Cerebral Asymmetry in Planum Temporale and its Implications in Language and Auditory Processing

The planum temporale, a triangular region in the posterior superior temporal gyrus, is a highly lateralized brain structure involved in language and music processing. Studies have shown that the planum temporale is up to ten times larger in the left cerebral hemisphere than the right, with this asymmetry being more prominent in men. This asymmetry can be observed in gestation and is present in up to 70% of right-handed individuals.

Recent research suggests that the planum temporale also plays an important role in auditory processing, specifically in representing the location of sounds in space. However, reduced planum temporale asymmetry has been observed in individuals with dyslexia, stuttering, and schizophrenia. These findings highlight the importance of cerebral asymmetry in the planum temporale and its implications in language and auditory processing.

The patient is experiencing rapid cycling bipolar disorder, which NICE recommends managing similarly to conventional bipolar disorder. Lithium monotherapy is the preferred first-line treatment for long-term management, while valproate should be avoided due to the patient’s potential for childbearing.

Bipolar Disorder: Diagnosis and Management

Bipolar disorder is a lifelong condition characterized by episodes of mania or hypomania and episodes of depressed mood. The peak age of onset is 15-19 years, and the lifetime prevalence of bipolar I disorders is estimated to be around 2.1%. The diagnosis of bipolar disorder is based on the presence of manic or hypomanic episodes, which are characterized by elevated of expansive mood, rapid speech, and increased activity of energy. Psychotic symptoms, such as delusions and hallucinations, may also be present.

Bipolar depression differs from unipolar depression in several ways, including more rapid onset, more frequent episodes, and shorter duration. Rapid cycling is a qualifier that can be applied to bipolar I of bipolar II disorder and is defined as the presence of at least four mood episodes in the previous 12 months that meet the criteria for a manic, hypomanic, of major depressive episode.

The management of bipolar disorder involves acute and long-term interventions. Acute management of mania or hypomania may involve stopping antidepressants and offering antipsychotics of mood stabilizers. Long-term management may involve psychological interventions and pharmacological treatments such as lithium, valproate, of olanzapine.

It is important to note that valproate should not be offered to women of girls of childbearing potential for long-term bipolar disorder unless other options are ineffective of not tolerated and a pregnancy prevention program is in place. Aripiprazole is recommended as an option for treating moderate to severe manic episodes in adolescents with bipolar I disorder.

Overall, the diagnosis and management of bipolar disorder require a comprehensive approach that takes into account the individual’s symptoms, history, and preferences.

The Maudsley Guidelines recommend the combination of venlafaxine and mirtazapine, also known as California Rocket Fuel (CRF), due to its effectiveness in quickly controlling depressive symptoms. This combination works by combining the selective serotonin-noradrenaline reuptake inhibitor properties of venlafaxine with the noradrenergic-specific serotonergic properties of mirtazapine, resulting in a powerful noradrenergic and serotonergic effect. It is important to avoid other options as they can lead to serious interactions.

Depression (Refractory)

Refractory depression is a term used when two successive attempts at treatment have failed despite good compliance and adequate doses. There is no accepted definition of refractory depression. The following options are recommended as the first choice for refractory depression, with no preference implied by order:

– Add lithium
– Combined use of olanzapine and fluoxetine
– Add quetiapine to SSRI/SNRI
– Add aripiprazole to antidepressant
– Bupropion + SSRI
– SSRI (of venlafaxine) + mianserin (of mirtazapine)

These recommendations are taken from the 13th edition of the Maudsley Guidelines.

Herbal Remedies for Depression and Anxiety

Depression can be treated with Hypericum perforatum (St John’s Wort), which has been found to be more effective than placebo and as effective as standard antidepressants. However, its use is not advised due to uncertainty about appropriate doses, variation in preparations, and potential interactions with other drugs. St John’s Wort can cause serotonin syndrome and decrease levels of drugs such as warfarin and ciclosporin. The effectiveness of the combined oral contraceptive pill may also be reduced.

Anxiety can be reduced with Piper methysticum (kava), but it cannot be recommended for clinical use due to its association with hepatotoxicity.

Both males and females are equally likely to experience OCD, according to most studies. While some discrepancies have been reported, the majority support a 1:1 ratio.

Maudsley Guidelines

First choice: SSRI of clomipramine (SSRI preferred due to tolerability issues with clomipramine)

Second line:

– SSRI + antipsychotic
– Citalopram + clomipramine
– Acetylcysteine + (SSRI of clomipramine)
– Lamotrigine + SSRI
– Topiramate + SSRI

Clozapine is an effective antipsychotic drug used in the management of treatment-resistant schizophrenia (TRS). It was reintroduced in the 1990s with mandatory blood monitoring due to the risk of agranulocyte

Both the NICE Guidelines and the Maudsley Guidelines suggest using SSRIs as the primary treatment for OCD, with the Maudsley also mentioning clomipramine as an option. However, the Maudsley advises trying SSRIs first due to potential tolerability concerns with clomipramine. It is recommended to follow both sets of guidelines consistently whenever feasible.

Maudsley Guidelines

First choice: SSRI of clomipramine (SSRI preferred due to tolerability issues with clomipramine)

Second line:

– SSRI + antipsychotic
– Citalopram + clomipramine
– Acetylcysteine + (SSRI of clomipramine)
– Lamotrigine + SSRI
– Topiramate + SSRI

While NICE recommends mirtazapine for the treatment of PTSD, its license only permits its use for major depression.

Antidepressants (Licensed Indications)

The following table outlines the specific licensed indications for antidepressants in adults, as per the Maudsley Guidelines and the British National Formulary. It is important to note that all antidepressants are indicated for depression.

– Nocturnal enuresis in children: Amitriptyline, Imipramine, Nortriptyline
– Phobic and obsessional states: Clomipramine
– Adjunctive treatment of cataplexy associated with narcolepsy: Clomipramine
– Panic disorder and agoraphobia: Citalopram, Escitalopram, Sertraline, Paroxetine, Venlafaxine
– Social anxiety/phobia: Escitalopram, Paroxetine, Sertraline, Moclobemide, Venlafaxine
– Generalised anxiety disorder: Escitalopram, Paroxetine, Duloxetine, Venlafaxine
– OCD: Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Clomipramine
– Bulimia nervosa: Fluoxetine
– PTSD: Paroxetine, Sertraline

To diagnose anorexia nervosa, a persistent pattern of restrictive eating of other behaviors aimed at maintaining an abnormally low body weight is required. These behaviors may include excessive exercise, purging, of the use of laxatives. In some cases, a low body weight may not be the essential feature, and significant weight loss within six months may replace this requirement if other diagnostic criteria are met. For individuals in recovery from anorexia nervosa who have achieved a healthy weight, the diagnosis should be retained until a full and lasting recovery is achieved, which includes maintaining a healthy weight and ceasing behaviors aimed at reducing body weight for at least one year following treatment. Intermittent bingeing may also be consistent with a diagnosis of anorexia nervosa, and a specifier of binge-purge pattern may be applied.

Eating disorders are a serious mental health condition that can have severe physical and psychological consequences. The ICD-11 lists several types of eating disorders, including Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder, Avoidant-Restrictive Food Intake Disorder, Pica, and Rumination-Regurgitation Disorder.

Anorexia Nervosa is characterized by significantly low body weight, a persistent pattern of restrictive eating of other behaviors aimed at maintaining low body weight, excessive preoccupation with body weight of shape, and marked distress of impairment in functioning. Bulimia Nervosa involves frequent episodes of binge eating followed by inappropriate compensatory behaviors to prevent weight gain, excessive preoccupation with body weight of shape, and marked distress of impairment in functioning. Binge Eating Disorder is characterized by frequent episodes of binge eating without compensatory behaviors, marked distress of impairment in functioning, and is more common in overweight and obese individuals. Avoidant-Restrictive Food Intake Disorder involves avoidance of restriction of food intake that results in significant weight loss of impairment in functioning, but is not motivated by preoccupation with body weight of shape. Pica involves the regular consumption of non-nutritive substances, while Rumination-Regurgitation Disorder involves intentional and repeated regurgitation of previously swallowed food.

It is important to seek professional help if you of someone you know is struggling with an eating disorder. Treatment may involve a combination of therapy, medication, and nutritional counseling.

Systematic desensitization is a therapeutic technique used to treat phobias by gradually exposing the individual to the feared object of situation in a controlled and safe environment, while teaching them relaxation techniques to manage their anxiety.

Exposure and response prevention is a cognitive-behavioral therapy used to treat obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD). It involves exposing the individual to their obsessive thoughts of compulsive behaviors, while preventing them from engaging in their usual response. This helps to break the cycle of anxiety and compulsions, and teaches the individual to tolerate their distress without resorting to their usual rituals.

Maudsley Guidelines

First choice: SSRI of clomipramine (SSRI preferred due to tolerability issues with clomipramine)

Second line:

– SSRI + antipsychotic
– Citalopram + clomipramine
– Acetylcysteine + (SSRI of clomipramine)
– Lamotrigine + SSRI
– Topiramate + SSRI

The rate is considerably greater than that of adults who are of working age.

Suicide Rates Following Self-Harm

Most individuals who engage in self-harm do not go on to commit suicide, which makes risk assessment challenging. A study conducted in the UK in 2015 by Hawton found that 0.5% of individuals died by suicide in the first year following self-harm, with a higher rate among males (0.82%) than females (0.27%). Over the two-year period following self-harm, 1.6% died by suicide, with more occurrences in the second year. Interestingly, a study by Murphy in 2012 found that the rate of suicide following self-harm was higher in the elderly (those over 60), with a rate of 1.5 suicides in the first 12 months. The only significant risk factor for suicide following self-harm in this study was the use of a violent method in the initial episode.

Binge eating disorder has a higher rate of remission compared to other eating disorders, and remission can occur spontaneously of as a result of treatment. The disorder is characterized by frequent episodes of binge eating, which can be assigned as a diagnosis after a shorter period if they occur multiple times a week and cause significant distress. Onset typically occurs during adolescence of young adulthood but can also begin in later adulthood. Binge eating episodes can be objective of subjective, but the core feature is the experience of loss of control overeating. If an individual engages in inappropriate compensatory behaviors following binge eating episodes, the diagnosis of bulimia nervosa should be assigned instead of binge eating disorder, as the two diagnoses cannot coexist.

Eating disorders are a serious mental health condition that can have severe physical and psychological consequences. The ICD-11 lists several types of eating disorders, including Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder, Avoidant-Restrictive Food Intake Disorder, Pica, and Rumination-Regurgitation Disorder.

Anorexia Nervosa is characterized by significantly low body weight, a persistent pattern of restrictive eating of other behaviors aimed at maintaining low body weight, excessive preoccupation with body weight of shape, and marked distress of impairment in functioning. Bulimia Nervosa involves frequent episodes of binge eating followed by inappropriate compensatory behaviors to prevent weight gain, excessive preoccupation with body weight of shape, and marked distress of impairment in functioning. Binge Eating Disorder is characterized by frequent episodes of binge eating without compensatory behaviors, marked distress of impairment in functioning, and is more common in overweight and obese individuals. Avoidant-Restrictive Food Intake Disorder involves avoidance of restriction of food intake that results in significant weight loss of impairment in functioning, but is not motivated by preoccupation with body weight of shape. Pica involves the regular consumption of non-nutritive substances, while Rumination-Regurgitation Disorder involves intentional and repeated regurgitation of previously swallowed food.

It is important to seek professional help if you of someone you know is struggling with an eating disorder. Treatment may involve a combination of therapy, medication, and nutritional counseling.

Clozapine is an effective antipsychotic drug used in the management of treatment-resistant schizophrenia (TRS). It was reintroduced in the 1990s with mandatory blood monitoring due to the risk of agranulocyte

The recommended options for augmentation are olanzapine and quetiapine.

Psychotic Depression

Psychotic depression is a type of depression that is characterized by the presence of delusions and/of hallucinations in addition to depressive symptoms. This condition is often accompanied by severe anhedonia, loss of interest, and psychomotor retardation. People with psychotic depression are tormented by hallucinations and delusions with typical themes of worthlessness, guilt, disease, of impending disaster. This condition affects approximately 14.7-18.5% of depressed patients and is estimated to affect around 0.4% of community adult samples, with a higher prevalence in the elderly community at around 1.4-3.0%. People with psychotic depression are at a higher risk of attempting and completing suicide than those with non-psychotic depression.

Diagnosis

Psychotic depression is currently classified as a subtype of depression in both the ICD-11 and the DSM-5. The main difference between the two is that in the ICD-11, the depressive episode must be moderate of severe to qualify for a diagnosis of depressive episode with psychotic symptoms, whereas in the DSM-5, the diagnosis can be applied to any severity of depressive illness.

Treatment

The recommended treatment for psychotic depression is tricyclics as first-line treatment, with antipsychotic augmentation. Second-line treatment includes SSRI/SNRI. Augmentation of antidepressant with olanzapine or quetiapine is recommended. The optimum dose and duration of antipsychotic augmentation are unknown. If one treatment is to be stopped during the maintenance phase, then this should be the antipsychotic. ECT should be considered where a rapid response is required of where other treatments have failed. According to NICE (ng222), combination treatment with antidepressant medication and antipsychotic medication (such as olanzapine or quetiapine) should be considered for people with depression with psychotic symptoms. If a person with depression with psychotic symptoms does not wish to take antipsychotic medication in addition to an antidepressant, then treat with an antidepressant alone.

It should be noted that there is no indication of impaired reciprocal interaction of restrictive/repetitive behaviors, which would not support a diagnosis of autism spectrum disorder. Additionally, Asperger’s and infantile autism are no longer recognized as diagnoses in the ICD-11. Based on the presented case, it appears that the individual may have a personality disorder with detachment, which requires evidence of long standing interpersonal dysfunction and social/emotional distance. It is important to note that while this may share similarities with avoidant personality disorder in the DSM-5, it is not the same diagnosis.

Personality Disorder: Avoidant

Avoidant Personality Disorder (AVPD) is characterized by a pervasive pattern of social inhibition, feelings of inadequacy, and hypersensitivity to negative evaluation. According to the DSM-5, individuals with AVPD exhibit at least four of the following symptoms: avoidance of occupational activities that involve interpersonal contact, unwillingness to be involved unless certain of being liked, restraint in intimate relationships due to fear of ridicule, preoccupation with being criticized of rejected in social situations, inhibition in new interpersonal situations due to feelings of inadequacy, viewing oneself as inept and inferior to others, and reluctance to take personal risks of engage in new activities due to potential embarrassment.

In contrast, the ICD-11 does not have a specific category for AVPD but instead uses the qualifier of detachment trait. The Detachment trait domain is characterized by a tendency to maintain interpersonal and emotional distance. Common manifestations of Detachment include social detachment (avoidance of social interactions, lack of friendships, and avoidance of intimacy) and emotional detachment (reserve, aloofness, and limited emotional expression and experience). It is important to note that not all individuals with Detachment will exhibit all of these symptoms at all times.

The Maudsley Guidelines and NICE guidance both recommend the use of a tricyclic antidepressant in combination with an antipsychotic for the treatment of psychotic depression. This approach is also supported by a systematic review which found that augmentation was superior to using an antidepressant or antipsychotic alone. The review was conducted by Kruizinga in 2021 and published in the Cochrane Database of Systematic Reviews.

Psychotic Depression

Psychotic depression is a type of depression that is characterized by the presence of delusions and/of hallucinations in addition to depressive symptoms. This condition is often accompanied by severe anhedonia, loss of interest, and psychomotor retardation. People with psychotic depression are tormented by hallucinations and delusions with typical themes of worthlessness, guilt, disease, of impending disaster. This condition affects approximately 14.7-18.5% of depressed patients and is estimated to affect around 0.4% of community adult samples, with a higher prevalence in the elderly community at around 1.4-3.0%. People with psychotic depression are at a higher risk of attempting and completing suicide than those with non-psychotic depression.

Diagnosis

Psychotic depression is currently classified as a subtype of depression in both the ICD-11 and the DSM-5. The main difference between the two is that in the ICD-11, the depressive episode must be moderate of severe to qualify for a diagnosis of depressive episode with psychotic symptoms, whereas in the DSM-5, the diagnosis can be applied to any severity of depressive illness.

Treatment

The recommended treatment for psychotic depression is tricyclics as first-line treatment, with antipsychotic augmentation. Second-line treatment includes SSRI/SNRI. Augmentation of antidepressant with olanzapine or quetiapine is recommended. The optimum dose and duration of antipsychotic augmentation are unknown. If one treatment is to be stopped during the maintenance phase, then this should be the antipsychotic. ECT should be considered where a rapid response is required of where other treatments have failed. According to NICE (ng222), combination treatment with antidepressant medication and antipsychotic medication (such as olanzapine or quetiapine) should be considered for people with depression with psychotic symptoms. If a person with depression with psychotic symptoms does not wish to take antipsychotic medication in addition to an antidepressant, then treat with an antidepressant alone.

The study incorporated clozapine during its second phase.

CATIE Study: Comparing Antipsychotic Medications for Schizophrenia Treatment

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study, funded by the National Institute of Mental Health (NIMH), was a nationwide clinical trial that aimed to compare the effectiveness of older and newer antipsychotic medications used to treat schizophrenia. It is the largest, longest, and most comprehensive independent trial ever conducted to examine existing therapies for schizophrenia. The study consisted of two phases.

Phase I of CATIE compared four newer antipsychotic medications to one another and an older medication. Participants were followed for 18 months to evaluate longer-term patient outcomes. The study involved over 1400 participants and was conducted at various treatment sites, representative of real-life settings where patients receive care. The results from CATIE are applicable to a wide range of people with schizophrenia in the United States.

The medications were comparably effective, but high rates of discontinuation were observed due to intolerable side-effects of failure to adequately control symptoms. Olanzapine was slightly better than the other drugs but was associated with significant weight gain as a side-effect. Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications. Movement side effects primarily associated with the older medications were not seen more frequently with perphenazine than with the newer drugs.

Phase II of CATIE sought to provide guidance on which antipsychotic to try next if the first failed due to ineffectiveness of intolerability. Participants who discontinued their first antipsychotic medication because of inadequate management of symptoms were encouraged to enter the efficacy (clozapine) pathway, while those who discontinued their first treatment because of intolerable side effects were encouraged to enter the tolerability (ziprasidone) pathway. Clozapine was remarkably effective and was substantially better than all the other atypical medications.

The CATIE study also looked at the risk of metabolic syndrome (MS) using the US National Cholesterol Education Program Adult Treatment Panel criteria. The prevalence of MS at baseline in the CATIE group was 40.9%, with female patients being three times as likely to have MS compared to matched controls and male patients being twice as likely.

The patient’s reported symptoms are indicative of postural hypotension, which is likely a side effect of the olanzapine medication they were given.

Maudsley Guidelines: Antipsychotics for Postural Hypotension

When postural hypotension is a concern, it may be necessary to switch to an antipsychotic that is less likely to cause this side effect. The following antipsychotics are recommended by the Maudsley Guidelines:

– Amisulpride
– Aripiprazole
– Haloperidol
– Sulpiride
– Trifluoperazine

These medications have a lower risk of causing postural hypotension compared to other antipsychotics such as risperidone, clozapine, olanzapine, paliperidone, quetiapine, and ziprasidone. It is important to discuss any concerns about side effects with a healthcare provider before making any changes to medication.

The discontinuation of clozapine can have a significantly negative impact on the prognosis of patients, therefore it is crucial for them to continue taking the medication if possible. While seizures may occur, the addition of an antiepileptic drug such as sodium valproate can often allow for safe continuation of clozapine. It is important to note that carbamazepine should not be used in conjunction with clozapine due to the increased risk of agranulocytosis.

Clozapine is an effective antipsychotic drug used in the management of treatment-resistant schizophrenia (TRS). It was reintroduced in the 1990s with mandatory blood monitoring due to the risk of agranulocyte

The NICE Guideline recommends family therapy as the primary treatment option. For adults, guided self-help is the preferred first-line option, while medications are not advised for either children of adults.

Eating Disorders: NICE Guidelines

Anorexia:
For adults with anorexia nervosa, consider individual eating-disorder-focused cognitive behavioural therapy (CBT-ED), Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), of specialist supportive clinical management (SSCM). If these are not acceptable, contraindicated, of ineffective, consider eating-disorder-focused focal psychodynamic therapy (FPT). For children and young people, consider anorexia-nervosa-focused family therapy (FT-AN) of individual CBT-ED. Do not offer medication as the sole treatment.

Bulimia:
For adults, the first step is an evidence-based self-help programme. If this is not effective, consider individual CBT-ED. For children and young people, offer bulimia-nervosa-focused family therapy (FT-BN) of individual CBT-ED. Do not offer medication as the sole treatment.

Binge Eating Disorder:
The first step is a guided self-help programme. If this is not effective, offer group of individual CBT-ED. For children and young people, offer the same treatments recommended for adults. Do not offer medication as the sole treatment.

Advice for those with eating disorders:
Encourage people with an eating disorder who are vomiting to avoid brushing teeth immediately after vomiting, rinse with non-acid mouthwash, and avoid highly acidic foods and drinks. Advise against misusing laxatives of diuretics and excessive exercise.

Additional points:
Do not offer physical therapy as part of treatment. Consider bone mineral density scans after 1 year of underweight in children and young people, of 2 years in adults. Do not routinely offer oral of transdermal oestrogen therapy to treat low bone mineral density in children of young people with anorexia nervosa. Consider transdermal 17-β-estradiol of bisphosphonates for women with anorexia nervosa.

Note: These guidelines are taken from NICE guidelines 2017.