Badari Birur

Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder—a systematic review of the magnetic resonance neuroimaging literature

Since Emil Kraepelin’s conceptualization of endogenous psychoses as dementia praecox and manic depression, the separation between primary psychotic disorders and primary affective disorders has been much debated. We conducted a systematic review of case–control studies contrasting magnetic resonance imaging studies in schizophrenia and bipolar disorder. A literature search in PubMed of studies published between January 2005 and December 2016 was conducted, and 50 structural, 29 functional, 7 magnetic resonance spectroscopy, and 8 combined imaging and genetic studies were deemed eligible for systematic review. Structural neuroimaging studies suggest white matter integrity deficits that are consistent across the illnesses, while gray matter reductions appear more widespread in schizophrenia compared to bipolar disorder. Spectroscopy studies in cortical gray matter report evidence of decreased neuronal integrity in both disorders. Functional neuroimaging studies typically report similar functional architecture of brain networks in healthy controls and patients across the psychosis spectrum, but find differential extent of alterations in task related activation and resting state connectivity between illnesses. The very limited imaging-genetic literature suggests a relationship between psychosis risk genes and brain structure, and possible gene by diagnosis interaction effects on functional imaging markers. While the existing literature suggests some shared and some distinct neural markers in schizophrenia and bipolar disorder, it will be imperative to conduct large, well designed, multi-modal neuroimaging studies in medication-naïve first episode patients that will be followed longitudinally over the course of their illness in an effort to advance our understanding of disease mechanisms.

Sex Differences in the Peripheral Immune System in Patients with Depression

Background Females are twice as likely as males to experience depression. Recent findings indicate a relationship linking inflammation with depression. Whether the higher prevalence of depression in women is sex-specific or if inflammation contributes to a higher prevalence of depression in females is unclear. Thus, the objective was to determine whether depressed females show higher inflammation compared to males in a cross-sectional study. Materials and methods Two hundred participants were enrolled. Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), and blood samples were collected from all participants to measure inflammatory blood markers. Results Higher rates of suicidal thoughts, pessimism, and lassitude measured by the MADRS were seen in depressed females compared with depressed males. Among all inflammatory markers measured, there were no significant differences in depressed males vs. male controls. Increased levels of interleukin (IL)-8, interferon-γ, and leptin, and decreased levels of IL-5 and adiponectin were observed in depressed females compared to female controls. Compared with depressed males, IL-6 and leptin levels were significantly elevated in depressed females after controlling for body mass index. Correlation analysis revealed that depression severity negatively correlated with IL-12 in males, and positively correlated with IL-1β and tumor necrosis factor (TNF)-α in females. IL-1β and TNF-α correlated with suicidal thoughts, lassitude, and pessimism in depressed females. Conclusion Our findings indicate a sex-specific relationship between inflammation and depression, which may be important in identifying potential psychopathology and suggesting novel immunomodulatory treatments for depressed females.

The Life Span Model of Suicide and Its Neurobiological Foundation

The very incomprehensibility of the suicidal act has been occupying the minds of researchers and health professionals for a long time. Several theories of suicide have been proposed since the beginning of the past century, and a myriad of neurobiological studies have been conducted over the past two decades in order to elucidate its pathophysiology. Both neurobiology and psychological theories tend to work in parallel lines that need behavioral and empirical data respectively, to confirm their hypotheses. In this review, we are proposing a “Life Span Model of Suicide” with an attempt to integrate the “Stress-Diathesis Model” and the “Interpersonal Model of Suicide” into a neurobiological narrative and support it by providing a thorough compilation of related genetic, epigenetic, and gene expression findings. This proposed model comprises three layers, forming the capability of suicide: genetic factors as the predisposing Diathesis on one side and Stress, characterized by epigenetic marks on the other side, and in between gene expression and gene function which are thought to be influenced by Diathesis and Stress components. The empirical evidence of this model is yet to be confirmed and further research, specifically epigenetic studies in particular, are needed to support the presence of a life-long, evolving capability of suicide and identify its neurobiological correlates.

An evidence-based review of early intervention and prevention of posttraumatic stress disorder

We present an evidence-based review of post-trauma interventions used to prevent posttraumatic stress disorder (PTSD). Literature search of PubMed from 1988 to March 2016 using keywords “Early Intervention AND Prevention of PTSD” yielded 142 articles, of which 52 intervention studies and 6 meta-analyses were included in our review. Trauma-focused cognitive behavioral therapy and modified prolonged exposure delivered within weeks of a potentially traumatic event for people showing signs of distress have the most evidence in the treatment of acute stress and early PTSD symptoms, and the prevention of PTSD. Even though several pharmacological agents have been tried, only hydrocortisone prior to high-risk surgery, severe traumatic injury, or during acute sepsis has adequate evidence for effectiveness in the reduction of acute stress symptoms and prevention of PTSD. There is an urgent need to determine the best targets for interventions after trauma to accelerate recovery and prevent PTSD.

Dimensions of schizophrenia and their time course of response to a second generation antipsychotic olanzapine—A clinical study

BACKGROUND The pattern of symptom response to second generation antipsychotics (SGAs) has not been studied extensively. Understanding the time course of symptom response would help to rationally monitor patient progress. OBJECTIVE To determine the short-term differential time course of response of symptom dimensions of first episode schizophrenia viz., negative, positive symptoms and 5 factors of anergia, thought disturbance, activation, paranoid-belligerence and depression to treatment with SGA olanzapine. METHODS 57 drug naive patients with schizophrenia were treated for 4 weeks with olanzapine 10mg/day, increased to 20mg/day in 1 week. Weight was recorded and ratings with the Positive and Negative Syndrome scale (PANSS), the Simpson Angus Scale (SAS) were performed weekly. RESULTS 43 patients completed 4 weeks of assessment. Scores on all of the dimensions improved. By the end of week 1, only positive syndrome, thought disturbance and paranoid-belligerence dimensions improved. Maximum improvement was seen with paranoid-belligerence by week 1, followed by positive syndrome in week 2, and depression at week 3. The percentage improvement in positive syndrome was significantly greater than negative. Over 4 weeks there was a mean weight gain of 2kg and there were significant extrapyramidal symptoms. CONCLUSIONS Olanzapine produced reduction in all dimensions, but the pace of responding of individual dimensions differed. Longer-term studies comparing SGAs with first generation antipsychotics are needed.

Sensory Reduction on the General Milieu of a High-Acuity Inpatient Psychiatric Unit to Prevent Use of Physical Restraints: A Successful Open Quality Improvement Trial:

BACKGROUND: Impaired sensory gating in patients with acute mental illness predisposes to overstimulation and behavioral dyscontrol. OBJECTIVE: Explore use of sensory reduction interventions on a high-acuity inpatient milieu to reduce high assault/restraint rates. DESIGN: A multidisciplinary team using failure mode and effect analysis to explore high restraint use between 4:00 p.m. and 7:00 p.m. observed patient/staff overstimulation contributed to behavioral escalations. The team implemented sensory reduction/integration improvements over a 5-month period to prevent excessive restraint use. RESULTS: Restraint rates dropped immediately following light and sound reduction interventions and by 72% at 11 months postimplementation. Mann-Whitney statistics for unpaired 6-month comparisons, 1-year pre- and postintervention showed significant reductions: Assault rates (median pre = 1.37, post = 0.18, U = 4, p = .02); Restraint rates (median pre = 0.50, post = 0.06, U = 0, p = .002). CONCLUSION: Sensory reduction during a high-stress time period on a high-acuity psychiatric unit was associated with a reduction in assaults and restraints.

Psychosis as a sequelae of paraneoplastic syndrome in Small- Cell Lung Carcinoma: A psycho-neuroendocrine interface

In 2013 more than 150,000 Americans died from all types of lung cancer. Small cell lung cancer (SCLC) represents about 13% of all lung cancers and is notoriously associated with paraneoplastic syndromes (PNS). Here we present an interesting case of psychosis associated with one such PNS-- ectopic Cushing syndrome of SCLC. A 56 year old African-American male with no prior psychiatric history who was diagnosed with SCLC two months prior, presented to the ER for treatment of a right arm laceration he sustained while fighting off attackers, with high concern these individuals may have been part of hallucinatory experiences and well-systematized persecutory delusions regarding his wife. Physical assessment was notable for Cushingoid symptoms. Initial results of serum ACTH and cortisol were 221pg/ml (10-50pg/ml) and 37.1 mcg/dl (10-20mcg/dl) respectively. For psychosis, patient was started on Olanzapine which was titrated from 5 to final dose of 10mg nightly. Since patient was not a surgical candidate, he was treated with metyrapone 250 mg BID and radiation therapy was continued throughout hospitalization. Serum Cortisol level decreased steadily after initiation of metyrapone and psychotic symptoms dramatically reduced on olanzapine, metyrapone, and radiation therapy with apparently resolved persecutory delusions at discharge. This case broadens the available literature and provides data on successful symptomatic treatment with olanzapine while biological treatments of the underlying condition were beginning to take effect. As SCLC remains an important cause of morbidity and mortality in the US, it is imperative that physicians be aware of paraneoplastic syndromes and their psychiatric sequelae.