In this study, 298 patients initially met the traditional diagnostic criteria for psychiatric disorders. However, following symptomatic treatment, clinical symptoms worsened. Subsequently, after a series of additional specialized examinations, 101 cases were ultimately diagnosed with organic neurological diseases. This study emphasizes that when clinical symptoms worsen after symptomatic treatment for psychiatric disorders, a skeptical approach should be taken towards the initial diagnosis of psychiatric disorders. Careful consideration is needed to determine whether more accurate and comprehensive auxiliary examinations are necessary to reassess the etiology.Misdiagnosis of psychiatric disorders is a significant and common clinical problem [32]. Our hospital identified cases where organic neurological diseases were misdiagnosed as psychiatric disorders, with different frequencies observed between outpatient and inpatient settings. The misdiagnosis rate in inpatient care (32%) was lower than in outpatient care (39%), and half of the individuals experienced delayed treatment due to receiving symptomatic treatment in the psychiatric department for more than six months, resulting in a waste of medical resources [33].
Clinical practice often encounters organic diseases presenting primarily with psychiatric symptoms. Due to adherence to ICD-11 standards, the consideration is limited to the category of psychiatric disorders. With advancements in medical technology, the widespread and accurate application of CBA for testing antibodies in cerebrospinal fluid has become more common. Antibodies related to autoimmune encephalitis in cerebrospinal fluid were discovered in 2010 [34]. However, as of 2018, half of autoimmune encephalitis cases were found to initially present with psychiatric symptoms [35]. In this study, 57 patients initially misdiagnosed with psychiatric disorders were eventually diagnosed with autoimmune encephalitis. Functional neurological disorders and psychiatric disorders have become widely considered alternative diagnoses for autoimmune encephalitis. Therefore, distinguishing autoimmune encephalitis from psychiatric disorders poses a significant challenge [36]. Past literature reports a misdiagnosis rate of 13% for psychiatric disorders being misdiagnosed as autoimmune encephalitis [37]. In this study, 57 patients with psychiatric disorders were ultimately diagnosed with autoimmune encephalitis after an average of 4 months (median [IQR] time:4[2–6]months). The misdiagnosis rate of autoimmune encephalitis as psychiatric disorders was 19%.
With the recent advances in medical immunological testing technology, an increasing number of antibodies related to autoimmune encephalitis are being discovered, broadening the spectrum of autoimmune encephalitis [29]. This expansion leads to the reevaluation of cases that previously met the criteria for psychiatric disorders based on traditional diagnostic methods. Such cases are now definitively diagnosed with autoimmune encephalitis, thereby expanding the spectrum of diseases characterized by the onset or predominant manifestation of psychiatric symptoms [38]. The aforementioned highlights that as medical technology progresses, the broadening spectrum of autoimmune encephalitis poses a challenge to the diagnosis and treatment of psychiatric symptoms. It is essential to stay updated, and patients meeting the criteria for psychiatric disorders in clinical practice do not necessarily need early administration of psychiatric medications. Early cerebrospinal fluid tests (autoimmune encephalitis antibodies) and MRI imaging are recommended to aid in the early differentiation between psychiatric disorders and autoimmune encephalitis. Timely use of steroids for targeted treatment after early diagnosis is crucial for the prognosis of patients with autoimmune encephalitis.
Excluding autoimmune encephalitis (57%), another major misdiagnosis leading to psychiatric disorders is herpes simplex virus encephalitis, accounting for 22%. Previous studies have indicated that half of patients with viral encephalitis often present with psychiatric symptoms such as aggression and verbal abuse, which lead to initial psychiatric hospitalization [39]. However, with further examination, including lumbar puncture, cranial MRI, and antiviral treatment, rapid improvement occurs, and the correct diagnosis of viral encephalitis is established [40]. In this study, 22 patients, initially presenting with psychiatric symptoms for approximately 2 weeks (median [IQR] :0.5[0.1-1] month), were eventually diagnosed with herpes simplex virus encephalitis. Despite early symptomatic treatment for psychiatric symptoms, the patients did not show significant improvement, and their condition worsened. Subsequent cranial MRI and laboratory tests confirmed the diagnosis. After initiating antiviral treatment, the patients exhibited improvement [39]. The above findings suggest that clinicians, while symptomatically treating psychiatric disorders, can benefit from concurrently and empirically administering an adequate two-week antiviral treatment. This approach aids in the early experimental diagnosis and treatment of viral encephalitis, aiming to reduce the mortality and disability rates associated with this condition.
In addition, in this study, there were 3 cases diagnosed with CJD after 6 months, with a median (IQR) duration of 6 [5,6,7] months, presenting initially with psychiatric symptoms. Literature reports suggest that 25% of CJD patients have hidden typical symptoms in the early stages [41, 42], and 10% of patients begin with psychiatric symptoms such as depression, obsession, and personality changes [43]. According to reports [44], CJD patients with the onset of severe depression require approximately 6 months of disease course [42]. There is also research indicating that 15% of sporadic CJD patients will only exhibit symptoms suggestive of organic nervous system disease three months after the onset of depressive symptoms [45,46,47]. In this study, patients presented with early-onset isolated psychiatric symptoms for a duration of 4 months (median [IQR] time: 4 [2–6] months). They met the diagnostic criteria for psychiatric disorders, and routine traditional examinations (such as plain brain MRI) did not show significant abnormalities, making it challenging to distinguish them from individuals with genuine psychiatric disorders based on clinical presentation alone. Subsequent symptomatic treatment was ineffective, prompting additional specialized tests and examinations, including brain DWI, EEG, and cerebrospinal fluid 14-3-3 protein analysis, leading to the diagnosis of CJD. Therefore, patients meeting the criteria for psychiatric disorders should be considered for additional specialized tests and examinations, such as brain DWI, EEG, and cerebrospinal fluid analysis, even if traditional techniques like routine brain MRI show no abnormalities and symptomatic treatment for psychiatric symptoms proves ineffective [48]. Especially for patients and their families, recognizing the inevitable outcome of CJD underscores the importance of early diagnosis to prevent unnecessary waste of medical resources.
In this study, among patients with psychiatric symptoms as the initial manifestation, it is noteworthy that there were 14 cases ultimately diagnosed with N2O toxicity. These patients presented with isolated psychiatric symptoms for 6 months (median [IQR] duration: 6 [2–10] months). Despite receiving treatment for psychiatric disorders, there was no improvement. Through further investigation of medical history and additional specialized tests, the final diagnosis of subacute combined degeneration of the spinal cord caused by N2O abuse was confirmed within a period of 1 year (median [IQR] duration: 12 [8–20] months).
In recent years, N2O, as a novel substance of abuse, has become increasingly prevalent among young individuals [49]. The primary early characteristic symptom is often lower limb weakness [50]. Existing research indicates that psychiatric symptoms are also among the early manifestations of N2O abuse, with a duration of approximately 5 months [51, 52]. Therefore, when young patients around 22 years old (median [IQR] age 18–27 years) present with psychiatric symptoms that do not respond to prolonged treatment with psychiatric medications, the possibility of N2O intoxication should be considered. Clinical practitioners are encouraged to inquire in detail about a history of N2O abuse in young patients. If a young patient refuses to admit N2O abuse, clinicians may consider having a private conversation away from accompanying individuals to protect the patient’s dignity. This study emphasizes the importance of thorough and repeated inquiries into the medical history of young patients with psychiatric symptoms and prompt reevaluation of laboratory tests, including serum vitamin B12 levels. Early identification and intervention are crucial in managing psychiatric symptoms resulting from N2O abuse. By detecting potential vitamin B12 deficiency in a timely manner, clinicians can initiate treatment promptly. Early high-dose vitamin B12 supplementation can improve clinical symptoms and prevent further damage to the nervous system caused by vitamin B12 deficiency.
In actual clinical practice, patients may not undergo routine laboratory tests for infectious disease markers such as syphilis [53, 54]. In this study, three patients were initially diagnosed with mania in outpatient settings and were treated for psychiatric symptoms for 2 months (median [IQR] duration of 2 [1–3] months). However, their conditions worsened, leading to symptoms like memory decline, prompting hospitalization. Laboratory tests conducted during hospitalization revealed positive results for syphilis, confirming that syphilis was causing the psychiatric symptoms. Therefore, it is important to consider the possibility of syphilis before diagnosing psychiatric disorders in outpatient settings. Early testing for infectious disease markers can lead to an early diagnosis, reduce the duration of psychiatric medication use, and facilitate timely treatment for the underlying cause. Early targeted treatment can help control the progression of syphilis, reduce organic damage to patients, and slow down the development of the disease.
Among the misdiagnosed patients, there were two cases that took four months (median [IQR]duration of 4 [3–5] months) to be finally diagnosed with Hashimoto’s encephalopathy. In the early stages, these patients presented only with bipolar affective disorder, and their condition persisted for 2.5 months (median [IQR] duration of 2.5 [2–3] months). After ineffective symptomatic treatment, they were admitted for further care. Laboratory tests during hospitalization revealed elevated TSH, increased TgAb, and elevated serum TPOAb. Subsequent treatment with corticosteroids proved effective, leading to the diagnosis of Hashimoto’s encephalopathy [55, 56]. Therefore, thyroid function-related laboratory tests should be considered as part of the exclusionary diagnostic measures in the diagnostic criteria for psychiatric disorders.
Conforming to diagnostic criteria for psychiatric disorders and a lack of awareness regarding organic neurological disorders are the main reasons for misdiagnosis, leading to various problems. Firstly, misdiagnosis of psychiatric disorders increases the incidence rate of organic diseases due to the failure to initiate correct treatment for organic causes in a timely manner. Secondly, in this study, the median (IQR) duration of treatment for psychiatric symptoms using psychotropic medications was as long as 6 months (median (IQR) 6 (0.5–24) months), and prolonged use of psychotropic medications may often result in serious side effects, including gastrointestinal reactions such as nausea and vomiting, cardiac toxic reactions such as tachycardia or bradycardia, extrapyramidal symptoms of the nervous system, endocrine reactions like menstrual irregularities and decreased libido, and damage to liver and kidney function. Thirdly, in cases where long-term symptomatic treatment for psychiatric symptoms is ineffective, it increases the medical costs for patients.