Theories on the Overlap of Posttraumatic Stress Disorder With Schizophrenia
Several theories have been put forward, which attempt to account for the occurrence of psychotic symptoms in PTSD. These theories focus on the occurrence of similar psychotic symptoms in both PTSD and schizophrenia and other psychotic disorders. Current theories are: PTSD with psychotic symptoms is a distinct subtype of PTSD; PTSD with psychotic symptoms may be a misdiagnosis of prodromal schizophrenia; and comorbidity of PTSD and schizophrenia.
Posttraumatic Stress Disorder With Psychotic Symptoms is a Subtype of Posttraumatic Stress Disorder
The DSM-V describes within PTSD, symptoms of auditory pseudo hallucinations, more voices, as well as paranoid ideation. It also purposely mentions the diagnostic difficulty in which flashbacks must be distinguished from illusions, hallucinations and other perceptual disturbances that occur in schizophrenia (see Table 1).[1,11]
There have been relatively few studies directly comparing those with and without psychotic symptoms in PTSD (See Table 1). Despite the focus on structural changes in schizophrenia research, there are no available imaging studies examining brain structural changes in patients with and without psychotic symptoms and a diagnosis of PTSD.
There may be a Misdiagnosis of Posttraumatic Stress Disorder in Prodromal Cases of Schizophrenia
A reverse way of thinking about them could be that these cases may be a form of schizophrenia that results from 'cerebral damage' caused by experiencing a traumatic event or an interaction of the 'environmental' trauma with a genetic predisposition for psychosis. Thus, an alternative possibility is that there is misdiagnosis of PTSD when in fact the individual is in a prodromal (or early) stage to the onset of a schizophrenia-like illness. Because the symptoms overlap and extreme PTSD can look like psychosis, differential diagnosis by clinicians can be subjective and variable. When a trauma clearly took place prior to the emergence of symptoms, then the diagnosis may be biased toward PTSD. Thus, many people are being diagnosed with PTSD in their early 20s in the United States after having experienced combat in the military. These are the years in which the onset of schizophrenia is most frequent. There is also extensive literature on trauma, particularly in childhood associated with later development of schizophrenia (as well as with PTSD) and this should not be overlooked.[18,20] In addition, stress has long been thought to be associated with the onset of schizophrenia and anomalies in the physiological response to stress in schizophrenia were reported as early as 1949.
Auditory hallucinations are present in several nonpsychotic disorders, as well as a proportion of the 'normal' population. Auditory hallucinations in PTSD may be chance occurrences, which are perceived as threatening, secondary to the heightened arousal state of PTSD. Misdiagnosis is likely to persist without a longitudinal approach and understanding of the underlying biological basis for the illness and its later course, as the clinical presentation is difficult to differentiate on a cross-sectional basis. Symptoms such as hallucinations have been shown to be clinically indistinguishable in adolescents with PTSD or a psychotic disorder.
Patients with PTSD also exhibit the chronic debilitating social withdrawal, which is characteristic of schizophrenia. They are likely to become socially withdrawn and mistrustful of people, which can be misconstrued as paranoia. Hypervigilance as a symptom of PTSD can be easily confused with paranoia. They also have a high level of substance abuse, which is a risk factor for psychosis. Patients with substance abuse are then more likely to be involved in further traumatic events, which again increase their risk of both PTSD and psychosis.
There has been some effort examining cultural differences in patients with diagnoses of a psychotic illness, and DSM-IV-TR cultural formulation has been used in clarifying the diagnosis of psychotic disorders in those of ethnic minority and immigrant backgrounds. This approach, which takes into account the cultural identity of the patient and the cultural explanation of the individual's illness, led to a reclassification of psychotic disorders to nonpsychotic disorders in several cases. PTSD, depression and bipolar affective disorder were the most commonly diagnosed conditions following reclassification. This suggests that there may be considerable misdiagnosis of PTSD in particular when psychotic symptoms are present.
Independent Comorbidity of Posttraumatic Stress Disorder and Schizophrenia
Another possibility is that these are comorbid independent conditions and having one does not exclude the other or that someone who has schizophrenia is more vulnerable to PTSD or vice versa, but that they remain separate entities with different underlying causative mechanisms. There is considerable evidence for the development of PTSD in patients following a first psychotic episode or patients with schizophrenia who experienced a traumatic event either during childhood or afterwards[29,30] and who experience symptoms that overlap both disorders. PTSD is more prevalent in people with schizophrenia who have experienced a trauma than in trauma-exposed people without schizophrenia, suggesting that these disorders either potentiate each other or somehow interact. PTSD comorbid with schizophrenia has been shown to be most commonly secondary to the initial occurrence of psychosis, involuntary medication and the associated psychological stress.[32,33] PTSD is likely to be underdiagnosed in patients with psychotic disorders and this may contribute to their symptom severity.[13,35]
It follows then that the same premorbid factors that elevate risk for schizophrenia may elevate the risk for PTSD, whether they are biologic or psychosocial. Some of the known risk factors common to both disorders are particularly childhood sexual abuse,[36–39] a history of childhood psychotic symptoms, other prior psychiatric diagnoses such as depression and substance use disorder,[41,42] attention deficit hyperactivity disorder and/or other childhood psychiatric disorders,[43,44] ethno cultural minority status and additional life stressors.
Some genetic risk factors may also be shared between psychiatric disorders. A preliminary genome-wide association study (GWAS) of markers throughout the genome in a large meta-analysis of samples from over 20 research groups suggested excess overlap of risk genes between PTSD and schizophrenia.[46,47] However, there has never been a positive family study of PTSD or schizophrenia that would suggest that these disorders are genetically related,[48,49] although no recent studies have examined this issue and the previous studies were small. The one family study that does exist shows no increase in risk for psychosis in relatives of patients who developed PTSD with psychotic features when compared to relatives of PTSD patients without psychotic features. This suggests that PTSD with psychotic features is unlikely to be accounted for by a comorbid schizophrenia or familial tendency for schizophrenia.
There is little biological evidence that supports PTSD with psychotic features as having distinct biological processes as compared with PTSD without psychotic features and other psychotic disorders (see Table 1).[14,49,50] There have been few studies focusing on specific genes, which have been associated with PTSD. BDNF is a gene involved in neurodevelopment, regeneration, neurotransmission, learning and regulation of mood and stress response. The Met allele of BDNF, BDNFVal66Met is associated with psychotic disorders,[51,52] and a study has shown that BDNFVal66Met was carried more often by those with PTSD and psychotic features than by those with PTSD without psychotic features. This suggests that some of the same genes associated with psychosis in schizophrenia may also be associated with PTSD with psychosis. Another gene that has been recently studied in relation to PTSD is ADRB2, a gene involved in the adrenergic system and that has been shown to be associated with PTSD. The one available study on ARB2 receptors in schizophrenia showed no increase in ligand-binding; however, ARB1 was associated with a significant decrease in ligand-binding. The association between adrenergic activity and PTSD/psychosis remains unclear and requires further study. It has previously been associated with a predisposition to asthma, obesity and type 2 diabetes. The significance of the association in PTSD is unknown, but could be related to decreased resilience to stressors. There have been few studies examining the subgroup of patients with psychosis in PTSD.
Much more will need to be unravelled in the future to further the understanding of psychosis when it occurs in PTSD. To this end, brain structural and functional changes, which have long been reported in schizophrenia, will need to be studied in PTSD with and without psychosis to see whether they can distinguish these groups and will ultimately be important in determining whether PTSD with psychotic features is an independent comorbid psychotic condition instead of the manifestations of a particularly severe case of PTSD.[6,14,16,50]
Curr Opin Psychiatry. 2015;28(3):249-255. © 2015 Lippincott Williams & Wilkins