case managers
people who help patients find the services they need in order to function in the community. Essentially, the case manager acts as a broker, referring the patient to the people who will provide the needed service (e.g., help with housing, treatment, employment, and the like). Assertive community treatment programs are a specialized and more intensive form of case management. Typically, they involve multidisciplinary teams with limited caseloads to ensure that discharged patients don’t get overlooked and “lost in the system.” The multidisciplinary team delivers all the services the patient needs
Family Therapy
Research studies show that patients do better clinically and relapse rates are lower when families receive family treatment
Psychoeducation
Even when families are not involved, educating patients about the illness and its treatment (this approach is called psychoeducation) is beneficial (Xia et al., 2011). Patients who receive psychoeducation in addition to standard treatment are less likely to relapse or be readmitted to the hospital compared to patients who receive standard treatment only
functional outcomes and social skills training / social cognitive skills training.
Even when their symptoms are controlled by medications, patients with schizophrenia often have trouble forming friendships, finding and keeping a job, or living independently. How well patients do in their everyday lives is referred to as functional outcome. (This is in contrast to clinical outcome, which is concerned with symptoms.) Improving the functional outcomes of patients with schizophrenia is now an active area of research.
One way to help improve the functional outcomes of patients with schizophrenia is through social-skills training. Patients with schizophrenia often have very poor interpersonal skills (for a review, see Hooley, 2015). Social-skills training is designed to help patients acquire the skills they need to function better on a day-to-day basis
social cognitive skills training. This is designed to improve the deficits in social cognition we described earlier. For example, patients might be trained to recognize emotion in faces or to better recognize hints. The early findings suggest that these interventions do provide benefits to patients and help them function better in the community. However, positive and negative symptoms show little change
cognitive Remediation
A major treatment effort is also being devoted to cognitive remediation training. Using practice and other compensatory techniques, researchers are trying to help patients improve some of their neurocognitive deficits (e.g., problems with verbal memory, vigilance, and performance on card-sorting tasks). The hope is that these improvements will translate into better overall functioning (e.g., conversational skills, self-care, and job skills). On the whole, the findings give cause for optimism. Cognitive remediation training does seem to help patients improve their attention, memory, and executive functioning skills. Patients who receive cognitive remediation training also show improvements in their social functioning
Especially encouraging is that even when patients have been ill for many years, they still seem to benefit from this treatment approach (Pfammatter et al., 2006; Wykes et al., 2007). Cognitive remediation approaches may work best when they are added to other existing rehabilitation (employment skills) strategies and offered to patients who are already clinically stable
Cognitive-Behavior Therapy
Current data suggest that CBT is not very helpful for negative symptoms (Tandon et al., 2010). A recent meta-analysis also suggests that CBT is no better than control interventions (often supportive counseling) in the treatment of schizophrenia (Lynch et al., 2010). Nonetheless, the possibility that CBT works very well for some subgroups of patients is still a very real possibility.
excercise and cbt
moderate forms of exercise may help reduce positive and negative symptoms and improve patients’ cognitive and overall functioning (see Mittal et al., 2017). Exercise is known to improve brain health by stimulating the growth of neurons (neurogenesis), facilitating cell proliferation in key brain areas such as hippocampus, and slowing rates of cell death. Exercise also reduces inflammation, which we know seems to play a role in schizophrenia. Given all of this it is perhaps not surprising that exercise (especially when combined with cognitive remediation) might provide schizophrenia patients with some benefits. At the very least, exercise may help patients live longer and healthier lives by improving their cardiovascular functioning and reducing some of the weight gain caused by medications.
Why Are Recovery Rates in Schizophrenia Not Improving?
But how could something that is clinically beneficial in the short term be potentially harmful in the longer term? Standard antipsychotic medications block D2 receptors in the brain. This is the basis of their therapeutic action. But one result of dopamine blockade is that the density of receptors on the postsynaptic neuron increases, creating a supersensitivity to dopamine. Put more simply, neuroleptics put a brake on dopamine transmission. To compensate for this, the brain responds by pressing the dopamine accelerator (in the form of extra dopamine receptors). Withdrawal of neuroleptics removes the brake and puts the system out of balance because the system is now in an “accelerator-on” mode. Moreover, any return of symptoms is taken as evidence that the drugs were working and preventing relapse. This impression gets confirmed when the patient goes back on drugs again and the psychosis abates. As one physician noted, “The use of neuroleptics is a trap. … It is like having a psychosis-inducing agent built into the brain.”
difference between medicated and unmedicated outcomes
Can we attribute the poor clinical outcomes of the medicated patients to the continued use of antipsychotics? Harrow and colleagues (2012) suggest not. Rather, they suggest that the difference between the medicated and unmedicated groups exists because the patients who go off antipsychotics have other resources and strengths that eventually lead them to have a better long-term prognosis. So the patients with the most favorable clinical outcomes stop taking medications and the patients with the least favorable clinical outcomes keep taking medications. This may be so. But it is interesting that many of the patients who stopped taking their medications did so against professional advice. So, if these patients were somehow more resilient and destined to do better, their psychiatrists apparently did not recognize it.
It is also the case that patients who stop taking medications tend not to see their psychiatrists. So clinicians don’t see people who recover. This may be one reason why psychiatry as a whole has been slow to recognize that nonmedicated patients might be doing far better than expected. Also relevant here is the observation that patients in less industrialized countries tend to do better clinically than those in more developed countries. And these are the very patients who are much less likely to be maintained on antipsychotic medications.
