Epidemiology of Depressive Disorders in Patients With Liver Cirrhosis: A Population-Based Study in the United States.

Objective: Major depressive disorder (MDD) is a chronic, debilitating mood disorder associated with poor medical outcomes. MDD has a multifactorial etiology with numerous biopsychosocial factors implicated as risk factors. Functional and psychiatric impairments have been evaluated in patients with liver cirrhosis; however, less is known about the prevalence and risk factors for the development of MDD in those patients. The objective of this study was to evaluate the risk of developing depression among adult patients with liver cirrhosis in the United States.Methods: Data were collected using a commercial database, an aggregate of electronic health record data from 26 major integrated US health care systems consisting of 360 hospitals in the US from 1999 to 2019.The study cohort was retrieved by searching the database for a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of "cirrhosis of liver" during the designated period of the study.The following factors were adjusted for in the analyses: age, sex, race, smoking, alcohol, substance abuse, underlying mental disorders, and comorbidities.Results: 56,197,690 adults were identified between 1999 and 2019. Of those, 293,150 had a diagnosis of liver cirrhosis. The prevalence of depression among those cirrhotic patients was 23.93% versus 7.61% in the noncirrhotic control group (95% CI, 16.1836%-16.4770%; P < .0001). By applying a multivariate analysis model, cirrhotic patients were found to be more likely to develop depression (odds ratio = 2.172; 95% CI, 2.159-2.185; P < .0001) compared to patients with no prior history of liver cirrhosis.Conclusions: Liver cirrhosis is associated with increased risk of depression and is likely to be an independent risk factor in its development. Future efforts should focus on the identification and treatment of this debilitating condition in those with liver cirrhosis via an integrated care model.

Brain reward circuitry: The overlapping neurobiology of trauma and substance use disorders.

Mental health symptoms secondary to trauma exposure and substance use disorders (SUDs) co-occur frequently in both clinical and community samples. The possibility of a shared aetiology remains an important question in translational neuroscience. Advancements in genetics, basic science, and neuroimaging have led to an improved understanding of the neural basis of these disorders, their frequent comorbidity and high rates of relapse remain a clinical challenge. This project aimed to conduct a review of the field's current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD. A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders, and is summarized in detail, including evidence from both animal and clinical studies. Upon summarizing the relevant literature, this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward cues. It provides an overview of brain reward circuitry and its relation to the neurobiology, symptomology, and phenomenology of trauma and substance use. This review provides clinical insights and implications of the proposed theory, including the potential development of novel pharmacological and therapeutic treatments to address this shared neurobiology. Limitations and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.

A systematic review on the impact of psychotropic drugs on electroencephalogram waveforms in psychiatry.

OBJECTIVES: It is known that psychotropic medications have an impact on the readings found in Electroencephalogram (EEG). In the field of psychiatry, there are several psychotropics utilized by clinicians. This review seeks to investigate all the available data for psychotropic drugs and their impact on EEG changes. METHODS: A systematic review of all the published and ongoing literature was conducted via PubMed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was used for each search. Key words for searches include 'EEG and Psychotropics', 'EEG and Mood Stabilizers', 'EEG and Clozapine', 'EEG and Bupropion', 'EEG and SSRI', 'EEG and Lamotrigine', 'EEG and Carbamazepine', 'EEG and Lithium' and 'EEG and Valproate', 'EEG and Haloperidol', 'EEG and Aripiprazole', 'EEG and Methylphenidate', 'EEG and Topiramate', 'EEG and Gabapentin' and 'EEG and Oxcarbamazepine'. After applying the inclusion criteria, 201 articles were eligible and reviewed. RESULTS: Following an extensive review of selected studies from the 201 articles, the studies indicate that each of the psychotropic medications reviewed impact alpha, beta, delta and theta waves independently and differently from each other. Additionally, certain medications, particularly haloperidol and valproic acid, have dissimilar results exemplified in all waveforms. CONCLUSIONS: This PRISMA systematic review illustrates that while there is available data on psychotropic medications and their proposed effect on EEG activity, further research is needed to confirm these findings to help allow clinical correlations to be made between the patient's response and the psychotropic agent.

Can cannabis cause psychosis?

In recent years, increasing popular support for the medicinal and recreational use of cannabis has led to legalization for both medicinal and recreational purposes in the United States. To the extent that these changes in policy lead to increase widespread use, it is important to consider the association between heavy chronic cannabis use and the onset of psychotic illnesses, such as schizophrenia. This article provides a brief review of evidence that support cannabis use as a risk factor in the complex etiology of psychotic illness. In addition to reviewing psychopharmacology, longitudinal research, and clinical studies, the article addresses the potential implications of current research on public health policy.

Management of auditory hallucinations as a sequela of traumatic brain injury: a case report and a relevant literature review.

A patient with progressively worsening auditory hallucinations and 30-year history of traumatic brain injury (TBI) was reported. To formulate a comprehensive diagnostic and treatment approach to patients with auditory sensory disturbances and other neuropsychiatric sequela of a TBI, an electronic search of the major behavioral science databases (PubMed, PsycINFO, Medline) and a textbook review were conducted to retrieve studies detailing the clinical characteristics, biological mechanisms, and therapeutic approaches to post-TBI psychosis. Additional references were incorporated from the bibliographies of the retrieved articles. Although infrequent, auditory hallucinations is a debilitating complication of TBI that can manifest itself 4-5 years after the occurrence of TBI. Because the age range of TBI survivors is 15-24 years, and the chance of developing post-TBI psychosis is reported to be up to 20%, this chronic neuropsychiatric complication and the available treatment options warrant close scrutiny from the clinical and the biomedical research community. Our case report and literature review demonstrates a clear need for a large, well-designed randomized trials to compare properties and efficacies of different, available, and promising pharmacotherapy agents for the treatment of post-TBI psychosis.

Cognitive effects of quetiapine in a patient with dementia with Lewy bodies.

A recent large-scale randomized controlled clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study, found a significant worsening of cognitive functioning in a sample of patients with Alzheimer's disease. To date there have been no equally powered studies examining the cognitive effects of atypical antipsychotics in patients with dementia with Lewy bodies, the second most prevalent neurodegenerative disorder. This case report describes a significant cognitive improvement observed through the use of an atypical antipsychotic in a patient with dementia with Lewy bodies. The observed divergence in cognitive responsiveness is discussed mechanistically on both the clinical and neuromolecular level. Limitations to this case study design are presented and discussed. The prudence of caution in importing the results of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study to the dementia with Lewy bodies population is summarized and presented for psychiatrists, neurologists and primary care providers, with an intent to stimulate discussion and further research.

Long-acting injectable antipsychotics and the development of postinjection delirium/sedation syndrome (PDSS).

OBJECTIVES: Five long-acting injectable (LAI) antipsychotics are currently available in the United States for the treatment of schizophrenia: fluphenazine decanoate, haloperidol decanoate, risperidone microspheres, paliperidone palmitate, and olanzapine pamoate. Additionally, aripiprazole LAI is currently under FDA review. However, research into the safety and tolerability of these LAIs, with particular regard to the development of postinjection delirium/sedation syndrome (PDSS), is limited and has been focused mainly on olanzapine pamoate. This proposal seeks to review data regarding all currently available LAI antipsychotics to determine if a significant association exists between these depot formulations and the development of PDSS. METHODS: A review of all published literature from 2005 to the present was obtained via a PubMed search for current data regarding the topic of LAIs and the development of PDSS. Keywords used for the search were "long-acting injectable antipsychotics" in association with one of the following: "post-injection delirium/sedation syndrome," "PDSS, " "side effects, " and "tolerability." References to key articles were further explored for relevancy to this proposal. RESULTS: A case analysis based on all 8 olanzapine LAI clinical trials conducted between August 2000 and October 2008 showed an occurrence of PDSS in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). A second case analysis reviewing the clinical trial databases for 15 completed studies and the postmarketing safety database for risperidone LAI versus 10 completed clinical trials of paliperidone palmitate failed to demonstrate an occurrence of PDSS events in patients receiving either LAI treatment. However, one case of PDSS was identified in a placebo group. In 4 randomized, double-blind, placebo-controlled trials, treatment-emergent adverse events leading to treatment discontinuation were similar for paliperidone palmitate and placebo; however, among the most frequently occurring treatment-emergent adverse events was somnolence/sedation (5%-7% paliperidone palmitate group vs 3% placebo). CONCLUSIONS: Postinjection delirium/sedation syndrome is a potentially serious adverse event that has been shown to be associated with one currently available LAI antipsychotic, olanzapine pamoate. However, further data are still needed to both support this conclusion and determine if an association exists among other currently available LAIs and PDSS. With the bulk of current evidence coming from registration studies, head-to-head comparison studies between 2 LAIs would help to determine whether the risk of postinjection complications differs among different agents. Further observational studies are also needed to address the incidence, severity, and optimal clinical management of this syndrome.

Scopolamine as an antidepressant: a systematic review.

OBJECTIVES: The cholinergic-adrenergic hypothesis of mania and depression states that depression is characterized by an increase in central cholinergic activity relative to noradrenergic tone. Scopolamine is a centrally acting competitive inhibitor of the muscarinic cholinergic receptor site. This review seeks to find all available data investigating scopolamine as an antidepressant. METHODS: A systematic review of all the published and unpublished or ongoing literature was conducted via Ovid MEDLINE. Keywords used for the search were "scopolamine hydrobromide" in association with one of the following: "depression," "antidepressive agents," "depressive disorder," "depression, chemical," and "affect." PubMed was also searched using "scopolamine" (all fields) and "antidepressant" (all fields) or "depression" (all fields). RESULTS: A small study with elderly patients failed to show a statistically significant improvement in depression when measured at 120 minutes after infusion. A second small, well-controlled study using intramuscular scopolamine showed a small but statistically significant improvement in depression on the morning after the second dose was received. Two double-blind randomized placebo-controlled crossover trials with intravenous scopolamine 4.0 µg/kg infusions showed a significant improvement in depressive symptoms seen as soon as 3 days after the first treatment. Further data analyses showed a greater antidepressant effect in women, significant improvements in bipolar depression, and 85% success rates predicting who will respond to treatment. CONCLUSIONS: Scopolamine is an effective and rapid antidepressant in both unipolar and bipolar depression, working as quickly as 3 days after initial infusion. Independent replication would greatly enhance the literature.

Larger putamen size in antipsychotic-naïve individuals with schizotypal personality disorder.

OBJECTIVE: To (a) compare the size of the dorsal and ventral striatum (caudate and putamen) in a large sample of antipsychotic-naïve individuals with schizotypal personality disorder (SPD) and healthy control participants; (b) examine symptom correlates of striatal size in SPD. METHODS: The left and right caudate and putamen were hand-traced on structural MRI at five dorsal to ventral slice levels in 76 SPD and 148 healthy control participants. A Group×Region (caudate, putamen)×Slice (1-5: ventral, 2, 3, 4, dorsal)×Hemisphere (left, right) mixed-model MANOVA was conducted on size relative to whole brain. RESULTS: Primary results showed that compared with the controls, the SPD group showed (a) larger bilateral putamen size overall and this enlargement was more pronounced at the most ventral and dorsal levels; in contrast, there were no between-group differences in caudate volume; (b) larger bilateral size of the striatum ventrally, averaged across the caudate and putamen. Among the SPD group, larger striatal size ventrally, particularly in the left hemisphere was associated with less severe paranoid symptoms. CONCLUSIONS: Striatal size is abnormal in SPD and resembles that of patients with schizophrenia who respond well to antipsychotic treatment. The results suggest that striatal size may be an important endophenotype to consider when developing new pharmacological treatments and when studying factors mitigating psychosis.

Psychotherapy for schizophrenia: a review of modalities and their evidence base.

We reviewed the techniques and evidence base of four psychotherapeutic adjuncts to the pharmacological treatment of schizophrenia: Personal therapy, cognitive behavioral therapy, cognitive enhancement therapy, and psychodynamic psychotherapy. While there is a significant evidence base for the first three of these modalities, there is a paucity of research on psychodynamic treatments for schizophrenia. We review the history of psychodynamic treatment for schizophrenia and the ways in which it informs current treatment. In light of the limited efficacy of antipsychotic medications in the treatment of schizophrenic persons, there is increasing interest in the role of social and psychological approaches.

The importance of patient-provider communication in end-of-life care.

Successful formulation and implementation of end-of-life care requires ongoing communication with the patient. When patients, for reasons of general medical or psychiatric illness, fail to verbally communicate, providers must be receptive to messages conveyed through alternate avenues of communication. We present the narrative of a man with schizophrenia who wished to forgo hemodialysis as a study in the ethical importance of attention to nonverbal communication. A multilayered understanding of the patient, as may be provided by both behavioral and motivational models, can inform the provider's ability to receive, process, and represent communicated content to the patient or his or her surrogate decision-maker.

The effects of hypertension and body mass index on diffusion tensor imaging in schizophrenia.

Recently, the negative effects of hypertension and elevated body mass index on cognitive functioning in schizophrenia have been reported (Friedman et al., 2010). Data suggests that cognitive changes in hypertensive patients from the general population may be mediated, in part, by white matter damage. Therefore, we performed diffusion tensor imaging (DTI) in the same subjects studied by Friedman et al. (2010) to investigate the effects of hypertension and elevated body mass index on the fractional anisotropy (FA) of several major white matter tracts. Significant interactions between a diagnosis of schizophrenia and hypertension on FA in several white matter regions were detected. Hypertension was associated with lower FA in the schizophrenic group and higher FA in the same tracts in the non-schizophrenic subjects. These results suggest hypertension-induced compensatory mechanisms in the brains of non-schizophrenic patients with hypertension which may be impaired in persons with schizophrenia.

Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy.

Despite its superior efficacy, clozapine is helpful in only a subset of patients with schizophrenia unresponsive to other antipsychotics. This lack of complete success has prompted the frequent use of various clozapine combination strategies despite a paucity of evidence from randomized controlled trials supporting their efficacy. Pimozide, a diphenylbutylpiperidine, possesses pharmacological and clinical properties distinct from other typical antipsychotics. An open-label trial of pimozide adjunctive treatment to clozapine provided promising pilot data in support of a larger controlled trial. Therefore, we conducted a double-blind, placebo-controlled, parallel-designed 12-week trial of pimozide adjunctive treatment added to ongoing optimal clozapine treatment in 53 patients with schizophrenia and schizoaffective disorder partially or completely unresponsive to clozapine monotherapy. An average dose of 6.48 mg/day of pimozide was found to be no better than placebo in combination with clozapine at reducing Positive and Negative Syndrome Scale total, positive, negative, and general psychopathology scores. There is no suggestion from this rigorously conducted trial to suggest that pimozide is an effective augmenting agent if an optimal clozapine trial is ineffective. However, given the lack of evidence to guide clinicians and patients when clozapine does not work well, more controlled trials of innovative strategies are warranted.

Brain stimulation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration.