Case Reports

Challenges and Considerations in Treating Negative and Cognitive Symptoms of Schizophrenia Spectrum Disorders

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Background: The prototypical patient with schizophrenia spectrum disorders (SSDs) is often thought to possess positive symptoms. However, patients with SSDs can present with predominantly negative and cognitive symptoms, which can create diagnostic and treatment challenges.

Case Presentation: A 33-year-old female veteran presented to the emergency department with diminished speech output, markedly blunted affect, tangential speech, was not oriented to situation, and appeared to be responding to internal stimuli. Following inpatient admission, the veteran was diagnosed with schizoaffective disorder, which was misdiagnosed as major depressive disorder and borderline personality disorder during her military service. She was initially treated with olanzapine injections and psychotherapy but continued to experience worsening symptoms, resulting in multiple hospitalizations. After starting clozapine, she demonstrated marked improvement and continued with outpatient mental health care.

Conclusions: Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for the patient. Clozapine is a promising treatment for addressing these symptoms. This case demonstrates how careful multidisciplinary evaluations, review of health records, collateral information from family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.



Schizophrenia spectrum disorders (SSDs) represent some of the most debilitating mental health disorders.1 While these disorders have myriad presentations, the prototypical patient with SSD is often thought to possess positive symptoms. More recently, clinicians and researchers are raising awareness of another presentation of SSD: predominantly negative and cognitive symptoms. This symptom profile is not a novel phenomenon; for many years this presentation was recognized as a “deficit” presentation, referring to negative symptoms as the prominent feature.2,3 However, it presents unique diagnostic and treatment considerations that are often underappreciated in clinical settings.

Negative symptoms (blunted/flat affect, avolition, alogia, anhedonia, asociality) have long been identified as key features of SSD and are widely recognized as predictive of poor prognostic outcomes for patients with SSDs.1 In many patients, negative symptoms may precede the development of positive symptoms and emerge as a more robust predictor of functional outcomes than positive symptoms.1 Negative symptoms also appear to be inextricably linked to cognitive symptoms. Specifically, patients with primary negative symptoms seem to perform poorly on measures of global cognitive functioning.1 Similar to negative symptoms, cognitive symptoms of SSDs are a primary source of functional impairment and persistent disability.1 Despite this, little attention is given in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) to the neurocognitive and social cognitive deficits seen in patients with SSDs. Previous research highlights broad deficits in a range of neurocognitive abilities, including attention, working memory, processing speed, executive functioning, learning and memory, and receptive and expressive language.4 Similarly, patients also display deficits in domains of social cognition, such as emotion processing, identifying and utilizing social cues, evaluating attributions of others, and perspective-taking.5

A predominantly negative and cognitive symptom presentation can present diagnostic and treatment challenges. We present a case of a patient with such a presentation and the unique considerations given to diagnostic clarification and her treatment.

Case Presentation

A 33-year-old female veteran presented to the emergency department (ED) at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, in 2020. She was brought to the ED by local police following an attempted assault of her neighbor. Per collateral information from the police, the veteran stated she “had the urge to hurt someone” but was unable to provide any other information about this event. The veteran demonstrated diminished speech output, providing 2- to 3-word responses before refusing to speak entirely. She also presented with markedly blunted affect and tangential speech. She was not oriented to situation, stating confusion as to how she was brought to the hospital, and appeared to be responding to internal stimuli. She was subsequently admitted to the inpatient mental health unit due to unspecified psychosis.

The veteran presented as an unreliable historian, and much of her medical history was obtained via a review of US Department of Defense (DoD) records and collateral interview with her parents. Before her hospitalization, the veteran had been diagnosed with major depressive disorder (MDD) and adjustment disorder while serving in the Navy. Her psychiatric history before her military career was otherwise unremarkable. At that time, she began a trial of sertraline 50 mg and completed 10 sessions of psychotherapy. After approximately 1 year, she elected to stop taking sertraline due to improved mental health. However, shortly after this she began experiencing significant depressive symptoms and was ultimately released early from the Navy due to her mental health concerns.

The veteran’s parents provided interim history between her discharge and establishing care at MEDVAMC as the veteran was reluctant to discuss this period of her life. According to her parents the veteran had prior diagnoses of borderline personality disorder and MDD and had difficulty adhering to her current medications (bupropion and duloxetine) for about 1 month before her hospitalization. During the previous month, her parents observed her staying in her room around the clock and “[going] mute.”

The veteran remained hospitalized for about 1 month, during which she was diagnosed with schizoaffective disorder and stabilized on injections of long-acting olanzapine 210 mg (administered every 2 weeks). She was referred for outpatient psychotherapy in a specialty clinic for veterans with SSDs. However, she did not attend her initial intake assessment.


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