In this article, data are presented from Parts A and B of the Trail Making Test, which examined the effects of haloperidol vs risperidone on cognitive function in treatment-resistant scxhizophrenic patients. This report focuses on findings from the Trail Making Test. Overall, risperidone had a positive effect on Trail Making Part B performance following 4 weeks of treatment. These effects were due, at least in part, to the direct effects of risperidone. The possibility that an antipsychotic agent can enhance executive functioning through direct mechanisms, perhaps mediated by frontal cortex neurochemistry, indicates that the evaluation of antipsychotic medications in the treatment of schizophrenia should be expanded to include cognition.

The concept of anxiety as a distinct comorbid disorder in schizophrenia has recently been rediscovered after having been neglected for a long period of time due to both theoretical and clinical approaches adopted from the appearance of the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1950. This rediscovery was accentuated by the fact that the concept of comorbidity in various psychiatric disorders has recently won widespread favor within the scientific community, and that the use of atypical neuroleptic medication to treat patients with schizophrenia has been reported to lead to the emergence of anxiety symptoms. Of the atypical neuroleptic medications used to treat schizophrenia, clozapine has most frequently been reported to induce anxiety symptoms. In this paper, 12 cases of patients with paranoid schizophrenia who developed social phobia during clozapine treatment are reported, and their response to fluoxetine augmentation is assessed. Premorbid personality disorders were also investigated; patients were assessed using the Structured Clinical Interview for DSM-III-R—Patient Version and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). In addition, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Liebowitz Social Anxiety Scale (LSAS), the Frankfurt Beschwerde Fragebogen (Frankfurt Questionnaire of Complaints), and the Brief Psychiatric Rating Scale were used to rate clinical symptomatology. All patients were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine. In 8 (66.6%) of the 12 cases, symptoms responded (≥35% LSAS score reduction) to an adjunctive regimen of fluoxetine. Furthermore, in 7 (58.3%) of the 12 cases, an anxious personality disorder (avoidant=33.3%; dependent=25%) was identified, but no significant differences in the prevalence of comorbid personality disorders emerged in comparison with a group of 16 patients with paranoid schizophrenia treated with clozapine who did not show symptoms of social phobia. The clinical relevance of the assessment and treatment of anxiety disorders is discussed in light of a clinical therapeutic approach that overcomes the implicit hierarchy of classification. Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with schizophrenia (or, at least for those treated with clozapine) should be adopted.

Trichotillomania (TTM) is increasingly being recognized as a prevalent disorder. Nevertheless, few data are available regarding the effects of TTM on quality of life or the economic costs associated with this disorder. Two hundred members of the Obsessive-Compulsive Disorder Association of South Africa were surveyed in this pilot study, using a detailed self-report questionnaire. Of the 75 respondents, 27 reported hair pulling as a symptom. Results from this investigation indicate that hair pulling may be associated with substantial morbidity, including significant effects on occupational, academic, social, and family functioning. Additional costs may be incurred by delays in seeking treatment and incorrect diagnoses. While further work in a larger sample of patients is clearly needed, psychoeducation of practitioners and the public on TTM may result in earlier referral, diagnosis, treatment, and greater cost savings in the long term.

Secondary mania develops in as many as 9% of persons with traumatic brain injuries.The treatment of posttraumatic mania is not well defined, and agents traditionally used for the treatment of idiopathic manic episodes may not be well suited for use among individuals with traumatic brain injuries. Atypical antipsychotics are indicated for the treatment of idiopathic bipolar disorder, and have been used for other purposes among individuals with posttraumatic neuropsychiatric disturbances. This article offers the first description of the treatment of posttraumatic mania using the atypical antipsychotic quetiapine. Beneficial effects of this agent on posttraumatic mania, cognitive impairments, and functional disability in the subacute post-injury period are described. Possible mechanisms of action are discussed and the need for additional investigation of quetiapine for posttraumatic mania is highlighted.

Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.

Social cognition involves automatic and stimulus-driven processes; these may be important in mediating stereotypes in the community and schemas and transference in the clinic setting. Significant differences in self-related processing and other-related processing may also lead to important biases in our view of the other. The psychobiology of social cognition is gradually being delineated, and may be useful in understanding these phenomena, and in responding appropriately. In the clinic, schemas can be rigorously assessed, and schema-focused psychotherapy may be useful in a number of indications.

Separation anxiety has long been of interest in psychiatry. The term refers to both a phenomenon of normal psychological development and to the symptoms of a common childhood psychiatric disorder, classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition (ICD 10), as separation anxiety disorder. Available epidemiological studies suggest a prevalence rate of this disorder of about 4%. Treatment studies using cognitive behavioral therapy and/or medication are reported in the literature. There is also evidence that symptoms of separation anxiety may occur in adulthood, though this is far less widely known. We consider childhood and adult separation anxiety to be a component of panic spectrum, described in other papers of this issue.

A small and somewhat confusing literature addresses the question of outcome of childhood separation anxiety disorder, with support for a weak association between childhood separation anxiety and adult panic disorder. We believe there is a suggestion of a stronger association of the childhood condition with persistence of a similar syndrome of adult separation anxiety. Symptoms of adult separation anxiety may be a manifestation of panic spectrum, as we suggest. Such symptoms may represent a separate, specific clinical entity, or symptomatic separation anxiety may occur as a manifestation of a range of Axis I disorders, and may respond to treatment of these disorders. In any case, we urge researchers and clinicians to begin to attend to the possibility that adult psychiatric patients may suffer from clinically significant symptoms of adult separation anxiety.

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids.The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

Treatment nonadherence is a concern among patients with bipolar disorder and posttraumatic stress disorder (PTSD). PTSD is common among patients with bipolar disorder and those with this comorbidity often have a more severe course of illness. While many factors have been associated with nonadherence in bipolar disorder patients and in PTSD patients, almost no research has focused on the factors associated with non-adherence in bipolar disorder patients with comorbid PTSD. Studies in primary bipolar disorder samples reveal patient, illness, drug and clinician characteristics associated with nonadherence while studies in primary PTSD samples reveal a significantly shorter list of patient, illness and drug characteristics. Shared risk factors between these two populations and the characteristics that predict noncompliance in only one population but often present in the other, suggest a high likelihood of nonadherence in the bipolar disorder-PTSD population. For bipolar disorder-PTSD patients with early childhood trauma, noncompliance may be related to the trauma-related meanings attributed to interactions with their physicians and their prescribed medications. Given the high side effect burden of bipolar disorder treatments and the importance of lifelong adherence, clinicians should vigilantly monitor for nonadherence in their bipolar disorder-PTSD patients and be particularly aware of patient-physician psychodynamics that might contribute to this behavior.

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.

Pseudobulbar affect, thought by many to be a relatively newly described condition, is in fact a very old one, described as early as the 19th century. It refers to those who experience inappropriate affect, disconnected from internal state, or mood, generally thought to be the result of an upper motor neuron injury or illness. One possible explanation for this condition’s relative obscurity is the dearth of treatment options; clinical medicine is not typically in the habit of identifying conditions that cannot be modified. Now, however, there is good evidence for the treatment of pseudobulbar affect, and even a therapy approved for use by the U.S. Food and Drug Administration (FDA). As a result, appropriate identification and subsequent management of pseudobulbar affect is more important than ever. This article purports to summarize the origins of pseudobulbar affect, most current hypotheses as to its physiopathology, clinical identification, and evidence for management.

The major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. These manifestations of neuronal plasticity occur in the peripheral nerve, spinal cord, and brain. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-D-aspartate receptor antagonists, and opioid analgesics. The use of these adjuvant analgesics, either alone or in combination, should result in the alleviation of neuropathic pain in most patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities.

Community studies indicate that 19% of men and 31% of women will develop some type of anxiety disorder during their lifetime. The impact of gender is profound in that it increases the likelihood of developing an anxiety disorder by 85% in women compared to men. Sex difference in prevalence rates are apparent as early as age 6, when girls are twice as likely as boys to have an anxiety disorder. In the National Comorbidity Survey, the prevalence rates for panic disorder in women and men were 5% and 2%, respectively. Agoraphobia, which often coexists with panic disorder, has a lifetime prevalence rate of 7% in women and 3.5% in men. Prevalence of trauma is increased in young women as well, and is experienced earlier in life; 62% of sexual assaults are inflicted on females ≤18 years of age, and 29% occur in children < 11 years of age. Comorbidity of anxiety in women complicates other medical conditions as well. For example, panic disorder is highly comorbid with CHD, which remains the leading cause of death in women in developed countries. Fluctuations in reproductive hormone levels during the female life cycle is thought to be responsible for modulating anxiety. This is often implicated in the later age of onset, the more sudden and acute symptom emergence, and the more episodic course of OCD in women, and in the high prevalence (47.4%) of PMDD. Pregnancy appears to be a protective period for some anxiety disorders, including panic, while for others, such as OCD, it may be associated with onset. Hormonal changes during pregnancy, such as increased prolactin, oxytocin, and cortisol, may contribute to the suppression of stress response that occurs during this period. Despite a large and growing body of literature on anxiety disorders in general, the available data relating to women and girls falls short of informing aspects of diagnosis, treatment, and prevention that may entail sex differences. Additional work is required to understand the biological and psychosocial causes of these differences.

Studies on schizophrenia (SZ) have documented an increased presence of cavum septi pellucidi (CSP) in individuals suffering from the illness. Moreover, the presence of CSP has been cited in support of the early neurodevelopmental hypothesis in SZ. Our objective was to assess the magnetic resonance imaging (MRI) scans of first-episode patients and healthy controls to evaluate the frequency of CSP. The presence and the size of CSP were visually assessed on the MRI scans of 40 first-episode SZ patients, 19 nonpsychotic child and high-risk adolescent offspring of patients with SZ or schizoaffective disorder, and 59 controls. Our analysis revealed an absence of statistically significant differences in the occurrence of CSP between SZ patients, high-risk subjects, and controls. Even when the analysis was restricted to large CSP, no differences were found. Furthermore, no association between CSP and sex or handedness was observed. The absence of CSP abnormalities in first-episode SZ subjects might indicate that SZ is not characterized by developmentally mediated alterations in CSP. Also, family history of SZ might not increase likelihood for CSP.

What is the effect of melatonin on jet lag syndrome? Jet lag desynchronizes the internal sleep-wakefulness cycle with the environmental light/dark cycle. Advance (but not delay) of light onset is known to abolish pineal N-acetyltransferase activity and urine excretion of 6-sulphatoxymelatonin. Measurements of pineal serotonin, the substrate of melatonin biosynthesis; N-acetylserotonin (NAS), the immediate melatonin precursor; and melatonin (high-performance liquid chromatography-fluorimetric method) in the animal (rat) model of jet lag revealed that prolonged delay of darkphase onset disrupted the rhytms in comparable ways as the advance of light-phase onset. Advance of dark phase onset resulted in less severe disturbances of rhythms as compared with the advance of light phase onset. Melatonin, but not NAS, injections at the beginning of a new dark period accelerated recovery of NAS and melatonin, but not serotonin, rhythms. Spontaneously hypertensive rats were more sensitive to advance of light onset and less responsive to melatonin injections than normotensive rats. NAS and methylene blue, an inhibitor of monoamine oxidase A, attenuated light-induced disruption of NAS but not melatonin rhythms. We draw the following conclusions from our data: the beginning of the dark period may be preferable to the beginning of light period as the arrival time on eastward flights; the efficacy of melatonin in alleviating jet lag may be enchanced by administering it before, during and after rapid transition through time zones; and hypertension may exaggerate jet lag syndrome.