Neuroprotective effects of psychotropic drugs in Huntington's disease.

Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc.) are commonly prescribed to treat Huntington's disease (HD). In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium), histone acetylation (lithium, valproate, lamotrigine), miR-222 (lithium-plus-valproate), mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin), neurogenesis (lithium, valproate, fluoxetine, sertraline), and BDNF (lithium, valproate, sertraline) and downregulated AP-1 DNA binding (lithium), p53 (lithium), huntingtin aggregation (antipsychotics, lithium), and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin). In HD live mouse models, delayed disease onset (nortriptyline, melatonin), striatal preservation (haloperidol, tetrabenazine, lithium, sertraline), memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine), motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine), and extended survival (lithium, valproate, sertraline, melatonin) have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan) and downregulated histone deacetylase (HDAC; valproate) await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3) suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine.

Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease.

Psychotropics are widely prescribed in Alzheimer disease (AD) without regard to their pathobiological effects. Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression for 52 genes linked to AD. Pending future investigations, current data indicate that atypical antipsychotics, lithium, and fluoxetine reduce AD risk, whereas other drug classes promote risk. Risk may be attenuated by antipsychotics and lithium (down-regulate TNF), atypical antipsychotics (down-regulate TF), risperidone (down-regulates IL1B), olanzapine (up-regulates TFAM, down-regulates PRNP), fluoxetine (up-regulates CLU, SORCS1, NEDD9, GRN, and ECE1), and lithium coadministered with antipsychotics (down-regulates IL1B). Risk may be enhanced by neuroleptics (up-regulate TF), haloperidol (up-regulates IL1B and PION), olanzapine (down-regulates THRA and PRNP, up-regulates IL1A), and chlorpromazine, imipramine, maprotiline, fluvoxamine, and diazepam (up-regulate IL1B). There were no results for dextromethorphan-plus-quinidine. Fluoxetine effects on CLU, NEDD9, and GRN were statistically robust. Drug effects on specific variants, polymorphisms, genotypes, and other genes (CCR2, TF, and PRNP) are detailed. Translational AD risk applications and their limitations related to specific genes, mutations, variants, polymorphisms, genotypes, brain site, sex, clinical population, AD stage, and other factors are discussed. This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on AD-relevant genes.

Agomelatine in depressive disorders: its novel mechanisms of action.

Disruptions in sleep and sleep-wake cycle regulation have been identified as one of the main causes for the pathophysiology of depressive disorders. The search has been on for the identification of an ideal antidepressant that could improve both sleep disturbances and depressive symptomatology. Melatonin, the major hormone of the pineal gland, has been shown to improve sleep and is involved in the regulation of the sleep-wake cycle. Identification of high concentrations of MT1 and MT2 melatonergic receptors in the suprachiasmatic nucleus of the anterior hypothalamus, the structure concerned with regulation of circadian rhythms and sleep-wake cycles, has led to the development of melatonergic agonists with greater potency and longer durations of action. Agomelatine is one such melatonergic agonist that acts specifically on MT1/MT2 melatonergic receptors and at the same time exhibits 5-HT2C antagonism, a property that is utilized by current antidepressants that are in clinical use. Agomelatine has been shown to be effective in a number of animal models of depression. Clinical studies undertaken on patients with major depression, bipolar disorders, seasonal affective disorder, and generalized anxiety disorder have all shown that agomelatine is also very effective in ameliorating depressive symptoms and manifesting early onset of action with a good tolerability and safety profile. It improved sleep efficiency and also resynchronized the disrupted circadian rhythms. Hence, the melatonergic modulation by agomelatine is suggested as one of the mechanisms for its antidepressant effect. Agomelatine's action on dendritic neurogenesis in animal models of depression is also identified as yet another action.

Psychiatric comorbidities of chronic migraine in community and tertiary care clinic samples.

Although the association between episodic migraine and psychiatric comorbidities is well documented, few studies have focused on the comorbidity with chronic migraine (CM) and discrepancies exist between population-based and clinic-based data. The objective of this study is to compare demographic and psychiatric comorbidity correlates between CM samples drawn from the community and tertiary care. All inhabitants from a city borough were interviewed for the presence of headaches occurring 15 or more days per month. CM was diagnosed after subjects had been interviewed and examined by a headache doctor. Participants were also assessed with a structured interview by a psychiatrist, who assigned diagnoses based on the DSM-IV. The same investigators assessed all patients consecutively seen in a university-based outpatient headache center over a 4-month period. The samples consist of 41 individuals from the community and 43 from the headache center. Sociodemographic profiles were similar between groups with the exception of the mean number of years of formal education. Among individuals from the community, psychiatric diagnoses were present in 65.9 % of cases, relative to 83.7 % in those from the headache center (p = 0.06). Phobias (41.9 vs. 29.3 %) and depression (32.6 vs. 29.3 %) were more frequent in patients from the headache center, but this difference did not reach statistical significance. Thus the frequency of psychiatric disorders in patients with CM was elevated in both settings, being higher in the specialty care clinic.

Psychopharmacological neuroprotection in neurodegenerative diseases, part III: criteria-based assessment: a report of the ANPA committee on research.

Neuroprotective therapies for neurodegenerative diseases (NDDs) have proven elusive. The established psychotropic agents commonly used to treat the neuropsychiatric manifestations of NDDs are potential neuroprotective therapies, and neuropsychiatrists and others may benefit from a knowledge of the neuroprotective properties of these medications. This report identifies FDA-approved, first-line psychotropic drugs affecting intracellular mechanisms and meriting disease-modifying clinical trials in NDDs. The authors evaluated evidence for neuroprotection according to 1) preclinical; and 2) clinical criteria. Despite low-to-moderate preclinical evidence scores and scant clinical evidence, the most promising investigative priorities are 1) lithium and paroxetine in Alzheimer's disease (AD); 2) lithium in tauopathies (frontotemporal lobar degeneration [FTLD], FTDP-17); 3) lithium-plus-valproate in AD and amyotrophic lateral sclerosis; 4) pramipexole and valproate in Parkinson's disease; 5) amantadine and buspirone in multiple system atrophy; and 6) antidepressants in Huntington's disease. Preliminary clinical results signal caution regarding olanzapine use in AD and poor tolerability of lithium in progressive supranuclear palsy and corticobasal degeneration. These preliminary findings can lead to further clinical drug trials on the use of these well-known medications, not only for their psychotropic effects, but also for neuroprotection in NDDs.

Psychopharmacological neuroprotection in neurodegenerative disease: heuristic clinical applications.

In Part I of this report, the authors reviewed preclinical and clinical evidence of neuroprotection by psychotropics and proposed criteria to predict translational neuroprotection. Here, the authors review a broad array of neuroprotective mechanisms and, based on evidence reviewed in Part I, consider agents with pharmacodynamic mechanisms of action that may be associated with neuroprotection. The neuroprotective potential of the pharmacodynamic mechanisms discussed here are held in common with drugs that evidenced neuroprotective potential in Part I. The agents examined here have symptomatic utility in neurodegenerative disease neuropsychiatric disorders and combine the most promising pharmacodynamic mechanisms yet have received insufficient research to date. Modafinil, duloxetine, ziprasidone, s-zopiclone, and ramelteon are evaluated in terms of their putative neuropsychiatric symptomatic and heuristic neuroprotective disease-modifying potentials. The authors review these agents in terms of their potential for clinical neuroprotection and suggest a criterion-based research agenda for future studies of their neuroprotective potential. Further research is needed with regard to the 10 translational neuroprotective candidate criteria, neuroprotective clinical trials, the correlation of psychotropic pharmacodynamic mechanisms with neuroprotective actions, and the translational predictive utility of the proposed candidate criteria.

Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data.

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Differential pharmacological responses of catatonia-like signs in frontotemporal dementia.

Sequential therapeutic trials for catatonoid frontal signs in clinically-evident frontotemporal dementia (n = 2) revealed differential benefits for lorazepam, amantadine, memantine, pramipexole, aripiprazole, quetiapine, citalopram, and donepezil, although certain signs also worsened. Citalopram and donepezil were poorly tolerated. Ramelteon was without effect. While memantine appeared to improve cognition in case 1, this remains to be established by more reliable neuropsychological testing. Parkinsonism (case 2) responded to pramipexole, but not amantadine or levodopa. Possible relationships of catatonoid signs requiring future confirmation include insufficient GABA-A (multiple signs) and D2 (mutism) and excessive NMDA (immobility, rigidity), D2/D3 (mannerisms, verbal perseveration), and 5HT1a (staring) receptor stimulation. Low-dose lorazepam and quetiapine required close monitoring.

Mood and neurobehavioral correlates of cerebellar lesions.

OBJECTIVE: The authors studied mood disorder and neurobehavioral correlates of solitary focal cerebellar (CB) lesions. BACKGROUND: CB function has been correlated with cognitive, behavioral, and psychiatric conditions. Systematic study of uncomplicated CB pathology can further our understanding of these correlates. METHOD: Magnetic Resonance Images were blindly selected from 20,000 scans for solitary focal CB lesions after excluding other pathology. "Secondary" conditions (developing after lesion onset) were determined using structured clinical interviews (DIS and SCID) for psychiatric diagnoses while blind to MRI findings. Clinical correlates of lesions and a priori hypotheses were examined in 13 participants while controlling for alternative attributions (atrophy, hyperintensities, ventriculomegaly, disability, etc.). RESULTS: Bipolar disorders after CB lesions were more common than expected in normal populations (OR 28.62, 95% CI 3.51 < - >233.34, P=0.0001), replicating a previous finding. Secondary DSM-III and -IV depressive disorders correlated with posterolateral lesions of the right CB posterior lobe (P=0.0035); severity correlated with lesion size. Other lesion correlates included hypomania (anterolateral left CB posterior lobe), apathy (medial left anterior lobe, anterolateral right posterior lobe), disinhibition and dysexecution (medial left anterior lobe), agitation (central left and anterolateral right posterior lobe), and elation (anterolateral right posterior lobe). Although other structural cerebral and psychosocial variables did not explain the findings, much larger sample sizes will be needed to adequately control for these variables. CONCLUSIONS: Review of the literature reveals support for these findings, suggesting CB control of mood, behavior, and frontal cognition.

Differential regulation of prodynophin, c-fos, and serotonin transporter mRNA following withdrawal from a chronic, escalating dose regimen of D-amphetamine.

Several lines of evidence suggest that D-amphetamine (D-AMPH) withdrawal induces a syndrome with symptoms similar to major depressive disorder (MDD). Upregulation of dynorphin (DYN) may underlie the symptoms of MDD and contribute to the negative emotional symptoms associated with psychostimulant withdrawal. Changes in the serotonin transporter (SERT) have also been reported in MDD, and changes in the immediate early gene c-fos have been observed in the context of psychostimulant withdrawal. This study examined the effects of chronic, escalating doses of D-AMPH followed by 24 h of withdrawal on the expression of prodynorphin (PD) and c-fos mRNA in limbic regions of the brain, caudate putamen (CPu), and brainstem and SERT mRNA expression in the dorsal raphe nucleus (DRN). Male Sprague-Dawley rats were treated three times a day for 4 days with escalating doses of D-AMPH (1-10 mg/kg) and sacrificed 24 h after the last injection. Following 24 h of withdrawal, there was an increase in PD and c-fos mRNA expression in the CPu and nucleus accumbens (NAc), and a decrease in PD and c-fos expression in hippocampus and amygdala. SERT mRNA expression was decreased in the DRN, and PD mRNA expression was increased in the adjacent ventrolateral periaqueductal gray (VLPAG) following D-AMPH withdrawal. These data indicate that region-specific changes in PD and c-fos expression occur after withdrawal, while SERT mRNA expression is suppressed, similar to what has been reported in MDD. Alterations in PD, c-fos, and SERT expression could contribute to the depression-like syndrome associated with psychostimulant withdrawal.

Neuroanatomy of pathological laughing and crying: a report of the American Neuropsychiatric Association Committee on Research.

Pathological laughing and crying (PLC) is a clinical condition that occurs in patients with various neurological disorders. It is characterized by the presence of episodic and contextually inappropriate or merely exaggerated outbursts of laughter and/or crying without commensurate feelings. This review provides an in depth analysis of the neuroanatomy of lesions seen in patients with this clinical condition, discusses the relevant functional neuroimaging and electrophysiological stimulation studies in human subjects, and summarizes the current treatment options. It concludes with a presentation of the remaining questions and directions for future research.

Early psychiatric morbidity in a Brazilian sample of acute ischemic stroke patients.

OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians.

Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action.

BACKGROUND: Dextromethorphan (DM) is a widely-used antitussive. DM's complex central nervous system (CNS) pharmacology became of interest when it was discovered to be neuroprotective due to its low-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonism. REVIEW SUMMARY: Mounting preclinical evidence has proven that DM has important neuroprotective properties in various CNS injury models, including focal and global ischemia, seizure, and traumatic brain injury paradigms. Many of these protective actions seem functionally related to its inhibitory effects on glutamate-induced neurotoxicity via NMDA receptor antagonist, sigma-1 receptor agonist, and voltage-gated calcium channel antagonist actions. DM's protection of dopamine neurons in parkinsonian models may be due to inhibition of neurodegenerative inflammatory responses. Clinical findings are limited, with preliminary evidence indicating that DM protects against neuronal damage. Negative findings seem to relate to attainment of inadequate DM brain concentrations. Small studies have shown some promise for treatment of perioperative brain injury, amyotrophic lateral sclerosis, and symptoms of methotrexate neurotoxicity. DM safety/tolerability trials in stroke, neurosurgery, and amyotrophic lateral sclerosis patients demonstrated a favorable safety profile. DM's limited clinical benefit is proposed to be associated with its rapid metabolism to dextrorphan, which restricts its central bioavailability and therapeutic utility. Systemic concentrations of DM can be increased via coadministration of low-dose quinidine (Q), which reversibly inhibits its first-pass elimination. Potential drug interactions with DM/Q are discussed. CONCLUSIONS: Given the compelling preclinical evidence for neuroprotective properties of DM, initial clinical neuroprotective findings, and clinical demonstrations that the DM/Q combination is well tolerated, this strategy may hold promise for the treatment of various acute and degenerative neurologic disorders.

Defining and diagnosing involuntary emotional expression disorder.

Uncontrollable episodes of emotional expression occur in a variety of neurological conditions. This emotional disinhibition syndrome is characterized by episodes of crying or laughing that are unrelated to or out of proportion to the eliciting stimulus. This syndrome is common among patients with amyotrophic lateral sclerosis, multiple sclerosis, stroke, and traumatic brain injury and a variety of terms and definitions have been used to describe it. The confusing nomenclature has been a barrier to understanding, diagnosis, and treatment of this disorder. The authors propose a unifying term, involuntary emotional expression disorder (IEED), and provide diagnostic criteria for this disorder.

Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson's disease.

Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer's disease (AD) and the pre-motor stages of Parkinson's disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD. The literature of common psychotropics used in treating psychiatric disorders was reviewed for preclinical and clinical findings regarding microglial activation. Findings potentially compatible with reduced microglial activation or reduced microglial inflammogen release were evident for: antipsychotics including neuroleptics (chlorpromazine, thioridazine, loxapine) and atypicals (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone); mood stabilizers (carbamazepine, valproate, lithium); antidepressants including tricyclics (amitriptyline, clomipramine, imipramine, nortriptyline), SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), venlafaxine, and bupropion; benzodiazepine anxiolytics (clonazepam, diazepam); cognitive enhancers (donepezil, galantamine, memantine); and other drugs (dextromethorphan, quinidine, amantadine). In contrast, pramipexole and methylphenidate might promote microglial activation. The most promising replicated findings of reduced microglial activation are for quetiapine, valproate, lithium, fluoxetine, donepezil, and memantine but further study is needed and translation of their microglial effects to human disease still requires investigation. In AD-relevant models, risperidone, valproate, lithium, fluoxetine, bupropion, donepezil, and memantine have therapeutic microglial effects in need of replication. Limited clinical data suggest some support for lithium and donepezil in reducing MCI progression, but other drugs have not been studied. In PD-relevant models, lamotrigine, valproate, fluoxetine, dextromethorphan, and amantadine have therapeutic microglial effects whereas methylphenidate induced microglial activation and pramipexole promoted NO release. Clinical data limited to pramipexole do not as of yet indicate faster progression of early PD while the other drugs remain to be investigated. These tantalizing psychotropic neuroprotective findings now invite replication and evidence in AD-and PD-specific models under chronic administration, followed by consideration for clinical trials in MCI and early stage PD. Psychiatric features in early disease may provide opportunities for clinical studies that also employ microglial PET biomarkers.

Six psychotropics for pre-symptomatic & early Alzheimer's (MCI), Parkinson's, and Huntington's disease modification.

The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment (MCI) phase of AD: salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS) reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS findings show promise. Pre-symptomatic PD: lithium and valproate AMS findings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication (valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD) are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

Treatment Resistant Depression with Loss of Antidepressant Response: Rapid-Acting Antidepressant Action of Dextromethorphan, A Possible Treatment Bridging Molecule.

Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.1,2 This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days. Upon full relapse in DSM-5 MDD while taking 600 mg/day of the strong CYP2D6 inhibitor bupropion XL, a 300 mg oral loading dose of DM was given, followed by 60 mg po bid after an additional dose-finding period, without side effects. DM exhibited a ketamine-like rapid-acting antidepressant effect, thought to be mediated by mTOR activation (related to NMDA PCP site antagonism, sigma-1 and beta adrenergic receptor stimulation) and 5HTT inhibition, resulting in AMPA receptor trafficking, and dendritogenesis, spinogenesis, synaptogenesis, and increased neuronal survival (related to NMDA antagonism and sigma-1 and mTOR signaling). This report appears to be the first report of a rapid-acting effect in unipolar MDD and adds to antidepressant effects observed in the retrospective chart review of 77 patients with Bipolar II Disorder (Kelly and Lieberman 2014). If replicated, there is some reason to think that the administration of other agents with DM, such as lithium or D-cycloserine, might prolong the duration of the rapid-antidepressant effect.

Revisiting the neuropsychiatry of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease classified under the choreas. Besides motor symptoms, HD is marked by cognitive and behavioral symptoms, impacting patients' functional capacity. The progression of cognitive impairment and neuropsychiatric symptoms occur in parallel with neurodegeneration. The nature of these symptoms is very dynamic, and the major clinical challenges include executive dysfunction, apathy, depression and irritability. Herein, we provide a focused updated review on the cognitive and psychiatric features of HD.

A doença de Huntington (DH) é uma doença neurodegenerativa autossômica dominante classificada entre as coreias. Além de sintomas motores, a DH é caracterizada por sintomas cognitivos e comportamentais que impactam na capacidade funcional dos pacientes. A progressão dos sintomas neuropsiquiátricos e déficits cognitivos ocorre paralelamente à neurodegeneração. A natureza desses sintomas é muito dinâmica, sendo que os desafios clínicos mais comuns incluem disfunção executiva, apatia, depressão e irritabilidade. O presente artigo apresenta uma revisão atualizada sobre as manifestações cognitivas e psiquiátricas da DH.

The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content ad incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.