It is widely accepted that cholinergic activity at muscarinic receptors is required to maintain cognitive functions, including learning and memory. Memory domains are especially impaired in schizophrenia, which may explain difficulties in psychosocial rehabilitation of individuals with this illness. However, little is known about the mechanism of this impairment. To understand our current knowledge, we reviewed the literature since 1990 via a PubMed search for the terms “muscarinic”, “schizophrenia” “cognition,” “memory,” “learning,” and “agonist” in combination. We found 89 basic science/laboratory studies, case reports/series, case-control studies, cross-sectional studies, standardized controlled animal trials, standardized controlled human trials, and reviews. Although further research is required to fully understand the neuropharmacology of the cholinergic system in cognitive function in schizophrenia, we have examined the data currently available. In general, these data suggest that agonist activity at acetylcholine muscarinic type 1 (M1) receptors would enhance memory and learning in schizophrenia. We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1 muscarinic agonists.

Social anxiety disorder (SAD) is a condition characterized by pervasiveness and impairment in social functioning, with a prevalence in the general population between 1.9% and 12.1%. The most consistent findings on its neurobiological underpinnings involve a wide range of neurotransmitters (serotonin, norepinephrine, glutamate, and GABA) and neuropeptides (oxytocin), but no comprehensive hypothesis is yet available. In particular, oxytocin is becoming increasingly established as a “prosocial neuropeptide” and, as such, is a major focus of current research, with a great range of therapeutic applications including SAD treatment. Specifically, the amygdala plays a pivotal role in conditioning and processing of fear, and exaggerated amygdala responses in SAD patients have been observed during various social-emotional stimuli. In addition to the amygdala, other brain areas of interest in SAD-related circuitry are represented by the medial prefrontal cortex, dorsal raphe, striatum, locus coeruleus, prefrontal cortex, insular cortex, and anterior cingulate cortex. The aim of this review is to provide an update on neurobiological correlates of SAD, with a special focus on neurotransmitters and brain areas possibly involved, and suggestions for future research that could lead to more specific therapeutic interventions.

Early-life adversity is a well-established risk factor for the development of depression later in life. Here we discuss the relationship between early-life adversity and depression, focusing specifically on effects of early-life caregiver deprivation on alterations in the neural and behavioral substrates of reward-processing. We also examine vulnerability to depression within the context of sensitive periods of neural development and the timing of adverse exposure. We further review the development of the ventral striatum, a limbic structure implicated in reward processing, and its role in depressive outcomes following early-life adversity. Finally, we suggest a potential neurobiological mechanism linking early-life adversity and altered ventral striatal development. Together these findings may help provide further insight into the role of reward circuitry dysfunction in psychopathological outcomes in both clinical and developmental populations.

Repeated episodes of alcohol withdrawal may exacerbate the severity of future withdrawal occurrences. The progressive intensification of withdrawal symptoms may be manifested as a kindling-like mechanism. This sensitization process may reflect persistent perturbation in excitatory and inhibitory influences on brain function. Relapse is also thought to be affected by the kindling mechanism. Successive alcohol withdrawal experiences may also lead to neurologic damage and cognitive impairments. We review the research findings regarding the alcohol withdrawal kindling hypothesis and the implications of the kindling process on mechanisms of dependence, alcohol withdrawal treatment strategies, and the long-term repercussions of alcoholism.

Somatization disorder is a somatoform disorder that overlaps with a number of functional somatic syndromes and has high comorbidity with major depression and anxiety disorders. Proposals have been made for revising the category of somatoform disorders, for simplifying the criteria for somatization disorder, and for emphasizing the unitary nature of the functional somatic syndromes in future classifications. A review of the cognitive-affective neuroscience of somatization disorder and related conditions suggests that overlapping psychobiological mechanisms mediate depression, anxiety, and somatization symptoms. Particular genes and environments may contribute to determining whether symptoms are predominantly depressive, anxious, or somatic, and there are perhaps also overlaps and distinctions in the distal evolutionary mechanisms that produce these symptoms.

After providing background information on the definition and nature of generalized anxiety disorder, this article describes cognitive-behavioral therapy (CBT) methods that have been empirically supported in the treatment of this disorder. Subsequent to this description, relevant outcome literature is briefly reviewed, along with evidence that the addition of other techniques beyond traditional CBT methods may be necessary to maximize clinical outcome. A description is then provided of an integrated interpersonal/emotional processing therapy that the authors have recently added to their CBT protocol. CBT with and without this integrated treatment is currently being evaluated in an experimental trial.

Objective: This study examines the impact of comorbidity of attention-deficit/hyperactivity disorder (ADHD) with disruptive and anxiety disorders in childhood on clinical course and outcome. We consider the relative contribution of each comorbid symptom constellation, and also their interaction, to assess the following questions: (1) Does early comorbidity with conduct disorder (CD) and anxiety disorders define specific developmental trajectories?; (2) Is comorbid anxiety disorders in childhood continuous with anxiety disorders in adolescence?; (3) Does comorbid anxiety disorders mitigate the negative behavioral outcome of youth with ADHD?; and (4) Is there an interaction between comorbid CD and anxiety disorders, when they occur simultaneously, that predicts a different outcome than either comorbid condition alone?

Method: Thirty-two 15- to 18-year-old adolescent males, diagnosed with ADHD between 7 and 11 years of age, were re-evaluated for assessment of adolescent outcome 4.3–9.2 years later. Hierarchical regression analyses were run with each of the eight Child Behavior Checklist and Youth Self-Report problem scales, and the four anxiety symptom subscales of the Multidimensional Anxiety Scale for Children serving as outcome variables.

Results: Findings indicate that comorbid CD at baseline predicteds parent reports of behavior problems in adolescence, while comorbid anxiety disorders in childhood predicted youth reports of anxiety and social problems. Anxiety disorders without CD did not predict poor behavioral outcome. Children with both comorbid CD and anxiety disorder had the highest levels of parent-rated symptoms on follow up. In particular, adolescent social problems were best predicted by the combination of comorbid CD and anxiety disorder in childhood.

Conclusion: These data provide evidence that children with ADHD plus anxiety disorder do in fact have anxiety disorders, and that the combination of anxiety disorder and CD predicts a more rather than less severe course.

Karl Ludwig Kahlbaum originally described catatonia as a psychomotor disease that encompassed motor, affective, and behavioral symptoms. In the beginning of the 20th century, catatonia was considered to be the motoric manifestation of schizophrenia; therefore, neuropathologic research mostly focused on neuroanatomic substrates (ie, the basal ganglia underlying the generation of movements). Even though some alterations were found in basal ganglia, the findings in these subcortical structures are not consistent. Recently, there has been a reemergence of interest into researching catatonia. Brain imaging studies have shown major and specific alterations in a right hemispheric neural network that includes the medial and lateral orbitofrontal and posterior parietal cortex. This neural network may be abnormally modulated by altered functional interactions between γ-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This may account for the interrelationship among motor, emotional, and behavioral alterations observed in both clinical phenomenology and the subjective experiences of patients with catatonia. Such functional interrelationships should be explored in further detail in catatonia, which may also serve as a paradigmatic model for the investigation of psychomotor and brain function in general.

Gilles de la Tourette syndrome is a chronic and complex tic disorder accompanied by specific behavioral problems in the majority of patients. With its multifaceted interplay between motion and emotion, this condition is a paradigmatic example of the science and art of clinical neuropsychiatry. This review article encompasses the clinical phenomenology of motor and vocal tics and associated sensory experiences (premonitory urges), as well as the behavioral spectrum of the most common comorbidities, including obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, affective symptoms, and impulsivity. Knowledge of the contributions of both tics and behavioral problems to patients’ health-related quality of life across the lifespan should assist treating clinicians in formulating a targeted management plan. Although the exact pathophysiology of Gilles de la Tourette syndrome remains elusive, research into therapeutic interventions has expanded the range of available interventions across multiple domains. A thorough understanding of the neurology and psychiatry of this condition is of key importance to meet the needs of this patient population, from the formulation of an accurate diagnosis to the implementation of effective treatment strategies.

ISSUE:Ketamine induces rapid-onset and short-duration improvement in depressive and suicidal symptoms in both treatment-resistant unipolar depression and bipolar depression, and also reduces chronic pain after short intravenous infusions. In order to develop long-acting oral agents with the same clinical effects, the pharmacologic mechanism of action must be understood, and the leading hypotheses are discussed here.

Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of antidepressant drugs are mainly attributed to their actions on different monoamine neurotransmitters (serotonin, norepinephrine, and dopamine). Development of new antidepressants with novel targets beyond the monoamine pathways may fill the unmet need in treatment of MDD and TRD. The recent approval of intranasal Esketamine (glutamatergic agent) in conjunction with an oral antidepressant for the treatment of adult TRD patients was the first step toward expanding beyond the monoamine targets. Several other glutamatergic (AXS-05, REL-1017, AV-101, SLS-002, AGN24175, and PCN-101) and GABAergic (brexanolone, zuranolone, and ganaxolone) drugs are currently in different stages of clinical development for MDD, TRD and other indications. The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.

The authors assessed the ability of lorazepam and other benzodiazepines to affect the course of neuroleptic malignant syndrome (NMS). Records of inpatients who met both stringent research criteria and criteria under the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) (n=11) or DSM-IV criteria alone (n=5)for NMS were identified. All received lorazepam or related benzodiazepines within 24 hours of NMS onset or hospital admission. The records were reviewed for resolution of clinical signs NMS. Rigidity and fever abated within 24—48 hours, while secondary features of NMS were relieved within 64 hours. These results compared favorably with prior reports of 5-day to 10-day recovery periods. Benzodiazepine administration appeared to be well tolerated. Lorazepam and related benzodiazepines may reduce recovery time in NMS.

Anxiety disorders in the United States are prevalent, widespread, and disabling. These illnesses may account for almost one third of the $148 billion total mental health bill each year. Pharmacologic options include tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and anxiolytics. Psychological treatments include cognitive-behavioral therapy (CBT), cognitive therapy, exposure, and ritual prevention therapies. Despite insufficient evidence, many experts recommend combined treatment, generally medication with CBT. A literature review was conducted to examine studies with random assignment, adequate methods and sample sizes, blind assessments, sufficient dosages and durations of treatment, and satisfactory reporting of data, to determine whether combined treatment was superior to monotherapy. Twenty-six randomized clinical trials were identified; nine met review criteria. A review of relevant studies could not confirm the superiority of combined treatment over monotherapy. In one of four studies of obsessive-compulsive disorder, combined treatment produced better results than monotherapy.  There was no evidence of superiority for combined therapy over monotherapy for the treatment of social phobia or generalized anxiety disorder. There were no studies that met review criteria for either specific phobia or posttraumatic stress disorder (PTSD). With panic disorder, there was evidence that combined treatment might actually lead to worse outcome. Combined treatment is commonly recommended, but empirical support is limited. More research is needed. There are few well-designed studies, and little data regarding PTSD and specific phobias.

Sleep dysfunction is common among patients with Parkinson's disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinson's disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinson's disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinson's disease can also affect sleep. In patients with advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.

The worldwide economic crisis of the last decade, and still unresolved, led to a great recession involving all major economies. Since economic factors may influence mental wellbeing, not surprisingly a rise in poor mental health was observed in different countries, while representing a great challenge to psychiatric interventions. This paper aims at reviewing the available English literature focusing on the impact of the current economic crisis on mental health, with a special focus on depression and suicide. Available studies indicate that consequences of economic crisis, such as unemployment, increased workload or work reorganization, and reduced staff and wages, may constitute important stressing factors with a negative impact on mental health. Although data are not easily comparable in different countries, depression seems to be the most common psychiatric disorders especially in middle-aged men. Even suicide rates seem to be increased in men, mainly in countries with no public welfare or poor family relationships. All these findings require a careful attention from both governments that cut resources on public health instead of investing in it, and psychiatric associations that should implement appropriate strategies to face and to manage this sort of depression epidemic driven by economic crisis. Again, as available data suggest that the impact of the crisis might have been attenuated in countries with higher spending in social protection, they clearly urge policy makers to take into account possible health externalities associated to inadequate social protection systems.