Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.

Cognitive dysfunction is common in many psychiatric disorders. While it has long been described as a core feature in schizophrenia, more recent data suggest qualitatively similar impairments in patients with bipolar disorder and major depressive disorder. There is compelling evidence to suggest that cognitive impairment contributes directly to functional disability and reduced quality of like across these disorders. As current treatments focus heavily on “primary” symptoms of mood and psychosis, the standard of care typically leaves cognitive deficits unmanaged. With this in mind, the field has recently begun to consider intervening directly on this important symptom domain, with several ongoing trials in schizophrenia. Fewer studies have targeted cognition in bipolar disorder and still fewer in MDD. With progress toward considering this domain as a target for treatment comes the need for consensus guidelines and methodological recommendations on cognitive trial design. In this manuscript, we first summarize the work conducted to date in this area for schizophrenia and for bipolar disorder. We then begin to address these same issues in MDD and emphasize the need for additional work in this area.

Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.

Neuropsychiatric illnesses including mood disorders are accompanied by cognitive impairment, which impairs work capacity and quality of life. However, there is a lack of treatment options that would lead to solid and lasting improvement of cognition. This is partially due to the absence of valid and reliable neurocircuitry-based biomarkers for pro-cognitive effects. This systematic review therefore examined the most consistent neural underpinnings of cognitive impairment and cognitive improvement in unipolar and bipolar disorders. We identified 100 studies of the neuronal underpinnings of working memory and executive skills, learning and memory, attention, and implicit learning and 9 studies of the neuronal basis for cognitive improvements. Impairments across several cognitive domains were consistently accompanied by abnormal activity in dorsal prefrontal (PFC) cognitive control regions—with the direction of this activity depending on patients’ performance levels—and failure to suppress default mode network (DMN) activity. Candidate cognition treatments seemed to enhance task-related dorsal PFC and temporo-parietal activity when performance increases were observed, and to reduce their activity when performance levels were unchanged. These treatments also attenuated DMN hyper-activity. In contrast, nonspecific cognitive improvement following symptom reduction was typically accompanied by decreased limbic reactivity and reversal of pre-treatment fronto-parietal hyper-activity. Together, the findings highlight some common neural correlates of cognitive impairments and cognitive improvements. Based on this evidence, studies are warranted to examine the reliability and predictive validity of target engagement in the identified neurocircuitries as a biomarker model of pro-cognitive effects.

While impairments in cognitive emotional processing are key to the experience of mood disorders, little is understood of their shared and distinct features across major depressive disorder (MDD) and bipolar disorder (BD). In this review, we discuss the similarities and differences in abnormal emotional processing associated with mood disorders across the cognitive domains of perception, attention, memory, and reward processing, with a particular focus on how these impairments relate to the clinical profile of the disorders. We consider behavioral and neuroimaging evidence, especially that of the growing consensus surrounding mood-congruent biases in cognition, in combination with state- and trait-related characteristics in an attempt to provide a more comprehensive and translational overview of mood disorders. Special consideration is given to the shared phenomenon of mood instability and its role as a potential transdiagnostic marker across the prodrome and maintenance of mood disorders.

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.

Mild cognitive impairment (MCI) represents a transitional stage between healthy aging and dementia, and affects 10–15% of the population over the age of 65. The failure of drug trials in Alzheimer’s disease (AD) treatment has shifted researchers’ focus toward delaying progression from MCI to dementia, which would reduce the prevalence and costs of dementia profoundly. Diagnostic criteria for MCI increasingly emphasize the need for positive biomarkers to detect preclinical AD. The phenomenology of MCI comprises lower quality-of-life, greater symptoms of depression, and avoidant coping strategies including withdrawal from social engagement. Neurobiological features of MCI are hypoperfusion and hypometabolism in temporoparietal cortices, medial temporal lobe atrophy particularly in rhinal cortices, elevated tau and phosphorylated tau and decreased Aβ42 in cerebrospinal fluid, and brain Aβ42 deposition. Elevated tau can be identified in MCI, particularly in the entorhinal cortex, using positron emission tomography, and analysis of signal complexity using electroencephalography or magnetoencephalography holds promise as a biomarker. Assessment of MCI also relies on cognitive screening and neuropsychological assessment, but there is an urgent need for standardized cognitive tests to capitalize on recent discoveries in cognitive neuroscience that may lead to more sensitive measures of MCI. Cholinesterase inhibitors are frequently prescribed for MCI, despite the lack of evidence for their efficacy. Exercise and diet interventions hold promise for increasing reserve in MCI, and group psychoeducational programs teaching practical memory strategies appear effective. More work is needed to better understand the phenomenology and neurobiology of MCI, and how best to assess it and delay progression to dementia.

A growing body of research has shown that two domains of cognition, neurocognition and social cognition, predict different domains of real-world outcomes in people with schizophrenia. Social cognition has been shown to predict social outcomes but not non-social outcomes (e.g. living independently), and neurocognition provides minimal prediction of social outcomes (e.g. interpersonal relationships). The differing predictive value of neurocognition and social cognition has led to an exploration of potential factors that interact with cognition to influence everyday outcomes. Functional skills, negative symptoms, and self-assessment have shown particularly promising relationships with cognitive ability. Several consensus studies have pinpointed valid performance-based assessments. High-contact informant ratings have additionally been shown to be highly accurate. The emerging understanding of divergent patterns of predicting outcomes and reliable assessments present an opportunity to improve treatment targets and real-world outcomes for individuals with schizophrenia. In particular, a recently defined component of metacognition has shown particular promise. Introspective accuracy (IA) addresses how well individuals evaluate their own abilities. Emerging research has found that IA of neurocognitive ability better predicts everyday functional deficits than scores on performance-based measures of neurocognitive skills and has found that IA of social cognition accounts unique variance in real world disability above social cognitive abilities. Intriguingly, IA of neurocognition appears to preferentially predict non-social outcomes while IA of social cognition predicts social outcomes.

Major depression is a multidimensional disorder producing emotional dysregulation, cognitive impairment, and neuro-vegetative symptoms. A pathophysiological model of depression needs to explain how these dimensions interact to produce specific clinical phenotypes and how these interactions may predict remission to specific treatments. It is unlikely that major depression results from discrete brain lesions. Here we propose to define major depression as a disorder of neural networks. We review evidence suggesting that the dynamics of neural networks involved in allocation of attention resources to the internal and external world contribute to cognitive impairment, increased self-focus, and dysfunctional saliency detection in depression. We describe cognitive and emotional tasks that reveal abnormal cooperation between the Central Executive Network and the Default Mode Network. Finally we suggest that depression is associated with increased social rejection sensitivity. Studies on social rejection will shed light on how attachment relates to impairment in allocation of attention resources to produce depressive symptoms such as rumination and cognitive problems.

Cognitive impairments in substance use disorders have been extensively researched, especially since the advent of cognitive and computational neuroscience and neuroimaging methods in the last 20 years. Conceptually, altered cognitive function can be viewed as a hallmark feature of substance use disorders, with documented alterations in the well-known “executive” domains of attention, inhibition/regulation, working memory, and decision-making. Poor cognitive (sometimes referred to as “top-down”) regulation of downstream motivational processes—whether appetitive (reward, incentive salience) or aversive (stress, negative affect)—is recognized as a fundamental impairment in addiction and a potentially important target for intervention. As addressed in this special issue, cognitive impairment is a transdiagnostic domain; thus, advances in the characterization and treatment of cognitive dysfunction in substance use disorders could have benefit across multiple psychiatric disorders. Toward this general goal, we summarize current findings in the abovementioned cognitive domains of substance use disorders, while suggesting a potentially useful expansion to include processes that both precede (precognition) and supersede (social cognition) what is usually thought of as strictly cognition. These additional two areas have received relatively less attention but phenomenologically and otherwise are important features of substance use disorders. The review concludes with suggestions for research and potential therapeutic targeting of both the familiar and this more comprehensive version of cognitive domains related to substance use disorders.

Mental imagery refers to the experience of perception in the absence of external sensory input. Deficits in the ability to generate mental imagery or to distinguish it from actual sensory perception are linked to neurocognitive conditions such as dementia and schizophrenia, respectively. However, the importance of mental imagery to psychiatry extends beyond neurocognitive impairment. Mental imagery has a stronger link to emotion than verbal-linguistic cognition, serving to maintain and amplify emotional states, with downstream impacts on motivation and behavior. As a result, anomalies in the occurrence of emotion-laden mental imagery has transdiagnostic significance for emotion, motivation, and behavioral dysfunction across mental disorders. This review aims to demonstrate the conceptual and clinical significance of mental imagery in psychiatry through examples of mood and anxiety disorders, self-harm and suicidality, and addiction. We contend that focusing on mental imagery assessment in research and clinical practice can increase our understanding of the cognitive basis of psychopathology in mental disorders, with the potential to drive the development of algorithms to aid treatment decision-making and inform transdiagnostic treatment innovation.

Neuropsychological dysfunction is a well-established finding in individuals with bipolar disorder type I (BP-I), even during euthymic periods; however, it is less clear whether this also pertains to bipolar disorder type II (BP-II) or those with subthreshold states (SBP; subthreshold bipolar disorder), such as bipolar not otherwise specified (BP-NOS). Herein, we compare the literature regarding neuropsychological performance in BP-II vs BP-I to determine the extent of relative impairment, and we present and review all related studies on cognition in SBP. After systematically searching PubMed, Medline, PsycINFO, and The Cochrane Library, we found 17 papers that comprise all the published studies relevant for this review. The areas that are consistently found to be impaired in BP are executive function, verbal memory, visual spatial working memory, and attention. More studies than not show no significant difference between BP-I and BP-II, particularly in euthymic samples. Preliminary evidence suggests that patients experiencing major depressive episodes who also meet criteria for SBP show similar profiles to BP-II; however, these results pertain only to a depressed sample. SBP were found to perform significantly better than both MDD and healthy controls in a euthymic sample. A consensus on mood state, patient selection, and neuropsychological testing needs to be agreed on for future research. Furthermore, no studies have used the most recent DSM-5 criteria for SBP; future studies should address this. Finally, the underlying bases of cognitive dysfunction in these diagnostic groups need to be further investigated. We suggest recommendations on all of the above current research challenges.

A key message from the review of cognitive dysfunction in psychiatry published by Millan et al (2012) was not just that cognitive skills are often compromised in patients with psychiatric disorders, but that deficits in specific domains are common to a number of conditions. The review also highlighted that the magnitude of the observed deficits varied across disorders. A helpful element of the Millan et al study was the inclusion of a table in which the authors sought to convey the domains of cognition and a categorization of the magnitude of the observed deficits.

In previous articles, we have considered best practice for the assessment of cognition. In these contributions, we have argued not for the use of specific tests, but instead for measures that meet acceptable standards of reliability, validity, and sensitivity. In the course of our discussions, we have included reference to test validity in the context of considering whether selected measures index appropriate domains of cognition. In this article, we begin with a brief discussion of the requirements for good test selection, especially with respect to issues of sensitivity, reliability, and validity. Thereafter the focus of this article is on the issue of domain validity. We will critically review the specification of the cognitive domains proposed by Millan et al, as well as those selected by authors of meta-analyses characterizing cognitive deficits in major depressive disorders. This focus is solely to make the discussion tractable, though we propose that the issues raised will be applicable across all psychiatric and neurological disorders.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

The 2018 NEI Congress would like to congratulate the following scientific poster winners:

1stPlace:

20 - The Need for Speed: Adjunctive Triple Chronotherapy. An Accelerated Intervention in the Treatment of Acute Depression in the Adolescent Population

Diane Hurd, PMHNP; Mariela Herrera, MD; Nicholas Coombs, MS; Jeannine M. Brant, PhD, APRN, AOCN, FAAN; Eric Arzubi, MD

2ndPlace:

93 - Practical Outpatient Pharmacotherapy for Alcohol Use Disorder

Youngjung Kim, MD, PhD; Laura Hack, MD, PhD; Elizabeth Ahn, MD; Jungjin Kim, MD

3rdPlace:

95 - Differential Aspects Between Schizophrenia Treatment Approaches: Oral Antipsychotics vs. Aripiprazole Long-Acting Injectable

S Arques Egea; E Ros Cucurull; C Iranzo Tatay; C Parro-Torres; RF Palma-Álvarez; E Castrillo; MA Cantillo; P Aznar