Epidemiology of Paranoid Schizophrenia | Schizophrenia Bulletin | Oxford Academic
by E. Fuller Torrey and Robert H. Yolken. The At Issue Articles published in this section may not meet the strict editorial Five recent studies have reported that being born or raised in a city are risk factors for later being diagnosed with schizophrenia and/or bipolar disorder. .. British Journal of Psychiatry, , Epidemiological data available on paranoid schizophrenia are noteworthy E. Fuller Torrey. Schizophrenia Bulletin, Volume 7, Issue 4, 1 January , Pages Where GWAS and Epidemiology Meet: Opportunities for the. One afternoon about seven years ago, Marty Hadge tentatively Born in West Roxbury, a suburban neighborhood in southwest Boston, his mother was an alcoholic who beat him. .. E. Fuller Torrey, a medical researcher who specializes in “It's problematic that the only group meeting these needs for.
This alteration, especially in male patients with schizophrenia, has also been tentatively linked to abnormalities in prenatal testosterone exposure, a mechanism relevant to GID. Cerebral Laterality and Handedness Besides indicating sexual dimorphism, the finger length ratio is also an indicator of cerebral lateralization [ 56 ]. Alterations in cerebral lateralization may result in an excess of atypical hand dominance patterns, such as left-handedness or mixed laterality.
A meta-analysis of 40 published studies found that schizophrenia was consistently associated with increased atypical hand dominance, particularly left-handedness [ 57 ].
Similarly, both male and female transsexuals have higher rates of non-right-handedness than healthy controls [ 58 ], and this has been documented even in young boys with childhood GID [ 59 ]. These findings suggest an altered pattern of lateralisation [ 58 ], presumably of developmental origin and at least partly linked to genes involved in neurodevelopment [ 60 ].
Toxoplasma Infection, Gender Identity, and Schizophrenia Prenatal or childhood infection with the parasite Toxoplasma gondii has been identified as a risk factor for schizophrenia [ 6162 ]. Though evidence of this infection is not found in all patients with the disorder, it may be associated with a less favourable outcome [ 63 ] and with a higher risk of suicidal behaviour in younger patients with schizophrenia [ 64 ]. The exact mechanisms involved in this association are unknown but may include increased dopamine levels [ 61 ], alterations in brain development [ 65 ], or the activation of endogenous retroviruses [ 66 ].
In a follow-up study of seven adult patients with congenital toxoplasmosis, one male patient had developed a male-to-female GID and undergone gender-reassignment surgery [ 68 ].
It is therefore possible that Toxoplasma infection may be a common risk factor for both disorders, though this proposal needs to be tested serologically in individuals with GID. The link between Toxoplasma infection and suicidality is also not without relevance, as suicidal and self-injurious behaviour is very common in individuals with GID [ 1517 ].
The Role of Brain-Derived Neurotrophic Factor Brain-derived neurotrophic factor BDNF is a nerve growth factor that plays a key role in brain development, as well as in the maintenance of neural plasticity in adult brains. The activity of BDNF can be influenced by several factors, including sex hormones such as oestrogen and testosterone [ 69 ]. A meta-analysis of studies conducted in patients with schizophrenia has identified a consistent, moderate decrease in blood BDNF levels compared to healthy controls [ 70 ].
Yet, it is equally probable that low BDNF levels may signal a defect or deviation in normal brain development in this patient group [ 73 ], in the light of what is already known about the role of this molecule in the sexual differentiation of the brain [ 74 ].
Moreover, as discussed below, these two explanations are not mutually exclusive.
The Role of Childhood Attachment and Childhood Adversity It is now well established that disturbances in parent-child attachment, including severe adverse experiences such as physical and sexual abuse, are associated with an elevated risk of schizophrenia [ 75 ].
A variety of biological and psychological mechanisms may underlie this association, including sensitization of dopamine pathways, impaired mentalizing abilities, and distortions of internal representations of the self and others; moreover, childhood adversity can itself alter brain development to some extent [ 76 ]. A relationship between disturbed childhood attachment and GID has been recognized for decades [ 77 — 81 ] and has unfortunately led to simplistic, reductionistic approaches to the management of this condition in some cases [ 82 ].Parents of a 7-Year-Old Schizophrenic Share Their Daily Struggle - The Oprah Winfrey Show - OWN
The two conditions are also genetically linked; a family history of schizophrenia is a risk factor for ASD [ 86 ], and common genetic vulnerability loci have been identified [ 87 ]. Conversely, studies of individuals with GID have identified high levels of autistic traits [ 93 ] and comorbid ASD [ 9495 ], though some of these results appear to be gender-specific. Deficits in empathising, a feature of ASD, are also associated with GD, especially in female-to-male subjects [ 96 ].
Several converging lines of evidence, involving cerebral sexual dimorphism, laterality, prenatal infection, and childhood adversity, suggest that both these disorders have their roots in abnormal brain development and that their overlap may be explained by shared risk factors such as Toxoplasma infection or mechanisms such as abnormal lateralization and sexual brain differentiation via common biochemical pathways, such as prenatal hormonal imbalances or reduced BDNF expression and release.
Schizophrenia is also associated with disturbances in body image and concept [ 97 — 99 ], which may be mediated through a frontal-limbic-temporal-parietal neural network [ ].
Such processes would be relevant to an alternate model of GID, in which disturbances in body image representation, involving suppression or distortion of body maps in the parietal cortex, are considered to be the central feature [ 5].
In either case, the existence of a link between the two disorders is certainly more than possible. Yet another intriguing possibility is raised by studies showing an association between GID and social cognitive deficits.
It has been found by some researchers that individuals with female-to-male GID have deficits in empathising. Further Directions for Research The proposal outlined above can be tested in several ways.
Structural brain imaging studies can assess similarities and differences in sexually dimorphic structures in both groups and identify areas of overlap. Functional brain imaging and neuropsychological assessment may shed the light on anomalies of cerebral lateralization in these disorders.
Clinical studies could focus on identifying body and gender disturbances in patients with schizophrenia and their first-degree relatives and schizotypal-like traits in patients with GID. The contribution of individual risk factors, such as Toxoplasma infection, can be assessed serologically. Genetic studies could examine the links between gender dysphoria, schizophrenia spectrum disorders, and related conditions such as autistic spectrum disorders. The consistency of, and correlations between, information obtained through these various methods would either clarify the link between schizophrenia and GID or refute it.
Limitations of the above Proposal The model proposed above is not free of shortcomings. In the first place, it makes the assumption that schizophrenia and GID are both clear-cut syndromes, which is far from the case; schizophrenia is a heterogeneous disorder [ ], and some of the clinical and developmental marker studies mentioned above have identified differences between male-to-female and female-to-male GID [ 749 — 51 ]. Second, GID is comorbid with a variety of other psychiatric disorders, particularly mood and anxiety disorders, at rates higher than those reported for comorbid schizophrenia [ 7131618 ].
It is not known if these disorders are the psychological consequence of living with GID, if they reflect shared vulnerabilities that need to be examined in their own right, or if patients with GID are at a nonspecifically elevated risk for a variety of disorders. Third, there are no systematic large-scale studies on gender disturbances in schizophrenia, or schizophrenia-like or schizotypal traits in GID, which would strengthen the case for the association proposed in this paper.
Fourth, while the evidence presented earlier points towards a link between these two conditions, it does not explain the large differences between them. For example, factors such as migration, urbanicity, obstetric complications, cannabis use, and maternal viral infection are specifically linked to schizophrenia [ 6 ], but not to GID. Similarly, developmental antecedents of GID, such as early childhood cross-gender behaviour and same-sex sexual fantasies [ ], are not specifically associated within schizophrenia.
In the case of birth order, the relationship between GID and schizophrenia seems to be inverse; an earlier birth order is associated with schizophrenia in males [ ], while a later birth order is associated with male-to-female GID . These divergences suggest that the two conditions may share certain causal pathways but do not overlap completely.
A further note of caution must be introduced here. The fact that scientific evidence suggests a link between GID and schizophrenia must not be taken to imply that GID is a psychotic disorder, that a wish for gender change is a form of schizophrenic thought disorder [ ], or that such individuals must be treated with antipsychotic medication.
It is beyond the scope of this paper to address the social and political controversies surrounding the diagnosis of GID [ 3]. Research in this area should be driven by methodologically sound science rather than personal or political beliefs. Conclusion The available evidence, though limited, suggests that both gender identity disorder and schizophrenia are neurodevelopmental disorders and that they may share common causal mechanisms and risk factors. Considering the variety of social norms, attitudes, and beliefs about illness across cultures, the similarity of the subjective experience of core schizophrenic symptoms and of the age at which they first occur in males and females is striking.
The findings suggest that the disorders of perception, thought, and self-awareness characteristic of schizophrenia are likely to have a common pathophysiological basis across various cultures.
Notwithstanding such overall similarity, there are variations in the clinical presentation of schizophrenia in different cultures that may influence recognition and treatment of the disease. Lambo [ 13 ] described a characteristic symptom complex in Nigeria consisting of anxiety, depression, vague hypochondriacal symptoms, bizarre magico-mystical ideas, episodic twilight or confusional states, atypical depersonalization, emotional lability, and retrospective falsification of memory based on hallucinations or delusions.
Pfeiffer,[ 14 ] drawing on observations in Indonesia, concluded that the disease pictures are essentially the same as in Central Europe, but he also described several local characteristics, such as frequent confusion, an admixture of manic features, and rarity of systematized delusions. Certain subtypes of schizophrenia, such as the acute onset form and the catatonic subtype characterized by bizarre movement disorders are more common in developing countries than in the West.
In the WHO country study. In isolated groups, such as island, highlands, or tribal populations, schizophrenic psychoses may present with certain atypical features, most likely as a result of ancestral founder effects and genetic drift. A more common clinical problem in developing countries may be the differentiation of schizophrenia from psychoses due to infectious or parasitic diseases.
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Since a variety of infectious, parasitic, and nutritional diseases are endemic in the developing world, it has been suggested that a high proportion of the cases of schizophrenia in those populations may in fact be symptomatic psychoses accompanying physical diseases such as malaria or typhoid fever.
In the WHO country study,[ 11 ] only On the other hand, common febrile illnesses may be among the factors precipitating the onset of acute, brief transient psychoses that are relatively frequent in developing countries, but bear no relationship to schizophrenia.
The association between temporal lobe epilepsy and a chronic, interictal psychosis that is difficult to distinguish from schizophrenia has been well documented clinically. In Taiwan, data collected over a year period indicate that of all mental disorders followed up, schizophrenia was associated with the highest mortality, representing an 80 percent increase over the mortality of the general population. Whereas in the past, the excess mortality among individuals with schizophrenia was due mainly to communicable diseases such as tuberculosis, the leading causes of premature death among patients with schizophrenia at present are suicide, accidents, and common physical diseases.
In developed countries, the suicide risk associated with schizophrenia is now nearly as high as that associated with major depression 4 —6 percent lifetime risk.
At least part of this excess mortality is preventable. Both the positive and negative symptoms of the disease interfere seriously with a person's capacity to cope with the demands of daily living.
Patients with schizophrenia experience particular difficulty in dealing with complex demands and environments, especially those that involve social interaction and decoding of social communication. The intervention of schizophrenia at this stage results in a severely truncated repertoire of social skills and lifelong socio-economic disadvantage. Such outcomes are not uncommon in either developed or developing countries, although in the latter settings, traditional family and community structures are still capable of providing a protective environment, and probably fewer patients are marginalized by society.
The projections for are 2. In terms of DALYs, predicted demographic trends include more than a 50 percent increase in the disease burden attributable to schizophrenia in developing countries, a burden approaching that of malaria and nutritional deficiency.
The total cost of illness for schizophrenia is disproportionately high relative to the population point prevalence of the disease on average, 5 per or lifetime morbid risk on average, 1 percent. In developed market economies, the direct costs of schizophrenia, incurred by hospital or community-based treatment, supervised accommodation, and related services, amount to 1.
Most of the economic evidence on schizophrenia comes from studies conducted in the Western market economies. However, mental health economics is a young discipline. Thus evidence on the costs of schizophrenia even in developed countries is at present limited, and such data are quite scarce for the majority of developing countries, although individual studies provide some insight into the likely economic impact of the disease.
Thus although the generic cost-driving factors associated with schizophrenia are likely to be similar around the world management of the chronic or relapsing symptoms and impairments, provision of inpatient and outpatient care and medication, mortality, lost productivity and unemployability, impact on the family, and impact on the communitytheir relative weight and hence the structure of the direct and indirect costs of the illness are likely to vary considerably.
Hospital or other residential care, which generates more than 75 percent of the direct costs of schizophrenia in high-income countries,[ 3334 ] is likely to account for a smaller fraction in developing countries because of lower staffing and equipment costs. On the other hand, the proportion of direct costs attributable to dispensing of antipsychotic medication, which is less than 5 percent of the total direct costs in developed countries,[ 33 ] is likely to be higher in developing countries.
It is difficult to estimate the economic impact of schizophrenia on families in developing countries. Yet the aggregate family costs in developing countries may, in fact, be substantially higher since 1 a larger proportion of schizophrenic patients live with their families as compared to patients in Western societies; 2 the family, not mental health services, is likely to be the first line of treatment and management of psychotic episodes; and 3 the cost of purchasing prescribed maintenance medication is usually borne by the family.
Additional direct costs may be incurred by the necessity to travel, often long distances, to the nearest hospital or clinic, as well as by payment for the services of traditional healers. In many traditional communities, the stigma associated with mental illness may affect the family as a whole and restrict, for instance, marital opportunities for younger family members. While lost educational opportunities are likely to be a problem, lost paid employment is more difficult to quantify, and therefore less likely to appear prominently in estimates of the indirect illness burden in developing countries.
On the other hand, reintegration of a family member who has suffered a psychotic episode into the domestic economy may be much easier to achieve than formal employment, and this may be one factor in the better and longer remissions of patients with schizophrenia observed in developing countries.
Crimes committed by persons with schizophrenia tend to receive wide media coverage and to reinforce popular ideas about dangerousness associated with mental illness. It is important to dispel such prejudicial attitudes. However, the population-attributable fraction of such offenses committed by persons with schizophrenia is negligibly small compared with the total number of offenses in the community. Moreover, the rate of apprehension and incarceration is likely to be high among patients with schizophrenia because of their conspicuous behavior and appearance, rather than the seriousness of the offense.