• Neuroimaging
• Mood Disorders
• Personality Disorders

Psychotic and mood disorders are often diagnostically complicated. They affect various regions of the brain, and diagnostic criteria can be inconsistent. Additionally, these disorders are often progressive in nature, so signs and symptoms may change over time. Stephen M. Lawrie, MD, University of Edinburgh, Edinburgh, Scotland, discussed the challenges and possible diagnostic strategies that are specifically related to schizophrenia and psychosis.

Psychotic symptoms are unreliably elicited and are diagnostically nonspecific. Therefore, the use of DSM-IV schizophrenia criteria alone is not always the most viable method of diagnosis. According to Dr. Lawrie, the “gold standard” of schizophrenia diagnosis needs to be augmented with more reliable clinical data. He suggests a variety of diagnostic aids to ensure consistency throughout the clinical community.

Creating a reliable clinical profile of psychosis should begin in the clinical trial environment. Studies should be designed and analyzed with the real world in mind. The study population should include cohorts that will appropriately translate into clinical practice. The trial setting also should be considered when reporting clinically relevant statistics, such as sensitivity and specificity, positive and negative predictive value, and effect size.

Developmental abnormalities may also assist clinicians in identifying patients with schizophrenia. Early social, sensory-motor, and intellectual deficits and anomalies may predict schizophrenia and merit further evaluation as diagnostic tools. However, it is important to note that they may simply be trait effects and that predictability may be age-dependent [Tarbox et al. Psychol Bull 2008; Lawrie SM et al. B J Psych 2001; Pukrop R et al. Neurotox Res 2010].

Using imaging as a diagnostic aid may be the most reliable tool to date. Structural imaging, functional imaging, and the identification of imaging biomarkers show promise as diagnostic tools. Advances are being made in this area of technology, making early detection of psychosis more attainable. However, Dr. Lawrie cautions that technology with higher sensitivity tends to be more expensive and technically demanding. Furthermore, as more biomarkers and disease-predicting genotypes become available, false negative results may also be introduced and tend to compound the diagnostic burden.

Stephen M. Strakowski, MD, University of Cincinnati, Cincinnati, OH, detailed various imaging approaches in bipolar disorder (BPD). Amygdala and striatal enlargement has been associated with BPD in several imaging studies. However, there is some inconsistency across studies with regard to the amygdala findings [Strakowski SM et al. Mol Psychiatry 2005; Noga et al. 2001; Altschuler L et al. Arch Gen Psychiatry 1998; DelBello et al. Bipolar Disorders 2004].

BPD is a progressive disorder, and structural changes within the anterior limbic network (ALN) of the brain have been suggested in relation to disease progression. In fact, frequent episodes may alter brain structure. However, there also appears to be a developmental component to these structural modifications [Strakowski SM et al. Mol Psychiatry 2005]. Some observed structural changes include decreased cerebellar vermis volume, occurring in patients who have experienced multiepisodes; age-related fluctuations in amygdala volume; and increased ventricular volume, correlating with the number of episodes [Delbello et al. 1999; Chen at al. 2004; Strakowski et al 2002; Brambilla et al. 2001; Strakowski SM et al. Mol Psychiatry 2005].

Aggressive psychopharmacological treatment may help prevent disease progression. The use of proton magnetic resonance spectoscopy (¹H-MRS) has elucidated some metabolic processes that are associated with drug treatment and suggests contributing factors in BPD, such as abnormalities in mitochondrial metabolism, membrane metabolism, and second messenger systems [Stork & Renshaw. Mol Psychiatry 2003]. Glutamatergic excitotoxicity may also contribute to observed progressive brain changes.

According to ¹H-MRS studies, there is considerable neurochemical variability that is associated with different drug therapies. For example, while lithium decreases glutamate, glutamine, and gamma-aminobutyric acid (Glx) concentration, valproate does not [Friedman SD et al. Biol Psychiatry 2004]. Lithium also increases N-acetyl-aspartate (NAA) in the brain [Moore GJ et al. Biol Psychiatry 2000]. These factors suggest that lithium may be neuroprotective. In an ¹H-MRS study by Delbello and colleagues that investigated the effects of olanzapine on neurochemistry in manic adolescents, NAA levels increased in treatment remitters (p=0.05) and decreased in nonremitters (p=0.03). Additionally, investigators suggested that olanzipine-induced increases in choline may lead to abnormalities in cell membrane metabolism or second messenger pathways that are thought to play a role in BPD pathology [Delbello MP et al. Neuropyschopharmacol 2005].

Functional magnetic resonance imaging (fMRI) may also reveal how treatment impacts brain function. Overactivation of the ALN has been implicated in disease progression, according to fMRI studies, specifically related to increased amygdala activation and decreased prefrontal modulation [Eliassen et al. Biol Psychiatry 2006; Olson et al. Biol Psychiatry 2006].

Advances in technology and psychopharmacology have increased our understanding of the pathophysiology of psychotic and mood disorders, such as schizophrenia and BPD. While definitive diagnoses are not always feasible, we are now able to identify potential biomarkers and may be able to use imaging to predict treatment success and disease risk. Metabolic abnormalities and structural changes within the brain have also provided insight into disease pathology. Established protocols are still being developed concerning optimal treatment strategies for psychosis and mood disorders, but clinical practice is beginning to move toward an imaging-based approach to diagnosis and treatment.

• © 2010 MD Conference Express